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Model Standards for Pharmacy Compounding of Non

1. Pursuant to these Model Standards sterility is also required for the 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 4 ABBREVIATIONS The following abbreviations are used in this document Alcohol based hand rub ACD Automated compounding device ACPH Air changes per hour BUD Beyond use date CAI Compounding aseptic 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 TSP Technical support personnel USP United States Pharmacopeia Draft 2A Non hazardous Sterile Products July 24 2014 6 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 sterile preparations This person may share or delegate these responsibilities to a pharmacist or pharmacy technician who will be designated
2. The quality absence of contamination and efficacy of the final preparation depend upon among other things full compliance with compounding procedures e The sterile compounding supervisor must establish the content of policies and procedures providing detailed descriptions of all activities in the pharmacy s compounding of non hazardous sterile products see Appendix 1 The 10 United States Pharmacopeial Convention USP General chapter lt 1075 gt good compounding practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 867 13 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 ny Pharmacy Compounding Accreditation Board 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 Draft 2A Non hazardous Sterile Products July 24 2014 14 supervisor must also ensure application of and compliance with these policies and 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 4 may be used as a model for developing these procedures e The sterile compounding supervisor must ensure that all establi
3. National Association of Pharmacy Regulatory Authorities adapted with permission from Pr paration de produits st riles non dangereux en pharmacie Norme 2014 01 Ordre des pharmaciens du Qu bec 2014 Draft 2A Non hazardous Sterile Products July 24 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 non dangereux en pharmacie Norme 2014 01 to create this national document Model Standards for Pharmacy Compounding of Non 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 Special thanks are extended to these individuals list of members will be added CONTENTS 1 INTRODUCTION 2 OBJECTIVES 3 REGULATORY FRAMEWORK 4 ABBREVIATIONS 5 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 2 Compounded sterile preparation protocols 6 3 Compounded sterile preparation log 6 4 Patient file 6 5 Conduct of personnel in areas reserved for the compou
4. 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 used 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 compounding areas
5. 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 few 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 micro organisms found to establish corrective and preventive actions if necessary the sterile compounding supervisor should consult a microbiologist or infectious diseases specialist 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 per
6. Cleaning with water and germicidal detergent followed by rinsing with sterile water for injection and then disinfecting with sterile 70 isopropyl alcohol 6 6 5 Aseptic technique for compounding sterile products 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 LAFW or CAI or after gloves have come into contact with a microbiologically Draft 2A Non hazardous Sterile Products July 24 2014 53 contaminated surface If gloves are torn hands must be washed before new gloves are donned Gloves must be changed regularly 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 disinfected must be disinfected with sterile 70 isopropyl alcohol before being introduced into the LAFW or CAI Non shedding wipes or sterile swabs must be changed regularly while equipment is being disinfected Ophthalmic solutions prepared from sterile powder products that require di
7. 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 Pharmacy Compounding Accreditation Board 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 paf 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 ldemv pdf nvshglp ldemv eng padf 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 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 Angeles CH Effect of two work practice chan
8. contaminants from accumulating Dust collecting overhangs such as door sills utility pipes and windowsills must be avoided There must be no curtains or blinds 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 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 a7 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 368 372 373 USP response provided by USP for these facilities March 21 2012 38 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 p
9. pp 373 5 Draft 2A Non hazardous Sterile Products July 24 2014 65 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 viable 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
10. 30 mL vials of 5 mg mL morphine undiluted number of empty vials must be counted Draft 2A Non hazardous Sterile Products July 24 2014 102 APPENDIX 10 TEMPERATURES FOR DIFFERENT TYPES OF STORAGE 25 C to 10 C 2 to 8 C 8 C to 15 C 15 C to 20 Ct 15 C to 30 C United States Pharmacopeial 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 Non hazardous Sterile Products July 24 2014 APPENDIX 11 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 Actions Responsible Deadline v Describe the actions to be taken and the Draft 2A Non hazardous Sterile Products July 24 2014 steps
11. COMPETENCIES KNOWLEDGE OR SKILLS COVERED IN TRAINING 1 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 me compatibility and incompatibility osmolality and osmolarity 1 4 Know pharmaceutical and medical abbreviations X X X 15 Know and understand the importance of particulate and microbial xX X x contamination 16 Perform pharmacy sterile product compounding tasks meticulously precisely xX X xX 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 ca
12. 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 Draft 2A Non hazardous Sterile Products July 24 2014 101 APPENDIX 9 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 syringe Mied wit a single product prepared from a 300 g 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 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
13. 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 LAFWs CAIs etc must be performed when no compounding is in progress before cleaning and disinfection operations All LAFW and CAI maintenance including maintenance of filters and pre filters must be noted on a form and entered in the general maintenance log paper based or computerized The sterile compounding supervisor must ensure that LAFW or CAI 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 non hazardous sterile products Equipment used to compound 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 sterile product compounding 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 surface sampling etc All necessary devices instruments and accessories must be cleaned and disinfected before being placed in a
14. Pharm 2005 62 22 2386 92 Trissel LA Gentempo JA Saenz LM Woodard MY Angeles 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 Draft 2A Non hazardous Sterile Products July 24 2014 10 All new personnel involved in sterile product compounding must successfully complete a workplace training and competency assessment program pertinent to the type of preparations to be produced Compliance with operating procedures and use of appropriate techniques for sterile product compounding must be evaluated as part of the competency assessment program for personnel involved in sterile product compounding 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 Personnel assigned to the compounding of non hazardous sterile products The initial training and assessment program for compounding personnel must have the following components e reading and understanding the policies and procedures related to sterile product compounding see Appendix 1 e theoretical training with assessment covering various topics including those listed in Appendix 3 e individualized practical
15. Pharmacy Compounding and involved extensive consultation 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 is intended for ease of reference by practitioners according to the type of practice The current document covers non hazardous compounded sterile preparations The companion document discusses 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 non 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
16. The sterile compounding supervisor is responsible for the training of and competency assessment program for all employees involved in compounding sterile products The supervisor may e delegate the training portion of the program to a pharmacist pharmacy technician or TSP on the supervisor s team but must perform the assessment portion OR 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 third party must be a professional peer pharmacist or pharmacy technician with expertise in compounding sterile products e the sterile compounding supervisor must ensure that the external evaluator is qualified to fulfill the mandate e the external evaluator must have training that covers compounding sterile products certification that competencies in this area are being maintained and developed and proof of passing the annual competency assessment e the external evaluator s 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
17. 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 testing 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 expiration date based on chemical and physical stability reference texts according to storage time related to risk of microbial contamination microbiological 9376 stability related to the compounding process 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 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 73 Trissel LA Handbook on injectable drugs 17th ed Bethesda MD American Society of Health System Pharmacists 2013 is King JC King guide to parenteral admixtures electronic version Napa CA King Guide Publications Inc updated quart
18. 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 Draft 2A Non hazardous Sterile Products July 24 2014 28 the clean area of the anteroom into the clean room Interlocking door system 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 depicting the need for special care hazards restricted access dress code etc 5 3 2 12 Facility maintenance Facility maintenance involves ke
19. are in place for its use and maintenance and for the surveillance of required temperatures Personnel must be properly trained to read the results The containers filled with 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 111 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 pp 900 8 112 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 365 8 113 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 365 8 us United States Pharmacopeial Convention USP General chapter lt 51 gt antimicrobial effectiveness In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 pp 706 8 lie United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 365 9 Draft 2A Non hazardous Sterile Products July 24 2014 68 If two temperatures are used the containers should be incubated for 7 consecutive days at each of the temperatures starting with the
20. as the sterile compounding supervisor 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 non hazardous compounded sterile preparations in the pharmacy 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 non hazardous sterile products This person works with the pharmacy manager and with the pharmacists and pharmacy technicians assigned to perform compounding duties The sterile compounding supervisor develops organizes and oversees all activities related to sterile product compounding These responsibilities are delegated by the health care 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
21. be removed after the product enters the clean room from the anteroom At this point only 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 wipes or swabs must be used for disinfection The wipes or swabs must be changed regularly during disinfection of equipment and products 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 Bins 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 bin at the demarcation line in the anteroom and are then introduced into the clean room a United States Pharmacopeial Convention USP 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 7 sa United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding st
22. complaint or a product recall shows that the grade or quality of a product or preparation does not meet expectations the pharmacist must be able to e identify patients who have received the 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 compounded sterile preparations recorded in the patient s file and the preparation log must be sufficient to allow users to track recipients of compounded sterile preparations The sterile compounding supervisor must ensure that a procedure for recall of compounded sterile preparations has been developed and approved 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 ve United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 384 5 Draft 2A Non hazardous Sterile Products July 24 2014 60 The causes of the problem that led to the recall must be reviewed and corrective and preventive measures must be identified and implemented regardless of the location of the pharmacist s practice 6 11 Incident and accident management When an incident or accident inv
23. controlled area Devices instruments and accessories to be used in controlled areas should not be removed without good reason 37 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 373 38 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 Draft 2A Non hazardous Sterile Products July 24 2014 32 Maintenance of 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 LAFW However the ACD may be positioned outside the LAFW if this allows compounding to be performed while maintaining critical sites within the LAFW A larger LAFW must be provided for an ACD dedicated to total parenteral nutrition 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 recommendation
24. 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 Table 7 Levels of risk for microbial contamination assume that preparations are compounded in a compliant certified LAFW 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 specify certain criteria for 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 e 1 vial of sterile water for injection represents 1 sterile unit 79 Cundell AM USP Commit
25. for non 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 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 8r United States Pharmacopeial Convention USP General chapter lt 1072 gt disinfectants and antisepsis In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 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 4929 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compou
26. hand hygiene and garbing activities of personnel working in both clean rooms The functional parameters of the shared anteroom for the compounding of non hazardous and 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 33 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 375 Draft 2A Non hazardous Sterile Products July 24 2014 24 e a space or area referred to as microbiologically clean but possibly chemically contaminated located adjacent to the clean room for the compounding of non hazardous sterile products and the clean room for the compounding of 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
27. in CETA CAG 002 006 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 VVVVVVVVV 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 certification 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 Non hazardous Sterile Products July 24 20
28. isopropyl alcohol before the person enters the clean room 5 3 4 Cleaning and disinfecting in areas reserved for the compounding of non hazardous sterile products 5 3 4 1 General Cleaning and disinfecting housekeeping in areas reserved for the compounding of non hazardous sterile products must be performed to ensure the cleanliness required for the quality and integrity of final sterile preparations Cleaning and disinfecting procedures must be strictly enforced in the clean room and the anteroom 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 procedures Only trained and qualified cleaning and disinfecting personnel may be allowed to clean areas reserved for sterile compounding 5 3 4 2 Disinfectant p7 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 7 a United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 6 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 Draft 2A Non hazardous Sterile Products July 24 2014 36
29. 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 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 the 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 information related to preparations made by another pharmacist 6 5 Conduct of personnel in areas reserved for the compounding of sterile products Draft 2A Non hazardous Sterile Products July 24 2014 4 7 Compounding personnel must behave in a professional manner following policies and procedures 6 5 1 Conditions that may affect preparation quality 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 uncontrolled weeping skin condition affecting face neck or arms or that might cause significant skin desquamation or contamination burns to the skin including sunburns cold sores active herpes simplex viral infection conjunctivitis viral or bacterial active respiratory infection with coughing r
30. lower temperature 7 5 Quality assurance of compounded sterile preparations The sterile compounding supervisor must establish a quality assurance program to ensure that 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 of labels affixed to containers with legislation and regulations e compliance with required documentation in a patient s compounded sterile preparations log and the batch compounded sterile preparations log ensuring the performance of all 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 as 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 micro organisms 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 mediu
31. 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 Draft 2A Non hazardous Sterile Products July 24 2014 7 preparation e Policies and procedures covering all activities are developed regularly updated and always followed see Appendix 1 e The facilities and equipment used to compound 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 The available recognized scientific literature is used to determine stability and to establish the beyond use date BUD for each sterile preparation 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 2 lists required publications and suggestions for supplementary documentation e All records required by the Model Standards are comple
32. 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 carpets or rugs Anti fatigue mats must be avoided because 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 sa United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 3 i 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 Non hazardous Sterile Products July 24 2014 27 Functional parameter control systems Control systems indicating the temperature and differential pressure between controlled areas 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
33. 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 Aseptic techniques Steps in the aseptic process that include all manipulations performed inside the laminar airflow workbench by compounding personnel Assessment Action of assessing and defining an employee s performance and competency 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 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 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 118 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 United States Phar
34. 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 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 that 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 of 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 Draft 2A Non hazardous Sterile Products July 24 2014 7 1 Controlled area or room An area or space where the only activities taking place are those related to
35. products pharmacy technician TSP and driver receive training on the transport and delivery procedures The pharmacist must dispose of any unused compounded sterile preparation returned from a patient s home In health care facilities unused preparations returned from the patient care unit to the pharmacy may be reused if it can be shown that 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 compounded sterile preparations When a private carrier is to deliver compounded sterile preparations to a patient the sterile compounding supervisor must ensure that the transport conditions will comply with the required storage conditions 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 the product is delivered to the patient 6 10 Recall of sterile products or final compounded sterile preparations In community or hospital pharmacies when information obtained as a result of internal control a
36. program for monitoring facilities and the LAFW or CAI must include a plan for sampling viable and non viable particles 7 3 2 2 Certificate provided by manufacturer in factory The sterile compounding supervisor should retain for all HEPA filters and for the LAFW or CAI the manufacturers certificates issued in the factory before delivery 7 3 2 3 Environmental verification 193 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 Draft 2A Non hazardous Sterile Products July 24 2014 63 An environmental verification program must be established to ensure that facilities maintain established specifications and uphold the quality 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 verification e know the specifications for each parameter being verified 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 verified and documented at least once a day The differential press
37. the products and conirolled areas Testing of Clean rooms following steps e Count of non viable particles in operational dynamic IEST RP CC 006 3 Testing Clean Rooms state ISO 14644 1 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 Tripod for the room Tripod for the LAFW or BSC 0 3 um filter for cleaning 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 2A Non hazardous Sterile Products July 24 2014 95 APPENDIX 7 TEMPLATE FOR THE DRAFTING OF COMPOUNDING PROTOCOLS TO BE COMPLETED FOR EACH DRUG Name of compounded product Concentration Pharmaceutical form Route of administration FORMULA Effective date Authorized by Protocol number and version e g 001 01 dd mm yyyy
38. this area is limited to handwashing and donning of clean room garb No drugs are stored in the shared anteroom 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 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 i Direction de l expertise et de la normalisation R pertoire des guides de planification immobili re aires r serv es aux pr parations st riles Unit de pharmacie Qu bec QC Minist re de la sant et des services sociaux Publications du Qu bec 2013 pp 18 22 35 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 368 3 International Orga
39. training and assessment in the workplace clean room see section 7 and Appendix 3 e assessment of aseptic techniques based on gloved fingertip sampling GFTS and a media fill test for the various types of sterile products to be compounded Any compounding employee who has successfully completed the initial workplace training and assessment program may begin work in the compounding of sterile products In situations involving employees with limited experience additional attention must be given to their supervision Cleaning and disinfecting personnel The initial training and assessment program for cleaning and disinfecting personnel must have the following components e theoretical training and assessment covering the issues and particularities of cleaning and disinfecting the premises and equipment see Appendix 3 for a list of the competencies required for theoretical assessment of cleaning and disinfecting personnel e practical training and assessment in the areas reserved for compounding sterile products Any cleaning and disinfecting employee who has successfully completed theoretical and practical training in the workplace may perform cleaning duties in the sterile product compounding facilities in accordance with established procedures The sterile compounding supervisor must ensure appropriate training of all new cleaning Draft 2A Non hazardous Sterile Products July 24 2014 11 and disinfecting personnel In
40. 133 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Draft 2A Non hazardous Sterile Products July 24 2014 74 Personal protective equipment PPE All garo 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 the worker from exposure to physical or chemical risks 34 7 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 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 Pharmacist Registrant in good standing of one of the pharmacy regulatory authorities in Canada An adult who has ea
41. 14 91 APPENDIX 6 CERTIFICATION OF CONTROLLED ROOMS LAMINAR AIRFLOW WORKBENCHES AND BIOLOGICAL SAFETY CABINETS Laminar airflow workbench vertical or horizontal laminar flow hoods s Draft 2A Non hazardous Sterile Products IEST RP CC 002 3 Unidirectional Flow Clean Air Devices ISO 14644 1 1 In accordance with IEST RP CC 002 3 Measurement of air supply profile HEPA filter integrity test LAFW certification includes steps carried out 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 e e Thermal anemometer e Smoke machine e Photometer July 24 2014 92 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 Measurement 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 Il Type B2 BSC In a
42. 4 A policy for return of expired or unused compounded sterile preparations from the patient s 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 compounded sterile preparation rather than delegation to another person and during return of medications waste and sharp or pointed items sa United States Pharmacopeial Convention USP General chapter lt 1079 gt good storage and shipping practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 880 a United States Pharmacopeial Convention USP General chapter lt 1079 gt good storage and shipping practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 879 Draft 2A Non hazardous Sterile Products July 24 2014 59 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
43. 6 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 Tests 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 w
44. 9 The sterile compounding supervisor must ensure that the certification is completed according to certification standards currently in force see Appendix 6 An LAFW or CAI must operate continuously 24 hours a day If the LAFW or CAI 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 sterile products is undertaken The LAFW or CAI 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 CAI 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 manipulation area Location of LAFW CAI and other furniture The LAFW CAI and other pieces of furniture should be positioned to avoid interfering with facility ventilation systems To facilitate cleaning and disinfecting activities such as cleaning the floor and exterior of the LAFW or CAI and to avoid interfering with the operation of the LAFW or CAI there must be sufficient clearance around the LAFW or CAI usually 0 3 m Some types of LAFW can be built into the wall and se
45. 97 gt pharmaceutical compounding sterile preparations 1al 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 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Draft 2A Non hazardous Sterile Products July 24 2014 72 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 drugs 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 Standar
46. 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 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 disinfecting 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 area also see item 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
47. ETA 2006 revised 2008 Dec 8 Available from http www cetainternational org reference CETACompoundinglsolatorTestingGuide2006 pdf 34 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 55 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 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 padf Draft 2A Non hazardous Sterile Products July 24 2014 31 Maintenance of LAFW and CAI LAFWs and CAls must be maintained in accordance with the manufacturer s recommendations LAFWs and CAls must be certified e twice a year e when relocated e after major repairs e when sterility controls show that the LAFW or CAI may not be in compliance with specifications If an LAFW or CAI on wheels is moved e g to clean under the wheels and then moved back to exactly the same place re certification is not necessary LAFW or CAI 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
48. H 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 Draft 2A Non hazardous Sterile Products July 24 2014 110 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 Awww cdc gov niosh docs 201 2 150 pdfs 201 2 150 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 Awww osha gov dts osta otm otm_vi otm_vi_2 html 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 Patel PR Larson AK Castel AD Ganova Raeva LM Myers RA Roup BJ et al Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies
49. ION 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 cdc 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
50. OMPETENCIES KNOWLEDGE OR SKILLS COVERED IN TRAINING PH PT TSP c amp D FOR CLEANING AND DISINFECTING THE GENERAL AREA FOR l 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 xX X xX general area for compounding of sterile preparations z FOR CLEANING AND DISINFECTING THE AREA USED FOR COMPOUNDING HAZARDOUS STERILE PREPARATIONS Draft 2A Non hazardous Sterile Products July 24 2014 Know correctly perform and document cleaning and disinfecting tasks for the 2 1 k X general area for compounding of hazardous sterile preparations 29 Know and use personal protective equipment specifically for handling X x hazardous products 23 Know and use the emergency measures to be applied in case of accidental X x exposure accidents or spills PH pharmacist PT pharmacy technician TSP technical support personnel C amp D cleaning and disinfecting personnel Draft 2A Non hazardous Sterile Products July 24 2014 APPENDIX 4 PROCEDURE TEMPLATE Pharmacy name Procedure Or i Revise
51. 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 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 Non hazardous Sterile Products July 24 2014 82 APPENDIX 3 TRAINING OF COMPOUNDING PERSONNEL AND CLEANING AND DISINFECTING PERSONNEL A Training of compounding personnel
52. TERILE 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 Xx 2 3 Know and apply deactivation measures X X X Know and use the protection measures necessary to avoid exposure to 2 4 X Xx X hazardous substances Know and use personal protective equipment specifically for handling 2 5 Xx xX X hazardous products 26 Safely handle hazardous drugs i e receive unpack store and deliver xX X xX hazardous drugs Draft 2A Non hazardous Sterile Products July 24 2014 Know and apply the appropriate aseptic technique for hazardous drugs in the 2 7 xX Xx X workplace Know and use the emergency measures to be applied in the case of 2 8 A i Xx X X accidental exposure accidents or spills 29 Know how to safely destroy hazardous drugs and the materials used in their X xX X preparation FOR THE COMPOUNDING OF HIGH RISK NON HAZARDOUS AND 3 HAZARDOUS STERILE PREPARATIONS MADE WITH NON STERILE PRODUCTS 3 1 Have the competency 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 B Training of cleaning and disinfecting personnel C
53. The use of other technologies techniques materials and procedures may be 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 1 Bussi res JF Prot S Perspectives sur les pr parations magistrales en pharmacie au Qu bec Pharmactuel 2004 37 3 File 1 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 Patel PR Larson AK Castel AD Ganova Raeva LM Myers RA Roup BJ et al Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies JAMA 2006 296 16 2005 11 Kastango ES The cost of quality in pharmacy Int J Pharm Compound 2002 6 6 404 7 Draft 2A Non hazardous Sterile Products July 24 2014 4 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 medications has always been an integra
54. a quality assurance program that has four components 1 verification of equipment including the LAFW or CAI 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 12 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 investigation 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 Equipment that supports compounding activities especially refrigerators freezers incubators and air sampling devices must be certified with respect to its installation and Draft 2A Non hazardous Sterile Products July 24 2014 62 operation and must be calibrated before being put into service A maintenance plan must be established taking into account the manufacturer s recommendations for ea
55. able 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 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 in real compounding conditions in the particular 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 compounded sterile preparations with low or medium risk of microbial contamination the nutrient medium must be sterile For 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 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 the incubator is certified periodically and that procedures
56. acility 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 Compounded sterile preparation log for products prepared in batches Draft 2A Non hazardous Sterile Products July 24 2014 46 The log of sterile products prepared in batches must contain the following information e preparation identification name and concentration e compounding procedure e for each ingredient including primary and secondary diluents name quantity volume measured 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 compounded sterile preparation that has already 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 file must allow users to accurately reproduce the prescribed preparation at a
57. acists 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 or scope of practice Therefore individuals who do not have the training expertise facilities or equipment required to compound sterile products must refer patients to a pharmacist who does offer this service or where permitted by provincial territorial legislation ask a colleague to compound the product 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 E E E E E 2 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 Draft 2A Non hazardous Sterile Products July 24 2014 5
58. 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 into the clean room from a non controlled area R Canadian Society of Hospital Pharmacists CSHP Sterile preparation of medicines guidelines for pharmacists Ottawa ON CSHP 1996 29 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 3 Draft 2A Non hazardous Sterile Products July 24 2014 20 30 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 des
59. aining 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 date 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 ha
60. aled or wall mounted and sealed but this is not possible with other types When positioning an LAFW or CAI 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 a United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 80 i United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 80 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 46 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 4 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 48 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 r
61. andards specifically adequate facilities and equipment compliance with garbing requirements and application of stringent housekeeping and aseptic techniques 6 1 4 1 Beyond use dates for immediate use preparations In health care facilities a pharmacy department providing compounded sterile preparations must ensure that compounded doses are ready to be administered without further handling by another health care professional and must develop its services in accordance with this requirement Compounded sterile preparations prepared for immediate use in the patient s room or on patient care units must comply with the following conditions e The preparation does not exceed three sterile units e The preparation does not contain any hazardous drugs e g chemotherapeutic agents e For each unit used there are no more than two punctures at the injection site of a preservative free sterile product e Aseptic technique does not require more than 1 hour of continuous preparation e Aseptic technique is rigorously applied e Compounding is performed in a critical situation where immediate administration to the patient is required United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 361 Draft 2A Non hazardous Sterile Products July 24 2014 43 The following BUDs apply with no requirement for additional steril
62. ant detergent followed by sterile 70 isopropyl alcohol at the start or end of the day or shift minimum twice per day e Follow the cleaning method described in the pharmacy s procedures with regard to equipment sequence movements 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 LAFW or CAI e Record cleaning and disinfecting activities in the maintenance log sia United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 391 Draft 2A Non hazardous Sterile Products July 24 2014 52 Table 10 Surface Frequency Cleaning producist Germicidal disinfecting All surfaces At the start of each day detergent followed by sterile At the end of each workday 70 isopropyl alcohol minimum twice daily Before starting any sterile product preparation At each shift change Work surface Where surface contamination Sterile 70 isopropyl alcohol is suspected If there has been non compliance with aseptic techniques Work surface and any surface that has been splashed When there is a spill Rinsing with sterile water for injection or irrigation followed by sterile 70 isopropyl alcohol All surfaces and subfloor Weekly at the end of a work day or as recommended by the manufacturer
63. at 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 equipment and products used must be verified before and after compounding An additional verification method by counting vials ampoules and remaining material should be implemented Appendix 9 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 content verification to TSP requires strict supervision including e implementation of policies and procedures e implementation of a quality assurance program including regular evaluations of the TSP involved Draft 2A Non hazardous Sterile Products July 24 2014 55 e verification of a percentage of preparations by the supervisor Some provincial territorial jurisdictions have standards for delegating duties to TSP ina pharmacy Each preparation must be inspected by a person other than the individual who performed the aseptic preparation This person must inspect each unit against a black and white background for evidence of par
64. ate particles must be controlled Draft 2A Non hazardous Sterile Products July 24 2014 15 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 um ISO Class Number diameter measured under dynamic operating conditions particles per m 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 5 3 1 2 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 The conditions required for the compounding of hazardous sterile products are presented in the companion document Model Standards for Pharmacy Compounding of Hazardous Sterile Products In addition NIOSH published an alert on preventing occupational exposure to antineoplastic and other hazardous drugs in 2004 5 3 2 Facilities reserved for the compounding of non hazardous sterile products The requirements for facilities vary depe
65. ber of people working in it a greater number of ACPH may be required e The temperature of the clean room 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 clean room Figure 1 page 23 ea United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 A United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 72 Direction de l expertise et de la normalisation r pertoire des guides de planification immobili re aires r serv es aux pr parations st riles Unit de pharmacie Qu bec QC Minist re de la sant et des services sociaux Publications du Qu bec 2013 p 16 3 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 74 Available from http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php 2 United States Pharmacope
66. bserved regardless of where the products are stored warehouse pharmacy delivery vehicle loading dock etc For final compounded sterile preparations or products used for preparations the storage temperature must be controlled and must remain within the limits specified in Appendix 10 regardless of the season Information on monitoring of room refrigerator and other temperatures and controls related to implementation of the storage procedure must be recorded in the general maintenance log A biomedical refrigerator or freezer must be available for storing products ingredients and final compounded sterile preparations that need to be refrigerated or frozen see section 5 3 3 2 Alternative storage must be provided when conditions are beyond acceptable temperature variations and when refrigerators and freezers are being cleaned Products that have been stored must be inspected before use for evidence of deterioration A procedure for verifying the BUDs of stored compounded sterile preparations and the expiration dates of commercial products must be developed and implemented to ensure that unusable products and compounded sterile preparations are quickly discarded 6 9 Transport and delivery of final compounded sterile preparations Policies and procedures must be developed and implemented for the transport of compounded sterile preparations and their delivery to patient care units patients and dispensing pharmacists see Appendix
67. ccess 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 Bringing equipment and products into the clean room and laminar airflow workbench Determining beyond use date of products used in a preparation Determining beyond use date of final preparations Hand and forearm hygiene Garbing in compounding areas and for compounding Cleaning and disinfecting the Laminar Airflow Workbench DIA PIwWyy re Draft 2A Non hazardous Sterile Products July 24 2014 7 Aseptic techniques with details for each of the techniques used 8 Verification of the compounding process including validation of calculations by a pharmacist and of final preparations 9 Labelling of final preparations 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
68. ccordance with ISO 14644 1 Count of non viable particles 0 5 um in operational dynamic state at rest state is optional Measurement of air intake velocity Equipment used Particle counter Thermal anemometer Smoke machine and aerosol generator Photometer Direct volume measurement device Compounding aseptic isolator Primarily manufacturer s Isolator certification includes steps carried out according to recommendations manufacturer s recommendations with reference to CETA CAG 002 2006 CETA CAG 002 2006 Compounding Isolator Testing Guide Specific tests used e 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 Draft 2A Non hazardous Sterile Products July 24 2014 93 Compounding aseptic containment isolator e Primarily manufacturer s recommendations e Count of non viable particles e CETA CAG 002 2006 Compounding Equipment used Isolator Testing Guide 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 Draft 2A Non hazardous Sterile Products July 24 2014 94 Clean room for the compounding of sterile NEBB Procedural Standards for Certified Certification of controlled areas and rooms includes
69. ch 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 7 3 2 Verification of controlled rooms and LAFW or CAI 7 3 2 1 Certification The controlled areas of facilities and the LAFW or CAI must be certified by a recognized organization e atleast every 6 months e during installation of new equipment or a new controlled area e during maintenance or repair of equipment repair of LAFW 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
70. d YesO No O Hospital XYZ pharmacy department Approved by Date Effective date Procedure title L U OI 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 Othemts OOoOooo Required facilities equipment and material Include the following types of information here Facilities and equipment required to apply the procedure Materials e g devices instruments required to apply the procedure Products to be used Containers to be used Logs to be used or completed VVVVYV Draft 2A Non hazardous Sterile Products July 24 2014 nn _ _____LLLL____________________________________________________ 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 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 E References Indicate here the references used to d
71. d the HICPAC SHEA APIC IDSA Hand Hygiene Task Force MMWR Morb Mortal Wkly Rep 2002 51 RR 16 1 48 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 reptox csst qc ca Documents SIMDUT GuideAng Htm GuideAng htm 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 CET ACompoundinglsolatorTestingGuide2006 pdf Draft 2A Non hazardous Sterile Products July 24 2014 109 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 SG Felizardo G Barnes S et al APIC position paper safe injection infusion and medication vial practices in health care Am J Infect Control 2010 38 3 167 72 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 gu
72. devices are being transferred into and out of the CAI 2 Particulate sampling from 15 to 30cm upstream of the critical exposure site within the CAI shows ISO Class 5 air quality during compounding 3 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 CAI The sterile compounding supervisor must obtain the following information from the manufacturer e documentation indicating that the CAI 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 CAI must comply with the garbing procedure for the compounding of sterile products 7 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 52 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 53 Controlled Environment Testing Association CETA CETA compounding isolator testing guide CAG 002 2006 Raleigh NC C
73. ds 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 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 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 Label for identifying a sterile Label that identifies the drugs prepared or sold with or without a preparation prescription It is usually computer generated and adhesive It must bear the information required by federal provincial territorial regulations 123 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 Availabl
74. e 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 for moving from one area to another thus keeping the areas isolated from one another The anteroom helps to maintain the pressure differential in the clean room 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 a space or area referred to as microbiologically dirty located at the entrance to the anteroom in the section adjacent to the pharmacy e a space or area referred to as microbiologically clean adjacent to the 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 The functional parameters of the anteroom for the compounding of non hazardous sterile products are explained in Table 3 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
75. e from http www cdc gov niosh docs 2004 165 pdfs 2004 165 pdf bad 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 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 quide safe handling of hazardous drugs html i Controlled Products Regulations SOR 88 66 1987 Available from http laws lois justice gc ca eng regulations SOR 88 66 sd 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 reptox csst qc ca Documents SIMDUT GuideAng Htm GuideAng htm Draft 2A Non hazardous Sterile Products July 24 2014 73 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 particulates Laminar
76. e 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 and the aseptic compounding process see Appendix 3 e apractical test in the workplace clean room including GFTS and a media fill test to evaluate compliance with operating procedures and knowledge of aseptic compounding processes Cleaning and disinfecting personnel A competency assessment program for cleaning and disinfecting personnel must be implemented in the workplace see Appendix 3 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 elements previously failed In case of repeated failures a decision must be made regarding permanent termination of sterile product compounding or cleaning and disinfecting activities Draft 2A Non hazardous Sterile Products July 24 2014 13 5 1 2 4 Management of the competency assessment program Sterile compounding supervisor and delegation of employee training
77. ed for an external patient care dispensing pharmacist where permitted by provincial territorial legislation ensure that each patient management activity is performed by 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 stakeholders 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 Draft 2A Non hazardous Sterile Products July 24 2014 9 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 pharmaci
78. eference CETACompoundinglsolatorTestingGuide2006 pdf aad 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 7 9 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention guide safe handling of hazardous drugs html Direction de l expertise et de la normalisation R pertoire des guides de planification immobili re aires r serv es aux pr parations st riles Unit de pharmacie Qu bec QC Minist re de la sant et des services sociaux Publications du Qu bec 2013 p 17 Draft 2A Non hazardous Sterile Products July 24 2014 30 LAFW gt 52 53 The LAFW must be positioned in an ISO Class 7 clean room that is adjacent to an ISO Class 8 anteroom and must not be placed near doors or other sources of drafts that might adversely affect unidirectional airflow If multiple LAFWs are used they must be positioned to prevent interference with one another CAI 55 56 The CAI must be positioned in an ISO Class 7 clean room or better adjacent to an ISO Class 8 anteroom However ISO Class 8 air quality in a clean room and anteroom may be acceptable if all of the following conditions are met 1 The CAI maintains an ISO Class 5 environment see Table 1 at all times during compounding including when ingredients equipment and
79. eing 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 i Direction de l expertise et de la normalisation R pertoire des guides de planification immobili re aires r serv es aux pr parations st riles Unit de pharmacie Qu bec QC Minist re de la sant et des services sociaux Publications du Qu bec 2013 p 16 International Organization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 Draft 2A Non hazardous Sterile Products July 24 2014 22 Figure 1 Pressure diagram A A Pressure differentials to be 1 12 5 Pa 2 Pc Pp 2 5 0 maintained at all times 2 12 5Pa2 Ps Pa 25 0 E Legend A facilities environment B C sterile compounding room P pressure Pa pascal SI unit of measure for pressure Draft 2A Non hazardous Sterile Products July 24 2014 23 Area for unpacking supplies Space should be provided for unpacking supplies To limit the presence of dust and particles supplies must be removed from cardboard boxes outside the clean room and the anteroom 5 3 2 6 Shared facilities Compounding of non hazardous and hazardous sterile products Facilities in community pharmacies or health care
80. emv eng pdf o3 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 Draft 2A Non hazardous Sterile Products July 24 2014 34 The incubation temperature must be controlled 20 C to 25 C or 30 C to 35 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 general pharmacy Camera 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 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 al
81. epeated sneezing or runny nose fresh piercings 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 entering the anteroom Before entering the anteroom compounding personnel must take the following steps remove personal outerwear e g coat hat jacket scarf sweater vest boots and dirty outdoor shoes which tends to shed particles or squamous Cells remove jewelry studs and other accessories from fingers wrists forearms neck and other body parts if they might interfere with the effectiveness of PPE e g for adjusting gloves and sleeves and for antiseptic washing of hands and forearms 35 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 7 e United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 376 7 Draft 2A Non haza
82. eping the compounding areas operational within specifications or bringing facility systems including HVAC back to satisfactory operating condition after an interruption Maintenance must be also 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 5 3 3 1 Laminar airflow workbench and compounding aseptic isolator The LAFW or CAI is positioned in the clean room The equipment 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 Before an LAFW or CAI is used e personnel must read and understand the user s manual e the LAFW or CAI must be installed according to the manufacturer s recommendations and certified by a qualified certifier see Appendix 5 e cleaning and disinfection must be performed t United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 362 4 372 4 Draft 2A Non hazardous Sterile Products July 24 2014 2
83. er e equipment to be used to ensure that packaging protects compounded sterile preparations against freezing and excessive heat packaging must maintain a temperature between 2 C and 8 C for compounded sterile preparations requiring refrigeration and a temperature between 19 C and 25 C for compounded sterile preparations to be kept at room temperature e method to be used to confirm whether the temperature of compounded sterile preparations has been maintained during transport use of temperature maintenance indicator min max thermometer certified cooler etc e packaging to be used to protect against extreme temperatures i e excessive heat or freezing during transport of compounded sterile preparations unless information is available demonstrating stability at these temperatures 6 8 Storage 7 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 384 Draft 2A Non hazardous Sterile Products July 24 2014 58 The sterile compounding supervisor must develop a storage procedure see Appendix 4 and this procedure must be followed at all times All commercial products used for preparations must be stored immediately upon receipt In addition they must be handled and stored so as to prevent cross contamination and incompatibilities Product storage conditions specified by the manufacturer must be strictly o
84. erile preparations USP 36 Rockville MD USP 2013 p 376 7 Draft 2A Non hazardous Sterile Products July 24 2014 5 1 6 6 4 Cleaning and disinfecting the laminar airflow workbench or compounding aseptic isolator Only compounding personnel are allowed to clean and disinfect the LAFW or CAI They must take the following steps e Follow hand and forearm hygiene and garbing procedures e Disinfect the work surface of the LAFW or CAI according to existing procedures ensuring the minimum frequency of disinfection outlined in Table 10 If a different frequency is followed it should be established and justified by the results of environmental control testing All specialized devices or instruments used for compounding sterile preparations including the LAFW must be cleaned and disinfected before they are introduced into the clean room in accordance with manufacturer s recommendations Personnel must comply with the following requirements when 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 LAFW or CAI Ensure that the head and upper body do not enter the LAFW or CAI Use non shedding disposable swabs Avoid contaminating the surface of swabs used for cleaning and disinfecting Change swabs after completing disinfection of each section of the LAFW or CAI Disinfect the LAFW or CAI with clean swabs and germicidal disinfect
85. erile products Beyond use dates BUDs for compounded sterile preparations when a preservative free vial is used Contamination risk levels Beyond use dates BUDs for compounded sterile preparations according to risk of microbial contamination Summary of beyond use dates BUDs for compounded sterile preparations in short term critical situations Minimum frequency and areas of the laminar airflow workbench to be cleaned and disinfected by compounding personnel Draft 2A Non hazardous Sterile Products July 24 2014 77 11 APPENDICES APPENDIX 1 POLICIES AND PROCEDURES FOR THE COMPOUNDING OF NON HAZARDOUS AND HAZARDOUS STERILE PRODUCTS Policy Topic v 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 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 A
86. erly TS Trissel LA Trissel s 2 clinical pharmaceutics database electronic database Cashiers NC TriPharma Communications updated regularly United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 365 7 382 3 Draft 2A Non hazardous Sterile Products July 24 2014 39 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 specified in the following three subsections 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 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 e Six hours after initial needle puncture the sterile product e g vial minibag cannot be used to prepare a batch Table 6 Beyond use dates BUDs for 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
87. ermine whether the pharmacy technicians and TSP are complying with aseptic processes in order to quickly detect any risk of error and possible contamination e must pass the practical section of the training program regarding assessment of the aseptic compounding process the media fill test and GFTS if there is a possibility that this pharmacist will compound sterile products on an occasional basis Duty pharmacist in a health care facility A pharmacist on duty in a health care facility must receive the same training as a compounding pharmacist and must undergo annual assessment of competency in sterile product compounding Draft 2A Non hazardous Sterile Products July 24 2014 12 Frequency of assessment Compounding personnel All personnel pharmacists pharmacy technicians and TSP assigned to the compounding of sterile products must undergo assessment at the following frequencies e at least once a year in the workplace for preparations with low or medium risk level e at least 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 All cleaning and disinfecting personnel must be evaluated at least once a year in the workplace The results of these assessments must b
88. es 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 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 Bussi res JF Prot S Perspectives sur les pr parations magistrales en pharmacie au Qu bec Pharmactuel 2004 37 3 File 1 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 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 htm 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 Centers for Disease Control and Prevention Guideline for hand hygiene in health care settings Recommendations of the Healthcare Infection Control Practices Advisory Committee an
89. f there is full compliance with 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 Table 9 otherwise the preparation must be discarded 94 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 365 Draft 2A Non hazardous Sterile Products July 24 2014 44 Table 9 Summary of beyond use dates BUDs for compounded sterile preparations in short term critical situations BUDs for compounded sterile preparations in short term critical situations without additional sterility test Type of preparation At controlled room With storage in With temperature the refrigerator storage in the freezer Immediate use 1 hour 1 hour NA preparation Preparation in LAFW 12 hours 12 hours NA ISO Class 5 or better in an environment where conditions do not meet ISO Class 7 standards for LAFWs or ISO Class 8 standards for CAIs NA not applicable The container must always be correctly identified In addition to mandatory information on the drug label the compounding start date and time and the BUD should be included on the label 6 2 Compounded sterile preparation protocols Protocols for compounded s
90. facilities that compound both non hazardous and hazardous sterile products must have two clean rooms one for the compounding of sterile non hazardous products and the other for the compounding of sterile 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 non hazardous sterile products and another for hazardous sterile products there may be only one shared anteroom This layout is not recommended but if space constraints dictate that facilities for compounding non hazardous and 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 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 the Model Standards for Pharmacy Compounding of Hazardous Sterile Products Shared anteroom The sole anteroom is connected to both clean rooms for the compounding of sterile products non hazardous and hazardous and is shared for
91. facility pharmacy provided that the incubator used is certified periodically 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 classification The following examples indicate contamination levels that would trigger corrective action with different types of sampling 1a United States Pharmacopeial Convention USP General chapter lt 51 gt antimicrobial effectiveness In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 p 706 8 108 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 375 109 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 375 379 Draft 2A Non hazardous Sterile Products July 24 2014 66 Volumetric sampling of facility air e Areas requiring ISO Class 5 air quality threshold contamination gt 1 CFU m
92. final sterile preparation including performing hand and forearm hygiene garbing of personnel 37 Centers for Disease Control and Prevention 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 Morb Mortal Wkly Rep 2002 51 RR 16 1 48 88 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 80 Draft 2A Non hazardous Sterile Products July 24 2014 49 disinfecting and introducing products and equipment into the clean room disinfecting the LAFW or CAI disinfecting and introducing products and equipment into the LAFW or CAI using aseptic techniques to compound sterile products in the LAFW or CAI verifying labelling and packaging final compounded sterile preparations Personnel must develop work techniques to minimize the risk of cross contamination to avoid errors and to maximize performance of the LAFW or CAI 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 appropria
93. 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 129 a designated role and framework Maintenance of facilities and Operations for maintaining the proper functioning of facilities or equipment 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 saf h MSD aterial salely data shest 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 techniques of compounding perso
94. g sequence Knows the required procedure for washing and disinfecting hands before putting on gloves and entering a controlled room 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 drugs Performs the work meticulously and professionally Draft 2A Non hazardous Sterile Products July 24 2014 89 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 00
95. ges 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 notices and requirements In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 Draft 2A Non hazardous Sterile Products July 24 2014 111 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 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 United States Pharmacopeial Convention USP General chapter lt 1075 gt good compounding practices In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 United States Pharmacopeial Convention USP Feneral 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 Draft 2A Non hazardous Sterile Products July 24 2014 112
96. go before the specific sterile compounding procedure is implemented Draft 2A Non hazardous Sterile Products July 24 2014 99 N References consulted Indicate the source of the specific sterile compounding procedure Indicate any documentation supporting the stability of the final compounded sterile preparation 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 Non hazardous Sterile Products July 24 2014 100 APPENDIX 8 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 whena 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 vial 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
97. he 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 3a United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Draft 2A Non hazardous Sterile Products July 24 2014 42 Administration of the compounded sterile preparation must start before the BUD has been exceeded High risk preparations must always be sterilized the BUDs in the high risk row of 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 sterile product preparations see Table 8 in the following situations e when sterile products 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 e when there has been more than 6 hours 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 compounded sterile preparation services must meet the requirements specified in these Model St
98. 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 e The sterile compounding supervisor must have undergone training i e courses in the compounding of sterile products and must have demonstrated the required qualifications e The sterile compounding supervisor must also have the competency required to manage a safe high quality sterile product compounding department Assessment e The sterile compounding supervisor must be evaluated at least every 3 years by a third party a peer external to the compounding environment with expertise in sterile product compounding 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 A pharmacist whose activities are limited to supervising a pharmacy technician or TSP during sterile product compounding 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 det
99. hp United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 372 3 Draft 2A Non hazardous Sterile Products July 24 2014 26 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 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
100. i 0001 eng php Health Canda 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 Awww hc sc gc ca dhp mps compli conform gmp bpf docs gui 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 Kastango ES The cost of quality in pharmacy Int J Pharm Compound 2002 6 6 404 7 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 electroiq com issue issue 2302 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 NIOS
101. ial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 25 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 26 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 a International Organization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 Draft 2A Non hazardous Sterile Products July 24 2014 19 Given the clothing 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 verification of 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 It also ensures the safety of compounding and other personnel Anteroom Th
102. igerator before being placed in a cooler 6 6 6 2 Process for verification 94 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 80 35 Buchanan EC Schneider PJ Compounding sterile preparations 3rd ed Bethesda MD American Society of Health System Pharmacists 2009 p 29 Draft 2A Non hazardous Sterile Products July 24 2014 54 Verification 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 LAFW 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 LAFW with a camera connected to a monitor Such verification must be performed before the compounded sterile preparation is delivered to the patient However in this situation if the verifying pharmacist notices that one or more procedures have not been followed correctly all 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 8 gives examples of compounded sterile preparations th
103. igned specifically for use in a controlled area i e the anteroom e mirror or other means to verify garbing e waste container 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 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 Other essential equipment may be stored in the anteroom as long as the anteroom s ISO air quality classification is maintained 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 Draft 2A Non hazardous Sterile Products July 24 2014 21 Table 3 The following functional parameters must be met e The anteroom must be kept under positive pressure
104. inal preparation units along with auxiliary labels indicating required storage conditions and special precautions The compounding pharmacist or pharmacy technician must similarly label 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 3 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 381 Draft 2A Non hazardous Sterile Products July 24 2014 56 required by the respective provincial territorial regulatory authority before administering the compounded sterile preparation received from the compounding pharmacist to the patient a supplementary document must be prepared if required The label affixed by the 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 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 re
105. ing sterile preparations USP 36 Rockville MD USP 2013 pp 373 5 Draft 2A Non hazardous Sterile Products July 24 2014 64 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 LAFW or CAI 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 LAFW ventilation system etc or a controlled area repair of hole in a wall e during investigation of a contamination problem or a problem involving 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 LAFW or CAI certification Sampling of non viable particles in air Non viable particles in the air in controlled areas and the LAFW 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
106. ions USP 36 Rockville MD USP 2013 p 379 Draft 2A Non hazardous Sterile Products July 24 2014 33 The refrigerator and freezer used to store medications must be commercial biomedical grade units Domestic refrigerators and freezers must not be used Use and placement Refrigerators and freezers must be used only for storing medications They must not be used to store food Ideally refrigerators and freezers are placed outside controlled areas Depending on workflow refrigerators may be placed in anterooms provided there is control of particulates through the use of air returns and provided the number of air changes per hour is sufficient to maintain the required ISO air quality classification Refrigerators with two doors Refrigerators with doors on two sides pass through refrigerators may be used to store sterile products provided they are designed for clean rooms and the refrigeration system is not located on the clean room side If such a refrigerator is installed the sterile compounding supervisor is responsible for ensuring that the required characteristics for any compounding rooms affected by its installation are met under operating conditions Temperature and temperature control The tested storage temperature in these units must meet the following parameters e controlled refrigeration temperature 2 C to 8 C e controlled freezing temperature 25 C to 10 C Accurate temperature probes gauges or
107. ith ISO 14644 1 gt Proceeds with the count of non viable particles gt Verifies the count of non viable particles 0 5 um in diameter gt 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 Non hazardous Sterile Products July 24 2014 90 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 gt Proceeds with the count of non viable particles gt Verifies the count of non viable particles 0 5 um in diameter gt 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 Recommends that LAFW pre filters be changed if required 4 Certification of CAl 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
108. ity tests e Controlled room temperature 1 hour e Refrigerator 1 hour e Freezer does not apply Administration of the preparation must begin less than 1 hour after the start of compounding otherwise the preparation must be discarded The container must always be correctly identified In addition to mandatory information on the drug label the compounding start date and time should be included on the label 6 1 4 2 Preparations with beyond use dates of 12 hours or less For compounded sterile preparations made in an LAFW that maintains the requirements 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 Preparations are low risk only e Preparations contain no hazardous products 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 and 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 Chapter lt 797 gt of the USP NF states that the microbial contamination risks associated with compounding such products under these conditions remain high even if only low risk products are compounded and even i
109. l 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 Verification that preparation matches e In accordance with the quality assurance program prescription PREPARATION TET r 9 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 Non hazardous Sterile Products July 24 2014 108 12 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 non dangereux en pharmacie Norme 2014 01 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 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 Association paritaire pour la sant et la s curit du travail du secteur affaires social
110. l 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 regulatory 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 pharm
111. l 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 Packaging Describe the type of packaging in which the final compounded sterile preparation shall be presented to the patient i 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 Draft 2A Non hazardous Sterile Products July 24 2014 98 Labelling Indicate mandatory information that must be on the label of the compounded sterile preparation A When kept at the pharmacy or sent to another pharmacy B When dispensed to a patient Training Sample label 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 under
112. librate the devices used Be able to recognize errors in the compounding technique of compounding 1 9 personnel Draft 2A Non hazardous Sterile Products July 24 2014 Have a good command of the pharmaceutical calculations required to 1 1 X Xx X 9 compound sterile products 1 11 Understand the importance of and apply accurate measurements X X X Apply disinfection measures for sterile product compounding rooms facilities 1 12 X Xx Xx 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 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 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 S
113. ling of hazardous drugs Montr al QC ASSTSAS 2008 Available from http www asstsas qc ca publications publications specialisees guides de prevention prevention quide safe handling of hazardous drugs html 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 padf i United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 263 Draft 2A Non hazardous Sterile Products July 24 2014 75 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 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 be adopted in specific clinical circums
114. low 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 products Waste containers A sufficient number of easy to clean waste containers of suitable size and made of materials resistant to damage from cleaning products must be available The waste containers must be emptied and cleaned at least once a day outside of compounding hours 5 3 3 3 Personal protective equipment and clothing Compounding personnel and anyone else who accesses controlled areas must wear appropriate protective clothing This PPE is described in Table 5 Draft 2A Non hazardous Sterile Products July 24 2014 35 Table 5 PPE to be worn for the compounding of non hazardous sterile products and when accessing facilities for the compounding of non hazardous sterile products includes the following pair of shoe covers hair cover beard cover if applicable surgical mask clean non shedding protective gown enclosed at the neck and with sleeves that fit snugly around the wrists e pair of non powdered sterile gloves compounders only Personnel entering the clean room to perform tasks other than compounding including those who perform verification of final compounded sterile preparations may wear non sterile gloves donned after aseptic handwashing The gloves must be disinfected with sterile 70
115. lution 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 LAFW or CAI to reduce the risk of errors and air turbulence 6 6 6 Verification of final compounded sterile preparations 6 6 6 1 Role of personnel in verification The sterile compounding supervisor Compounding pharmacist or pharmacy technician must perform the following activities e ensure that all 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 unit 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 compounded sterile product 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 compounded sterile preparations must be cooled in the refr
116. m readings should be documented on a separate form for each type of sampling All completed documentation concerning components of the environmental verification of controlled areas the LAFW or CAI 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 LAFW All completed documentation concerning the quality assurance program for the aseptic Draft 2A Non hazardous Sterile Products July 24 2014 69 compounding process for personnel by GFTS and media fill test including nutrient medium readings should be retained and made accessible 8 0 SOURCE FOR ADDITIONAL INFORMATION For more information on sterilization of high risk compounds depyrogenation by dry heat and use of allergen extracts and radiopharmaceuticals as compounded sterile products please refer to chapter lt 797 gt in the most recent edition of USP NF 9 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 Anteroom TPP Iy only
117. macopeial Convention USP General chapter lt 1072 gt disinfectants and antisepsis In USP pharmacists pharmacopeia Rockville MD USP 2008 2009 Draft 2A Non hazardous Sterile Products July 24 2014 70 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 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 aseptic isolator CAI Isolator specifically used for compounding non hazardous sterile products Designed to ensure an aseptic environment during the transfer of material and drugs and during the performance of aseptic technique It must not allow any exchange of air between the air inside the clean room and the isolator unless the air is first filtered by a high efficiency particulate air filter Compounding personnel Pharmacists pharmacy technicians or technical support personnel assigned to the compounding of sterile products Compounding
118. mples of sterile preparations that do not require verification during the compounding process Appendix 10 Temperatures for different types of storage Appendix 11 Incident accident reporting and follow up form Appendix 12 Components of a quality assurance program 12 BIBLIOGRAPHY Draft 2A Non hazardous Sterile Products July 24 2014 3 1 INTRODUCTION Parenteral therapies are becoming more complex and patients may now receive continuous antibiotic therapy or chemotherapy among other therapies 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 gt 4 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 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
119. n hazardous Sterile Products July 24 2014 5 7 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 e put all final compounded sterile preparations in packaging that maintains each preparation s stability integrity and storage conditions e place items with an attached needle in a second rigid container e indicate storage requirements on the final package e g temperature protection from light e indicate additional precautions on the final packaging e g if product is an irritant e indicate transportation precautions e g temperature fragility safety and instructions name and address of patient on the outside packaging of each item 6 7 2 Packaging procedure To maintain the integrity of compounded sterile preparations and the safety of patients and delivery personnel the sterile compounding supervisor must develop and implement a packaging procedure for final compounded sterile preparations Appendix 4 presents a model for writing such procedures The packaging procedure must specify the following details e equipment to be used to prevent breakage contamination spills or degradation of the compounded sterile preparation during transport and to protect the carri
120. nch 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 http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php 17 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 4 Draft 2A Non hazardous Sterile Products July 24 2014 17 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 sterile product preparation e Simulation of a typical sterile product preparation 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 and the laminar airflow workbench LAFW or the compounding aseptic isolator CAI The particle count may also be measured by a qualified certifier see Appendices 5 and 6 Return air intakes must be installed at the bottom of 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 LAFW to ensure that the location of the return air in
121. nd 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 cleaning and disinfecting facility certification and maintenance LAFWs CAls and other equipment used verification of proper operation of equipment and instruments calibration refrigerator temperatures etc All records must be retained as per standards of practice of the respective provincial territorial regulatory authority and in accordance with the principles of confidentiality 71 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 p S2 47 Draft 2A Non hazardous Sterile Products July 24 2014 38 6 PRODUCT AND PREPARATION REQUIREMENTS 6 1 Beyond use date and dating methods 6 1 1 Beyond use date for preparations For the purposes of these Model Standards the BUD is the date and time after which the compounded sterile preparation cannot be used or administered to a patient It is based on the date and time when the sterile preparation was compounded The BUD also specifies the storage time and temperature conditions that must be in effect before
122. nding 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 2007 21 8 44 48 Available from http electroig com issue issue 2302 Draft 2A Non hazardous Sterile Products July 24 2014 37 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 sterile or non disposable gloves disinfected with sterile 70 isopropyl alcohol before starting work 5 3 4 5 Cleaning frequency 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 performed from the cleanest area to the dirtiest area i e from the closed e
123. nding of sterile products 6 6 Aseptic compounding of non hazardous sterile products 6 7 Packaging 6 8 Storage 6 9 Transport and delivery of final compounded sterile preparations 6 10 Recall of sterile products or final compounded sterile preparations 6 11 Incident and accident management 6 12 Waste management 7 QUALITY ASSURANCE PROGRAM 7 1 Program content 7 2 Results and action levels 7 3 Verification of equipment and facilities 7 4 Quality assurance of personnel involved in aseptic compounding 7 5 Quality assurance of compounded sterile preparations 7 6 Documentation of quality control activities 8 SOURCE FOR ADDITIONAL INFORMATION 9 GLOSSARY Draft 2A Non hazardous Sterile Products July 24 2014 2 10 LIST OF TABLES 11 APPENDICES Appendix 1 Policies and procedures for the compounding of non hazardous and hazardous sterile products Appendix 2 Mandatory and supplemental documentation Appendix 3 Training of compounding personnel and cleaning and disinfecting personnel Appendix 4 Procedure template Appendix 5 Best practice indicators for certification of controlled rooms laminar airflow workbenches and biological safety cabinets Appendix 6 Certification of controlled rooms laminar airflow workbenches and biological safety cabinets Appendix 7 Template for the drafting of compounding protocols to be completed for each drug Appendix 8 Examples of sterile preparations that must be verified at each stage of compounding Appendix 9 Exa
124. nding on whether the sterile products to be compounded are non hazardous or hazardous although several of these requirements are similar for the two types of products The companion document Model Standards for 13 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 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 Draft 2A Non hazardous Sterile Products July 24 2014 16 Pharmacy Compounding of Hazardous Sterile Products describes the facilities required for the compounding of hazardous products 5 3 2 1 Dimensions Areas reserved for the compounding of non 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 facilita
125. nization for Standardization ISO ISO 14644 4 Cleanrooms and associated controlled environments Part 4 Design construction and start up Geneva Switzerland ISO 2001 Draft 2A Non hazardous Sterile Products July 24 2014 25 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 chapter lt 797 gt of the United States Pharmacopeia National Formulary USP NF for non hazardous and 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 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
126. nnel 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 is performed t Multiple dose vial Commercial drug container in multiple dose format for parenteral administration only The product usually contains an antimicrobial 133 preservative 128 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 ans Canadian Nurses Association Joint position statement Promoting continuing competence for registered nurses Ottawa ON The Association 2004 Available from http www cna aiic ca media cna page content pdf en ps77_promoting_competence_e pdf 3 Commission de la sant et de la s curit du travail CSST Material safety data sheet user s guide CSST 2010 Available from http Awww reptox csst qc ca Documents SIMDUT GuideAng Htm GuideAng htm United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 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 http www hc sc gc ca dhp mps compli conform gmp bpf docs gui 0001 eng php
127. ntion USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 80 Draft 2A Non hazardous Sterile Products July 24 2014 50 e Allow hands to dry e Don sterile gloves This handwashing 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 sterile products whether compounding is performed in an LAFW or a CAI Compounding personnel must don 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 Shoes dedicated to walking in the clean area of the anteroom and the clean room may also be used If so they must be cleaned and disinfected regularly If dedicated shoes are worn outside the clean area of the anteroom they must be disinfected before being used again in the clean area of the anteroom or the clean room otherwise shoe covers must be worn 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
128. o has earned a vocational school diploma for completing a pharmacy technician assistant course or any adult who has received proper training that is deemed equivalent Training Acquisition 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 137 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 138 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 Draft 2A Non hazardous Sterile Products July 24 2014 76 10 LIST OF TABLES Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Classes of air cleanliness for airborne particulates in clean rooms and clean areas according to ISO 14644 1 Functional parameters of the compounding clean room Functional parameters of the anteroom for the compounding of non hazardous sterile products Functional parameters of a shared anteroom for the compounding of non hazardous and hazardous sterile products Personal protective equipment PPE for the compounding of non hazardous st
129. 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 5 describes certification activities The values obtained must comply with the specifications established for each controlled area ISO 14644 1 classification 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 non 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 5 and 6 describe certification activities and the standards used by certifiers 103 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 373 5 li United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013
130. olving a compounded sterile preparation occurs the compounding personnel must complete an event report and explanation form see Appendix 11 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 re occurrence 6 12 Waste management In the performance of assigned duties the pharmacist must e ensure that medications and sharp or pointed instruments are disposed of safely in compliance with environmental protection laws in force in the jurisdiction e ensure that medications to be destroyed are safely stored in a location separate from other medications in inventory e develop and implement a procedure for destruction of pharmaceutical waste 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 7 QUALITY ASSURANCE PROGRAM Pharmacists who prepare non hazardous compounded sterile preparations must establish a quality assurance program to ensure the clear definition applica
131. ompliance 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 of each preparation e 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 compound
132. ontaminants It must be physically separated from contiguous areas by walls doors and pass throughs 1 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 373 12 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 3 Draft 2A Non hazardous Sterile Products July 24 2014 18 Use The clean room is used only for the compounding of non hazardous sterile products Contents The primary engineering control is installed in the clean room For non hazardous compounding the primary engineering controls may be LAFWs or CAIs Table 2 Functional parameters of the compounding clean room The following functional parameters must be met e The clean room must be kept under positive pressure relative to the anteroom and adjacent areas e The pressure differential must be at least 5 0 Pa ideally between 5 0 Pa and 12 5 Pa equivalent to 0 02 to 0 05 inches water column relative to the anteroom Smaller pressure differentials may be more difficult to measure and maintain e ISO Class 7 air quality must be maintained in the clean room under dynamic operating conditions e There must be at least 30 or more air changes per hour ACPH Depending on the size of the room and the num
133. pharmacist Ingredients Quantities Draft 2A Non hazardous Sterile Products Physical description Other information July 24 2014 96 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 eee IIIN 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 E EE Required devices instruments and materials Indicate all materials and equipment that will be required to compound the sterile products EE EEE Compounding method Describe all steps of the sterile product compounding process Draft 2A Non hazardous Sterile Products July 24 2014 97 Quality controls Specify the procedure for determining the lot number of the final compounded sterile preparation Specify all quality contro
134. 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 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 conversations 2 Training and assessment of personnel Draft 2A Non hazardous Sterile Products July 24 2014 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 Tr
135. quired 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 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 an irritant e storage method e date when the 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 that could not be included on the main label e details concerning mode of administration e special precautions related to drug 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 Draft 2A No
136. r 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 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 Non hazardous Sterile Products July 24 2014 106 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 buil
137. raft 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 FullO Partial O Amended version YesO NoO Change made Revised by pharmacist Date dd mm yyyy Revision Full O Partial O Amended version Yes NoO Change made Draft 2A Non hazardous Sterile Products July 24 2014 APPENDIX 5 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 Before certification Ideally meets the client sterile compounding supervisor to discuss the certification process during the meeting the certifier gt asks whether problems have occurred since the last certification gt 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 garbin
138. rdous Sterile Products July 24 2014 48 remove all cosmetics makeup false eyelashes perfume and hair products such as hairspray which can produce particles that are possible sources of contamination tie back long hair remove nail polish or any nail application extensions or other synthetic nail lengthening products ensure that nails are short and that skin around the nails is undamaged ensure that skin of hands and forearms is undamaged change into dedicated low shedding apparel suitable for the controlled area e g scrubs fully cover legs and feet and wear closed shoes and socks wash hands 6 5 3 Conduct in controlled areas clean room and anteroom In controlled areas the following measures should be taken Food items drinks chewing gum candy and smoking are prohibited Food items or drinks must not be stored in refrigerators reserved for storing compounded sterile preparations All access doors to controlled areas must be kept closed Anyone who enters the anteroom or a clean room must be authorized and must follow all hand hygiene and garbing procedures Only essential conversations are allowed to minimize the risk of particulate contamination Coughing sneezing and talking in the direction of the LAFW should also be avoided 6 6 Aseptic compounding of non hazardous sterile products 6 6 1 General The aseptic compounding process includes all activities leading to completion of the
139. relative to the non controlled room adjacent to the anteroom e The pressure differential must be at least 5 0 Pa ideally between 5 0 Pa and 12 5 Pa equivalent to 0 02 to 0 05 inches water column relative to the non controlled room adjacent to the anteroom Smaller pressure differentials may be more difficult to measure and maintain e ISO Class 8 air quality must be maintained in the anteroom under dynamic operating conditions e There must be at least 20 air changes per hour ACPH Depending on the size of the room and the number of people working in it a 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 included PPE has been donned Medication storage temperatures must not exceed 25 C Note See also the pressure diagram for the anteroom and clean room Figure 1 page 23 Doors between the anteroom and the clean room and between the pharmacy and the anteroom must have windows to prevent accidents involving personnel entering 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 prepared and implemented to prevent both doors from b
140. required to correct the situation with a specific timeline Determine who will be responsible for implementation Monitoring Verifications Verifications to ensure that the corrections and changes are effective and fully implemented Responsible Closing of the file Pharmacist responsible for follow up signature Date 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 Non hazardous Sterile Products July 24 2014 APPENDIX 12 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 ai
141. rned a college degree or diploma from an accredited pharmacy technician program and has passed the national examination Pharmacy technician Such persons are licensed or authorized by a provincial territorial health professional regulatory authority to practice 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 these principles 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 PEC Equipment ensuring ISO Class 5 level for the quality of high efficiency particulate air filtered air at the critical sites exposed during the aseptic technique The primary engineering control for non hazardous products includes laminar airflow workbenches and compounding aseptic isolators The primary engineering controls for compounding hazardous preparations are called biological safety cabinets and compounding aseptic containment 1 136 isolators Procedure All steps to be taken the means to be used and the methods to be followed in performing a task nee Association paritaire pour la sant et la s curit du travail du secteur affaires sociales ASSTSAS Prevention guide safe hand
142. s 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 dedicated to the clean area of the anteroom may enter the clean room 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 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 should be made of stainless steel or very good quality plastic should be smooth non friable non porous and resistant to damage from cleaning products and should have easy to clean casters Carts should be cleaned and disinfected on a regular basis Refrigerator and freezer Choice ad United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 379 a United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparat
143. 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 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 equipped 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 Health Canda 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 gui 0069 eng php 62 Public Health Agency of Canada PHAC National vaccine storage and handling guidelines for immunization providers Ottawa ON PHAC 2007 p 19 Available from http www phac aspc gc ca publicat 2007 nvshglp Idemv pdf nvshglp Id
144. shed policies and procedures are promptly updated whenever there is a change in practice In addition polices and procedures must be reviewed at least every 3 years 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 e Where compounding is undertaken by another pharmacy as permitted by provincial territorial legislation pharmacists who dispense but do not compound medications should include in their general procedures information about procedures for acquiring compounded sterile preparations for their patients choice of supplier entry in the file delivery etc 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 Sterile product compounding facilities 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 1S014644 1 classification describes air cleanliness requirements in facilities and clean rooms This standard specifies the allowable concentration of airborne particles for each class To achieve and maintain the ISO class for a clean room all sources that gener
145. sonnel as mentioned in section 5 1 2 2 7 4 1 Gloved fingertip sampling GFTS must include e a sample 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 110 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 p 378 Draft 2A Non hazardous Sterile Products July 24 2014 67 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 resterilized 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 GFTs as set out in section 7 3 2 3 subsection Sampling of vi
146. st 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 sterile product compounding 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 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 Pharmacists and pharmacy technicians involved in the organization training compounding supervision and quality control of sterile product preparations must have the appropriate mix of education and experience 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 3 Thomas M Sanborn M Couldry R IV admixture contamination rates traditional practice site versus a class 1000 cleanroom Am J Health Syst
147. t 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 assurance dynamic conditions program Viable and non viable particles air e When anew LAFW is installed and surfaces e When the LAFW is maintained or repaired According to a sampling plan e When a contamination 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 Non hazardous Sterile Products July 24 2014 107 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 practica
148. takes does not hinder the compounding process 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 areas 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 LAFW CAI is located and an anteroom located next to the clean room Clean room The clean room is a room in which 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 see Table 2 The room is designed to minimize introduction generation and retention of particles 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 c
149. tances 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 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 ym 8 Technical support personnel TSP An adult wh
150. te drugs equipment and devices have been selected The pharmacist must also ensure that compounding personnel follow the protocol for compounding the sterile product and must validate the preparations log All stages of compounding non hazardous sterile products must be performed in an LAFW or CAI 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 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 has evaporated 99 United States Pharmacopeial Conve
151. te 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 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 the risk of airborne contamination in controlled rooms It must also be designed to achieve and maintain the appropriate ISO class for clean rooms and anterooms see section 5 3 2 5 Table 2 and Table 3 The air supplied to areas used for compounding non hazardous sterile products must pass through a high efficiency particulate 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 non hazardous sterile products The air quality in controlled rooms must comply with ISO 14644 1 according to the specifications listed in Table 1 under dynamic operating conditions as follows is United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 pp 372 4 16 Health Canada Health Products and Food Bra
152. ted 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 compounding 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 e ensure compliance with policies and procedures related to the compounding of non hazardous sterile products e enforce or ensure compliance with required aseptic hygienic cleanliness and safety rules Draft 2A Non hazardous Sterile Products July 24 2014 8 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 c
153. tee on Analytical Microbiology stimuli to the revision process Pharmacopeial Forum 2002 28 6 Draft 2A Non hazardous Sterile Products July 24 2014 41 Table 7 Low Medium High e Final product compounded using up to 3 sterile units e No more than 2 septum punctures at the injection site for each sterile unit e Simple aseptic transfer technique e Drug prepared for one patient patient specific dose Final product compounded using 4 or more sterile units Complex manipulations Prolonged preparation time Batch preparations for more than one patient Non sterile ingredients or equipment used for preparation Exposure for more than 1 hour of sterile material or content of sterile commercial products to an environment with air quality below ISO Class 5 requirements Non sterile preparations containing water stored for more than 6 hours before sterilization Table 8 BUD without additional sterility testing Risk of At controlled room With storage in With storage in contamination temperature refrigerator freezer Low 48 hours 14 days 45 days Medium 30 hours 9 days 45 days High 24 hours 3 days 45 days 8 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 81 American Society of Health System Pharmacists ASHP T
154. terile preparation must include all information required to prepare the compound eoeee eee 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 Appendix 7 presents a model for writing compounded sterile preparation protocols for each Draft 2A Non hazardous Sterile Products July 24 2014 45 drug All protocols for 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 sterile preparation log A compounded sterile preparation log must be completed during the compounding process The pharmacy must keep such a log for individual patients as well as a log for sterile preparations made in batches Computerized information and information recorded with cameras may be used as a record if all required information is present and easy to track 6 3 1 Compounded sterile preparation log for one patient individual preparations The 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 s identification number if compounded in a health care f
155. tes most of the pathogens present on an object or 121 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 related to the validation including therapeutic appropriateness preparation and packaging of a patients medication prepared pursuant to a prescription Final sterile preparation A 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 thumbtips and fingertips into the contact plate agar Both hands are tested 122 in this manner 118 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 119 USP 36 Rockville MD USP 2013 USP 36 Rockville MD USP 2013 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations United States Pharmacopeial Convention USP General chapter lt 7
156. 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 118 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 Critical area Work area inside a laminar airflow workbench ensuring ISO Class 5 air in which 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 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 elimina
157. ticulates 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 preparation log 6 6 7 Labelling of final compounded sterile preparations 6 6 7 1 General The sterile compounding supervisor must establish a policy for the labelling of 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 compounded sterile preparations must meet the requirements of the applicable legislation and regulations All active ingredients must be identified on the label The label must also include the concentration of each ingredient Each container for a 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 compounded sterile preparations e each unit of a compounded sterile preparation for an individual patient along with required auxiliary labels e each unit of sterile preparations compounded in batches with at a minimum drug name concentration route of administration batch number and BUD e each package containing f
158. time of initial needle puncture BUD for compounded final preparation stored in refrigerator calculated from time of initial needle puncture BUD for compounded final 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 e Administration of the compounded sterile preparation must start before the BUD has been exceeded e To properly manage risk a label must be affixed to the vial indicating the time of initial needle puncture The vial must be punctured in an LAFW that maintains ISO Class 5 air quality or a CAI that meets the requirements of these Model Standards Once the vial is removed from the ISO Class 5 LAFW or CAI it must be discarded a United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 8 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compounding sterile preparations USP 36 Rockville MD USP 2013 40 Draft 2A Non hazardous Sterile Products July 24 2014 6 1 2 2 Open ampoule e BUD immediate use 6 1 2 3 Multiple dose vial containing a preservative
159. tion and verification of all activities that will affect the quality of compounded sterile preparations and the protection of personnel 101 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 19 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 Draft 2A Non hazardous Sterile Products July 24 2014 61 The quality assurance program is established to give personnel and other responsible individuals information showing that the personnel facilities and equipment LAFW CAI etc of the facility attain and maintain the conditions required for contamination free compounding of sterile preparations and also that 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
160. ure between controlled areas must be kept constant according to the specifications described in section 5 3 2 5 see Tables 2 3 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 LAFW CAI 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 the LAFW or CAI A sampling plan for controlled areas and the LAFW or CAI must be established Sampling plan 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 1 United States Pharmacopeial Convention USP General chapter lt 797 gt pharmaceutical compound
161. zardous sterile products 11 Packaging of hazardous compounded sterile preparations 12 Labelling of hazardous compounded sterile preparations 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 Draft 2A Non hazardous Sterile Products July 24 2014 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 1 Verification and maintenance of equipment 2 Environmental control of facilities and biological safety cabinet 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 1 Environmental monitoring of chemical contamination Draft 2A Non hazardous Sterile Products July 24 2014 APPENDIX 2 MANDATORY AND SUPPLEMENTAL DOCUMENTAT

Model Standards for Pharmacy Compounding of Non

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