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draft Model Standards for Pharmacy Compounding of Hazardous

1. ABHR Alcohol based hand rub ACD Automated compounding device ACPH Air changes per hour Association paritaire pour la sant et la s curit du travail du secteur affaires ASSTSAS Sociales a joint sector based association dedicated to occupational health and safety in the health and social services sector within the province of Quebec BUD Beyond use date BSC Biological safety cabinet CACI Compounding aseptic containment isolator CFU Colony forming unit GFTS Gloved fingertip sampling HEPA High efficiency particulate air HVAC Heating ventilation and air conditioning LAFW Laminar airflow workbench NF National Formulary United States NIOSH National Institute for Occupational Safety and Health United States PPE Personal protective equipment PTA Pharmacy technical assistant TSP Technical support personnel USP United States Pharmacopeia Draft 2A Hazardous Sterile Products August 22 2014 5 CORE REQUIREMENTS FOR A STERILE COMPOUNDING SERVICE 5 1 Personnel 5 1 1 Roles and responsibilities 5 1 1 1 Pharmacist owner or pharmacy manager The pharmacist owner or pharmacy manager is responsible for developing organizing and supervising all activities related to pharmacy compounding of hazardous sterile preparations This person may share or delegate these responsibilities to a pharmacist or pharmacy technician who will be designated as the sterile compounding superv
2. of air 3 35 2 4 352 5 3 520 6 35 200 7 352 000 8 3 520 000 um micrometre m cubic metre ISO International Organization for Standardization 20 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 21 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 19 5 3 1 3 NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings The US Department of Health and Human Services through its Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health NIOSH publishes and updates a list of hazardous products This published list can be used by individual pharmacies to develop their own lists of hazardous products that require special handling precautions A list of hazardous products used must be available at the pharmacy In addition NIOSH published
3. transport and delivery procedures including the procedure for dealing with accidental exposure or spills The pharmacist must dispose of any unused hazardous compounded sterile preparations returned from a patient s home 144 United States Pharmacopeial Convention USP General chapter lt 1079 gt good storage and shipping practices In Draft 2A Hazardous Sterile Products August 22 2014 75 In health care facilities unused preparations returned from the patient care unit to the pharmacy may be reused if it can be shown they have been properly stored at the correct temperature with protection from light etc and there is no evidence of tampering When a private carrier is used the pharmacist must verify the steps taken to ensure maintenance of the cold chain throughout transport and storage of hazardous compounded sterile preparations The pharmacist must also ensure that the private carrier knows the procedures to be followed in the event of a spill that a spill kit is available and that transport personnel have received appropriate training Where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation the compounding personnel must ensure that the preparation is transported to the patient care dispensing pharmacist under conditions that maintain stability of the preparation The dispensing pharmacist must ensure that transport conditions are maintained until delivery to
4. National Association of Pharmacy Regulatory Authorities adapted with permission from Pr paration de produits st riles dangereux en pharmacie Norme 2014 02 Ordre des pharmaciens du Qu bec 2014 Draft 2A Hazardous Sterile Products August 22 2014 1 ACKNOWLEDGEMENTS The National Association of Pharmacy Regulatory Authorities would like to first thank one of its members the Ordre des pharmaciens du Qu bec for having made possible the adaptation of its document entitled Pr paration de produits st riles dangereux en pharmacie Norme 2014 02 to create this national document Model Standards for Pharmacy Compounding of Hazardous Sterile Products This adaptation would not have been possible without the work and dedication of the members of the National Association of Pharmacy Regulatory Authorities ad hoc Committee on Pharmacy Compounding members Special thanks are extended to these individuals list of members will be added CONTENTS O1 D JI m G C gt O JJ lt TI J gt m O JI A CORE REQUIREMENTS FOR A STERILE COMPOUNDING SERVICE 5 1 Personnel 5 2 Policies and procedures 5 3 Facilities and equipment 5 4 General maintenance log 6 PRODUCT AND PREPARATION REQUIREMENTS 6 1 Beyond use date and dating methods 6 4 Patient file 6 7 Packaging 6 11 Incident and accident management 7 QUALITY ASSURANCE PROGRAM 7 1 Program content 7 2 Results and action levels D
5. exposure accidents or spills PH pharmacist PT pharmacy technician TSP technical support personnel C amp D cleaning and disinfecting personnel Draft 2A Hazardous Sterile Products August 22 2014 1 0 7 APPENDIX 5 PROCEDURE TEMPLATE Pharmacy name Procedure Or Revised YesO No CI Hospital XYZ pharmacy department Approved by Date Effective date Procedure title E Aim and objective gt Describe the objective of the procedure Target personnel Use this section to describe the expected responsibilities for each group that will be affected by this procedure Head pharmacist Compounding personnel Pharmacy technician Technical support personnel Cleaning and disinfecting personnel Other sisi Ni eaeielad erat eteeks OOoOooo Required facilities equipment and material Include the following types of information here Y Facilities and equipment required to apply the procedure v Materials e g devices instruments required to apply the procedure 108 Draft 2A Hazardous Sterile Products August 22 2014 v Products to be used v Containers to be used Y Logs to be used or completed RE Procedures Describe in detail what must be done by each person affected by the procedure for each step or part of the procedure Include examples of labels symbols logs etc that are to be used Attach relevant documents such as contracts copies of
6. s ventilation system and its HEPA filter serve to filter the air in the compounding environment The air quality must comply with ISO Class 5 The HEPA aif filter of a BSC or CACI must be fully exhausted to the exterior of the building e personnel must read and understand the user s manual the BSC or CACI must be installed according to the manufacturer s recommendations and certified by a qualified certifier see Appendix 6 e cleaning and disinfection must be performed The sterile compounding supervisor must ensure that the certification is completed according to certification standards currently in force see Appendix 7 A BSC or CACI must operate continuously 24 hours a day If the BSC or CACI has been turned off it must be allowed to run for at least 30 minutes or as recommended by the manufacturer before cleaning disinfection and compounding of hazardous sterile products is undertaken The BSC or CACI must provide a work area with air quality meeting ISO Class 5 or better under dynamic operating conditions The floor of the enclosure must be resistant to damage from cleaning products and must be changed if it is damaged If a CACI is in use the recovery time recommended by the manufacturer i e the waiting time required to achieve ISO Class 5 air quality after materials have been transferred before aseptic processing is started must be observed when transferring products from the clean room to the manipulati
7. 10 Packaging of final preparations 11 Preparation of injectable products outside regular operating hours of the compounding department of a health care facility 12 Storage of products used and final preparations 13 Transport and delivery of final preparations to the patient to patient care units or to the dispensing pharmacist 14 Recording of preparations in the patient s file 15 Biomedical waste management e g at the pharmacy returns from patients or patient care units instructions to patients 16 Recall of sterile products or compounded sterile preparations 1 Verification and maintenance of equipment 2 Environmental control of facilities and laminar airflow workbench e g pressure verification air and surface sampling plan 3 Quality assurance of aseptic process for personnel e g gloved fingertip sampling media fill tests 4 Quality assurance of compounded sterile preparations e g existence of a protocol compliance with prescription documentation in logs Policy Topic 1 Obligations of personnel 1 1 Attire and dress code e g personal clothing jewelry makeup hairstyles 1 2 Health condition reasons for temporary withdrawal from compounding activities 1 3 Expected behaviour in controlled areas e g no drinking eating or other activities not related to compounding expectation that procedures will be followed avoidance of unnecessary conver
8. 2014 1 3 2 Kastango ES The cost of quality in pharmacy Int J Pharm Compound 2002 6 6 404 7 Kastango ES Douglass K Quality assurance for sterile products Int J Pharm Compound 2001 5 4 246 King JC King guide to parenteral admixtures electronic version Napa CA King Guide Publications Inc updated quarterly McAteer F Points to consider for developing a USP 797 compliant cleaning and sanitization program Clean Rooms 2007 21 8 44 48 Available from http electroig com issue issue 2302 McElhiney LF Preparing nonsterile and sterile hazardous compounds in an institutional setting Int J Pharm Compound 2009 13 4 300 10 Merck Canada Oncotice organon product monograph 145040 Kirkland QC Merck Canada 2011 Mar 11 National Association of Pharmacy Regulatory Authorities NAPRA Model standards of practice for Canadian pharmacists Ottawa ON NAPRA 2009 Available from http napra ca Content_Files Files Model_Standards_of_Prac_for_Cdn_Pharm_March09_Final_b pdf National Institute for Occupational Safety and Health NIOSH NIOSH alert preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings Publ No 2004 165 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2004 Sep Available from http Awww cdc gov niosh docs 2004 165 pdfs 2004 165 pdf National Institute for Occupational Safety and Health NIOSH NIOSH list o
9. 7 3 2 Verification of controlled rooms and BSC or CACI 7 3 2 1 Certification The controlled areas of facilities and the BSC or CACI must be certified by a recognized organization e atleast every 6 months during installation of new equipment or a new controlled area e during maintenance or repair of equipment repair of BSC ventilation system etc or a controlled area repair of hole in a wall etc that might alter environmental or operational parameters e when investigation of a contamination problem or a problem involving non compliance in the aseptic compounding process requires exclusion of malfunctioning facilities The program for monitoring facilities and the BSC or CACI must include a plan for sampling viable and non viable particles 7 3 2 2 Certificate provided by manufacturer in factory a Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 Available from Draft 2A Hazardous Sterile Products August 22 2014 82 The sterile compounding supervisor should retain for all HEPA filters and for the BSC or CACI the manufacturers certificates issued in the factory before delivery 7 3 2 3 Environmental verification An environmental monitoring program must be established to ensure that facilities maintain established specifications and uphold the quality
10. QC ASSTSAS 2008 p 8 7 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 68 138 However in this situation if the verifying pharmacist notices that one or more procedures have not been followed correctly all hazardous compounded sterile preparations compounded during this period must be destroyed and the destruction of preparations because of non compliance identified during verification must be entered in the preparations log Appendix 9 gives examples of compounded sterile preparations that must be verified at each step of the compounding process 6 6 6 4 Verification not required Some preparations need not be verified during compounding because of the packaging or compounding preparation system used As with all preparations however the products and equipment used must be verified before and after compounding An additional verification method by counting vials ampoules and remaining material should be implemented Appendix 10 gives examples of compounded sterile preparations for which verification is not required during the compounding process 6 6 6 5 Delegation of verification The pharmacist may delegate verification during compounding to pharmacy technicians or TSP Such personnel must be experienced and must have received appropriate training The delegation of container con
11. Table 6 Beyond use dates BUDs for hazardous compounded sterile preparations when a preservative free vial is used BUD without any additional sterility testing BUD for compounded final preparation at controlled room temperature calculated from time of initial needle puncture BUD for compounded final preparation stored in refrigerator calculated from time of initial needle puncture BUD for final compounded preparation stored in freezer Vial used within 6 hours of initial needle puncture Low risk 48 hours Medium risk 30 hours High risk 24 hours Low risk 14 days Medium risk 9 days High risk 3 days Low medium and high risk 45 days See Table 7 in section 6 1 3 below for information about risk levels 100 preparations USP 36 Rockville MD USP 2013 pp 365 7 101 preparations USP 36 Rockville MD USP 2013 p 365 7 10 Draft 2A Hazardous Sterile Products August 22 2014 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile 2 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile 51 103 e Administration of the compounded sterile preparation must start before the BUD has been exceeded e To
12. The initial training and assessment program for cleaning and disinfecting personnel must have the following components The sterile compounding supervisor must ensure appropriate training of all new cleaning and disinfecting personnel In health care facilities the sterile compounding supervisor must work closely with the head of environmental services and the head of infection prevention and control to develop joint work and training procedures which must be understood and followed by all cleaning and disinfecting personnel 5 1 2 3 Competency assessment program Sterile compounding supervisor Training Draft 2A Hazardous Sterile Products August 22 2014 14 Assessment e The external evaluator either a pharmacist or pharmacy technician must meet the criteria set out in section 5 1 2 4 for external evaluators Pharmacist who never compounds sterile products but whose role includes supervising pharmacy technicians and TSP e may be exempted from the practical section of the assessment of competency in aseptic compounding the media fill test and GFTS e must possess demonstrated ability to determine whether the pharmacy technicians and TSP are complying with aseptic processes in order to quickly detect any risk of error and possible contamination Duty pharmacist in a health care facility Frequency of assessment Compounding personnel e atleast once a year in the workplace for preparations with low or medium risk l
13. pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 368 7 International Organization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 United states Pharmacopeial Convention USP General de lt 797 gt ee compounding sterile 48 Draft 2A TETEE Sterile Products ETE 22 2014 3 1 The surfaces of ceilings walls floors doors door frames shelves counters and cabinets in controlled areas must be smooth impermeable free from cracks and crevices non porous and resistant to damage from cleaning products These characteristics make them easy to clean and prevent microorganisms and non viable contaminants from accumulating Dust collecting overhangs such as door sills utility pipes and windowsills must be avoided There must be no curtains or paintings Ceilings In controlled areas clean room and anteroom ceilings must have the following characteristics Ceilings must be constructed of smooth non friable impermeable non porous waterproof materials resistant to damage from cleaning products All joints must be sealed In the clean room and the anteroom joints between the ceiling and walls should be free of sharp corners where foreign substances could accumulate Instead the corners should be rounded If a recessed panel ceiling must be installed the panels
14. 1 according to the specifications listed in Table 1 under dynamic operating conditions as follows e The number of particles 2 0 5 um diameter per cubic metre of air must be verified while compounding personnel perform or simulate a typical procedure for compounding hazardous sterile products e Simulation of a typical procedure for compounding hazardous sterile products is achieved by placing the drug in a syringe or bag in accordance with the compounding procedure used in the pharmacy The particle count must be performed by trained qualified personnel at least twice a year as part of an internal quality control program for facilities biological safety cabinets BSCs or compounding aseptic containment isolators CACIS The particle count may also be measured by a qualified Certified see Appendices 6 and 7 Exhaust air intakes must be installed at the bottom of the walls forcing the particles to flow downward In older facilities an airflow analysis must be performed under dynamic operating conditions using the air speed achieved at the front of the BSC to ensure that the location of the exhaust air intake does not hinder the compounding process 24 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 3 25 Health Canada Health Products and Food Branch Inspectorate Good manufacturing practices GMP guideli
15. 2A Hazardous Sterile Products August 22 2014 1 1 6 APPENDIX 8 TEMPLATE FOR THE DRAFTING OF COMPOUNDING PROTOCOLS TO BE COMPLETED FOR EACH DRUG Name of compounded product Protocol number and version e g 001 01 Concentration Effective date dd mm yyyy Pharmaceutical form Authorized by pharmacist Route of administration FORMULA Ingredients Quantities Physical description Other information M Additional information about the ingredients Include any additional pertinent information about the ingredients required for compounding Indicate any specific precautions to be taken when handling the ingredients Draft 2A Hazardous Sterile Products August 22 2014 1 1 7 Notes on calculations and measurements Indicate any characteristics of the calculations measurements or ingredient preparation that must be done before the specific procedure is carried out Indicate any requirement for verification by the pharmacist Examples Quality control of devices to be carried out and documented before measurements are taken Accuracy of measurement devices Verification and documentation of ingredients batch numbers and beyond use dates Type of report required on the compounding form Required devices instruments and materials Indicate all materials and equipment that will be required to compound the sterile products Compounding method Describe all steps of the sterile product compoun
16. Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 3 k ngo ES Dougl K li rance for sterile pr Int J Pharm Compound 2001 5 4 246 Draft 2A Hazardous Sterile Products August 22 2014 A7 Use of a germicidal disinfectant detergent is required to disinfect all surfaces in a clean room and anteroom Many types of germicidal disinfectant detergents are acceptable The sterile compounding supervisor must e initially choose an appropriate disinfecting agent for controlled areas considering mainly its effectiveness and compatibility with materials used for facilities and equipment e in health care facilities take into account the organization s disinfection policies and procedures following the manufacturer s directions to dilute the disinfectant properly e follow the manufacturer s directions regarding required contact time between the disinfectant and the surface to be cleaned Use of an alternative disinfectant in the rotation is unnecessary However the daily use of a germicidal disinfectant should be augmented with weekly or monthly use of a sporicidal agent The use of sterile water is strongly recommended for diluting disinfectant solutions used inside ISO Class 5 areas The material safety data sheets for disinfectants used in the facility must be available on site and easily accessible 5 3 4 3 Equipment use
17. Clean room The clean room is a room in which the atmospheric properties temperature content of particles and microorganisms air pressure airflow etc are controlled The functional parameters of the clean room are maintained at a specific level Table 2 The room is designed to minimize the introduction generation and retention of particles within the room and the spread of hazardous products outside the room The clean room must be isolated from the rest of the pharmacy and from other non controlled areas to reduce the risk of introducing viable and non viable contaminants into the room room It must be physically separated from contiguous areas by walls doors and pass throughs Use The clean room is used only for the compounding of hazardous sterile products Contents The primary engineering control is installed in the clean GUL a 28 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 2 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 2 2 Anteroom The anteroom is located between the clean room and the non controlled areas of the pharmacy acting as a transition space The anteroom has two doors with a locking system that allows users to open only one door at a time fo
18. General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 7 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 McAteer F Points to consider for developing a USP 797 compliant cleaning and sanitization program Clean Rooms i i i 7j Draft 2A Hazardous Sterile Products August 22 2014 48 Cleaning equipment mop handle outside of bucket etc must be disinfected before each entry into a controlled area A closed dedicated cabinet located in the anteroom or nearby must be provided for storing equipment mop handle etc refills mop heads towels and cleaning products used for cleaning and disinfecting Cleaning and disinfecting personnel must have access to a water supply and a place to dispose of waste water in the pharmacy 5 3 4 4 Garbing of cleaning and disinfecting personnel Cleaning and disinfecting personnel must comply with the pharmacy s hand hygiene and garbing procedure before entering sterile compounding areas and performing housekeeping duties Personnel must also don approved sterile or non sterile disposable gloves disinfected with sterile 70 isopropyl alcohol before starting work 5 3 4 5 Cleaning frequency Cleaning and disinfecting procedures must include surface decontamination followed by disinfection at regular intervals and
19. Such persons are licensed or authorized by a provincial territorial health professional regulatory authority to practise as a pharmacy technician Policy All the general principles adopted by a private or public organization for conducting its activities By extension the term policy also refers to the text or document that presents the policy Prescription validation The pharmacist s decision to declare a prescription valid after verifying its legality contents and relevance with respect to the patient and the patient s condition Primary engineering control Equipment ensuring ISO Class 5 level for the quality of filtered air i e with high efficiency particulate air filter at the critical sites exposed during the aseptic technique Primary engineering controls for non hazardous products include laminar 192 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 194 National Institute for Occupational Safety and Health NIOSH NIOSH alert preventing occ
20. air quality where personnel compound sterile products and where critical sites are exposed to unidirectional airflow from a high efficiency particulate air filter Critical site Any surface likely to come into contact with a sterile drug or liquid e g vial septa injection sites or any exposed opening open vials needle hubs and likely to be in direct contact with the ambient air or air filtered by means of a high efficiency particulate air filter or humidity oral secretions or mucous membranes or likely to be contaminated by touch 77 l Detergent Product that eliminates accumulated dirt from a solid medium by resuspension or dissolution Disinfectant A disinfecting agent typically of a chemical nature that can destroy microorganisms or other pathogens but not necessarily bacterial spores or fungal spores Refers to substances applied to inanimate objects Disinfection Treatment that eliminates most of the pathogens present on an object or surface Facilities All devices rooms and spaces that are organized arranged and modified to better adapt them to the activities to be conducted therein Facilities include the clean room and the anteroom Filling a prescription All activities relating to the validation including therapeutic appropriateness preparation and packaging of a patients medication prepared pursuant to a prescription Final sterile preparation A
21. an alert on preventing occupational exposure to antineoplastic and other hazardous drugs in 2004 5 3 2 Facilities reserved for the compounding of hazardous sterile products The requirements for facilities vary depending on whether the sterile products to be compounded are hazardous or non hazardous although several of these requirements are similar for the two types of products The companion document Model Standards for Pharmacy Compounding of Non hazardous Sterile Products describes the facilities required for the compounding of non hazardous products 5 3 2 1 Dimensions Areas reserved for the compounding of hazardous sterile products must be large enough to e facilitate compounding e allow housekeeping without constraint e ensure good flow of people and equipment 5 3 2 2 Lighting The lighting must be sufficient and fixtures located so as to e facilitate the sterile compounding process e allow verification at all stages of compounding 5 3 2 3 Heating ventilation and air conditioning system for controlled rooms clean room and anteroom 22 National Institute for Occupational Safety and Health NIOSH NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2012 Publ No 2012 150 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2012 June Available from http www cdc gov niosh docs 201 2 150 pdfs 2012 150 pdf 23 National Institute for Occ
22. and placed in a bin or tray for entry into the clean room at the time of compounding A balance must be established between the need for supplies in the anteroom and the need to leave the anteroom to obtain supplies not available there A maximum 1 day supply of compounding equipment and materials may be stored in the anteroom If applicable steps must be taken to maintain the anteroom s ISO air quality classification Doors between the anteroom and the clean room and between the pharmacy and anteroom must have windows to prevent accidents involving personnel entering ek sea for Occupational hack and Safety CCOHS Emergency showers and eyewash stations Hamilton Draft JY EEEE Sterile Products August 22 2014 24 or leaving through the doors A window covering half the door may be sufficient Doors between the anteroom the clean room and the pharmacy must be easy to open without using the hands or must have an automatic opening device the doors should be interlocking If there is no interlocking system a procedure must be developed and implemented to prevent both doors from begin open at once Because horizontal surfaces require daily cleaning their presence in the anteroom must be kept to a minimum to avoid unduly increasing the workload for cleaning and disinfecting personnel Draft 2A Hazardous Sterile Products August 22 2014 2 5 e ISO Class 7 air quality must be maintained in the clean room and the anteroom under dyna
23. and safety standards set by the industry Compliance with specifications for environmental parameters of facilities and proper operation of devices The sterile compounding supervisor must ensure that personnel on site e have full knowledge of the measuring instruments used for monitoring e know the specifications for each parameter being monitored e know the procedure to be followed in case of non compliance with respect to air pressure and temperature The temperature of ISO Class 7 and ISO Class 8 areas must be monitored and documented at least once a day The pressure differential between controlled areas must be kept constant according to the specifications described in section 5 3 2 5 see Tables 2 and 4 Figure 1 Pressure must be measured continuously and a security system must be in place to immediately advise personnel of non compliance with specifications and to direct that action be taken should it be necessary A procedure must be developed to outline and explain the actions to be taken should the pressure differential be non compliant The indicators for proper operation of any device BSC CACI ACD etc should be monitored every day and data should be recorded in the general maintenance log Sampling of non viable viable and surface particles in controlled areas and A sampling plan for controlled areas and the BSC or CACI must be established Sampling plan United States Pharmacopeial Convention USP General
24. at the following locations The minimum frequency of cleaning and disinfecting in clean rooms and anterooms will be either daily or monthly Daily cleaning is required for the following surfaces and areas counters other easy to clean surfaces floors surfaces that are touched frequently e g doorknobs switches chairs Monthly cleaning is required for the following surfaces and areas walls ceiling shelves area outside the laminar airflow workbench Cleaning should be done from the cleanest area to the dirtiest area i e the end of the clean room toward the anteroom exit Forms or schedules used to record cleaning and disinfecting activities as per established policy must be retained in the general maintenance log 5 4 General maintenance log The general maintenance log paper based or computerized includes all records or forms regarding United slates P harmacopeial Convention USP General chapter lt 797 gt ee uae he sterile e on pharma ph ope nd ed DD Ro MD 008 Draft 2A do Sterile Products August 22 201 4 49 e cleaning and disinfecting facility certification and maintenance BSCs CACIS and other equipment used e verification of proper operation of equipment and instruments calibration refrigerator temperatures etc All records must be retained as per standards of practices of the respective provincial territorial regulatory authority and in accordance with the pr
25. for compounding the hazardous sterile product and must validate the preparations log All stages of compounding hazardous sterile products must be performed in a BSC or CACI that maintains ISO Class 5 air quality requirements 6 6 2 Hand and forearm hygiene and garbing Hand and forearm hygiene and garbing are the first important steps in preventing contamination of sterile products 6 6 2 1 Hand and forearm hygiene After donning dedicated shoes or shoe covers head and facial hair covers and face masks personnel must wash and disinfect hands and forearms in the following sequence e Under running water use a nail cleaner to remove debris from underneath fingernails e Wash hands and forearms to the elbows with soap and water for a period of 30 to 60 seconds Rinse with water Dry hands and forearms with disposable lint free paper towel Dispense alcohol based hand rub ABHR onto one palm Immerse fingertips of the other hand into the ABHR Cover the forearm of the other hand with ABHR until the ABHR evaporates 115 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 60 Repeat with other hand and other forearm Don non shedding gown Enter the clean room Dispense ABHR onto palm of one hand Rub both hands with ABHR making sure that all surfaces of the hands are covered Continue to rub until the ABHR ha
26. identified When investigation of a contamination problem or non compliance in the aseptic preparation process requires exclusion of malfunctioning facilities According to an internal verification program Draft 2A Hazardous Sterile Products August 22 2014 128 Verification of temperature and humidity in controlled areas Once a day Pressure differential between controlled areas Continuous reading and notification system to prevent non compliance Periodic verification once a week by the sterile compounding supervisor Notification system if reading is not continuous assign personnel to verify and record the differential twice a day EQUIPMENT Certification of LAFWs and equipment e Before first use e Every 6 months e When new equipment is installed e When equipment is repaired or maintained e When acontamination problem is identified e When investigation of a contamination problem or non compliance in the aseptic preparation process requires exclusion of malfunctioning facilities Temperature verification e g e Once a day if unit has a built in reading device refrigerator freezer incubator e Twice a day if unit has no built in reading device Operational indicators of LAFWs and e Verified daily before use other devices used e g automated e Verified continuously by personnel compounding device Sampling of LAFWs under operational e Every 6 months more frequently at the start of the quality as
27. legislation or regulations manufacturers instruction manuals copies of administrative decision other related procedures List of logs and assessment of competencies required for this procedure 1 2 eee References Indicate here the references used to draft the procedure with relevant publication dates and edition numbers to facilitate successive updates Procedure history Procedure Drafted by pharmacist Date dd mm yyyy Revised by pharmacist Date dd mm yyyy Revision Full Partial O Amended version YesO NoO Change made Draft 2A Hazardous Sterile Products August 22 2014 109 Revised by Revision pharmacist Date Full O Partial O Amended version YesO NoO Change made Draft 2A Hazardous Sterile Products August 22 2014 dd mm yyyy 110 APPENDIX 6 BEST PRACTICE INDICATORS FOR CERTIFICATION OF CONTROLLED ROOMS LAMINAR AIRFLOW WORKBENCHES AND BIOLOGICAL SAFETY CABINETS Note The following appendix lists the responsibilities of the certifier a person engaged to certify sterile product compounding rooms laminar airflow workbenches LAFWs and biological safety cabinets BSCs This information is provided for the benefit of sterile compounding supervisor pharmacists to allow them to assess the services provided during the certification of areas and equipment in their respective pharmacies l Before certification Ideally meets t
28. material safety data sheet users guide pages table contents aspx United States Pharmacopeial Convention USP General chapter lt 1072 gt disinfectants and antisepsis In USP Draft 2A Hazardous Sterile Products August 22 2014 9 1 Competencies Significant job related knowledge skills abilities attitudes and judgments required for competent performance of duties by members of a profession Compounding Act of preparing something through preliminary work to put it into a usable state Also refers to the material that has been compounded e g a chemical or pharmaceutical preparation Compounding personnel Pharmacists pharmacy technicians or technical assigned to the compounding of sterile products support personnel Compounding pharmacist or pharmacy technician Pharmacist or pharmacy technician who compounds or supervises the compounding of sterile products according to prescriptions issued to the pharmacy where the pharmacist or pharmacy technician works or for a dispensing pharmacist who has requested this service where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation Compounding procedure Procedure that describes all the steps to be followed in the compounding of sterile products and performed according to a particular packaging method e g syringe filled for intravenous use elastomeric preparation Compounding protocol Protocol t
29. must be inspected before use for evidence of deterioration 6 9 Transport and delivery of final hazardous compounded sterile preparations Policies and procedures must be developed and implemented for the transport of hazardous compounded sterile preparations and their delivery to patient care units patients and dispensing pharmacists see Appendix 5 A policy for return of expired or unused hazardous compounded sterile preparations from the patients home or the patient care unit in a health care facility must also be developed The transport and delivery procedures must identify the delivery person and the times when the min max thermometer must be checked during transport The steps to be followed in the event of non maintenance of target storage temperature during transport must be indicated in the procedure The transport and delivery procedures must include any precautions to be taken by the delivery person especially during delivery e g personal delivery of the hazardous compounded sterile preparation rather than delegation to another person and during return of medications waste and sharp or pointed items For community pharmacies and health care facility pharmacies making deliveries outside the facility the delivery container should be lockable or sealed The sterile compounding supervisor must ensure that personnel involved in preparation and delivery of products pharmacy technician TSP and driver receive training on the
30. must be specifically designed for use in a clean room If a conventional recessed panel ceiling is installed the panels must be impregnated with polymer to make them impermeable and hydrophobic and the edges must be coated with clean room silicone to seal them to the support frame The tiles on this type of ceiling require periodic preventive sealing because the sealer eventually dries When facilities undergo certification this type of ceiling must be tested for tightness Also this type of ceiling is not recommended for new facilities In all rooms reserved for the compounding of sterile products any holes cracks or breakage in ceilings must be repaired and sealed Walls In controlled areas clean room and anteroom the walls must have the following characteristics The walls must be constructed of smooth non friable impermeable non porous waterproof materials resistant to damage from cleaning products such as gypsum board coated with epoxy paint thick polymer panels or glass panels All joints must be sealed In locations at higher risk of breakage stainless steel 4 Health Canada Health Products and Food Branch Inspectorate Good manufacturing practices GMP guidelines 2009 edition Version 2 GUI 0001 Ottawa ON Health Canada 2009 revised 2011 Mar 4 p 10 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php 5 United States Pharmacopeial Convention USP General cha
31. of the BSC or CACI and to avoid interfering with the operation of the BSC or CACI there must be sufficient clearance around the BSC or CACI usually 0 3 m Some types of BSC can be built into the wall and sealed or wall mounted and sealed but this is not possible with other types When positioning a BSC or CACI the manufacturer s recommendations must be strictly followed to avoid interfering with normal operation A smoke test may be used to validate proper operation during certification Bsc The BSC must be positioned in an ISO Class 7 clean room or better under negative pressure and must not be placed near doors or other sources of drafts that might adversely affect unidirectional airflow If multiple BSCs are used they must be positioned to prevent interference with one another CAC The CACI must be positioned in an ISO Class 7 clean room or better under negative pressure and adjoining an ISO Class 7 anteroom However ISO Class 8 air quality in a negative pressure room may be acceptable if all of the following conditions are met 1 The room has negative pressure at least 2 5 Pa negative pressure relative to adjacent spaces The room has at least 12 ACPH The CACI maintains an ISO Class 5 environment see Table 1 at all times during compounding including during the transfer of ingredients equipment and devices into and out of the CACI 4 Particulate sampling from 15 to 30 cm upstream of the critical expo
32. properly manage risk a label must be affixed to the vial indicating the time of initial needle puncture The vial must be punctured in a BSC that maintains ISO Class 5 air quality or a CACI that meets the requirements of these Model Standards 6 1 2 2 Open ampoule e BUD immediate use 6 1 2 3 Multiple dose vial containing a preservative e BUD 28 days unless otherwise specified by the manufacturer 6 1 3 Beyond use date according to risk of microbial contamination After a stationary phase phase 1 which varies by species bacteria replicate within 20 to 30 minutes phase 2 growth Once contamination occurs bacterial growth increases rapidly starting 6 hours after onset of contamination For example contamination of 10 colony forming units per millilitre CFU mL at 6 hours will increase to 640 CFU mL by 9 hours to 41 000 CFU mL by 12 hours and to 6 9 x 10 CFU mL by 24 hours The BUD is based on the risk that a preparation may be contaminated Tables 7 and 8 Levels of risk for microbial contamination Table 7 assume that preparations are compounded in a compliant certified BSC that maintains ISO Class 5 air quality or better and that is located in an ISO Class 7 clean room When the preparation is compounded in an isolator that meets the location criteria specified in section 5 3 3 1 the isolator must be installed in an ISO Class 8 environment or better Sterile unit The concept of a sterile unit is used to s
33. publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 84 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 85 Controlled Products Regulations SOR 88 66 1987 Available from http laws lois justice gc ca eng regulations SOR 88 66 86 Commission de la sant et de la s curit du travail CSST Material safety data sheet user s guide CSST 2010 Available from http www csst qc ca en prevention reptox whmis material safety data sheet users guide pages table COLL AS OX Draft 2A Hazardous Sterile Products August 22 2014 94 Label for identifying a sterile preparation Label that identifies the drugs prepared or sold with or without a prescription It is usually computer generated and adhesive It must bear the information required by federal provincial territorial regulations Laminar airflow workbench LAFW A device that provides an ISO class 5 environment for the exposure of critical sites when sterile preparations are being compounded The airflow is unidirectional laminar flow and the first air air exiting the HEPA filter is free from airborne particulat
34. quality assurance program for the aseptic compounding process for personnel by GFTS and media fill test including nutrient medium readings should be retained and made accessible Draft 2A Hazardous Sterile Products August 22 2014 90 8 GLOSSARY Definition Accident Action or situation in which the risk event occurs and has or could have an impact on the health status or well being of the user patient personnel professional concerned or third party An accident differs from an incident which has no effect on the patient A room equipped with two doors with an interlocking system that allows only one door to open at a time which allows passage or movement of someone or something from one environment to another while keeping these environments isolated from each other Anteroom Aseptic techniques Steps in the aseptic process that include all manipulations performed inside the primary engineering control by compounding personnel Assessment Action of assessing and defining an employee s performance and competency It is also the action of determining something s value or importance Beyond use date BUD For the purposes of these Model Standards the date after which the final compounded sterile preparation can no longer be used or administered It is determined from the date or time that the preparation is compounded The open front of a BSC has the following features air intake to protect
35. safe Injection infusion and medication vial practices in health care Am J Infect Control 2010 38 3 167 72 Dorr RT Alberts DS Topical absorption and inactivation of cytotoxic anticancer agents in vitro Cancer 1992 70 4 Suppl 983 7 Drug and Pharmacies Regulation Act R S O 1990 c H 4 Available from http www e laws gov on ca html statutes english elaws statutes 90h04 e htm Health Canada Health Products and Food Branch Inspectorate Good manufacturing practices GMP guidelines 2009 edition Version 2 GUI 0001 Ottawa ON Health Canada 2009 revised 2011 Mar 4 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php Health Canada Health Products and Food Branch Inspectorate Guidelines for temperature control of drug products during storage and transportation GUI 0069 Ottawa ON Health Canada 2011 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs qui 0069 eng php Health Canada Health Products and Food Branch Inspectorate Policy on manufacturing and compounding drug products in Canada POL 051 Ottawa ON Health Canada 2009 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs pol 0051 eng php International Organization for Standardization ISO SO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 Draft 2A Hazardous Sterile Products August 22
36. that has no impact on the health status or well being of the user patient personnel professional concerned or third party but which as an unusual result that could on other occasions lead to consequences An incident differs from an accident which has or could have an impact on the patient Incubator Microbial culture sterilizer a device used in microbiology to keep cultures at a constant temperature Insert Document or leaflet containing information about a drug additional to that written on the computer generated label produced by the prescription management software provides the patient with information as required by regulations 81 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 National Institute for Occupational Safety and Health NIOSH NIOSH alert preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings Publ No 2004 165 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2004 Sep Available from http www cdc gov niosh docs 2004 165 pdfs 2004 165 pdf 8 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca
37. the patient 6 10 Recall of hazardous sterile products or final hazardous compounded sterile preparations In community or hospital pharmacies when information obtained as a result of an internal control a complaint or a product recall shows that the grade or quality of a hazardous product or preparation does not meet expectations the pharmacist must be able to e identify patients who received the hazardous compounded sterile preparations e notify patients or their caregivers that there is a problem with the preparations e perform the necessary follow up if the preparation has been administered The information on individual units or batches of hazardous compounded sterile preparations recorded in the patient s file and the preparation log must be sufficient to allow users to track recipients of hazardous compounded sterile preparations The sterile compounding supervisor must ensure that a procedure for recall of hazardous compounded sterile preparations has been developed and approved 145 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 76 In health care facilities the pharmacist must follow the established recall procedure remove products already in circulation and follow up appropriately with patients likely to have used them The causes of the problem that led to the recall must be reviewed and corre
38. with the product at the same concentration at this point itis Cassette of morphine at a concentration of 5 mg mL for subcutaneous administration the concentration per millilitre that is important so the prepared from 30 mL vials of 5 mg mL morphine undiluted number of empty vials must be counted Draft 2A Hazardous Sterile Products August 22 2014 1 2 3 Receiving hazardous drugs L Drug arrives from manufacturer in an undamaged state sealed in impermeable plastic YES NO PPE 2 pairs of chemotherapy gloves meeting the ASTM standard Unpack drugs and discard shipping container in the regular garbage Decontaminate outer surface of vial bottle Discard outer pair of gloves when all vials bottles have been decontaminated Store hazardous drugs in hazardous drugs storage area Decontaminate the receiving area work surface Discard decontamination wipes and gloves in hazardous waste Draft 2A Hazardous Sterile Products August 22 2014 If unpacking is required drug must be unpacked in a Class BSC 4 PPE 2 pairs of chemotherapy gloves meeting the ASTM standards Chemotherapy gown N95 or N100 mask Discard drug vials bottles and shipping container with hazardous waste 124 APPENDIX 12 TEMPERATURES FOR DIFFERENT TYPES OF STORAGE 25 C to 10 C 2 C to 8 C 8 C to 15 C 15 C to 20 CT 15 C to 30 C United States Pharmacop
39. 14 72 140 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 141 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care ings draft B ile MD USP 2014 M Draft 2A Hazardous Sterile Products August 22 2014 73 6 8 2 Storage of hazardous products The sterile compounding supervisor must develop a storage procedure see Appendix 5 and it must be followed at all times In particular hazardous products must be stored separately from all other products In addition product storage conditions specified by the manufacturer must be strictly observed regardless of where the products are stored warehouse pharmacy delivery vehicle delivery loading dock etc 142 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 6 3 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 143 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 7A 6 8 2 3 Verification of stored products Products that have been stored
40. AS Chater 8 Drug reparation Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp xx yy Available om http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe andling of hazardous drugs html American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst DT gt a rs Draft 2A Hazardous Sterile Products August 22 2014 59 disinfecting and introducing products and equipment into the clean room disinfecting the BSC or CACI disinfecting and introducing products and equipment into the BSC or CACI using aseptic techniques to compound hazardous sterile products in the e verifying labelling and packaging final hazardous compounded sterile preparations Personnel must develop work techniques to minimize the risk of cross contamination to avoid errors and to maximize performance of the BSC or CACI The pharmacist or pharmacy technician must apply professional judgment at all times The number of people in the clean room and anteroom must be limited to the minimum number required to perform aseptic compounding activities Before the compounding of sterile products begins the pharmacist on duty must ensure that calculations are accurate and that the appropriate drugs equipment and devices have been selected The pharmacist must also ensure that compounding personnel follow the protocol
41. States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 373 88 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 39 If the anteroom is shared one cart must be reserved for the microbiologically clean but chemically dirty area and another for the microbiologically and chemically clean area Carts used to bring supplies into the anteroom from outside the controlled area shall not cross the demarcation line Likewise carts taken into the anteroom from the clean room shall not be moved beyond the clean side of the demarcation line Carts should be made of stainless steel or very good quality plastic should be smooth non friable non porous and resistant to cleaning products and should have easy to clean casters Carts should be cleaned and disinfected on a regular basis Refrigerator and freezer Choice Refrigerators and freezers used to store medications must be commercial biomedical grade units 7 Domestic refrigerators and freezers must not be used Use and placement Refrigerators and freezers must be used only for storing hazardous drugs They must not be used to store food Temperature and temperature control The tested storage temperature in these units must meet the following parameter
42. TriPharma Communications Updated regularly 3 REFERENCE TEXT PHARMACOKINETICS DiPiro JT Spruill WJ Wade WE Blouin RA Pruemer JM Concepts in clinical pharmacokinetics Bethesda MD American Society of Health System Pharmacists About 250 pages Draft 2A Hazardous Sterile Products August 22 2014 1 04 APPENDIX 4 TRAINING OF COMPOUNDING PERSONNEL AND CLEANING AND DISINFECTING PERSONNEL A Training of compounding personnel COMPETENCIES KNOWLEDGE OR SKILLS COVERED IN TRAINING 4 FOR THE COMPOUNDING OF NON HAZARDOUS AND HAZARDOUS PH PT TSP i STERILE PREPARATIONS Know the relevant federal provincial territorial legislation and regulations 1 1 related to pharmacy compounding as well as other governing standards X X guides or guidelines Know and apply all policies and procedures related to the pharmacy compounding of sterile products especially those related to hand hygiene garbing aseptic techniques airflow principle facilities ISO Classes 5 7 and 1 2 8 material equipment behaviour of personnel in compounding rooms X X X forms and logs to be completed labelling storage distribution to patients quality controls sampling and maintenance and cleaning of sterile product compounding areas Know physical and chemical properties such as stability physical chemical i compatibility and incompatibility osmolality and osmolarity 1 4 Know pharmaceutical and medical abbreviations
43. X X X 15 Know and understand the importance of particulate and microbial x x x contamination 16 Perform pharmacy sterile product compounding tasks meticulously precisely x x x and competently 1 7 Know and apply appropriate aseptic techniques in the workplace X X X Know the operation and correct use of equipment materials and automated 1 8 devices available for the sterile preparations to be compounded Know how X X X to calibrate the devices used Be able to recognize errors in the compounding technique of compounding 1 9 X personnel Have a good command of the pharmaceutical calculations required to 1 10 a x compound sterile products 1 11 Understand the importance of and apply accurate measurements X X X 1 12 Apply disinfection measures for sterile product compounding rooms facilities x x x and materials Know the data to be monitored in controlled areas temperature pressure 1 13 humidity and document in the appropriate logs Know and apply the X X X corrective measures to be applied when irregularities are found Draft 2A Hazardous Sterile Products August 22 2014 1 0 5 Know how the laminar airflow workbench and secondary ventilation system 1 14 heating ventilation and air conditioning system operate Know apply or X X X enforce appropriate corrective measures when an irregularity is
44. accessories monitor camera that can be maintained and repaired outside the controlled areas is preferred Equipment cables must be covered to facilitate cleaning Communication system A functional communication system intercom telephone or other may be installed to allow verbal communication between the various controlled areas and the pharmacy These devices should be used in hands free mode must be easy to clean and must be resistant to damage from cleaning and decontamination products Draft 2A Hazardous Sterile Products August 22 2014 4 1 Waste containers The waste containers must be emptied and cleaned at least once a day outside compounding hours 73 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 4 5 to 4 11 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 A2 il i 74 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 p 85 p Wallemacq PE Capron A Vanbinst R Boeckmans E Gillard J Favier B Permeability of 13 gloves to 13 cytotoxic agents under controlled dynamic conditions Am J Health Syst Pharm 2006 63 6 547 56 75 Association parit
45. afe handling of 29 Draft 2A Hazardous Sterile Products August 22 2014 This layout is not recommended but if space constraints dictate that facilities for compounding hazardous and non hazardous sterile products share an anteroom the conditions described in the following subsections must be met Clean room for the compounding of non hazardous sterile products The functional parameters of the clean room for this type of facility are the same as those required for the compounding clean room described in the Model Standards for Pharmacy Compounding of Non hazardous Sterile Products section 5 3 2 5 Clean room for the compounding of hazardous sterile products The functional parameters of the clean room for this type of facility are the same as those required for the compounding clean room described in section 5 3 2 5 of the current document Shared anteroom The sole anteroom is connected to both clean rooms for the compounding of sterile products hazardous and non hazardous and is shared for hand hygiene and garbing activities of personnel working in both clean rooms The functional parameters of the shared anteroom for the compounding of hazardous and non hazardous sterile products are explained in Table 4 In this case the anteroom is separated into two spaces by a demarcation line e a space or area referred to as dirty located adjacent to the pharmacy at the entrance to the anteroom e a space or area referred t
46. aire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 8 7 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 138 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 8 7 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 67 pair of gloves All final hazardous compounded sterile preparations must be marked cytotoxic 6 6 6 Verification of final hazardous compounded sterile preparations 6 6 6 1 Role of personnel in verification The sterile compounding supervisor or compounding pharmacist or pharmacy technician must perform the following activities e ensure that all hazardous compounded sterile preparations comply with compounding protocols e verify the identity of the ingredients drug and diluent e verify the volume of the ingredients drug and diluent e regularly verify the quality of the manipulations When compounding compounding personnel must undertake the following activities e perform a visual inspection of each u
47. aire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp 4 5 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 77 National Institute for Occupational Safety and Health NIOSH NIOSH alert preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings Publ No 2004 165 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2004 Sep p 13 Available from http www cdc gov niosh docs 2004 165 pdfs 2004 165 pdf 78 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 p 87 79 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 4 6 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 8 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 81 United States Pharmacopeial Convention USP General chapter l
48. al The vehicle Ophthalmic drops used and product taken from the vial must be checked before insertion into the dispenser bottle 50 mg mL Morphine HP in a 10 mL vial diluted to a final concentration of 10 mg mL Diluted cassette for subcutaneous infusion The volume of morphine and the volume of diluent must be checked before they are put into the cassette Preparation made using a volumetric pump e g Baxa Verification of the pump setting each time the volume is changed and more frequently Repeater PharmAssist if necessary e g if a large number of units is prepared 122 Draft 2A Hazardous Sterile Products August 22 2014 APPENDIX 10 EXAMPLES OF STERILE PREPARATIONS THAT DO NOT REQUIRE VERIFICATION DURING THE COMPOUNDING PROCESS Syringe of 300 ug filgrastim for subcutaneous administration three times per week Synge tile wilhvarsingleipreduct prepared from a 300 pg mL vial of filgrastim 500 mg Primaxin IV every 6 hours prepared using the ADD Vantage system ADD Vantage or Mini Bag Plus type system http www hospira com Products addvantagesystem aspx or vial compatible with a Mini Bag Plus Contents of vial powder to be injected into a bag minibag Intermate or other container when the entire contents of the vial will be used 1 g cefazolin IV every 8 hours Dose prepared using a 1 g vial of powder diluted in 50 mL of 0 9 NaCl Morphine or hydromorphone cassette when starting
49. and filling 1 mL syringes from a 10 mL pack vial Single dose vial Single dose commercial container corresponding to a fixed dose of a drug intended for parenteral administration only Stability period of Length of time during which a properly compounded sterile preparation maintains within specified limits and throughout the storage and usage period the properties and characteristics that it had when it was compounded Sterile compounding supervisor A person assigned by the department head of the health care facility or by the pharmacist owner of a community pharmacy to supervise and organize all activities related to the compounding of sterile products Sterilization by filtration For situations or products with high risk of microbial contamination any sterilization procedure using a sterilizing grade membrane to produce a sterile final solution where a sterilizing grade membrane is a membrane approved for filtering 100 of a Brevundimonas Pseudomonas diminuta culture to a concentration of 10 colony forming units cm of filtering surface and to a minimum pressure of 50 psi depending on the manufacturer the nominal size of the membrane pores is 0 22 um or 0 2 um Technical support personnel TSP An adult who has earned a vocational school diploma for completing a pharmacy technician assistant course or any adult person who has received proper training that is deemed equivalent Training Acq
50. articular environment and must represent the most complex preparations according to the microbiological risk level of preparations made there A tryptic soy agar low sulphur content or soybean casein digest nutrient medium must be used For hazardous compounded sterile preparations with low or medium risk of microbial contamination the nutrient medium must be sterile For hazardous compounded sterile preparations with a high risk of microbial contamination the nutrient medium must be non sterile and must include simulation of sterilization by filtration The proliferation capacity of every batch of the nutrient medium used must have been tested by the manufacturer and the certificate for this test result must be retained by the compounding pharmacy The containers used for media fill tests should be sent to a certified external laboratory or may be incubated in the pharmacy provided that the incubator is certified periodically and that procedures are in place for its use and maintenance and for the surveillance of required temperatures Personnel must be properly trained to read the results 157 United States Pharmacopeial Convention USP General chapter lt 1116 gt microbial evaluation of clean rooms and other controlled environments In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 900 8 168 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding ste
51. ate file closed An accident is an action or situation in which the risk event occurs and has or could have an impact on the health status or well being of the user patient personnel professional concerned or third party An incident is an action or situation that has no impact on the health status or well being of the user patient personnel professional concerned or third party but which has an unusual result that could on other occasions lead to consequences Draft 2A Hazardous Sterile Products August 22 2014 127 APPENDIX 14 COMPONENTS OF A QUALITY ASSURANCE PROGRAM FACILITIES Certification of clean rooms and anteroom Every 6 months When the controlled area is installed When new equipment is installed When rooms or equipment are maintained or repaired When a contamination problem is identified When investigation of a contamination problem or non compliance in the aseptic preparation process requires exclusion of malfunctioning facilities Sampling of controlled areas under operational dynamic conditions Viable and non viable particles air and surfaces According to a sampling plan Every 6 months more frequently at the start of the quality assurance program When the controlled area is installed When new equipment is installed When the controlled area or equipment is repaired or maintained e g high efficiency particulate air filter changed When a contamination problem is
52. azardous waste bin Sharps waste used in aseptic techniques for the compounding of hazardous Sterile products must be placed in rigid containers designated for sharps placed inside the BSC or CACI decontaminated and then discarded into a hazardous waste container or sent for destruction e Non sharps waste used in the compounding of hazardous sterile products must be placed in a sealable plastic bag inside the BSC or CACI or in a rigid container and then discarded in a hazardous waste container 149 American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 150 National Institute for Occupational Safety and Health NIOSH NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2012 Publ No 2012 150 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2012 June Available from http www cdc gov niosh docs 2012 150 pdfs 2012 150 pdf 151 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 12 2 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 152 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compoundin
53. ble air sampler to ensure that it is regularly calibrated according to the manufacturer s recommendations and to properly train personnel in its use e use the appropriate nutrient medium for plating of samples tryptic soy agar low sulphur content or soybean casein digest medium for air samples tryptic soy agar with lecithin and polysorbate for surface samples e assure the microbial proliferation capacity of each batch of nutrient medium used the certificate for this test provided by the manufacturer must be retained The samples obtained must be either e sent to a certified external laboratory or e incubated in the community or health care facility pharmacy provided that the incubator used is certified periodically 182 United States Pharmacopeial Convention USP General chapter lt 51 gt antimicrobial effectiveness In USP Draft 2A Hazardous Sterile Products August 22 2014 85 163 procedures are in place for use and maintenance of the incubator and for surveillance of temperatures personnel are properly trained and are competent to read and interpret the results and to take appropriate preventive or corrective actions Samples must be incubated in an inverted position between 30 C and 35 C to be read in 48 to 72 hours alternatively another equivalent method must be used The contamination level at which corrective action is required will vary depending on the desired ISO air classificati
54. ble limit is 3520 particles Recommends that LAFW pre filters be changed if required 4 Certification of CAI and CACI Certifies devices according to the manufacturer s recommendations referring to CETA CAG 002 2006 Compounding Isolator Testing Guide Certifies using the following tests at minimum other tests are indicated in CETA CAG 002 006 v Airflow test Verification of internal pressure Verification of installation site Verification of HEPA filter Containment integrity and enclosure leak test Recovery time test Smoke test Test of preparation entry and output Count of non viable particles SAAN NARS IV After certification Answers questions and requests from the sterile compounding supervisor related to the certification and its procedure Does the required quick cleaning of rooms and devices Groups all waste contaminated by hazardous products and disposes of it as hazardous waste in the appropriate containers Verifies that all certification labels are correctly printed and affixed Provides the sterile compounding supervisor with a preliminary report recommended but not mandatory in writing or at a minimum verbally Submits a final certification report that includes all information required by pharmacy regulatory authorities to confirm certification Submits recent calibration certificates for the devices used in the certification attached to the final certificati
55. cation for air quality See Table 1 for the classifications of air cleanliness by concentration of particles in controlled rooms and areas according to the ISO standard and section 5 3 2 on the installation of areas reserved for activities related to the compounding of hazardous sterile products Calibration certificates for the equipment used to conduct the certification must accompany the report prepared after each certification The sterile compounding supervisor must ensure that the certification is performed in accordance with the most recent certification standards in force for the facilities and equipment used to compound sterile products Appendices 6 and 7 describe the certification activities and the standards used by the certifiers Sampling of viable particles in air and on surfaces Sampling for viable particles must include e sampling of viable particles per cubic metre of air for each established sampling site using an air sampler e surface sampling of each established sampling site using a direct contact or swabbing method The sampling of viable air and surface particles must be performed by a qualified certifier or by employees of the community or health care facility pharmacy provided that an established sampling procedure is followed and personnel have received and successfully completed the proper training The sterile compounding supervisor must e obtain from the manufacturer a calibration certificate for the via
56. cations publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html Expert consensus based on 1 no known product for deactivating all hazardous products 2 sodium hypochlorite is recommended in the material safety data sheets for multiple hazardous products 3 sodium hypochlorite can damage thiosul ilabl Draft 2A Hazardous Sterile Products August 22 2014 6 5 6 6 5 Aseptic techniques for compounding hazardous sterile products 6 6 5 1 General Compounding personnel should prepare one batch of drugs or one type of preparation at a time In the event of non compliance with aseptic technique the preparation must be discarded In this situation new supplies must be used Gloved hands must be disinfected with sterile 70 isopropyl alcohol before re introduction into the BSC or CACI or after gloves have come into contact with a microbiologically contaminated surface If gloves are torn hands must be washed before new gloves are donned Gloves must be changed regularly i e gloves must be removed before hands are removed from the BSC The frequency and circumstances of glove changes must be defined in a procedure The external packaging of products and supplies must be intact dry and unsoiled Otherwise the products and supplies must be discarded Containers e g bags of solution vials and ampoules must be examined before use All equipment with surfaces that can be disinfe
57. centration compounding procedure for each ingredient including primary and secondary diluents Draft 2A Hazardous Sterile Products August 22 2014 5 6 name quantity volume batch number expiration date e quantity prepared e prepared batch number e compounding date e preparation BUD e compounder and verifier at each stage of the process The log paper based or computerized must be filed and retained for future reference 6 4 Patient file For any hazardous compounded sterile preparation that has been dispensed all information required for review and assessment of the patient s file by pharmacists and for subsequent treatment of the patient must be recorded in the patient s file In community pharmacies information recorded in the patient s file must allow users to accurately reproduce the prescribed preparation at a later date or identify the compounding pharmacist if necessary The patient care dispensing pharmacist must record in the patient s file the origin of the hazardous compounded sterile preparation that is being dispensed if the dispensing pharmacist did not compound the preparation where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation In health care facilities the pharmacist must keep track of preparations compounded externally by a community pharmacy etc In addition the patient care dispensing pharmacist must be able to track info
58. chapter lt 797 gt pharmaceutical compounding sterile preparations In USP pharmacists pharmacopeia 2nd ed Suppl 2 Rockville MD USP 2008 Section Sampling plan United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 83 The plan for sampling air for viable and non viable particles and surfaces must be established according to the specifications of a recognized standard such as ISO 14644 1 The air and surface sampling plan must include for each controlled area clean room and anteroom e sampling site diagram e type of sampling to be done e sampling methods to be used e number of samples to be obtained at each site e frequency of sampling e number of CFUs triggering action The sampling plan must allow for three types of samples e non viable particles per cubic metre of air e viable particles per cubic metre of air e viable surface particles Sampling specifications Samples must be obtained at least every 6 months from the air in controlled areas and in the BSC or CACI and every time that the following conditions are present e during installation of new equipment or a new controlled area e during maintenance or repair of equipment repair of BSC ventilation system etc or a controlled area repair of hole in the wall e during investigation of a contamination problem or a problem invo
59. ciety of Health System Pharmacists 2013 King JC King guide to parenteral admixtures electronic version Napa CA King Guide Publications Inc updated quarterly Trissel LA Trissel s 2 clinical pharmaceutics database electronic database Cashiers NC TriPharma Communications updated regularly Draft 2A Hazardous Sterile Products August 22 2014 5 0 To establish a longer BUD specific sterility tests must be performed for a given preparation or batch The pharmacy s operating procedures must describe the method used to establish the BUD and the storage conditions 6 1 2 Beyond use dates for commercial products according to type of container with or without preservative During compounding the use of commercially available products must have priority More specifically if a sterile product is commercially available compounding personnel must not use non sterile ingredients to compound a sterile preparation The BUDs for commercial products used for compounding of hazardous sterile preparations specified in the following three sections 6 1 2 1 6 1 2 2 and 6 1 2 3 apply when the products are stored in the original package and container 6 1 2 1 Preservative free sterile product including bulk packaging e BUD up to 6 hours controlled room temperature or refrigerator temperature see Table 6 e The contents of a bulk vial cannot be divided for the sole purpose of extending stability
60. ckville MD USP 2013 p 391 21 Sessink PJM Boer KA Scheefhals APH Anzion RB Box RP Occupational exposure to antineoplastic agents at several departments in a hospital Environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers Int Arch Occup Environ Health 1992 64 2 105 12 22 Dorr RT Alberts DS Topical absorption and inactivation of cytotoxic anticancer agents in vitro Cancer 1992 70 4 Suppl 983 7 2 American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 24 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Chapter 7 Planning the Oncology Pharmacy Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp 7 3 Available from http www asstsas qac ca publications publications specialisees guides de prevention prevention Draft 2A Hazardous Sterile Products August 22 2014 63 Draft 2A Hazardous Sterile Products August 22 2014 6 D Work surface in Before start of compounding Work surface in On each preparation change ya A Re anmannan At the start or end of each shift Where surface contamination is suspected If there has been non compliance with aseptic techniques At start of workday 7 Al surfaces inside CAGI has not been used for BSC o
61. compounding personnel from hazardous sterile preparations descending air curtain filtered with a high efficiency particulate air filter to protect the hazardous sterile product air evacuation system equipped with high efficiency particulate air filters for environmental protection Cleaning and disinfecting Cleaning activities involving the removal of dirt dust and other substances housekeeping that may host microorganisms guaranteeing access to a clean and healthy 174 environment Clean room A room in which atmospheric properties temperature humidity particle and microorganism content pressure airflow etc are controlled The room s functional parameters are kept at a specific level The room is designed to minimize introduction generation and retention of particles Commercial container Container holding a commercially manufactured drug or sterile nutrient the consumption and sale of which are authorized in Canada if the drug or sterile nutrient is authorized by Health Canada s Special Access Programme such consumption and sale may be limited 172 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Commission de la sant et de la s curit du travail CSST Material safety data sheet user s guide CSST 2010 Available from http www csst qc ca en prevention reptox whmis
62. cted must be disinfected with sterile 70 isopropyl alcohol before being introduced into the BSC or CACI Non shedding wipes or sterile swabs must be changed regularly while equipment is being disinfected Ophthalmic solutions prepared from sterile powder products that require dilution must always be filtered with a 5 um filter Filtration is not necessary when the products used are available as sterile solutions in vials Vials must not be allowed to accumulate in the BSC or CACI to reduce the risk of errors and air turbulence 131 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 380 2 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health Draft 2A Hazardous Sterile Products August 22 2014 66 Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 Available from https www osha gov dts osta otm otm_vi otm_vi_2 html Si Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 p 5 Available from https www osha gov dts osta otm otm_vi otm_vi_2 html 135 Association parit
63. ctive and preventive measures must be identified and implemented regardless of the location of the pharmacist s practice 6 11 Incident and accident management 146 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 12 5 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 147 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 12 5 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 77 6 11 3 Incidents and accidents When an incident or accident involving a hazardous compounded sterile preparation occurs the compounding personnel must complete an event report and explanation form see Appendix 13 In health care facilities a form developed or selected by the facility may be used Complaints accidents incidents and reported side effects must be evaluated to determine their cause and the necessary steps must be taken to prevent recurrence 6 12 Hazardous waste management In the performance of assigned duties th
64. cy BCCA Module 1 Safe handling of hazardous drugs In BC Cancer Agency pharmacy practice Draft 2A Hazardous Sterile Products August 22 2014 62 Personnel must comply with the following requirements for cleaning and disinfecting e Disinfect non powdered sterile gloves with sterile 70 isopropyl alcohol and allow to dry before starting to clean and disinfect the BSC or CACI e Ensure that the head and upper body do not enter the BSC or CACI e Use non shedding disposable swabs e Avoid contaminating the surface of swabs used for cleaning and disinfecting e Change swabs after completing disinfection of each section of the BSC or CACI e Clean the BSC or CACI with clean swabs and sterile water at the start or end of the day or shift minimum once per day e Follow the cleaning method described in the pharmacy s procedures with regard to equipment sequence movements Fully disinfect the BSC or CACI with sterile 70 isopropyl alcohol or another disinfecting agent using sterile swabs at the start and end of the day or shift minimum twice per day e Follow the disinfecting method described in the pharmacy s procedures e Wait until the disinfectant has dried before compounding the first preparation in the BSC or CACI e Record cleaning and disinfecting activities in the maintenance log 20 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Ro
65. d States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 375 164 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 86 Lil ih 7 4 Quality assurance of personnel involved in aseptic compounding The quality assurance program for the aseptic compounding process for personnel must include GFTS and a media fill test which are the two final steps of initial and periodic qualification of personnel as mentioned in section 5 1 2 2 7 4 1 Gloved Fingertip Sampling GFTS must include e asample obtained after sterile gloves are put on after aseptic washing of hands and forearms but before application of sterile 70 isopropyl alcohol disinfecting gloves with sterile 70 isopropyl alcohol immediately before sampling would lead to false negatives e asample obtained after the media fill test making sure that the employee has not applied sterile 70 isopropyl alcohol to his or her gloves in the minutes before sampling 155 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention
66. d for cleaning and disinfection and its storage Equipment used for cleaning and disinfecting must be accessible To avoid cross contamination and to protect cleaning and disinfecting personnel cleaning equipment mop heads towels etc must be reserved exclusively for cleaning areas used for the compounding of hazardous sterile products Non shedding lint free equipment mop heads towels preferably made of cellulose or microfibre must be used for cleaning controlled areas This equipment mop heads towels etc should preferably be disposable If reusable accessories are used they must be reserved for cleaning and disinfecting within the facility must be washed and dried after each use and must be stored in a clean cabinet dedicated to storing this equipment The outside of containers for detergent and other cleaners must be kept clean Small formats are preferred and smaller containers filled from bulk containers must be disposable 2 United States Pharmacopeial Convention USP General chapter lt 1072 gt disinfectants and antisepsis In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 31 Okeke CC Allen LV Jr Considerations for implementing United States Pharmacopeia chapter lt 797 gt pharmaceutical compounding sterile preparations Part 4 Considerations in selection and uses of disinfectants and antiseptics Int J Pharm Compound 2007 11 6 492 9 2 United States Pharmacopeial Convention USP
67. d there are no unsealed windows and no doors to the exterior of the building Furthermore the preparation area is not in a high traffic area or adjacent to construction sites warehouses or food preparation sites The microbial contamination risks associated with compounding such products under these conditions remain high even if there is full compliance with hand hygiene asepsis garbing and maintenance rules Given the associated risks the compounding of sterile products under these conditions must be only a temporary measure and administration must start within 12 hours after the start of compounding otherwise the preparation must be discarded 6 2 Compounded sterile preparation protocols O Protocols for the compounding of hazardous sterile preparations must include all information required to prepare the compound e name pharmaceutical form all required ingredients quantity and source of ingredients necessary equipment instructions for compounding the preparation storage method BUD references draft and revision date pharmacist s signature 0e 0e Appendix 8 presents a model for writing compounded sterile preparation protocols for each drug All protocols for hazardous pharmacy compounded sterile preparations must be stored together and readily available for quick consultation The protocols must be reviewed and approved by the sterile compounding supervisor or delegate 6 3 Compounded st
68. dc gov niosh docs 2012 150 pdfs 201 2 150 pdf Trissel LA Handbook on injectable drugs Bethesda MD American Society of Health System Pharmacists United States Pharmacopeial Convention USP USP pharmacists pharmacopeia Rockville MD USP 2008 2009 contains all USP chapters useful to pharmacists including General Chapter lt 797 gt Pharmaceutical Compounding Sterile Preparations B Supplemental documentation 1 GENERAL TEXTS ON STERILE PREPARATIONS Volumes Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 481 pages Periodicals American Journal of Health System Pharmacists Available at www ajhp org Canadian Journal of Hospital Pharmacy Available from http www cjhp online ca index php cjhp International Journal of Pharmaceutical Compounding Available at www ijpc com Websites associations and agencies ASHP Sterile Compounding Resource Center www ashp org compounding Pharmacy Compounding Accreditation Board www pcab info 2 REFERENCE TEXTS PHYSICAL CHEMICAL STABILITY COMPATIBILITY AND STABILITY Compendium of pharmaceuticals and specialties Ottawa ON Canadian Pharmacists Association Updated yearly King JC King guide to parenteral admixtures electronic version Napa CA King Guide Publications Inc Updated quarterly Trissel LA Trissel s 2 clinical pharmaceutics database electronic database Cashiers NC
69. de the concentration of each ingredient Each container for a hazardous compounded sterile preparation must be labelled A label must be affixed to each prepared unit accompanied if necessary by a supplementary document see section 6 6 7 2 to complete the required information Compounding personnel must label the following items e final hazardous compounded sterile preparations e each unit of a hazardous compounded sterile preparation for an individual patient along with required auxiliary labels e each unit of hazardous sterile preparations compounded in batches with at a minimum drug name concentration route of administration batch number and BUD e each package containing final preparation units along with auxiliary labels indicating required storage conditions and special precautions The compounding pharmacist or pharmacy technician must similarly label hazardous sterile preparations that have been compounded for a patient care dispensing pharmacist where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation The patient care dispensing pharmacist must add a label containing all information required by the respective federal provincial territorial regulatory authority before administering the hazardous compounded sterile preparation received from the compounding pharmacist to the patient a supplementary document must be prepared if required The label affixed by th
70. ding process Draft 2A Hazardous Sterile Products August 22 2014 118 Quality controls Specify the procedure for determining the lot number of the final compounded sterile preparation Specify all quality control procedures that are to be carried out during compounding and documented by the pharmacy technician and or pharmacist Specify all quality controls are to be carried out by the pharmacist on the final compounded sterile preparation Indicate the expected specifications Example Expected specification Quality control Appearance of the preparation Clear colourless solution with no visible particles a Packaging Describe the type of packaging in which the final compounded sterile preparation shall be presented to the patient eS Stability and storage Specify the preservation requirements of the compounded sterile preparation Specify the shelf life of the compounded sterile preparation beyond use date Indicate the references used to determine shelf life Labelling Sample label Indicate mandatory information that must be on the label of the compounded sterile preparation Draft 2A Hazardous Sterile Products August 22 2014 1 19 A When kept at the pharmacy or sent to another pharmacy B When dispensed to a patient Training References consulted Draft 2A Hazardous Sterile Products August 22 2014 Indicate the source of the specific sterile co
71. duct usually contains an antimicrobial 192 preservative Patient care dispensing pharmacist Pharmacist providing care to patients who delivers or administers a product after verification of its therapeutic appropriateness the product may be prepared by the patient care dispensing pharmacist or by compounding personnel in another pharmacy where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation Personal protective equipment PPE All garb and accessories such as mask gloves smock and safety goggles that protect the sterile preparation and the worker It enables compliance with the expected specifications of a controlled environment and protects 193 194 the worker from exposure to physical or chemical risks i Pharmacist Registrant in good standing of one of the pharmacy regulatory authorities in Canada Pharmacy bulk vial Commercial container for parenteral sterile preparations intended for packaging containing several individual doses Such packaging is used only by pharmacies with an intravenous admixture program During the final packaging in several doses the pharmacy bulk vial must be perforated with a transfer device only once by introducing a needle or transfer spike Pharmacy technician An adult who has earned a college degree or diploma from an accredited pharmacy technician program and has passed the national examination
72. e compounding pharmacist or pharmacy technician must be retained 6 6 7 2 Label and insert The computer generated self adhesive label printed by the prescription and file management software may be too small to carry all relevant information to ensure safe appropriate use of the hazardous compounded sterile preparation by the patient In that situation an insert must be prepared The insert is considered to be an integral part of the label Together the label and insert must provide all information required for proper use of the drug by the patient or for safe administration by a third party The label must contain the following information at a minimum Draft 2A Hazardous Sterile Products August 22 2014 70 e pharmacy identification name address and telephone number of the compounder s or dispenser s pharmacy e drug identification active ingredients concentration form route of administration volume solute amount prepared e special precautions e g if product is cytotoxic e storage method e date when the hazardous sterile preparation was compounded e BUD e preparation batch number The package insert must include the following information e all information required by federal provincial territorial legislation and regulations regarding the labelling of medications and poisons that could not be included on the main label e details concerning mode of administration e special precautions related to dr
73. e pharmacist must 148 ensure that medications and sharp or pointed instruments are disposed of safely in compliance with the environmental protection laws in force in the jurisdiction ensure that medications to be destroyed are safely stored in a location separate from other medications in inventory develop and implement a procedure for destruction of pharmaceutical waste National Association of Pharmacy Regulatory Authorities NAPRA Model standards of practice for Canadian prarmacists Ottawa ON NAPRA 2009 Available from ap en VIO of_P a a O m_ IVI Draft 2A TEETE Sterile TT August 22 201 7 78 Pharmaceutical products that are expired or otherwise no longer usable are considered pharmaceutical waste Hazardous products must be destroyed in accordance with regulations governing such products A list of hazardous products in use must be available in the pharmacy The list produced by NIOSH which is part of the US Centers for Disease Control and Prevention can be used to determine if a particular product is hazardous e All personnel involved in the management of hazardous product waste must All equipment products and vials used in the compounding of hazardous sterile products must be discarded in a container reserved for hazardous waste e Bins reserved for hazardous waste must be identified with a self adhesive label EC a fli GLS sealed Personnel should never attempt to compress the contents of a h
74. eas should be positioned together Functional parameters require constant monitoring so the controls should be installed where it is easy for personnel to take frequent readings Control systems must be connected to a notification system to alert personnel when operating parameters are outside preset limits This allows personnel to make the necessary adjustments quickly while avoiding contamination of controlled areas and the problems that may result including service interruption 52 Canadian Centre for Occupational Health and Safety CCOHS Anti fatigue mats Hamilton ON CCOHS 1997 confirmed current 2006 Available from http www ccohs ca oshanswers ergonomics mats html Draft 2A Hazardous Sterile Products August 22 2014 3 3 Instruments for measuring differential pressure between controlled areas must be calibrated at least once a year or as recommended by the manufacturer 5 3 2 10 Work surfaces and furniture Work surfaces Work surfaces and furniture must be constructed of smooth non porous non friable and impermeable materials preferably stainless steel Any material used for work surfaces must be able to withstand repeated cleaning and be resistant to damage from cleaning products Any breakage must be repaired and sealed A horizontal surface for donning gloves should be installed in the clean room Furniture Furniture in the clean room and anteroom must be designed and placed to facilitate cleaning and disinfec
75. eial Convention USP General notices and requirements In USP pharmacists pharmacopeia Rockville MD USP 2008 p 29 tUnited States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Draft 2A Hazardous Sterile Products August 22 2014 1 2 5 APPENDIX 13 INCIDENT ACCIDENT REPORTING AND FOLLOW UP FORM Note This form is intended for pharmacists who do not use a health care facility s suggested form Date and time of incident accident Reported by Name of patient affected if applicable Full address Phone number Pharmacy personnel involved Summary of the situation and consequences Causes Options for corrections or changes Corrections or changes Identify causes of the problem Assess potential corrections or chosen changes to be made Indicate the corrections or changes to be made Draft 2A Hazardous Sterile Products August 22 2014 1 2 6 Actions Responsible Deadline Describe the actions to be taken and the steps required to correct the situation with a specific timeline Determine who will be responsible for implementation Monitoring Verifications Responsible Verifications to ensure that the corrections and changes are effective and fully implemented Closing of the file Pharmacist responsible for follow up signature D
76. ency required to compound sterile preparations X 3 2 Know and correctly perform the filter integrity verification X 3 3 Know and correctly perform sterilization by filtration X 3 4 Know and correctly perform the analytical method to test for pyrogens X Draft 2A Hazardous Sterile Products August 22 2014 106 B Training of cleaning and disinfecting personnel COMPETENCIES KNOWLEDGE OR SKILLS COVERED IN TRAINING PH PT TSP C amp D 1 FOR CLEANING AND DISINFECTING THE GENERAL AREA FOR i COMPOUNDING OF NON HAZARDOUS STERILE PREPARATIONS Know all policies and procedures related to cleaning and disinfecting the 1 1 equipment furniture and facilities notably those related to hygiene and X X X asepsis personal protective equipment and cleaning and disinfecting tasks 1 2 Know and don the correct garb 1 3 Know and correctly apply hand hygiene 14 Know correctly perform and document cleaning and disinfecting tasks for the x x x general area for compounding of sterile preparations 2 FOR CLEANING AND DISINFECTING THE AREA USED FOR l COMPOUNDING HAZARDOUS STERILE PREPARATIONS 21 Know correctly perform and document cleaning and disinfecting tasks for the x x x general area for compounding of hazardous sterile preparations Know and use personal protective equipment specifically for handling 2 2 X X X hazardous products 23 Know and use the emergency measures to be applied in case of accidental x x x
77. ention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 J 3 Contents The contents of the anteroom must be limited to facilitate maintenance and to maintain the target ISO air quality classification The anteroom must contain the following items e PPE accessories and storage space for hair covers and shoe covers placed in the correct order to allow users to follow the correct garbing sequence e easy to clean wall sink ideally made of stainless steel or other material not harmed by cleaning products and large enough to allow users to wash their hands and forearms without touching the sides of the sink with minimal splashing e soap dispenser cartridge or disposable non refillable unit e long acting alcohol based hand gel dispenser e hand drying system lint free paper towels with a dispenser preferred air hand dryer designed specifically for use in a controlled area i e the anteroom e mirror or other means to verify garbing e cytotoxic waste bin e eyewash station if available if not located in the anteroom the eyewash station must be installed nearby e cart reserved for use in the clean area of the anteroom and the clean room Supplies In principle supplies are not kept in the clean room The supplies drugs labels and other items required for each preparation or batch are gathered and assembled in the anteroom
78. er things full compliance with compounding procedures e Procedures must be clear must follow a standard format and must include an index for easy access to information when it is needed Appendix 5 may be used as a model for developing these procedures e The sterile compounding supervisor must ensure that all established policies and procedures are promptly updated whenever there is a change in practice In addition policies and procedures must be reviewed at least every 3 years United States Pharmacopeial Convention USP General chapter lt 1075 gt good compounding practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 867 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 44 47 54 55 Pharmacy Compounding Accreditation Board PCAB Standard 1 40 Standard operating procedures compliance noicators In PCAB accreditation manual Washington De PGAD 2011 p 7 Available from A Draft 2A Hazardous Sterile Products TES 22 2014 17 e The drafting and revision dates the date of each change and the names of authors and reviewers must be included in each policy or procedure 5 3 Facilities and equipment Facility design spaces ventilation materials etc as well as the conduct and competency of personnel helps to achieve the objectives of these Model Standards Facilities
79. erile preparation log O Draft 2A Hazardous Sterile Products August 22 2014 5 5 A hazardous compounded sterile preparation log either paper based or computerized must be completed during the compounding process The pharmacy must keep such a log for individual patients as well as a log for hazardous sterile preparations made in batches Computerized information and information recorded with cameras may be used as a record if all the required information is present and easy to track 6 3 1 Hazardous compounded sterile preparation log for one patient individual preparations The hazardous compounded sterile preparation log for an individual patient must contain the following information patient s name prescription number if compounded in a community pharmacy patient identification number if compounded in a health care facility preparation identification name and concentration compounding procedure for each ingredient including primary and secondary diluents name quantity volume measured batch number expiration date compounding date preparation BUD compounder and verifier at each stage of the process The log paper based or computerized must be filed and retained for future reference 6 3 2 Hazardous compounded sterile preparation log for products made in batches The log of hazardous sterile products prepared in batches must contain the following information preparation identification name and con
80. es Laminar flow hood See Laminar airflow workbench Log Book or notebook in which data are recorded or compiled to demonstrate that the quality of the pharmacy aseptic compounding process has been maintained A log may be in computerized format Maintenance of competency Continued ability to integrate and apply knowledge know how judgment and personal qualities necessary to practise in a safe and ethical fashion in 188 a designated role and framework Maintenance of facilities and equipment Operations for maintaining the proper functioning of facilities or equipment according to established specifications or for re establishing the satisfactory operational condition of facilities including the heating ventilation and air conditioning system and related equipment Material safety data sheet MSDS A document that provides information on a controlled product namely its toxic effects the protective measures for avoiding overexposure or chemical hazards and the procedures to follow in an emergency The supplier sends the MSDS to the employer when the product is sold It must be kept on the premises by the employer in a location known by the workers and be easily and rapidly accessible to those who are likely to come in contact with the product The employer should have it before a product is used for the first time Media fill test Test used to qualify aseptic techni
81. es for several days at home Consequently attention must be paid to the environment in which these products are prepared the training of personnel and quality assurance procedures to prevent complications and protect the public more generally Evolving practice and increased awareness of the inherent dangers of compounding sterile products for the health of both patients and compounding personnel led to the need to review the Guidelines to Pharmacy Compounding published by the National Association of Pharmacy Regulatory Authorities NAPRA in October 2006 The new NAPRA Model Standards for Pharmacy Compounding of Sterile Products have been adapted from standards originally developed by the Ordre des pharmaciens du Quebec which are in turn based on General Chapter lt 797 gt of the United States Pharmacopeia National Formulary USP NF in effect in the United States since 2004 Their preparation was led by the NAPRA ad hoc Committee on Pharmacy Compounding and involved extensive consultations with experts and stakeholders The Model Standards for Pharmacy Compounding of Sterile Products have been divided into two documents one pertaining to non hazardous and the other to hazardous cytotoxic compounded sterile preparations Similar information is found in some sections of the two documents but elsewhere the information differs according to the type of product non hazardous or hazardous The creation of separate documents i
82. estigation immediate corrective action and or preventive action are needed to avoid return to non compliance 7 3 Verification of equipment and facilities 7 3 1 Verification of equipment supporting compounding activities 7 3 1 1 Certification Draft 2A Hazardous Sterile Products August 22 2014 8 1 Equipment that supports compounding activities especially refrigerators freezers incubators and air sampling devices must be certified with respect to its installation and operation and must be calibrated before being put into service A maintenance plan must be established taking into account the manufacturer s recommendations for each device If no manufacturer s recommendations are available maintenance activities must be performed at least once a year by a qualified technician The maintenance report must be saved in the general maintenance log 7 3 1 2 Temperature readings At least once a day compounding personnel must check the temperature log of equipment with an integrated recording device e g refrigerator freezer incubator to review temperatures over the previous 24 hours and must take corrective actions in case of substantial variance with respect to specified parameters When a thermometer is used as a verification instrument the temperature must be read twice a day at specified but different times of day e g morning and night The pharmacist must record and retain proof of calibration of the thermometer
83. evel e atleast once a year in the workplace for hazardous products e atleast twice a year in the workplace for preparations with high risk level The risk levels of various preparations are explained in section 6 1 3 The results of these assessments should be noted in each employee s file Cleaning and disinfecting personnel Draft 2A Hazardous Sterile Products August 22 2014 1 5 All cleaning and disinfecting personnel must be evaluated at least once a year in the workplace The results of these assessments must be retained for the period specified by the provincial territorial regulatory authority Content of assessment Compounding personnel A competency assessment program for all compounding personnel pharmacists pharmacy technicians and TSP must be implemented in the workplace This program must include the following e a theoretical test measuring required knowledge of policies and procedures the aseptic compounding process and accidental exposure and spills see Appendix 4 Cleaning and disinfecting personnel A competency assessment program for cleaning and disinfecting personnel must be implemented in the workplace see Appendix 4 for more details on the training required Failures all personnel Compounding personnel and cleaning and disinfecting personnel who fail the written or practical assessment must immediately stop work and redo their training An individual may resume assigned duties after passing the ele
84. eyond use dates BUDs for hazardous compounded sterile preparations according to risk of microbial contamination Table 9 Minimum frequency of surface decontamination deactivation and disinfection of the inside of a BSC or CACI by compounding personnel Draft 2A Hazardous Sterile Products August 22 2014 98 10 APPENDICES APPENDIX 1 EXCERPTS FROM AN ACT RESPECTING OCCUPATIONAL HEALTH AND SAFETY PROVINCE OF QUEBEC All workers and employers have legal responsibilities related to health and safety Chapter III of the Quebec Act Respecting Occupational Health and Safety sets out the rights and obligations of both workers and employers as follows General rights of the worker Section 9 Every worker has a right to working conditions that have proper regard for his health safety and physical well being Obligations of the worker Section 49 A worker must 1 become familiar with the prevention program applicable to him 2 take the necessary measures to ensure his health safety or physical well being General rights of the employer Section 50 Every employer is entitled in particular in accordance with this Act and the regulations to training information and counselling services in matters of occupational health and safety General obligations of the employer Section 51 Every employer must take the necessary measures to protect the health and ensure the safety and physical well being of his worker He must in particular 1
85. ezer temperature Low 48 hours 14 days 45 days Medium 30 hours 9 days 45 days High 24 hours 3 days 45 days 104 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 105 American Society of Health System Pharmacists ASHP The ASHP discussion guide on USP chapter lt 797 gt for compounding sterile preparations Summary of revisions to USP chapter lt 797 gt Bethesda MD ASHP with Baxter Healthcare Corporation 2008 Available from http www ashp org s_ashp docs files discguide797 2008 pdf 106 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 5 3 Administration of the compounded sterile preparation must start before the BUD has been exceeded High risk preparations must always be sterilized the BUDs in Table 8 apply to high risk sterile preparations Sterility and control test A bacterial endotoxin sterility and control test must be performed for high risk hazardous compounded sterile preparations see Table 7 in the following situations e when hazardous sterile preparations are compounded in batches of over 25 identical units e when there has been more than 12 hours of exposure time at a temperature between 2 C and 8 C before sterilization when there has been more than 6 ho
86. f antineoplastic and other hazardous drugs in healthcare settings 2012 Publ No 2012 150 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2012 June Available from http www cdc gov niosh docs 2012 150 pdfs 2012 150 pdf Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 Available from https www osha gov dts osta otm otm_vi otm_vi_2 htm Okeke CC Allen LV Jr Considerations for implementing United States Pharmacopeia chapter lt 797 gt pharmaceutical compounding sterile preparations Part 4 Considerations in selection and uses of disinfectants and antiseptics Int J Pharm Compound 2007 11 6 492 9 Ordre des pharmaciens du Qu bec OPQ La manipulation des m dicaments dangereux en pharmacie Bulletin d informations professionnelles 2010 169 3 Patel PR Larson AK Castel AD Ganova Raeva LM Myers RA Roup Bu et al Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies JAMA 2006 296 16 2005 11 Peters GF McKeon MR Weiss WT Potentials for airborne contamination in turbulent and unidirectional airflow compounding aseptic isolators Am J Health Syst Pharm 2007 64 6 622 31 Draft 2A Hazardous Sterile Products August 22 2014 1 3 3 Pharmacy Compounding Accreditation Boa
87. f devices instruments and accessories must be recorded in the general maintenance log Automated compounding device and balance The automated compounding device ACD and the balance if required for manipulations must be positioned in the BSC However the ACD may be positioned outside the BSC if this allows compounding to be performed while maintaining critical sites within the BSC If the ACD is a peristaltic pump this device must be calibrated several times during compounding of each batch The ACD must also be calibrated between batches The ACD must be calibrated at least once a day after cleaning then as needed according to the manufacturer s recommendations The balance must be calibrated before each use after it is moved after cleaning and as needed according to the manufacturer s recommendations The ACD and the balance are to be maintained according to the manufacturer s recommendations The results of calibration must be entered in the preparation log or general maintenance log for each batch at a minimum Carts If carts are used one cart must be reserved for the dirty area of the anteroom and must remain there A second cart must be reserved for use in the clean area of the anteroom and in the clean room 56 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 373 57 United
88. f each preparation ensure that preparations are packaged and labelled in accordance with provincial territorial requirements and that a BUD is included on the label see section 6 1 e where appropriate provide the patient care dispensing pharmacist orally or in writing the information required for storing and transporting any medication prepared at the dispensing pharmacist s request storage method precautions suggested BUD etc e ensure that the final preparation is properly stored until delivery to the patient or to the pharmacist who ordered it where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation e where appropriate notify the patient care dispensing pharmacist when a preparation must be recalled e if a sterile preparation has been compounded for an external patient care dispensing pharmacist where permitted by provincial territorial legislation ensure that each patient management activity is performed by Draft 2A Hazardous Sterile Products August 22 2014 1 1 the dispensing pharmacist and or the compounding pharmacist or pharmacy technician to ensure continuity of care e where appropriate collaborate with the patient care dispensing pharmacist and share information on the preparation for the patient s benefit and to optimize treatment results e ensure that patient management is adequate and consistent with agreements among the various stakeho
89. for the compounding of hazardous sterile products must be designed and built in accordance with these Model Standards with provincial territorial and local regulations and for health system facilities with other applicable standards regulating the construction of government buildings 5 3 1 Useful references 5 3 1 1 ISO Standard 14644 1 The ISO 14644 1 classification describes air cleanliness requirements in facilities and clean rooms This standard specifies the allowable concentration of airborne particles for each class Table 1 To achieve and maintain the ISO class for a clean room all sources that generate particles must be controlled 18 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 19 International Organization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Draft 2A Hazardous Sterile Products August 22 2014 18 Table 1 Classes of air cleanliness for airborne particulates in clean rooms and clean areas according to ISO 14644 1 Maximum concentration of non viable particles 2 0 5 ISO Class Number um diameter measured under dynamic operating conditions particles m
90. ft 2A Hazardous Sterile Products August 22 2014 1 3 1 Canadian Centre for Occupational Health and Safety CCOHS Emergency showers and eyewash stations Hamilton ON CCOHS 2010 Available from http www ccohs ca oshanswers safety haz emer showers html Canadian Nurses Association CNA Joint position statement Promoting continuing competence for registered nurses Ottawa ON CNA 2004 Available from http www cna aiic ca media cna page content pdf en ps77 promoting competence e pdf Canadian Society of Hospital Pharmacists CSHP Sterile preparation of medicines guidelines for pharmacists Ottawa ON CSHP 1996 Commission de la sant et de la s curit du travail CSST Material safety data sheet user s guide CSST 2010 Available from http www csst qc ca en prevention reptox whmis material safety data sheet users guide pages table contents aspx Controlled Environment Testing Association CETA CETA compounding isolator testing guide CAG 002 2006 Raleigh NC CETA 2006 revised 2008 Dec 8 Available from http www cetainternational org reference CETACompoundinglsolatorTestingGuide2006 pdf Controlled Products Regulations SOR 88 66 1987 Available from http laws lois justice gc ca eng regulations SOR 88 66 Cundell AM USP Committee on Analytical Microbiology stimuli to the revision process Pharmacopeial Forum 2002 28 6 Dolan SA Felizardo G Barnes S Cox TR Patrick M Ward KS et al APIC position paper
91. g sterile preparations USP 36 Rockville MD USP 2013 p 369 153 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 12 2 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 154 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 12 3 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 79 WL 7 QUALITY ASSURANCE PROGRAM Pharmacists who prepare hazardous compounded sterile preparations must establish a quality assurance program to ensure the clear definition application and verification of all activities that will affect the quality of the hazardous compounded sterile preparations and the protection of personnel 155 Merck Canada Oncotice organon product monograph 145040 Kirkland QC Merck Canada 2011 Mar 11 Aesceialion des leony des tablissements de sant du a nae Regroupement des pharmaciens en d info ph ig en on M Q 00 evised 2003 O 156 Draft 2A EEEE Sterile Products Aigues 22 201 4 80 T
92. gram prescription PREPARATION ee f 2 Verification of label compliance e In accordance with the quality assurance program Entry in logs e In accordance with the quality assurance program Draft 2A Hazardous Sterile Products August 22 2014 1 3 0 11 BIBLIOGRAPHY Note to readers The references cited in these Model Standards reflect the references appearing in the source document Pr paration de produits st riles dangereux en pharmacie Norme 2014 02 published by the Ordre des pharmaciens du Qu bec 2014 Where possible certain details have been verified against the source documents URLs for online documents are current as of July 2014 American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 American Society of Health System Pharmacists ASHP The ASHP discussion guide on USP chapter lt 797 gt for compounding sterile preparations Summary of revisions to USP chapter lt 797 gt Bethesda MD ASHP with Baxter Healthcare Corporation 2008 Available from http Awww ashp org s_ashp docs files discguide797 2008 pdf An Act Respecting Occupational Health and Safety C Q L R c S 2 1 Available from http www2 publicationsduquebec gouv qc ca dynamicSearch telecharge php type 2 amp file S_2_1 S2_1_A html Corresponding regulation Regulation Respecting Occupational Health and Safety C Q L R S 2 1 r 13 Available from http www2 publicationsdu
93. greater number of ACPH may be required e The temperature of the anteroom must be less than or equal to 20 C taking into account employees comfort once all clean room garb including PPE has been donned Medication storage temperature must not exceed 25 C Excluding the clean room for the compounding of non hazardous sterile products The air diffusers must be positioned so that the particle stream is directed toward the dirty area of the anteroom All air flowing within the shared anteroom must be exhausted to the exterior of the building The air flowing into the anteroom must not be recycled 5 3 2 7 All other facilities The specifications recommended in the previous sections are similar to the recommendations for facilities laid out in General Chapter lt 797 gt of the United States Pharmacopeia National Formulary USP NF for hazardous and non hazardous sterile product compounding rooms Other approaches could also be suitable For facilities where the functional parameters must differ in some respect explanations and justifications must be provided Other technologies techniques materials and procedures require prior approval from the provincial territorial regulatory authority 5 3 2 8 Materials and finishes 45 United States Pharmacopeial Convention USP Response provided by USP for a shared anteroom March 21 2012 6 United States Pharmacopeial Convention USP General chapter lt 797 gt
94. gs Performs the work meticulously and professionally Draft 2A Hazardous Sterile Products August 22 2014 1 1 1 III Certification steps 1 Certification of controlled areas Begins the certification of a clean room by measuring non viable particles according to ISO 14644 1 specifications Uses the criteria of standard IEST RP CC 006 3 for the certification of the clean room Measures the volume of air supply or the velocity for each HEPA filter in the room Measures the air velocity profile for each terminal or line HEPA filter as applicable in the controlled room if the air volume for the HEPA filter cannot be measured Calculates the air volume for the HEPA filter if the velocity profile was measured Verifies the integrity of the HEPA filter with a photometer Verifies temperature Verifies humidity Verifies sound noise level Verifies light level Verifies the behaviour of the room and its equipment using smoke tests Ensures that the doors to each room are fully closed when measuring pressure differentials between rooms Obtains the dimensions of the room and its total volume of air supply to allow calculation of number of air changes per hour Note The frequency of certain verifications such as sound and light levels may vary depending on needs and agreements 2 Certification of BSC Certifies the BSC according to NSF Standard 49 2012 Appendix F Field Tes
95. harmacopeial Convention USP General chapter lt 1079 gt good storage and shipping practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 United States Pharmacopeial Convention USP General chapter lt 1116 gt microbial evaluation of clean rooms and other controlled environments In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 Wallemacg PE Capron A Vanbinst R Boeckmans E Gillard J Favier B Permeability of 13 gloves to 13 cytotoxic agents under controlled dynamic conditions Am J Health Syst Pharm 2006 63 6 547 56 135 Draft 2A Hazardous Sterile Products August 22 2014
96. hat describes all steps to be followed in the compounding of a specific sterile preparation and with which the compounder must comply The protocol must include all of the information to be recorded in the preparation log Containment system Arrangement or equipment to contain the particles of hazardous products in the chosen space Contiguous A term describing a location or space that adjoins another Example The clean room is contiguous with the anteroom and the surrounding pharmacy areas Synonyms neighbouring adjacent adjoining bordering abutting surrounding Controlled area or room An area or space where the only activities taking place are those related to the compounding of sterile products In such locations to obtain the specified ISO class parameters the concentration of viable and non viable particles suspended in the air is verified according to a sampling plan Corrective measures are taken when necessary so that the area remains at the expected ISO class level The clean room and anteroom are examples of controlled areas May also be known as a classified area or room 175 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2053 os Draft 2A Hazardous Sterile Products August 22 2014 92 Critical area Work area inside a laminar airflow workbench ensuring ISO Class 5
97. he compounding of sterile non hazardous products as well an anteroom for each type of compounding In some community pharmacies and smaller health care facilities space may be limited Although separate clean rooms are still required for each type of preparation i e one for hazardous sterile products and another for non hazardous sterile products there may be only one shared anteroom 42 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 6 4 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 43 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Chapter 4 General Preventive Measures Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp 4 4 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 4 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 7 9 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide s
98. he pharmacy manager and with pharmacists and pharmacy technicians assigned to perform compounding duties The sterile compounding supervisor develops organizes and oversees all activities related to compounding of hazardous sterile products These responsibilities are delegated by the health facility s pharmacy department head the pharmacist owner or the pharmacy manager The sterile compounding supervisor may by writing a delegation policy and procedure and using appropriate quality control measures delegate technical tasks related to sterile product compounding and auditing including the compounding of hazardous sterile products to pharmacy technical support personnel TSP In jurisdictions allowing regulated pharmacy technicians such delegation may be unnecessary if the technicians scope of practice includes product preparation Responsibilities The sterile compounding supervisor ensures that the following requirements are met e A personnel training and assessment program is implemented e Personnel know and fully comply with policies and procedures e Appropriate measures are taken to ensure the safety of personnel during each preparation e Policies and procedures covering all activities are developed regularly updated and always followed see Appendix 2 10 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Mo
99. he client sterile compounding supervisor to discuss the certification process during the meeting the certifier v asks whether problems have occurred since the last certification v asks whether there are any concerns about the operation of rooms or devices LAFW BSC CAI CACI Knows the PPE required to enter a controlled room and the garbing sequence Knows the required procedure for washing and disinfecting hands before putting on gloves and entering a controlled room ll General precertification requirements Cleans and disinfects all equipment brought into the controlled rooms Performs certification of the controlled rooms LAFWs or BSCs following the steps and methods recommended by the applicable standards Uses the applicable standards for certification see Appendix 6 Uses the devices required by the standards see Appendix 6 Uses calibrated devices that are in good condition Knows the standards to be used for certification and knows how to apply them Wears the appropriate PPE to enter and work in the compounding rooms for hazardous and non hazardous sterile products Is familiar with the products used especially if they are hazardous Does not touch hazardous products if touching a hazardous product is required asks qualified personnel to do so If applicable sets up a protective wall plastic or other before opening the device to limit contamination of the controlled room by hazardous dru
100. he quality assurance program is established to give personnel and other responsible individuals information showing that the personnel facilities and equipment BSC CACI etc attain and maintain the conditions required for contamination free compounding of hazardous sterile preparations and also that the hazardous sterile preparations are being compounded in compliance with established procedures The verifications required by the quality assurance program help to acquire data and identify trends which in turn allow corrective and preventive actions to be taken if necessary 7 1 Program content The sterile compounding supervisor must establish a quality assurance program that has four components 1 verification of equipment including the BSC or CACI 2 verification of controlled areas clean room and anteroom 3 verification of aseptic compounding processes 4 verification of final preparations Each component of the quality assurance program and its activities must be documented see Appendix 14 7 2 Results and action levels For each of the specified components the sterile compounding supervisor must establish a verification process the results of which are assigned one of three levels e compliance no action required mandatory specifications have been attained e alert tendency toward non compliance increased vigilance is required to prevent non compliance e action required non compliant more in depth inv
101. her activities not related to compounding expectation that procedures will be followed avoidance of unnecessary conversations 2 Training and assessment of personnel 2 1 Initial training and assessment program 2 2 Program to assess maintenance of competency 2 3 Training and assessment of cleaning and disinfecting personnel 3 Delegation of activities 3 1 Delegation of pharmaceutical activities to persons other than pharmacists 4 Facilities and equipment 4 1 Access to controlled areas 4 2 Necessary facilities and equipment 4 3 Maintenance of facilities and equipment e g certification of rooms and devices calibration maintenance of pre filters and HEPA filters verification of pressure 4 4 Cleaning and disinfecting activities for facilities and equipment 1 Bringing equipment and products into the clean room and laminar airflow workbench 2 Determining beyond use date of products used in a preparation 3 Determining beyond use date of final preparations 4 Hand and forearm hygiene 5 Garbing in compounding areas and for compounding 6 Cleaning and disinfecting the Laminar Airflow Workbench 7 Aseptic techniques with details for each of the techniques used Draft 2A Hazardous Sterile Products August 22 2014 100 8 Verification of the compounding process including validation of calculations by a pharmacist and of final preparations 9 Labelling of final preparations
102. identified 115 Know and apply quality assurance measures for the various compounded x x x sterile preparations 1 16 Know and follow the pharmacist s verification process X X X 1 17 Know and use the incident and accident documentation logs X X X 1 18 Know drug delivery systems X X X 1 19 Know and establish levels of risk and beyond use dates X 1 20 Know and if applicable perform additional sterility testing X X X 2 FOR THE COMPOUNDING OF HAZARDOUS STERILE PREPARATIONS PH PT TSP 2 1 Have the competency required to compound sterile preparations X X X 2 2 Identify hazardous drugs in the composition of sterile preparations X X X 2 3 Know and apply deactivation measures X X X Know and use the protection measures necessary to avoid exposure to 2 4 X X X hazardous substances Know and use personal protective equipment specifically for handling 2 5 X X X hazardous products Safely handle hazardous drugs i e receive unpack store and deliver xX 2 6 X X hazardous drugs 27 Know and apply the appropriate aseptic technique for hazardous drugs in the x x x f workplace Know and use the emergency measures to be applied in the case of 2 8 X X X accidental exposure accidents or spills 29 Know how to safely destroy hazardous drugs and the materials used in their x x x preparation FOR THE COMPOUNDING OF HIGH RISK NON HAZARDOUS AND 3 HAZARDOUS STERILE PREPARATIONS MADE WITH NON STERILE PRODUCTS 3 1 Have the compet
103. inciples of confidentiality 6 PRODUCT AND PREPARATION REQUIREMENTS 6 1 Beyond use date and dating methods 6 1 1 Beyond use date of preparations For the purposes of these Model Standards the BUD is the date and time after which the hazardous compounded sterile preparation cannot be used or administered to a patient It is based on the date and time when the hazardous sterile preparation was compounded The BUD also specifies the storage time and temperature conditions that must be in effect before administration The method used to establish the BUD depends on the type of commercial container with or without preservative used for the preparation and or the preparation s risk of microbial contamination Where no specific sterility test is performed for a preparation or batch the sterile compounding supervisor must assign a BUD based on the following criteria The BUD must not exceed the earliest of the dates established by the following two criteria 9798 99 according expiration date based on chemical and physical stability to reference texts storage time related to risk of microbial contamination microbiological stability related to the compounding process 6 United States Pharmacopeial Convention USP General chapter lt 795 gt pharmaceutical compounding nonsterile preparations USP 36 Rockville MD USP 2011 97 Trissel LA Handbook on injectable drugs 17th ed Bethesda MD American So
104. ipped with a continuous temperature recorder In the latter situation the data recorded by this device must also be verified and stored Temperature probes must be maintained and calibrated at least once a year or in accordance with the manufacturer s instructions Calibration of these instruments must be noted in the general maintenance log Incubator An incubator is a device used in microbiology laboratories to maintain a constant temperature for the culture of microorganisms The incubation temperature must be controlled 20 C to 25 C or 30 C to 35 C depending on the culture medium and incubation period When the incubator is in operation the incubator temperature must be read and recorded in the general maintenance log at least once a day The incubator must be calibrated and maintained according to the manufacturer s recommendations The incubator must not be placed in the clean room or the anteroom It may be located in the pharmacy or another room nearby Cameras and computer equipment Audio visual and computer equipment used for verification during compounding camera monitor pedal system is allowed in the clean room under certain conditions Preference must be given to audio visual and computer equipment that features hands free operation and that is made of smooth non porous cleanable materials with low particulate emission and resistance to damage from cleaning products The use and installation of
105. isor for these activities If the designated pharmacist or pharmacy technician chooses not to perform these activities the pharmacist owner or pharmacy manager must assume the responsibilities of sterile compounding supervisor and must prepare hazardous compounded sterile preparations in the pharmacy American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 7 American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 8 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Draft 2A Hazardous Sterile Products August 22 2014 8 If these responsibilities are delegated the pharmacist owner or pharmacy manager must ensure that the sterile compounding supervisor fulfills them adequately 5 1 1 2 Sterile compounding supervisor Definition A pharmacist or pharmacy technician designated to supervise activities related to the compounding of hazardous sterile products This person works with t
106. l verification steps required during and after compounding 7 6 Documentation of quality control activities Written documentation related to the quality assurance program must be verified analyzed and signed by the sterile compounding supervisor and retained for a period designated in federal provincial territorial regulations The sterile compounding supervisor must e investigate missing documentation situations of non compliance where action is required and deviations from protocols e identify trends concerning microbial load in controlled areas and types of microorganisms found e consult a microbiology specialist if necessary e take corrective and preventive actions For the sampling of viable air and surface particles the nutrient medium readings should be documented on a separate form for each type of sampling 17 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 89 All completed documentation concerning components of the environmental verification of controlled areas the BSC or CACI and support equipment must be filed and retained with other compounding records in an easily accessible location inside the pharmacy Documents concerning purchase organization and certification must be accessible throughout the entire service life of the facility and the BSC All completed documentation concerning the
107. l Association of Pharmacy Regulatory Authorities NAPRA Model standards of practice for Canadian pharmacists Ottawa ON NAPRA 2009 Available from Np napra onten ViOde naara Draft 2A Hazardous Sterile Products O a On a da a August 22 2014 12 chemical contamination of the environment Stringent work methods are therefore required Integration and maintenance of required competencies is achievable only with adequate training and assessment Compounding personnel must keep their compounding knowledge up to date 5 1 2 1 Conditions The assessment results and any corrective measures imposed must be recorded and these records must be retained The sterile compounding supervisor must ensure that all compounding personnel have the knowledge and competency required to perform quality work 5 1 2 2 Initial training and assessment program 13 Thomas M Sanborn M Couldry R I V admixture contamination rates traditional practice site versus a class 1000 cleanroom Am J Health Syst Pharm 2005 62 22 2386 92 Trissel LA Ro JA Saenz LM Woodard MY Angeles CH eee of two work practics changes o on A microbial 00 Draft 2A Hazardous Sterile Products August 22 2014 e theoretical training with assessment covering various topics including those in Appendix 4 e individualized practical training and assessment in the workplace clean room see section 7 and Appendix 4 Cleaning and disinfecting personnel
108. lders 5 1 1 4 Patient care dispensing pharmacist Definition The pharmacist who dispenses a sterile preparation to a patient or another health care professional The dispensing pharmacist may be same person as the compounding pharmacist alternatively the dispensing pharmacist may ask another pharmacist or pharmacy technician to compound the preparation The patient care dispensing pharmacist shares professional responsibilities with the compounding pharmacist or pharmacy technician When the patient care dispensing pharmacist is also the compounding pharmacist the dispensing pharmacist assumes the responsibilities associated with both roles Responsibilities When providing patient care that includes dispensing medications or medication therapies the patient care dispensing pharmacist must follow the standards of practice for Canadian pharmacists 5 1 1 5 Other employees Employees must follow and comply with specific procedures for the compounding of hazardous sterile products 5 1 2 Training and assessment Compounding personnel and cleaning and disinfecting personnel have a major impact on the risks associated with contamination of preparations and with 11 National Association of Pharmacy Regulatory Authorities NAPRA Model standards of practice for Canadian pharmacists Ottawa ON NAPRA 2009 Available from http napra ca Content_Files Files Model_Standards_of_Prac_for_Cdn_Pharm_March09_Final_b pdf 12 Nationa
109. lving non compliance of personnel with aseptic processes Samples for determining the number of non viable particles per cubic metre of air viable particles per cubic metre of air and viable surface particles must always be obtained under dynamic operating conditions during each facility and BSC or CACI certification Sampling of non viable particles in air Non viable particles in the air in controlled areas and the BSC must be sampled at least every 6 months as follows e by the qualified certifier during certification of facilities e by employees of the community or health care facility pharmacy provided the employees have been trained within the framework of an internal verification program including training in use of a calibrated particle meter to ensure proper operation of facilities and equipment The sterile compounding supervisor must ensure the competency of the certifier and the personnel chosen to conduct the sampling Appendix 6 describes the certification activities United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 374 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 84 The values obtained must comply with the specifications established for each controlled area ISO 14644 1 classifi
110. ments previously failed In case of repeated failures a decision must be made regarding permanent termination of sterile product compounding or cleaning and disinfecting activities 5 1 2 4 Management of the competency assessment program Sterile compounding supervisor and delegation of employee training of hazardous sterile products The supervisor may e delegate the training portion of the program to a pharmacist pharmacy technician or TSP on the supervisors team but must perform the assessment portion OR Draft 2A Hazardous Sterile Products August 22 2014 1 6 e delegate both training and assessment of personnel to an external evaluator a pharmacist or pharmacy technician with expertise in compounding sterile products from a workplace external to the supervisor s environment External evaluator If the sterile compounding supervisor delegates training and assessment of compounding personnel and cleaning and disinfecting personnel to a third party e the sterile compounding supervisor must ensure that the external evaluator is qualified to fulfill the mandate the external evaluators annual competency assessment must include the same elements as the competency assessment program for the compounding personnel pharmacists pharmacy technicians and TSP described above 5 2 Policies and procedures The quality absence of contamination and efficacy of the final preparation depend upon among oth
111. mic operating conditions e There must be at least 30 or more air changes per hour ACPH in the clean room and the anteroom Depending on the size of the rooms and the number of people working in them a greater number of ACPH may be required e The temperature in the controlled rooms must be less than or equal to 20 C taking into account employees comfort once all clean room garb including PPE has been donned Medication storage temperatures must not exceed 25 C Note There is no requirement for relative humidity refer to the recommendations of the Canadian Society of Hospital Pharmacists See also the pressure diagram for the anteroom and the clean room Figure 1 page 27 32 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 368 33 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 34 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 368 35 International Organization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 38 United States Pharmacopeial Conve
112. mpounding procedure Indicate any documentation supporting the stability of the final compounded sterile preparation Name of preparation Date when preparation was made Lot Quantity prepared Beyond use date Shelf life Verified by Customer label In addition to the legally mandated information add lot number of compounded sterile preparation beyond use date precautions and pharmacovigilance Indicate the training that personnel must undergo before the specific sterile compounding procedure is implemented 120 Preparation data sheet history No Date drafted dd mm yyyy Drafted by Revised dd mm yyyy Revised by Change made Version number changed O YES ONO Revised dd mm yyyy Revised by Change made Version number changed O YES ONO Draft 2A Hazardous Sterile Products August 22 2014 121 APPENDIX 9 EXAMPLES OF STERILE PREPARATIONS THAT MUST BE VERIFIED AT EACH STAGE OF COMPOUNDING Contents of vial or ampoule to be injected into a bag 1 g cefazolin IV every 8 hours minibag Intermate or other container when the entire Dose prepared using a 10 g vial of powder diluted in 50 mL of 0 9 NaCl contents of the vial powder will not be used or when a The diluent and product taken from the vial must be checked for each dose before liquid product is packaged in a vial or ampoule injection into the bags 50 mg mL vancomycin ophthalmic solution prepared from a 500 mg vi
113. nes 2009 edition Version 2 GUI 0001 Ottawa ON Health Canada 2009 revised 2011 Mar 4 p 85 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php 26 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 27 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 2 1 An air conditioning system must be included in the HVAC system to help ensure the comfort of personnel wearing personal protective equipment PPE 5 3 2 4 Windows and openings Controlled rooms should have no windows or doors leading directly to the exterior of the building If any windows are present they must be sealed If any doors lead to the outside or to a non controlled area other than the doors designated for accessing the room they must be sealed An environmental control procedure and a housekeeping procedure including the cleaning of sealed windows and doors must be implemented by cleaning and disinfecting personnel 5 3 2 5 Compounding areas Compounding facilities must have at least two separate controlled rooms enclosed and physically separated by a wall a clean room where the primary engineering control e g BSC or CACI is located and an anteroom located next to the clean room
114. nformation from the manufacturer e documentation indicating that the CACI meets established standards when installed in an environment where the number of particles meets ISO Class 8 specifications e the waiting time required to achieve ISO Class 5 air quality after materials have been transferred before aseptic processing is started recovery time Compounding personnel working in a CACI must comply with the garbing procedure for compounding of hazardous preparations in a BSC to maintain air quality and to protect themselves from spills Maintenance of BSC and CACI BSCs and CACIS must be maintained in accordance with the manufacturer s recommendations BSCs and CACIS must be certified e twice a year e when relocated e after major repairs e when sterility controls show that the BSC or CACI may not be in compliance with specifications BSC and CACI pre filters must be accessible They should be inspected every 6 months and replaced if necessary or as recommended by the manufacturer Washable pre filters must not be used HEPA filters should be verified during installation and certification to ensure there are no leaks or damage to the filters after they have been transported or installed Preventive equipment maintenance for BSCs CACIs etc must be performed when no compounding is in progress before cleaning and disinfection operations All BSC and CACI maintenance including maintenance of filters and pre fil
115. ng pharmacist and the patient care dispensing pharmacist When the compounding pharmacist is also the patient care dispensing pharmacist the compounding pharmacist assumes the responsibilities associated with both roles Responsibilities The compounding pharmacist or pharmacy technician must e perform or supervise compounding activities Draft 2A Hazardous Sterile Products August 22 2014 10 e enforce or ensure compliance with required aseptic hygienic cleanliness and safety rules e ensure that all records related to ongoing activities are completed and initialled e ensure that all data required for monitoring and reproducing the preparation are recorded or digitized e ensure that the equipment instruments and space used are properly cleaned and maintained e ensure application of and compliance with existing compounding procedures e ensure that there is a compounding protocol for each preparation produced e ensure the accuracy of calculations and measurements e use appropriate equipment and instruments for the preparation to be produced e follow the compounding process defined in the compounding protocol e perform verification during the various stages of compounding and verify the final preparation or delegate such verification in accordance with the appropriate delegation procedure e ensure that all required verification and quality control measures are performed to ensure quality and sterility o
116. ngeles CH Effect of two work practice changes on the microbial contamination rates of pharmacy compounded sterile preparations Am J Health Syst Pharm 2007 64 8 837 41 United States Pharmacopeial Convention USP General chapter lt 51 gt antimicrobial effectiveness In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 United States Pharmacopeial Convention USP General chapter lt 795 gt pharmaceutical compounding nonsterile preparations USP 36 Rockville MD USP 2011 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations In USP pharmacists pharmacopeia 2nd ed Suppl 2 Rockville MD USP 2008 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar Draft 2A Hazardous Sterile Products August 22 2014 1 34 United States Pharmacopeial Convention USP General chapter lt 1072 gt disinfectants and antisepsis In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 United States Pharmacopeial Convention USP General chapter lt 1075 gt good compounding practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 United States P
117. nit for evidence of particulates to verify the clarity colour and volume of the solution to check the container for possible leaks and to verify the integrity of the container e validate the information on the label e place final hazardous compounded sterile preparations that require storage at 2 C to 8 C in the refrigerator pending verification and delivery to patients or the patient care unit ice packs are suitable for maintaining the temperature of a cooled item but cannot be used for the cooling process therefore final hazardous compounded sterile preparations must be cooled in the refrigerator before being placed in a cooler 6 6 6 2 Process for verification Verifications may be performed in one of three ways e direct observation during compounding e viewing of the identity and quantity of ingredients through an observation window located close to the BSC e remote observation using a digital camera connected to a monitor see section 6 6 6 3 for additional detail 6 6 6 3 Verification by image capture or live camera Verification may be conducted by capturing images of the critical site in the BSC with a camera connected to a monitor Such verification must be performed before the hazardous compounded sterile preparation is delivered to the patient Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al
118. ntering the anteroom Before entering the anteroom compounding personnel must take the following steps e remove personal outerwear e g coat hat jacket scarf sweater vest boots and dirty outdoor shoes which tends to shed particles or squamous cells e remove jewelry studs and other accessories from fingers wrists forearms neck and other body parts if they might interfere with the effectiveness of the PPE e g for adjusting gloves and sleeves and for antiseptic washing of hands and forearms e remove all cosmetics makeup false eyelashes perfume and hair products such as hairspray which can produce particles that are possible sources of contamination e tie back long hair 109 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 376 7 110 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 58 e remove nail polish or any nail application extensions or other synthetic nail lengthening products e ensure that nails are short and that skin around the nails is undamaged e ensure that skin of hands and forearms is undamaged e change into dedicated low shedding apparel suitable for the controlled area e g Scrubs e fully cover legs and feet and wear closed shoes and socks e
119. ntion USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 lt lt Should a specific page be indicated for this reference gt gt 37 Canadian Society of Hospital Pharmacists CSHP Sterile preparation of medicines guidelines for pharmacists Draft 2A Hazardous Sterile Products August 22 2014 2 6 Given the PPE that compounding personnel are required to wear the clean room must be maintained at a temperature that will ensure their comfort and allow them to do their work conscientiously These conditions increase the safety of the aseptic compounding process and minimize skin desquamation Access to the clean room must be restricted to compounding personnel and cleaning and disinfecting personnel To enable supervision and verification activities one or more observation windows must be installed Such windows reduce the number of times individuals need to enter and exit the clean room especially visitors or observers They also ensure the safety of compounding and other personnel Figure 1 Pressure diagram A Pressure differentials Pressure differentials to be 1 Pg Pa 2 5 0 Pa maintained at all times 2 Pa Pc gt 2 5 Pa SIERRA Legend A facilities environment B C compounding room P pressure Pa pascal SI unit of measure for pressure Draft 2A Hazardous Sterile Products August 22 2014 2 7 Area for unpackin r
120. ntr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Draft 2A Hazardous Sterile Products August 22 2014 9 e The facilities and equipment used to compound hazardous sterile products meet requirements and are maintained calibrated or certified according to specifications e The existing compounding process yields high quality final preparations that are safe for patients e A quality assurance program designed to ensure that preparation activities are performed in accordance with standards of practice scientific standards existing data and relevant information is implemented and followed e Mandatory and supplementary documentation is available and updated regularly Appendix 3 lists required publications and suggestions for supplementary documentation e All records required by the Model Standards are completed 5 1 1 3 Compounding pharmacist or pharmacy technician Definition A pharmacist or pharmacy technician who prepares or supervises the compounding of sterile products e for patients of the facility or pharmacy where the pharmacist or pharmacy technician is employed OR e for patients of another facility or pharmacy at the request of a pharmacist at that facility or pharmacy where permitted by provincial territorial legislation in this case responsibilities toward the patient are shared between the compoundi
121. nvention USP General chapter lt 1072 gt disinfectants and antisepsis In USP Draft 2A Hazardous Sterile Products August 22 2014 93 thumbtips and fingertips into the contact plate agar Both hands are tested in this manner 8 Hand hygiene All methods related to handwashing that is performed using soap and water followed by a waterless alcohol based hand rub containing for example chlorhexidine and alcohol Hazardous drug A drug for which research on humans or animals has shown that any exposure to the substance has the potential to cause cancer lead to a developmental or reproductive toxicity or damage organs Drugs are considered hazardous because they involve risks for the worker because of their effects Hazardous material A material that because of its properties constitutes a danger to an employee s health safety or physical integrity Hazardous materials are dangerous products regulated by a workplace hazardous material information system as such they are considered controlled products under the Controlled Products Regulations Hazardous products Substances that entail risks for the worker because of their effects For the purposes of these Model Standards the term hazardous product refers to both hazardous drugs and hazardous materials depending on the situation Housekeeping See Cleaning and disinfecting Incident An action or situation
122. o as microbiologically clean but possibly chemically contaminated located adjacent to the clean room for the compounding of hazardous sterile products and the clean room for the compounding of non hazardous sterile products If there is enough space the clean area of the anteroom may be further divided into two areas e a microbiologically clean but chemically contaminated space or area adjacent to the clean room for the compounding of hazardous sterile products e a microbiologically and chemically clean space or area adjacent to the clean room for the compounding of non hazardous sterile products It is important to take these clean and dirty areas into account when traversing the anteroom and when removing PPE If the anteroom is shared this area is limited to hand hygiene and donning of PPE No drugs are stored in the shared anteroom Draft 2A Hazardous Sterile Products August 22 2014 3 0 Table 4 The following functional parameters must be met e The anteroom must be kept under positive pressure relative to the adjacent areas e The pressure differential must be at least 5 0 Pa equivalent to 0 02 inches water column relative to the adjacent area e ISO Class 7 air quality must be maintained in the anteroom under dynamic operating conditions e There must be at least 30 air changes per hour ACPH Depending on the size of the room and the number of people working in it a
123. oducts 38 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 39 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 6 4 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Chapter 4 General Preventive Measures Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp 4 4 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide Draft 2A Hazardous Sterile Products August 22 2014 28 O o eer 5 3 2 6 Shared facilities Compounding of hazardous and non hazardous sterile products Facilities in community pharmacies or health care facilities that compound both hazardous and non hazardous sterile products must have two clean rooms one for the compounding of sterile hazardous products and another for t
124. on The following examples indicate contamination levels that would trigger corrective action with different types of sampling Volumetric sampling of facility air e Areas requiring ISO Class 5 air quality threshold contamination gt 1 CFU m of air e Areas requiring ISO Class 7 air quality threshold contamination gt 10 CFU m of air e Areas requiring ISO Class 8 air quality threshold contamination gt 100 CFU m of air Surface sampling of LAFW direct contact or swabbing method 55 mm agar plate e Areas requiring ISO Class 5 air quality threshold contamination gt 3 CFU plate e Areas requiring ISO Class 7 air quality threshold contamination gt 5 CFU plate e Areas requiring ISO Class 8 air quality threshold contamination gt 100 CFU plate GFTS total for two hands e Areas requiring ISO Class 5 air quality threshold contamination gt 3 CFU total During the first months of sampling the sterile compounding supervisor should ensure that samples are obtained more frequently than the minimum 6 month interval to create a baseline for comparison The sterile compounding supervisor must analyze the data obtained and the trends observed with respect to the microbial load in controlled areas as well as the types of microorganisms found to establish corrective and preventive actions if necessary the sterile compounding supervisor should consult a microbiologist or infectious diseases specialist Unite
125. on AK Castel AD Ganova Raeva LM Myers RA Roup Bu et al Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies JAMA 2006 296 16 2005 11 Kastango ES The costof quality in pharmacy lat J Pham Compound 2002 6 6 404 Z Draft 2A Hazardous Sterile Products August 22 2014 4 acceptable so long as they are proven to be equivalent or superior to those described here Such other technologies techniques materials and procedures require prior approval from the provincial territorial regulatory authority 3 REGULATORY FRAMEWORK Many health care professionals prepare compounded sterile products including nurses physicians pharmacists and pharmacy technicians However the majority of sterile compounding is performed by or under the supervision of pharmacists Therefore these standards pertain specifically to pharmacists pharmacy technicians and pharmacies where compounded sterile products are prepared The preparation of medication has always been an integral part of the practice of pharmacy It is essential to the delivery of health care and allows for personalized therapeutic solutions to improve patient care However it must always be carried out within an individual physician patient pharmacist relationship i e from a prescription or within a pharmacist patient relationship for a specific need e g with over the counter preparations Provincial territorial pharmacy regulato
126. on area Location of and other furniture The BSC CACI and other pieces of furniture should be positioned to avoid interfering with facility ventilation systems 54 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 Available from https www osha gov dts osta otm otm_vi otm_vi_2 html 56 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 380 57 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 58 Peters GF McKeon MR Weiss WT Potentials for airborne contamination in turbulent and unidirectional airflow compounding aseptic isolators Am J Health Syst Pharm 2007 64 6 622 31 59 Controlled Environment Testing Association CETA CETA compounding isolator testing guide CAG 002 2006 ses NC CETA 2006 revised 2008 Dec 8 Available from Draft 2A Hazardous Sterile Products August 22 2014 36 To facilitate cleaning and disinfecting activities such as cleaning the floor and exterior
127. on report CAI compounding aseptic isolator CACI compounding aseptic containment isolator CETA Controlled Environment Testing Association HEPA high efficiency particular air NSF NSF International public health and safety organization PPE personal protective equipment Draft 2A Hazardous Sterile Products August 22 2014 1 1 3 APPENDIX 7 CERTIFICATION OF CONTROLLED ROOMS LAMINAR AIRFLOW WORKBENCHES AND BIOLOGICAL SAFETY CABINETS TARGET CERTIFICATION STANDARDS CERTIFICATIONS Laminar airflow workbench e IEST RP CC 002 3 LAFW certification includes steps carried out Unidirectional Flow Clean Air Devices vertical or horizontal laminar flow hoods e ISO 14644 1 1 In accordance with IEST RP CC 002 3 Measurement of air supply profile HEPA filter integrity test 2 In accordance with ISO 14644 1 Count of non viable particles 0 5 um diameter in operational dynamic state at rest state is optional Measurement of air intake velocity Smoke test Equipment used Particle counter Thermal anemometer Smoke machine Photometer Biological safety cabinet Class Il type B2 NSF Standard 49 2012 Biological Safety Class Il type B2 BSC certification includes steps carried out Cabinetry Design Construction For certification of other types of BSC Performance and Field Certification In accordance with NSF Standard 49 2012 please refer to the standards ISO 14644 1 Measurement of air supply profile Meas
128. ons must refer patients to a pharmacist who does offer this service or 5 Health Canada Health Products and Food Branch Inspectorate Policy on manufacturing and compounding drug products in Canada POL 051 Ottawa ON Health Canada 2009 Available from http www hc sc gc ca dhp Draft 2A Hazardous Sterile Products August 22 2014 5 where permitted by provincial territorial legislation ask a colleague to compound the preparation for them Compounded sterile preparations include the following types of medications nasal sprays respiratory therapy solutions solutions for live organ and tissue or graft baths solutions for injection e g intramuscular intravenous intrathecal intradermal subcutaneous irrigation solutions for wounds and body cavities ophthalmic drops and ointments otic drops for intratympanic administration parenteral nutrition solutions dialysis solutions solutions for intradermal injection allergens topical preparations requiring sterility Pursuant to these Model Standards sterility is also required for reconstitution and certain manipulations according to manufacturers instructions of sterile products approved by Health Canada and for the repackaging of approved sterile products regardless of the route of administration Draft 2A Hazardous Sterile Products August 22 2014 6 4 ABBREVIATIONS The following abbreviations are used in this document Abbreviation Name
129. pecify certain criteria for determining the risk level and establishing the BUD A sterile unit is a vial ampoule or bag of drug or diluent The following examples illustrate the concept e 1 bag of solute represents 1 sterile unit e 2 vials of cefazolin represent 2 sterile units Cundell AM USP Committee on Analytical Microbiology stimuli to the revision process Pharmacopeial Forum Draft 2A Hazardous Sterile Products August 22 2014 5 2 e 1 vial of sterile water for injection represents 1 sterile unit Table 7 Low Medium High e Final product e Final product e Non sterile ingredients or compounded using up compounded using 4 or equipment used for to 3 sterile units more sterile units preparation e Nomore than 2 e Complex manipulations e Exposure for more than 1 septum punctures at the injection site for hour of sterile material or Prolonged preparation content of sterile each sterile unit timg commercial products to an e Batch preparations for environment with air quality Fi MP SAN more than one patient below ISO Class 5 transfer technique requirements e Drug prepared for one patient patient specific dose e Non sterile preparations containing water stored for more than 6 hours before sterilization Table 8 BUD without additional sterility testing Risk of At controlled With storage in With storage in contamination room refrigerator fre
130. prevention guide safe handling of hazardous drugs html 156 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 87 Using tryptic soy agar contact plates with lecithin and polysorbate the assessor takes thumbprints and prints of each gloved fingertip from both hands of the assessed employee asking the employee to gently press each thumb and fingertip on the agar in the contact plate When the sampling is complete the gloves must be taken off and thrown away and hands must be re sterilized according to established procedure The samples must be incubated between 30 C and 35 C to be read in 48 to 72 hours The results obtained for each hand must be recorded The number of CFUs determining the action level for gloved fingertips as set out in section 7 3 2 3 subsection Sampling of viable particles in air and on surfaces refers to the total for both hands 7 4 2 Media fill test The media fill test is a compounding simulation test conducted with nutrient media that promote bacterial growth to verify maintenance of the aseptic process for a given employee For more information on this test consult General Chapter lt 797 gt in the USP NF For the media fill test the simulation chosen for assessment of personnel must be representative of activities performed under real compounding conditions in the p
131. pter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 373 51 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 3 J plates should be installed to prevent walls from being damaged when furniture is moved In all rooms reserved for the compounding of sterile products any holes cracks or breakage in walls must be repaired and sealed Floors In controlled areas clean room and anteroom the floors must have the following characteristics Flooring must be non porous non friable flat smooth sealed and resistant to damage from cleaning products Any breakage must be repaired and sealed immediately In the clean room and anteroom the floor must be coved to the side wall There must be no mats or rugs Anti fatigue mats must be avoided they are typically made of porous materials 5 3 2 9 Accessories Ceiling fixtures In controlled areas clean room and anteroom ceiling fixtures must be recessed and flush mounted Their external surfaces whether made of glass or other material must be washable smooth and sealed Plumbing Water sources sinks and drains must not be located in a clean room but are permitted in the anteroom Functional parameter control systems Control systems indicating the temperature and differential pressure between controlled ar
132. quebec gouv qc ca dynamicSearch telecharge php type 3 amp file S_2_1 S2_1R13_A HTM Association des pharmaciens des tablissements de sant du Qu bec APES Regroupement des pharmaciens en oncologie Recueil d information pharmaceutique en oncologie Montr al QC APES 2001 revised 2003 Oct Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html BC Cancer Agency BCCA Module 1 Safe handling of hazardous drugs In BC Cancer Agency pharmacy practice standards for hazardous drugs Vancouver BC BCCA 2012 http Awww bccancer bc ca HPI Pharmacy GuidesManuals safehandling htm Boyce JM Pittet D Guideline for hand hygiene in health care settings Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC SHEA APIC IDSA Hand Hygiene Task Force MMWR Recomm Rep 2002 51 RR 16 1 45 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 Canadian Centre for Occupational Health and Safety CCOHS Anti fatigue mats Hamilton ON CCOHS 1997 confirmed current 2006 Available from http www ccohs ca oshanswers ergonomics mats htm Dra
133. ques of compounding personnel and the environment s ability to produce preparations that are sterile For this test a nutrient medium replaces the actual product when the aseptic technique 190 191 is performed en ps77_promoting_competence_e pdf contents aspx 87 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 88 Canadian Nurses Association CNA Joint position statement Promoting continuing competence for registered nurses Ottawa ON CNA 2004 Available from http www cna aiic ca media cna page content paf Commission de la sant et de la s curit du travail CSST Material safety data sheet user s guide CSST 2010 Available from http www csst qc ca en prevention reptox whmis material safety data sheet users guide pages table 90 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 91 Health Canada Health Products and Food Branch Inspectorate Good manufacturing practices GMP guidelines 2009 edition Version 2 GUI 0001 Ottawa ON Health Canada 2009 revised 2011 Mar 4 p 85 Available from Draft 2A Hazardous Sterile Products August 22 201 4 9 5 Multiple dose vial Commercial drug container in multiple dose format for parenteral administration only The pro
134. r Containment integrity and enclosure leak test Recovery time test Smoke test Test of preparation entry and output Count of non viable particles Equipment used e Thermal anemometer e Pressure measurement device in inches of water or pascals Tools for adjusting alarms Smoke machine Photometer Particle counter small Aerosol generator Chronometer Certification of controlled areas and rooms includes the following steps e Count of non viable particles in operational dynamic state ISO 14644 1 115 Certification of HEPA filter IEST RP CC 006 3 CETA CAG 003 Certification Guide for Verification of terminal or line HEPA filter Sterile Compounding Facilities Measurement of pressure differential between controlled rooms Verification of air changes per hour by measuring ISO 14644 1 section on number of volumes of air or room velocity particles particle counters and sampling Verification of behaviour of rooms and equipment using plan and methods smoke tests Temperature verification Relative humidity verification Measurement of luminosity Measurement of noise level sound Equipment used Particle counter e Tripod for the room e Tripod for the LAFW or BSC e 0 3 um filter for cleaning e Tent to capture air volume Thermal anemometer Smoke machine Photometer Pressure measurement device in inches of water or pascals Thermometer Hygrometer Light meter Sound level meter Draft
135. r CACT one or more days When there has been a spill ase a 7 subfloor of BSC or PY Manufacturer CACI amsuriacesinsido near ne eieaninowinwatenony v a SubfoorotBSOor issuspecien Surface decontamination cleaning with mixture of water and germicidal disinfectant detergent followed by rinsing with water Deactivation application of sodium hypochlorite and sodium thiosulfate Disinfection application of sterile 70 isopropyl alcohol 125 BC Cancer Agency BCCA Module 1 Safe handling of hazardous drugs In BC Cancer Agency pharmacy practice standards for hazardous drugs Vancouver BC BCCA 2012 p 11 126 American Society of Health System Pharmacists ASHP guidelines on handling hazardous drugs Am J Health Syst Pharm 2006 63 12 1172 93 Ter McElhiney LF Preparing nonsterile and sterile hazardous compounds in an institutional setting Int J Pharm Compound 2009 13 4 300 10 Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 p 5 Available from https www osha gov dts osta otm otm_vi otm_vi_2 html Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 pp 13 2 and 13 3 Available from http www asstsas qc ca publi
136. r and surface sampling plan 3 Quality assurance of aseptic process for personnel e g gloved fingertip sampling media fill tests 4 Quality assurance of compounded sterile preparations e g existence of a protocol compliance with prescription documentation in logs 1 Environmental monitoring of chemical contamination Draft 2A Hazardous Sterile Products August 22 2014 1 0 3 APPENDIX 3 MANDATORY AND SUPPLEMENTAL DOCUMENTATION Compounding personnel must be able to consult a wide variety of up to date references in the pharmacy at any time A Mandatory documentation At a minimum the sterile compounding supervisor must make a recent edition of the following publications available Standards guidelines and policies of the relevant pharmacy regulatory authority Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html National Institute for Occupational Safety and Health NIOSH NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2012 Publ No 2012 150 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH June 2012 Available from http www c
137. r moving from one area to another thus keeping the areas isolated from one another The anteroom helps to maintain pressure differentials It must therefore be adjacent to the clean room separate from the rest of the pharmacy and fully enclosed to provide the required seal and to meet and maintain the desired specifications Users usually enter the anteroom from the pharmacy The anteroom is separated into two spaces by a demarcation line e The first space or area referred to as microbiologically dirty is located at the entrance to the anteroom in the section adjacent to the pharmacy e The second space or area referred to as microbiologically clean is adjacent to the microbiologically dirty area on one side and the clean room on the other It is important to take these clean and dirty areas into account when traversing the anteroom and when removing PPE Use The anteroom is the location for activities with higher generation of particulates such as garbing hand hygiene labelling and staging of components Activity in the anteroom shall be kept to a minimum and shall be limited to those activities that are essential to or that directly support the work undertaken in the clean room Access of supplies equipment and personnel into the clean room shall be through the anteroom No supplies equipment or personnel shall enter the clean room from a non controlled area 30 United States Pharmacopeial Conv
138. raft 2A Hazardous Sterile Products August 22 2014 2 7 3 Verification of equipment and facilities 7 4 Quality assurance of personnel involved in aseptic compounding 7 6 Documentation of quality control activities 8 GLOSSARY 9 LIST OF TABLES 10 APPENDICES Appendix 3 Mandatory and supplemental documentation Appendix 4 Training of compounding personnel and cleaning and disinfecting personnel Appendix 5 Procedure template Appendix 6 Best practice indicators for certification of controlled rooms laminar airflow workbenches and biological safety cabinets Appendix 7 Certification of controlled rooms laminar airflow workbenches and biological safety cabinets Appendix 8 Template for the drafting of compounding protocols to be completed for each drug Appendix 9 Examples of sterile preparations that must be verified at each stage of compounding Appendix 10 Examples of sterile preparations that do not require verification during the compounding process Appendix 11 Procedure example Receiving unpacking and storing hazardous products Appendix 12 Temperatures for different types of storage Appendix 13 Incident accident reporting and follow up form Appendix 14 Components of a quality assurance program 11 BIBLIOGRAPHY Draft 2A Hazardous Sterile Products August 22 2014 3 1 INTRODUCTION Parenteral therapies are becoming more complex and patients may now receive continuous antibiotic therapy or chemotherapy among other therapi
139. rd PCAB Standard 1 40 Standard operating procedures compliance indicators In PCAB accreditation manual Washington DC PCAB 2011 p 7 Available from http www pcab org cms wp content themes pcab img PCAB Accreditation Manual pdf Public Health Agency of Canada PHAC National vaccine storage and handling guidelines for immunization providers Ottawa ON PHAC 2007 114 pp Available from http www phac aspc gc ca publicat 2007 nvshglp Idemv pdf nvshglp Idemv eng pdf Selenic D Dodson DR Jensen B Arduino MJ Panlilio A Archibald LK Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy Am J Health Syst Pharm 2003 60 14 1440 6 Sessink PJM Boer KA Scheefhals APH Anzion RB Box RP Occupational exposure to antineoplastic agents at several departments in a hospital Environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers Int Arch Occup Environ Health 1992 64 2 105 12 Thomas M Sanborn M Couldry R I V admixture contamination rates traditional practice site versus a class 1000 cleanroom Am J Health Syst Pharm 2005 62 22 2386 92 Trissel LA Handbook on injectable drugs 17th ed Bethesda MD American Society of Health System Pharmacists 2013 Trissel LA Trissel s 2 clinical pharmaceutics database electronic database Cashiers NC TriPharma Communications updated regularly Trissel LA Gentempo JA Saenz LM Woodard MY A
140. res In particular cleaning and Only trained and qualified cleaning and disinfecting personnel may be allowed to clean areas reserved for the compounding of hazardous sterile products 84 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 4 6 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 85 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 4 8 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 86 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 46 5 3 4 2 Disinfectant 87 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 88 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 13 2
141. rile preparations USP 36 Rockville MD USP 2013 pp 365 8 169 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 365 8 170 United States Pharmacopeial Convention USP General chapter lt 51 gt antimicrobial effectiveness In USP Draft 2A Hazardous Sterile Products August 22 2014 88 The containers filled with the nutrient medium to be used for the media fill test must be incubated between 20 C and 25 C or between 30 C and 35 C for 14 consecutive days If two temperatures are used the containers should be incubated for 7 consecutive days at each of the temperatures starting with the lower temperature 7 5 Quality assurance of hazardous compounded sterile preparations The sterile compounding supervisor must establish a quality assurance program to ensure that hazardous sterile preparations are compounded in compliance with established procedures The program must monitor among other things e the presence of a compounding protocol for each compounded sterile preparation e compliance of the preparation with the prescription issued e compliance with legislation and regulations of labels affixed to containers e compliance with required documentation in a patients hazardous compounded sterile preparations log and the batch hazardous compounded sterile preparations log ensuring the performance of al
142. rmation related to preparations made by another pharmacist 6 5 Conduct of personnel in areas reserved for the compounding of hazardous sterile products Compounding personnel must behave in a professional manner following policies and procedures 6 5 1 Conditions that may affect preparation quality Draft 2A Hazardous Sterile Products August 22 2014 5 7 The sterile compounding supervisor or delegate must assess the possibility of temporarily removing any compounding personnel with a condition that may affect preparation quality including e uncontrolled weeping skin condition affecting face neck or arms or that might cause significant skin desquamation or contamination e burns to the skin including sunburns e cold sores active herpes simplex viral infection e conjunctivitis viral or bacterial e active respiratory infection with coughing repeated sneezing or runny nose e fresh piercings e other fresh wounds A person with permanent tattoos may compound sterile products However a recent tattoo on the face neck or arms is considered a fresh skin wound and the individual must cease sterile compounding activities and wait until the skin is completely healed before resuming such activities Tattoos transferred from paper to the skin of the face neck or arms by wetting and henna tattoos are not acceptable and must be completely removed before the person resumes sterile compounding activities 6 5 2 Conduct before e
143. ry authorities are responsible for verifying a pharmacy s preparation services in these situations In situations involving requests to compound preparations outside an individual physician patient pharmacist relationship without a prescription the compounding activities fall under the federal legislative framework The same federal legislative framework applies to bulk preparation of compounded products and to shipments across provincial territorial borders Health Canada is the federal department responsible for the Food and Drugs Act and the Controlled Drugs and Substances Act and their associated regulations In January 2009 Health Canada developed its Policy on Manufacturing and Compounding Drug Products in Canada At the time these Model Standards were prepared Health Canada was examining this policy with a view to creating new standards for situations not covered within the practice of pharmacy or under the current federal licensing framework The NAPRA professional competencies for Canadian pharmacists and pharmacy technicians at entry to practice provide guidance for developing an ethical legal and professional practice One of these competencies specifies that a pharmacist or pharmacy technician must seek guidance when uncertain about his or her own knowledge skills abilities and scope of practice Therefore individuals who do not have the training expertise facilities or equipment required to compound sterile preparati
144. s e controlled refrigeration temperature 2 C to 8 C e controlled freezing temperature 25 C to 10 C Accurate temperature probes gauges or sensors must be installed to indicate the actual temperature A continuous recorder built into each unit is the preferred option because it will record the temperature history 59 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 70 Public Health Agency of Canada PHAC National vaccine storage and handling guidelines for immunization providers Ottawa ON PHAC 2007 p 22 Available from http www phac aspc gc ca publicat 2007 nvshglp ldemv pdf nvshglp Idemv eng pdf 71 Health Canada Health Products and Food Branch Inspectorate Guidelines for temperature control of drug products during storage and transportation GUI 0069 Ottawa ON Health Canada 2011 Available from http Avww hc sc gc ca dhp mps compli conform gmp bpf docs gui 0069 eng php 12 Drug and Pharmacies Regulation Act R S O 1990 c H 4 Available from http www e Draft 2A Hazardous Sterile Products August 22 2014 40 A notification system must be installed in each refrigerator and freezer to alert pharmacy personnel when temperatures deviate from specifications Refrigerator and freezer temperature readings must be recorded on a form stored in the general maintenance log unless the units are equ
145. s intended for ease of reference by practitioners according to the type of practice The current document covers hazardous compounded sterile preparations The companion document discusses non hazardous compounded sterile preparations 2 OBJECTIVES The aim of these Model Standards is to provide pharmacists and pharmacy technicians who compound and pharmacists who dispense hazardous sterile preparations with the standards necessary to evaluate their practice develop service related procedures and implement appropriate quality controls for both patients and compounding personnel with a view to guaranteeing the overall quality and safety of sterile preparations The Model Standards will come into effect once they have been reviewed and approved by provincial pharmacy regulatory authorities The Model Standards represent the minimum requirements to be applied in compounding sterile preparations however it is always possible to exceed these standards The use of other technologies techniques materials and procedures may be 1 Dolan SA Felizardo G Barnes S Cox TR Patrick M Ward KS et al APIC position paper safe injection infusion and medication vial practices in health care Am J Infect Control 2010 38 3 167 72 Selenic D Dodson DR Jensen B Arduino MJ Panlilio A Archibald LK Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy Am J Health Syst Pharm 2003 60 14 1440 6 3 Patel PR Lars
146. s evaporated e Allow hands to dry e Don sterile gloves The selected sequence must be documented in the policies and procedures and updated as appropriate 6 6 2 2 Garbing Personnel must wear the PPE required for compounding terile products whether compounding is performed in a When using CACIs compounding personnel must comply with the garbing procedure to preserve air quality Compounding personnel must don and remove garb in the sequence described in the policies and procedures The selected sequence must be documented and reviewed regularly Shoe covers are required at all times in the clean area of the anteroom and the clean room All shoes worn must be closed dry clean and easy to maintain 116 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 7 117 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health Draft 2A Hazardous Sterile Products August 22 2014 6 1 118 6 6 3 Introducing products and equipment into the clean room Before a product enters the anteroom it must be removed from cardboard shipping boxes The product must be wiped with a sporicidal agent since cardboard has been found to harbour mould spores Any remaining packaging must be removed after the product enters the clean room from the anteroom At this point onl
147. sations Draft 2A Hazardous Sterile Products August 22 2014 101 2 Training and assessment of personnel 2 1 Initial personnel training and competency assessment program including the details of compounding hazardous drugs 2 2 Program to assess maintenance of competency including the characteristics of compounding hazardous sterile products 2 3 Training and assessment of cleaning and disinfecting personnel including the characteristics of compounding hazardous sterile products 3 Delegation of activities 3 1 Delegation of pharmaceutical activities to persons other than pharmacists 4 Facilities and equipment 4 1 Access to controlled areas 4 2 Facilities and equipment for the compounding of hazardous sterile products 4 3 Reservation of facilities and equipment for the compounding of hazardous sterile products 4 4 Maintenance of facilities and equipment including the characteristics of compounding hazardous sterile products e g certification of rooms and devices calibration maintenance of pre filters and HEPA filters pressure verification 4 5 Cleaning and disinfecting activities for facilities and equipment B COMPOUNDED STERILE PREPARATIONS 1 Receiving and unpacking of hazardous sterile products 2 Storage of hazardous sterile products 3 Determining beyond use date of products used in a preparation 4 Determining beyond use da
148. see that the establishments under his authority are so equipped and laid out as to ensure the protection of the worker 5 use methods and techniques intended for the identification control and elimination of risks to the safety or health of the worker 7 supply safety equipment and see that it is kept in good condition 8 see that no contaminant emitted or dangerous substance used adversely affects the health or safety of any person at a workplace 9 give the worker adequate information as to the risks connected with his work and provide him with the appropriate training assistance or supervision to ensure that he possesses the skill and knowledge required to safely perform the work assigned to him Source An Act Respecting Occupational Health and Safety C Q L R c S 2 1 Available from http www2 publicationsduquebec gouv qc ca dynamicSearch telecharge php type 2 amp file S_2 1 2_1_A html Draft 2A Hazardous Sterile Products August 22 2014 99 APPENDIX 2 POLICIES AND PROCEDURES FOR THE COMPOUNDING OF NON HAZARDOUS AND HAZARDOUS STERILE PRODUCTS Policy Topic 7 1 Obligations of personnel 1 1 Attire and dress code e g personal clothing jewelry makeup hairstyles 1 2 Health condition reasons for temporary withdrawal from compounding activities 1 3 Expected behaviour in controlled areas e g no drinking eating or ot
149. sor must develop and implement a packaging procedure for final hazardous compounded sterile preparations Appendix 5 presents a model for writing such procedures The packaging procedure must specify the following details equipment to be used to prevent breakage contamination spills or degradation of the hazardous compounded sterile preparation during transport and to protect the carrier equipment to be used to ensure that packaging protects hazardous compounded sterile preparations against freezing and excessive heat packaging must maintain a temperature between 2 C and 8 for hazardous compounded sterile preparations requiring refrigeration and a temperature between 19 C and 25 C for hazardous compounded sterile preparations to be kept at room temperature method to be used to confirm whether the temperature of hazardous compounded sterile preparations has been maintained during transport use of temperature maintenance indicator min max thermometer certified cooler etc packaging to be used to protect against extreme temperatures i e excessive heat or freezing during transport of hazardous compounded sterile preparations unless information is available demonstrating stability at these temperatures 6 8 Receipt and storage of hazardous products 139 United States Pharmacopeial Convention USP General chapter lt 1079 gt good storage and shipping practices In Draft 2A Hazardous Sterile Products August 22 20
150. sterile preparation ready to be stored and then administered to a patient which has been prepared according to a preparation specific compounding protocol which respects the prescribing physician s prescription Gloved fingertip sampling GFTS A process that involves microbiological examination based on imprints from the person being assessed obtained by having the person press gloved hazardous drugs html hazardous drugs html 76 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 77 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of 79 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 United States Pharmacopeial Co
151. surance dynamic conditions program Viable and non viable particles air e When a new LAFW is installed and surfaces e When the LAFW is maintained or repaired According to a sampling plan e When acontamination problem is identified e When investigation of a contamination problem or non compliance in the aseptic preparation process requires exclusion of malfunctioning facilities According to an internal verification program Draft 2A Hazardous Sterile Products August 22 2014 129 PERSONNEL Competency assessment e At initial qualification theoretical and practical aspects e At periodic qualifications theoretical and practical aspects e When assessing incidents and accidents e When acontamination problem is identified Gloved fingertip sampling e At initial qualification theoretical and practical aspects e At periodic qualifications theoretical and practical aspects e When assessing incidents and accidents e When acontamination problem is identified Media fill tests e At initial qualification theoretical and practical aspects e At periodic qualifications theoretical and practical aspects e When assessing incidents and accidents e When acontamination problem is identified FINAL Verification of compounding protocols e In accordance with the quality assurance program COMPOUNDED usage and maintenance STERILE ne that preparation matches e In accordance with the quality assurance pro
152. sure site within the CACI used for hazardous sterile products shows ISO Class 5 air quality during compounding 5 Particulate sampling conducted as close as possible to the doors when materials are being transferred without obstructing the passageway shows no more than 3520 particles 0 5 um diameter or larger per cubic metre of air ISO Class 5 in the CACI Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe handling of hazardous drugs Montr al QC ASSTSAS 2008 p 7 9 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 1 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 52 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 83 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 64 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care 37 Draft 2A Hazardous Sterile Products August 22 2014 The sterile compounding supervisor must obtain the following i
153. t 800 gt hazardous drugs handling in health care settings draft Rockville MD USP 2014 Mar 82 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide Draft 2A Hazardous Sterile Products August 22 2014 43 http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html 83 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care Draft 2A Hazardous Sterile Products August 22 2014 44 BSC biological safety cabinet CACI compounding aseptic containment isolator N A not applicable NIOSH National Institute for Occupational Safety and Health United States Draft 2A Hazardous Sterile Products August 22 2014 ws wn i 5 3 4 Cleaning and disinfecting in areas reserved for the compounding of hazardous sterile products 5 3 4 1 General Cleaning and disinfecting housekeeping in areas reserved for the compounding of hazardous sterile products must be performed to ensure the cleanliness required for the quality and integrity of final compounded sterile preparations Policies and procedures for cleaning and disinfecting tasks must be developed and cleaning and disinfecting personnel must be trained and assessed on correct application of these policies and procedu
154. te of final preparations 5 Hand and forearm hygiene 6 Garbing in compounding areas and for compounding 7 Bringing equipment and products into the clean room and biological safety cabinet 8 Verification of the compounding process including validation of calculations by a pharmacist and of final preparations 9 Cleaning decontamination deactivation and disinfection of the biological safety cabinet 10 Aseptic techniques for compounding hazardous sterile products 11 Packaging of hazardous compounded sterile preparations 12 Labelling of hazardous compounded sterile preparations Draft 2A Hazardous Sterile Products August 22 2014 102 13 Storage of final hazardous compounded sterile preparations 14 Recording of preparations in the patient s file 15 Transport and delivery of final hazardous compounded sterile preparations to the patient patient care units or dispensing pharmacist 16 Hazardous waste management e g at the pharmacy returns from patients or patient care units instructions to patients 17 Accidental exposure of personnel to hazardous drugs e g eyewash station log 18 Spills e g spill management chemical cartridge respirator kit 19 Recall of hazardous products or final hazardous compounded sterile preparations 3 1 Verification and maintenance of equipment 2 Environmental control of facilities and biological safety cabinet e g pressure verification ai
155. tent verification requires strict supervision including e implementation of policies and procedures implementation of a quality assurance program including regular evaluations of the TSP involved e verification of a percentage of preparations by the supervisor Each preparation must be inspected by a person other than the individual who performed the aseptic technique This person must inspect each unit against a black and white background for evidence of particulates verify the clarity colour and volume of the solution check the container for possible leaks and verify its integrity Like the compounder the verifier must sign the preparations log 6 6 7 Labelling final hazardous compounded sterile preparations 6 6 7 1 General United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 69 The sterile compounding supervisor must establish a policy for the labelling of hazardous compounded sterile preparations and ensure that it is followed The information on labels must follow federal provincial territorial legislation and regulations for drugs prepared or sold with or without a prescription More specifically the labels for hazardous compounded sterile preparations must meet the requirements of the applicable legislation and regulation All active ingredients must be identified on the label The label must also inclu
156. ters must be noted on a form and entered in the general maintenance log paper based or computerized The sterile compounding supervisor must ensure that BSC or CACI maintenance has been performed The supervisor must review the results or ensure that the results have been reviewed and corrective measures taken as appropriate The supervisor must sign the maintenance form or log 5 3 3 2 Other devices instruments or accessories related to the compounding of hazardous sterile products 55 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 38 Equipment used to compound hazardous sterile products must be clean and made of materials resistant to damage from cleaning products The decision to place equipment instruments or accessories not directly related to the compounding of hazardous sterile products carts cabinets computer monitors etc in the clean room depends on whether such placement will have an impact on maintaining environmental conditions in the clean room air quality control and surface sampling etc All necessary devices instruments and accessories must be cleaned and disinfected before being placed in a controlled area 7 Devices instruments and accessories to be used in controlled areas should not be removed without good reason If they must be removed they must be decontaminated Maintenance o
157. ting including disinfecting all floor and wall surfaces All movable furniture must be cleaned and disinfected before being placed in the clean room A locked cabinet dedicated to storage of cleaning and disinfecting equipment may be installed in the pharmacy a so see section 5 3 4 Chairs used in controlled areas must be made of smooth non porous non friable washable materials resistant to damage from cleaning products Some chairs are specifically designed for use in clean rooms and these should be the preferred choice Pass through A pass through with or without ventilation should be installed for transferring products into and out of the clean room The pass through should be sealed and made of stainless steel or a smooth non porous antistatic material resistant to damage from cleaning products The pass through must be airtight It is also recommended that the pass through be equipped with an interlocking system that prevents both doors from being open at once Otherwise a door opening procedure must be implemented If there is no pass through the clean room cart may be used to transport materials from the clean area of the anteroom into the clean room Interlocking door system Occupational Safety and Health Administration OSHA OSHA technical manual OTM controlling occupational exposure to hazardous drugs Section VI Chapter 2 Washington DC US Department of Labor 1999 Available from Draft 2A Ha
158. ts and the manufacturer s specifications which can be found on the BSC information plate or in the report included with the BSC at the time of purchase when there is no information plate Takes readings to measure the velocity of the air supply of a BSC according to NSF Standard 49 2012 or the manufacturer s specifications In accordance with ISO 14644 1 v Proceeds with the count of non viable particles v Verifies the count of non viable particles 0 5 um in diameter Y Verifies the count of non viable particles in at rest optional and in operation dynamic states measured at five reading points with a minimum of two 1 minute and 1 m samples per reading point the acceptable limit is 3520 particles Draft 2A Hazardous Sterile Products August 22 2014 1 1 2 3 Certification of LAFW Certifies the LAFW in accordance with IEST RP CC 002 3 Measures the velocity of the LAFW s air supply by taking a minimum of eight readings in the centre of every 12 square inches at a distance 12 inches from the surface of the HEPA filter or protective screen In accordance with ISO 14644 1 v Proceeds with the count of non viable particles v Verifies the count of non viable particles 0 5 um in diameter v Verifies the count of non viable particles in at rest optional and in operation dynamic states measured at five reading points with a minimum of two 1 minute and 1 m samples per reading point the accepta
159. ug storage e g Caution contents must be refrigerated upon receipt store between 2 C and 8 C Do not freeze Do not store medication in the refrigerator door Keep out of reach of children e special precautions for disposal or destruction of the preparation e emergency contact information of the compounding pharmacy where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation provided there is mutual agreement between the compounding pharmacist and the dispensing pharmacist 6 7 Packaging Appropriate packaging must be used for all preparations to be delivered to patients or other health care providers Preparations to be delivered must be packaged and labelled to ensure the safety of both the patient and the shipper 6 7 1 Packaging process During packaging compounding personnel must Draft 2A Hazardous Sterile Products August 22 2014 7 1 e indicate storage requirements on the final package e g temperature protection from light e indicate additional precautions on the final packaging e g pictogram e indicate transportation precautions e g temperature fragility safety and instructions name and address of the patient on the outside packaging of each item 6 7 2 Packaging procedure To maintain the integrity of hazardous compounded sterile preparations and the safety of patients and delivery personnel the sterile compounding supervi
160. uisition of a totality of theoretical technical and practical knowledge concerning pharmacy preparation Unidirectional airflow Airflow moving in a single direction in a robust and uniform manner and at sufficient speed to reproducibly sweep particles away from the critical site 195 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 263 196 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile Draft 2A Hazardous Sterile Products August 22 2014 97 9 LIST OF TABLES Table 1 Classes of air cleanliness for airborne particulates in clean rooms and clean areas according to ISO 14644 1 Table 2 Functional parameters of the clean room and anteroom for the compounding of hazardous sterile products Table 3 Required conditions for a hazardous products storage area Table 4 Functional parameters of a shared anteroom for the compounding of hazardous and non hazardous sterile products Table 5 Masks and chemical cartridge respirators Table 6 Beyond use dates BUDs for hazardous compounded sterile preparations when a preservative free vial is used Table 7 Contamination risk levels Table 8 B
161. upational Safety and Health NIOSH NIOSH alert preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings Publ No 2004 165 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2004 Sep Available from Draft 2A Hazardous Sterile Products August 22 2014 2 0 The air in controlled rooms must be clean and levels of airborne particulates must be controlled Thus the facility s heating ventilation and air conditioning HVAC system must be designed to minimize both the risk of airborne contamination in controlled rooms used for the compounding of hazardous sterile products and the propagation of hazardous products in the work environment It must also be designed to achieve and maintain the appropriate ISO class for clean rooms and anterooms used for the compounding of hazardous sterile products see section 5 3 2 5 Table 2 The air supplied to areas used for compounding hazardous sterile products must pass through a high efficiency particular air HEPA filter to ensure a very high level of cleanliness The intake air must come from the ceiling via diffusers each fitted with a terminal HEPA filter All sources that generate particles must be controlled to achieve and maintain the ISO class for clean rooms and anterooms used to compound hazardous sterile products The air quality in controlled rooms must comply with the ISO 14644
162. upational exposures to antineoplastic and other hazardous drugs in health care settings Publ No 2004 165 Atlanta GA Department of Health and Human Services Centers for Disease Control and Prevention NIOSH 2004 Sep Available from Draft 2A Hazardous Sterile Products August 22 2014 96 airflow workbenches and compounding aseptic isolators Primary engineering controls for compounding hazardous preparations are called biological safety cabinets and compounding aseptic containment 195 isolators Procedure All steps to be taken the means to be used and the methods to be followed in performing a task Process for aseptic compounding All activities leading to completion of a final compounded sterile preparation especially hand hygiene and garbing introduction of products and materials into the clean room the disinfection of the primary engineering control use of aseptic techniques for compounding products in the primary engineering control and verification and labelling of compounded sterile preparations Its purpose is to maintain the sterility of a product or drug compounded from sterile components Protocol Document describing in detail all steps to be followed or behaviours to adopt in precise clinical circumstances Repack repacking The process of packing again or the action of repacking reprocessing Examples include making 12 tablet packages from a pack bottle of 100 tablets
163. urement of air intake velocity Smoke test HEPA filter integrity test Verification that interlock system between discharge probe and air supply motor is working properly for Class Il type B2 BSC Verification of device calibration less than 20 air loss in 15 seconds for Class II Type B2 BSC In accordance with ISO 14644 1 Count of non viable particles 0 5 um in operational dynamic state at rest state is optional 114 Draft 2A Hazardous Sterile Products August 22 2014 Compounding aseptic isolator Primarily manufacturer s recommendations CETA CAG 002 2006 Compounding Isolator Testing Guide Compounding aseptic containment isolator e Primarily manufacturer s recommendations e CETA CAG 002 2006 Compounding Isolator Testing Guide Clean room for the compounding of sterile products and controlled areas NEBB Procedural Standards for Certified Testing of Clean rooms e IEST RP CC 006 3 Testing Clean Rooms Draft 2A Hazardous Sterile Products August 22 2014 e Measurement of air intake velocity Equipment used Particle counter Thermal anemometer Smoke machine and aerosol generator Photometer Direct volume measurement device Isolator certification includes steps carried out according to manufacturer s recommendations with reference to CETA CAG 002 2006 Specific tests used e Airflow test Verification of internal pressure Verification of installation site Verification of HEPA filte
164. urs of exposure time at a temperature above 8 C before sterilization 6 1 4 Beyond use dates for preparations in short term critical situations Pharmacy departments and community pharmacies that provide hazardous compounded sterile preparation services must meet the requirements specified in these Model Standards specifically adequate facilities and equipment compliance with garbing requirements application of stringent housekeeping and impeccable aseptic technique 6 1 4 1 Beyond use dates for immediate use preparations 6 1 4 2 Preparations with beyond use dates of 12 hours or less For compounded sterile preparations made in a BSC that maintains the requirement for ISO Class 5 air quality or better but is not located in an environment in compliance with ISO Class 7 air quality the following conditions must be met e The room has a minimum of 12 ACPH 107 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 361 108 United States Pharmacopeial Convention USP General chapter lt 800 gt hazardous drugs handling in health care Draft 2A Hazardous Sterile Products August 22 2014 54 e One preparation is compounded at a time e The preparations are compounded in an area that is reserved for the compounding of sterile products and that minimizes contamination e There is no sink in the preparation area an
165. wash hands 6 5 3 Conduct in controlled areas clean room and anteroom In controlled areas the following measures should be taken e Food items drinks chewing gum candy and smoking are prohibited e Food items or drinks must not be stored in refrigerators reserved for storing compounded sterile preparations e All access doors to controlled areas must be kept closed e Anyone who enters the anteroom or a clean room must be authorized and follow all hand hygiene and garbing procedures e Only essential conversations are allowed to minimize the risk of particulate contamination Coughing sneezing and talking in the direction of the BSC should also be avoided 6 6 Aseptic compounding of hazardous sterile products 6 6 1 General The aseptic compounding process includes all activities leading to completion of the final sterile preparation including e performing hand and forearm hygiene e garbing of personnel Boyce JM Pittet D Guideline for hand hygiene in health care settings Recommendations of the Healthcare nfection Control Practices Advisory Committee and the HICPAC SHEA APIC IDSA Hand Hygiene Task Force MMWR Recomm Rep 2002 51 RR 16 1 45 2 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile reparations USP 36 Rockville MD USP 2013 p 380 3 Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTS
166. y packaging required for maintenance of sterility is retained Where packaging allows compounding equipment and products must be disinfected with sterile 70 isopropyl alcohol just before being introduced into the clean room for the compounding of sterile products Non shedding sterile wipes or swabs must be used for disinfection The wipes or swabs must be changed regularly during disinfection of products and equipment For introduction of compounding equipment and products into the clean room the items must be placed in a plastic or stainless steel bin to prevent errors The bin is then placed in the pass through for transfer to the clean room Bines used for this purpose must be disinfected before use If there is no pass through the equipment and products are transferred from the dirty cart or bin to the clean cart or bin at the demarcation line in the anteroom and then introduced into the clean room 6 6 4 Surface decontamination deactivation and disinfection of the biological safety cabinet or compounding aseptic containment isolator Only compounding personnel are allowed to clean decontaminate and disinfect the BSC or CACI They must take the following steps e Follow hand and forearm hygiene and garbing procedures United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 376 379 119 BC Cancer Agen
167. zardous Sterile Products August 22 2014 34 Access doors to controlled areas should be equipped with an interlocking system Such a system which allows only one door to be open at a time helps to maintain the pressure differential If this type of system is not installed a door opening procedure must be implemented and followed by compounding personnel and by cleaning and disinfecting personnel 5 3 2 11 Signage Each room must be identified with appropriate and informative signs usually pictograms indicating cytotoxicity the need for special care hazards restricted access dress code etc 5 3 2 12 Facility maintenance Facility maintenance involves keeping the areas for compounding of hazardous sterile products operational within established specifications or bringing facility systems including HVAC back to satisfactory operating condition after an interruption Maintenance must also be performed on equipment within the facility Facility maintenance activities must be recorded in the general maintenance log Filters and pre filters Existing clean room and anteroom pre filters must be inspected regularly and replaced as recommended by the manufacturer The efficiency of HEPA filters in the ventilation system must be tested during facility certification at least twice a year and replaced as recommended by the manufacturer 5 3 3 Equipment Draft 2A Hazardous Sterile Products August 22 2014 3 5 The device

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