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1. received a 21 month expiration based on data obtained during assay testing at three five and six months the FDAer commented The firm conducted stability testing in accelerated conditions for its Day Cream SPF 30 and Acne Relief Gel at one two and three months and gave both products a two year expiration date The company s contract manufactured Day Cream SPF 30 receives a three year expiration date There has been no testing done to support this expiration date Young stated Observation 3 There are no written proce dures for production and process controls designed to assure that the drug products have the identity strength quality and purity they purport or are rep resented to possess Specifically you have not established validated processes to ensure your drug products conform to quali ty standards of identity strength quality and purity Young observed This includes but is not limited to Manufacturing equipment Production processes Cleaning activities Product specifications Sampling justification Water system Observation 4 Procedures for the preparation of master production and control records are not de scribed in a written procedure and followed The investigator stated you have not prepared Master Manufacturing Records for each drug product you manufacture nor have you established a procedure for the Use this form to order a 12 month subscription to INSPECTION
2. that the inspection was regarding an ANDA under review SA Analytical is performing release testing on the active pharmaceutical ingredient API and the fin ished drug product as well as stability sample storage and testing in support of the product expiration date Leach noted the following issue according to the records Observation 1 Appropriate controls are not exercised over computers or related systems to as sure that change in master production and control records or other records are instituted only by author ized personnel The FDAer observed that the firm has not doc umented a validation for their intended use of the soft ware to ensure the analytical data obtained is secure from alteration I observed this software being used to control the generation and storage of raw analytical data for the approval and release of components and finished drug products During the inspection Leach noted The time and date code from the system was not secured from change to prevent the loss of data integrity e The firm has not assigned user roles for each employee using individual user names and passwords to restrict the ability to perform operations only author ized by management October 2014 Page 11 A written procedure does not exist for Quality Assurance to review analytical data to ensure it is accurately represented by the hard copy printouts of chromatograms used in the approval and release of drug
3. MONITOR 1 186 yr Email Check Enclosed P O Enclosed O Bill Firm Charge 0 Visa O MC AmEx Diners Signature required Subscriptions Dept P O Box 335 Card Exp Date Boyds MD 20841 301 528 7777 FAX 240 599 7679 support pnmsi com Please add 40 shipping if outside N America Mail this form with payment to Washington Information Source Co PO Box 335 Boyds MD 20841 0335 240 477 5577 Fax 240 477 5577Support PNMSI COM Page 6 October 2014 preparation of Master Manufacturing Records Observation 5 Batch production and control records do not include complete information relating to the production and control of each batch The firm s batch production records for Acne Relief Gel Acne Cleanser and Day Cream SPF30 lack re quired elements Young stated including accurate pro duction of Master Manufacturing Records documenta tion of the significant steps in manufacturing processing packing or holding identity of equipment used inspection of the packaging and labeling area yield calculations la beling control records a description of contain ets closures and sampling performed Additionally these batch production records were filled in using pencil Observation 6 The establishment of specifi cations and sampling plans including any changes thereto are not drafted by the appropriate organi
4. date the complaint was received the device type and a brief de scription of the complaint Glembin detailed According to this procedure if the complaint is device telated the complaint is to be categorized and placed in the appropri ate color coded folder red or white to facilitate identifi cation of potential medical device reportable events However she noted Your firm lacks a complaint log book and color coded folders Observation 6 Personnel training is not doc umented Specifically Glembin stated your firm lacks documented evidence of personnel training on several procedures that were created or revised in response to your firm s Warning Letter issued March 6 2013 Most of these personnel include management who are making key decisions related to quality system activities she add ed This inspection identified that a number of pro cedures are not followed by the firm and resulted in re peat or new observations the investigator stated includ ing procedures on complaint handling CAPA manage ment review nonconformances general sterilization vali dation protocol environmental monitoring of clean rooms cleaning of cleanrooms and the review of recorder and daily reading logs and temperature monitoring FDA issued a close out letter in November 2013 in which the agency stated that its evaluation of Continen tal Medical Lab s corrective actions determined that the firm had adequate
5. designs Yes 90 No 10 Page 2 October 2014 Do you allow use of prior knowledge or knowledge and data from similar processes to support regulatory filing Yes 63 No 37 Do you have documented risk assessment s as a re quirement for process design characterization Yes 88 No 12 What is the size number of batches of your process validation PPQ campaign excluding revalidation Three successful batches most of the time 74 Variable depends on the process 26 What method do you use to determine the size of process validation campaign number of batches Check all that apply Quantitative model method 58 Qualitative model method 64 Is there a requirement in your company to provide justification for the number of process valida tion PPQ batches planned prior the start of process validation PPQ Yes 56 No 44 Is your process validation campaign size number of batches same for USA FDA and rest of the world Yes 91 No 9 When determining number of samples required dur ing process validation PPQ do you use statistical methods Where it makes sense 68 No 27 Yes always 5 According to your company procedures when does Continued Process Verification Stage ITI or process monitoring start First batch of process validation PPQ 36 First batch post process validation PPQ 64 In your regulatory submissions do you include data from the following Continued Process Verificat
6. quirements The design input for laser quality of the Weberneedle Basic Laser did not fully define the laser quality including the laser power and acceptable tolerance the wavelength and the acceptable tolerance and the tol Page 10 October 2014 erance for the laser size Eich commented The design verification for the laser performance includes infor mation to support safety evaluation but not the character ization of the laser quality for the Weberneedle device FDA issued a warning letter to Weber Medical in May 2013 in which the agency referenced the inspectional observations and the firm s written responses to the 483 In most cases FDA found that it could not assess the ad equacy of the responses due to lack of documentation supporting the firm s corrective actions The agency it would need to conduct a follow up inspection to confirm that the corrective actions had been taken There was no record of a close out letter or re port of a follow up inspection available from FDA King Systems procedures inadequate inspection shows King Systems Corp Noblesville IN Detroit Disttict Medical device manufacturer King Systems Corp received a five item 483 from FDA investigator Joseph Strelnik after his July 31 Aug 14 2013 inspection re vealed nonconformities in the firm s procedures and pro cesses Strelnik reported the following issues Observation 1 A process whose results can not be fully ve
7. the manufacture of the Laser Module Observation 3 Procedures for finished device acceptance have not been adequately established T observed the testing of the Weberneedle Product Serial number 81212051 Eich reported The testing for the power of the laser did not provide a con sistent result The power level varied between 110mW to 140mW The expected power is 100mW with acceptance criteria of 100mW 20 There is no final test for the laser wavelength he stated Observation 4 Certain measuring and test equipment is not suitable for its intended purposes The testing of a Weberneedle system for laser power and wavelength as reported above was made us ing test system PM2 but consistent results could not be obtained Another test system PM3 was utilized Eich stated Testing device PM3 was due for recalibration in December 2012 Observation 5 Risk analysis is incomplete The firm s Device Hazard Analysis summary of software validation identifies a potential malfunction of failure of timer and an identified action that the patient has the opportunity to shut down the device by using the patient switch the FDAer stated However he ob served There is no discussion of the use of the patient switch in the user manual and no assurance that the switch is actually included with the product Observation 6 Design verification does not confirm that design output meets design input re
8. the responsibilities and proce dures for the quality control unit Observation 12 Written procedures are lack ing which describe in sufficient detail the receipt identification storage handling sampling testing approval and rejection of components drug product containers and closures Observation 13 Procedures designed to as sure that correct labels labeling and packaging ma terials are used for drug products are not written Greenway did not established written procedures for packaging and labeling operations for its drug prod Inspection Monitor ucts including but not limited to prevention of product mix ups label reconciliation handling of unlabeled drug products examination of packaging and labeling materi als and line clearance activities the inspection revealed Observation 14 Written distribution proce dures are not established The firm had not established distribution proce dures inclusive of recall operations No warning letter was located DEVICES Device maker cited for repeat observations of GMP nonconformities Continental Medical Labs Inc Waterford WI Minneapolis District During an Aug 5 14 2013 FDA inspection in vestigator Michelle Glembin found Continental Medical Labs lacking in adequate procedures for complaint han dling CAPA and other GMP requirements and observed two repeat nonconformities from the previous inspection Glembin reported the following observations a
9. Food amp Drug Inspection Monitor Analysis of FDA 483s amp EIRs for Drugs Devices amp Biologics Vol XTX No 10 Inspections Featured This Month Drugs Hospira Page 2 Omega Packaging Page 3 Greenway Research Lab Page 4 Devices Continental Medical Labs Page 7 Weber Medical GmbH Page 9 King Systems Page 10 Contract Testing Lab SA Analytical Page 11 Inspection Log Page 12 Just 56 of firms justify the number of PPQ batches before starting validation PDA survey says generics firms rank lower WASHINGTON A PDA survey of a pioneer and ge neric drug makers indicates that a high number 44 do not justify the number process performance qualifi cation PPQ batches before they start validation a num ber that surprised many seasoned quality assurance execu tives Addressing the PDA FDA Joint Conference here last month Scott Bozzone Ph D a Pfizer qualifications and validation executive said out of 131 responses 56 said they do PPQ batches but 44 said they do not This surprised me said Bozzone who helped oversee the survey To me I will interpret that to think they have no rhyme or reason to pick three so that was disappointing on that one and was little thought behind it It keeps it simple in doing that PDA opened the survey Feb 18 and closed it May 24 It was not scientific randomly sampled but was focused on PDA s Process Validation Interest Group October 2014
10. L MANAGEMENT BECKMAN COULTER PALATINE IL NONE GIVEN 2014 6795 JAMES ALEXANDER CORPORATION PANTHEON MISSISSAUGA ONT WREXHAM UK 2014 6846 SANDRA COLANTUONO CP PHARMACEUTICALS LTD WREXHAM UK 7 16 10 2014 6893 SIDNEY AUSTIN DR BERNADETTE D SOUZA NONE GIVEN NONE GIVEN 2014 6804 ALKERMES
11. at have been requested under the Freedom of Infor mation Act by various parties according to FDA s Freedom of Information FOI Log which Inspection Moni tor subscribers can obtain Copies of these 483s and EIRs which have to be obtained from FDA in most cas es and in some cases may NOT be available can be ordered through RECORD RETREIVE by referencing the FOIA file e g 2012 4082 or readers can submit requests on their own using the file number The FOIA Log in PDF can be purchased for 10 per entry which contains all FOIAs filed in that given week Weeks of AUGUST 11 15 and 18 22 2014 were used to compile this list To order the Log in PDF call RECORD RETRIEVE at 703 779 8777 or email us at SERVICE FDAINFO COM Plant Location 483 EIR Date FOIA File Requested by AKORN KILICH INDIA NONE GIVEN 2014 6654 STERNE AGEE MYLAN INSTITUTIONAL IRELAND NONE GIVEN 2014 6610 ELIOT WILBUR GE HEALTHCARE AARTI DRUGS BARRINGTON IL INDIA NONE GIVEN NONE GIVEN 2014 6724 2014 6748 GE HEALTHCARE ACETO CORPORATION VIGNESH LIFE SCIENCES INDIA NONE GIVEN 2014 6728 BLOOMBERG NEWS IPCA INDIA 7 18 14 2014 6740 MYLAN ATUL LIMITED NONE GIVEN 1 1 2012 2014 6744 MORGAN LEWIS amp BOCKIUS LLP COVIDIEN AUGUSTA GA NONE GIVEN 2014 6754 WOOD BURDITT GROUP HOSPIRA NONE GIVEN NONE GIVEN 2014 6773 ARISTOTLE CAPITA
12. bserved an employee holding coaxial pediatric breath ing circuits up to the occlusion tester on production line for amounts of time less than one second this did not al low the occlusion tester readings to stabilize Observation 3 Procedures for the control of storage areas and stock rooms have not been ade quately established The investigator found King Systems inventory management procedures inadequate he stated because raw materials in the warehouse are not stored in a man ner that would prevent mix ups He noted that during his inspection of the warehouse storage bin area some bins were found to contain components that were not the same as the components listed on the Physical Inventory Count Sheet Further Strelnik found the staging areas for the circuit assembly product lines were not organized appro priately to prevent confusion For example I observed lines of boxes from adjacent product lines coming togeth er in a manner so that we could not distinguish what components belonged to respective production lines without finding the job order for each line The investigator also observed that King Systems inventory management personnel supply boxes of unla beled raw materials for use in production A stack of boxes containing components was staged in front of the breathing mask assembly line he explained The top box was unlabeled and the identity of the components could only be verified by physi
13. cal comparison to the labeled boxes in the remaining stack Observation 4 Procedures for receiving re viewing and evaluating complaints by a formally des ignated unit have not been adequately established Strelnik found that King Systems complaint rec ords are not maintained in a manner that preserves the complaint details investigations performed and corrective actions taken to resolve a complaint Further when the firm did not investigate a complaint the files did not include a reason for the deci sion not to investigate nor the signature of the person who made the decision Observation 5 A violation of the FD amp C Act involving a device which might present a risk to health was not reported to FDA Strelnik referenced three incidents in which King Systems received complaints regarding mislabeled prod ucts including products that contained latex that were la Inspection Monitor beled latex free None of these incidents was reported to FDA CONTRACT TESTING LABORATORY Inspection finds two nonconformities at SA Analytical laboratory SA Analytical Mundelein IL Chicago District FDA investigator Christopher Leach noted just two observations on the 483 he issued to SA Analytical following a Jan 9 16 2013 inspection of the contract testing laboratory that performs component and finished drug testing exclusively for Nexus Pharmaceuticals Leach explained in the Establishment Inspection Report EIR
14. cedure Temperature readings taken from the digital dis play on the chart recorder in Continental s temperature controlled rooms are recorded on an internal form enti tled Daily Temperature Readings the inspector stated Several such readings showed temperatures out of the ac ceptable range and Out of Range Notification forms were not completed for these occurrences as required Purther Glembin noted the Daily Temperature Readings form lists a different acceptable temperature range from that set forth in the firm s procedural re quirement This was a tepeat observation from the previous inspection Observation 3 Procedures have not been ad equately established to control product that does not conform to specified requirements Your firm lacks objective evidence to support the final disposition of the dry alcohol swabsticks that were the subject of nonconformance 20 13 02NC evalu ated on 04 05 2013 Glembin wrote She further found that Continental lacks a procedure that defines the re sponsibility for review the authority for the disposition of nonconforming product and the review and disposition Inspection Monitor is Protected by U S and International Copyright Laws 20 000 reward offered for information Photocopying faxing or other electronic transfer of this publication even for routing internal purposes or F Y I memos without expressed permission of the publisher and outsid
15. e identity strength quality and purity they purport or are repre sented to possess Verdel stated that studies have not been con ducted to identify the critical manufacturing parameters Page 4 October 2014 and control strategies to be documented and monitored during the manufacture of mouthwash and toothpaste products Observation 3 Equipment and utensils are not cleaned maintained and sanitized at appropriate intervals to prevent contamination that would alter the safety identity strength quality or purity of the drug product Omega did not have the requited proce dures fot quality unit review of master production and control recotds and execut ed batch records to ensure the inclusion of complete instructions and all information critical to the batch Specifically there is no assurance that the clean ing of multiuse equipment used in the manufacturing of drugs and cosmetics is adequate to prevent contamination by microbials cleaning agents or residue from drugs or chemicals to drug products packaged or manufactured on the equipment Verdel wrote Cleaning validation stud ies have not been conducted for equipment including mixing tanks holding tanks and filling lines used in manufacturing mouthwash and toothpaste as well as cos metic products such as body lotions Observation 4 Buildings used in the manu facture processing packing or holding of drug products are not maintained in a clea
16. e the bounds of your company s license to IM is prohibited under federal copyright law 17 U S C Sec 101 et seq WIS offers up to 20 000 reward for information leading to a settlement or judg ment against any individual or company that willfully photocopies our publications Anonymity of callers re porting violations is assured Report all infractions to our Publisher at 703 779 8777 or via email at Pub lisher FDAINFO com Inspection Monitor process The company failed to follow its nonconform ance procedure which requires the following items to be documented in the Nonconformance Logbook e Detailed description of the nonconformance e Lot number e Product name e Disposition of nonconforming product e Person who evaluated the nonconformance and date e Test results A review of the Nonconformance Logbook re vealed the above items were not documented in the log book for the only two nonconformances logged to date the investigator observed Observation 4 Procedures for corrective and preventive action have not been adequately estab lished The inspection revealed that Continentals Cor rective and Preventive Action procedure is inadequate Glembin explained because it does not include the fol lowing requirements Verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device Implementing a
17. gency documents noted Observation 1 A process whose results can not be fully verified by subsequent inspection and test has not been adequately validated according to established procedures Your firm failed to follow the Sterilization Pro tocol for Custom Manufactured Kits the investigator stated Glembin explained that one step of the protocol requires a certain number of half cycle sterilizer runs of one half the normal exposure time to verify the validity of cycle A different step requires full cycle sterilizer runs meeting minimum acceptable cycle specification parame ters to be processed However the FDAer stated Your firm only conducted two runs after approval of the protocol Manufacturing records for the validation test samples do not exist Glembin also found There is no objective evidence to support the sterilization process was performed using your most challenging product package as required by 7 2 1 of ISO standard 11135 which your firm referenced as following the investigator wrote She also found that the firm lacks documented evidence of the sterilization process being validated to October 2014 Page 7 yout defined process parameters for the half and full cy cles at your contract sterilizer Further Glembin noted that Continental failed to ensure its contract sterilizer provided the firm with data and documentation for equipment validation and instru ment calibratio
18. ils to define what type of particulate noted dur ing the 100 visual inspection the investigators ob setved The Light Test form has the defect as only Par ticulate The lack of identification of what type of partic ulate will not allow an adequate investigation of com plaints related to glass particulate Hospira received complaints of glass particulate in several products lots and only the number of defects was recorded the 483 stated Observation 3 There are no written proce dures for production and process controls designed to assure that the drug products have the identity strength quality and purity they purport or are repre sented to possess Hospira should have classified the glass particu late as a critical defect since there is a potential for caus ing adverse health consequences Abt and Berryman stated The firm s procedure Sampling and Auditing of Light Inspected Product classifies glass particle as a Ma jor A defect instead of critical defect which would likely October 2014 Page 3 result in serious adverse health consequences they found In addition the inspectors wrote Your opera tors visual inspection for lyophilized drug product quali fication program does not include examples of glass par ticulate in vials for training purposes No record of a warning letter to Hospira regard ing this 483 was found Multiple deficiencies found during inspection of dr
19. in your response to the Warning Let ter Glembin added In another repeat observation from the previous inspection Glembin found that Continental failed to complete a validation of the current heat seal parameters as promised in your response to the Warning Letter Observation 2 Procedures to control envi ronmental conditions have not been adequately es tablished Your firm failed to document the procedure used the person performing the sampling the conditions and the equipment used for environmental sampling of your three clean rooms performed on April 5 2013 as required by the company s environmental monitoring procedure Glembin stated There is no documented evidence of cleaning procedures being performed in any of the designated Page 8 October 2014 clean rooms at your firm the investigator wrote A re quirement or schedule does not exist for the maintenance or frequency of filter changes within the clean rooms The company also failed to follow its procedure for Review of Recorder and Daily Reading Logs and Temperature Monitoring to ensure the temperature range recorded on the temperature charts is within the al lowed range in all temperature controlled rooms The temperature was out of range on the temperature charts on several days Glembin observed The investigator also found that an Out of Range Notification form was not completed for these occurrences as required by pro
20. ion 49 Process Monitoring 64 Inspection Monitor Do you trend and monitor the quality of incoming raw materials as part of the CPV program Yes 35 No 37 Under a different system 28 but not as part of the CPV program Have you had any regulatory inspections where the inspector s asked about or mentioned the 2011 FDA PV Guidance Yes 26 No 74 Have you had any regulatory inspections where the inspector s asked about or mentioned a Continued Process Verification Program CPV Yes 16 No 84 Bozzone who said PDA will be publishing the results soon said it was also interesting that nearly half the firms were not doing anything different with process validation since adoption of the 2011 guidance FDA had not updated the guidance since 1987 DRUGS Hospira faulted for its handling of complaints of glass in sterile drugs Hospita McPherson KS Kansas City District During their inspection of a Hospira facility in McPherson KS FDA investigators Shirley Ber ryman and Janet Abt observed GMP nonconformi ties related to the presence of glass particulates in some of its sterile drug products FDA conducted the inspection July 29 Aug 16 2013 and identified the following problems ac cording to the 483 issued by the investigators Observation 1 An NDA Field Alert Report was not submitted within three working days of re ceipt of information concerning significant chemical physical or other change or dete
21. lacked written procedures for multiple GMPs and failed to maintain adequate batch production and control records FDA investigator April Young found during her July 30 Aug 2 2013 inspection of the firm Inspection Monitor Young specifically noted Observation 1 Failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been al ready distributed One lot of the firm s Cosmetic Day Cream was purchased as a contract manufactured product and dis tributed under your brand the FDAer stated According to a Nonconformance Record the product had an issue which involved product turning bad Young wrote You retrieved bottles from your retail locations to return to the contract manufacturer but did not investigate nor document your actions You have not determined the root cause for the issue nor determined whether other batches of drug product were affected One lot of the firm s Acne Cleanser failed stabil ity testing during the accelerated six month study but was not investigated Young found The product was as signed a 21 month expiration based on the testing data and released for distribution The investigator also noted that water sample re sults were high for Total Aerobic Plate Counts but were not investigated Greenway did not develop specifications for water used as a component in drug p
22. ly addressed the violations detailed in the March 2013 warning letter No warning letter was found in reference to the August inspection FDA inspection shows Weber Medical lacking in records procedures for device manufacturing Weber Medical GmbH Lauentoetde Germany CDRH German device manufacturer Weber Medical GmbH which makes medical laser systems was cited for six nonconformities with GMPs by FDA investigator Stephen Eich at the conclusion of his Jan 14 17 2013 in spection October 2014 Page 9 According to the 483 Weber had the following objectionable conditions Observation 1 Records of acceptable suppli ers have not been adequately established Specifically the FDAer found Webet s supplier acceptance procedure indicates that new suppliers will have QM quality management systems However the contract manufacturer for the laser diode modules for the Webberneedle system does not have a QM system Eich stated There is no assurance that the contractor is fol lowing the Quality System Regulation for manufacturing of the Laser module device he wrote Also the supplier acceptance procedure involves grading of the suppliers for various elements including quality There were no cri teria in the SOP for when a supplier corrective action would be required Observation 2 A device history record has not been adequately maintained Eich noted that there is no design history record for
23. members The objective was to obtain feedback on FDA s 2011 update to General Principles of Process Validation guideline and see how folks are dealing with it Bozzone said He said 66 of the respondents were from pio neer firms and the remainder from generic houses The types of products respondents oversee were 70 phar maceutical 47 biotech 21 generics 11 animal health 15 devices 18 vaccines and 7 other such as consumer goods and excipients Bozzone said 2 of the respondents worked for firms with fewer than 200 employees 18 with 200 to 500 employees and 70 are with companies with 500 workers or mote The following are some of the questions and re sponses PDA received Have there been significant changes to how you do performance process validation since release of FDA s 2011 guidance Yes 55 No 45 How is process validation defined in the quality standards policies of your company One stage process validation 28 Three stages of process validation 65 Process Design Process Performance Qualification Continued Process Verification Other 7 Do you use the term Process Performance Qualification Yes 51 No 49 Do you consider the Process Performance Qualifica tion as a stage of Process Validation in the policies of your company Yes 91 No 9 Do you allow use of prior knowledge or knowledge and data from similar processes to support process characterizations or process
24. n and sanitary condition The investigator found that Omega s manufactur ing areas were in condition such that the product may become contaminated with filth she stated Verdel observed that a metal staircase leading to the mixing tank used during manufacture of mouthwash and the platform used to stage raw ingredients before they are added to the tank were rusted and covered with vari ous spilled substances She also observed rust on the outside of the mixing tank itself Near the mixing tank Verdel noted grime and debris visible on the floor and in the drain and in the floor cavity Raw materials are stored in the mixing room on broken dirty wooden pallets she further observed Fans located above a filling and packaging line for mouthwash were coated with dust Windows in the filling room are lacking protective screens with broken glass covered with cardboard and cloth Verdel saw dust and spider webs above the filling and packing line as well as missing and stained ceiling tiles located approximately four feet above the loading port for a mixing tank and holding tanks for mouthwash Inspection Monitor Observation 5 Equipment used in the manu facture processing packing or holding of drug products is not of appropriate design to facilitate op erations for its intended use The FDAer stated that Omega had not conduct ed studies of the equipment used to mix and package its drug products to a
25. n certification per the Responsibilities section of the protocol Continental released two loads prior to receipt of documented evidence of the sterility test results Your protocol states Test samples must meet acceptance criteria before final product release the inspector stated The sterilization process patameters for the Half Cycle Revision D approved 05 13 2013 list the mini mum and maximum limits of injection concentration as TBD to be determined Glembin pointed out This is a repeat observation that your firm promised to correct in your response to the Warning Letter The firm lacked validation data to support its es tablished expiration dating period and failed to address the resterilization process the investigator continued During the inspection you reported you are no longer resterilizing product however this is not documented in any procedures she wrote noting that this also was a repeat observation that your firm promised to correct in your response to the Warning Letter There is no documented evidence of clean ing ptocedures being performed in any of the designated clean rooms at your fitm Continental failed to compare the revalidation re sults from July 2012 with the original validation to con firm that the original performance has been maintained as required by its re validation procedure This is a repeat observation that your firm promised to correct
26. nd monitoring could occur at any location Observation 8 Washing and toilet facilities lack hot and cold water The FDA investigators observed that during the inspection the toilet facility adjoining changing room MWS04 of the Raw Material Storage area did not have running water for hand washing and toilet flushing The water supply was reportedly turned off during mainte nance and inadvertently left off Further the team noted there are no proce dures to direct employees to wash hands with soap and water after toilet use and prior to gowning and no ade quate facilities and procedures for employees to wash their feet prior to donning factory issued work sandals which expose bare feet and are authorized footwear in the unclassified areas Observation 9 Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during produc tion The Air Displacement Unit ADU used in tablet bottling operations does not contain adequate filters Page 12 October 2014 e g HEPA to prevent the release and recirculation of dust created during the bottling operation which creates a situation in which cross contamination may occut the FDAers reported Observation 10 Established test procedures are not documented at the time of performance The inspection found that the analytical green sheets used by analysts to record the testing of various materials do not co
27. nd recording changes in methods and procedures needed to correct and prevent identified quality problems Submitting relevant information on iden tified quality problems as well as corrective and preven tive actions for management review Your firm closed Corrective Action Request CAR 0001 regarding without any objective evidence to support the corrective actions taken by the supplier were effective she wrote In addition there is no objective evidence to support a review of other potentially affected product to ensure the problem was isolated to the impli cated lot only A CAR opened regarding a customer complaint of receipt of dry alcohol swabsticks does not address the actions taken with the im plicated lot that may have still been in available inventory at your firm the inspector added Observation 5 Procedures for receiving re viewing and evaluating complaints by a formally designated unit have not been adequately estab lished Your firm received a complaint via e mail re garding dry alcohol swabsticks a component which was included in their convenience kit the investigator report ed There is no documented evidence to support this customer feedback was processed as an entry in your complaint handling system Inspection Monitor Continental s procedure on handling complaints and product related feedback requires all complaints to be entered into a complaint log book with the
28. ntain sufficient information to verify actual reagents and apparatus used in analyses Microbi ology green sheets for certain finished products do not contain complete information on how analyses are per formed and some green sheets contain preprinted in structions that do not always contain relevant information on concentrations of reagents for certain analyses Observation 11 Written procedures are lack ing which describe in s ufficient detail the testing Inspection Monitor The approval of certain components the FDA team noted does not include a review of the monitoring system inputs to ensure the system is consistently func tioning as intended For example they explained your firm does not adequately monitor established operating parameters such as flow rate water pressure and pow er to ensure that appropriate operating conditions are met during the manufacture of certain components and products In addition the FDAers pointed out that the wa ter source is located outdoors and is not fully protected from entry of potentially contaminated water and filth such as rainwater runoff Raw water tanks have air vents not fully protected and ill fitting manhole covers that may allow access of pests and other contaminants No warning letter related to this inspection could be located approval and rejection of components INSPECTION LOG The following is a partial list of inspection documents th
29. products Observation 7 Routine checking of mechan ical equipment is not performed according to a writ ten program designed to assure proper performance Raw and in process material storage areas may not meet the established requirements in that studies to determine the optimal environmental monitoring loca tions for several storage warehouse areas were found to be deficient the FD Aerts stated They found no adequate rationale for the placement of the temperature and relative humidity moni toring device in Raw Materials Warehouse 1 because the permanent monitoring location differs from the worst case location as determined by a temperature mapping study The investigators also determined that there was inadequate data to support the placement of the temper ature and relative humidity monitoring device in Raw Ma terials Warehouse 2 in that there was missing data for several locations and scientific rationale was not utilized in accepting the study with missing data Further the im pact of that missing data was not assessed during the temperature mapping study for this facility There is no adequate justification for the place ment of the temperature and relative humidity monitoring device in In Process Storage 2 the FDAers stated be cause excursions from the predefined acceptance criteria were experienced and were not handled in accordance with the protocol that concluded the room was uniform a
30. rified by subsequent inspection and test has not been validated according to established procedures The investigator identified inadequacies in the company s validation procedures Extruders have not been validated to ensure that the process will continue to meet predetermined specifica tions Strelnik wrote These extruders are used to pro duce tubing to be assembled into the King Flex 2 King F2 King PedF2 and King F breathing circuits which are used to administer medical gases and or anesthetic gases to a patient during anesthesia for inhalation or respiratory care inhalation King Systems validation of the Flex 2 Assembly Automation system did not adequately determine if the leak test performed on finished product was capable of detecting leaks of varying size in various locations in the tubing of a collapsed circuit the FDAer stated Your firm has not conducted any studies on leak testing col lapsed tubing to ensure that holes of various sizes and lo cations can be accurately and precisely measured Inspection Monitor Observation 2 Procedures for the acceptance of in process product have not been adequately es tablished Strelnik commented that the firm s in process occlusion testing of coaxial pediatric breathing circuits is not performed in a manner that would detect noncon forming product and prevent it from leaving the facility He noted that on Aug 2 during the inspection I o
31. rioration in a distrib uted drug product Inspection Monitor NDA Field Alerts were not submitted within three working days of glass particulate complaints for sterile lyophilized drug products filled on line including one or more lots each of Erythrocin Lactobionate for ILV 500 mg Vancomycin Hydrochloride for injection USP 500mg and Vecuranium Bromide for Injection USP 500mg Observation 2 Failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed Your investigations of confirmed complaints of glass particulate in sterile lyophilized drug products have not been timely the FDAers wrote The results of investigations related to glass par ticulate complaints were not provided to the sponsor within the timeframes required For example a complaint was registered on April 25 2013 and the sample of prod uct pertaining to this complaint was received on May 20 Plant completed investigation and proposed verbiage was forwarded to the sponsor on June 24 2013 the in spectors noted Further a Drug Medical Assessment was not in itiated until 07 23 2013 and signed 07 31 2013 for Erythromycin Vancomycin Vecurontum Bromide and other drug products Hospita should have classified the glass patticulate as a critical defect since there is a potential for causing adverse health consequences The 100 visual inspection after lyophilization form fa
32. roducts that have been released for distribution one lot of Acne Relief Gel manufactured March 12 2013 using water as a compo nent and released for distribution One lot of Acne Cleanser was manufactured Jan 25 2012 using water as a component and released for distribution Results from samples of water taken just before during and after the manufacture of these products showed colony forming units CFLs per milliliter that were not acceptable In addition Young found that one lot each of Acne Relief Gel and Acne Cleanser were out of specification for viscosity These occurrences were not investigated and the product was released she reported Observation 2 Accelerated stability studies Food amp Drug Inspection Monitor Name Title Kenneth Reid Editor amp Publisher Kathy Thorne Subscriptions Company Rebecca Mashaw managing Editor Address Editorial Offices rn 19 B Wirt St SW City State Zip Leesburg VA 20175 Phone 703 779 8777 Fax 703 779 2508 www FDAINFO COM www FDADocuments org Payment Options check one October 2014 Page 5 combined with basic stability information used to support tentative expiration dates are not supported with ongoing full shelf life studies Specifically there have been no full shelf life studies conducted to support expiration dating on your drug products Young noted Greenway s acne cleanser failed stability testing at six months but
33. ssure that the equipment is qualified for its intended use Qualification studies for mixing tanks used for the manufacture of mouthwash and toothpaste drug products have not been conducted she noted The hold ing tanks used for these products have not been qualified for use nor had the firm conducted studies to qualify the filling machines used for the mouthwash and toothpaste products Observation 6 Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not per formed Verdel observed that Omega accepted all the components for its drug products per Certificate of Analysis upon the components receipt and did not per form any identity testing Observation 7 Laboratory records do not in clude the initials or signature of a second person showing that the original records have been reviewed for accuracy completeness and compliance with es tablished standards All laboratory tests for mouthwash and tooth paste products are performed reviewed and signed by one person Verdel stated In addition the same person is releasing the product to the customer No warning letter was found on the FDA web site Greenway Research Lab slapped with 14 item 483 for poor process and production controls inadequate procedures Greenway Research Lab Burnsville MN Minneapolis District Drug and cosmetic manufacturer Greenway Re search Lab
34. ug and cosmetic manufacturer Omega Omega Packaging Corp Totowa NJ New Jersey Disttict FDA investigator Helen Verdel found Omega Packaging Corp in violation of GMPs for manufactur ing drug and cosmetic products including failure to keep its facilities clean and in repair during her Jan 8 28 2013 inspection The investigator noted the following faults ac cording to the 483 issued Observation 1 The responsibilities and pro cedures applicable to the quality control unit are not in writing and fully followed Specifically Verdel noted the company had not established written quality control procedures to assure the qualification of all equipment used in the manufacture and packaging of mouthwash and toothpaste products The FDAer also found that Omega had not im plemented change control procedures and did not train its employees in drug GMPs Further Verdel observed that the firm did not have adequate cleaning procedures to en sure prevention of product contamination and its com plaint handling and investigation were inadequate She also found that Omega did not have the re quired procedures for quality unit review of master pro duction and control records and executed batch records to ensure the inclusion of complete instructions and all in formation critical to the batch Observation 2 There are not written proce dures for production and process control designed to assure that the drug products have th
35. upplier s analyses through appropriate valida tion of the supplier s test results at appropriate inter vals Greenway did not verify that components used in the manufacturing of drug products conformed to all written specifications including the active ingredients sali cylic acid titanium dioxide and zinc oxide octinoxate and benzoyl peroxide the investigator noted Additionally you have distributed your Day Cream SPF30 that you have contract manufactured with out establishing specifications for this product and verify ing the product meets the quality standards of identity purity strength and composition Young added Observation 9 Procedures describing the handling of written and oral complaints related to drug products are not written or followed The company had not established written proce dures for handling complaints the inspection showed Observation 10 Written procedures are not established for evaluations done at least annually and including provisions for a review of complaints re calls returned or salvaged drug products and inves tigations conducted for each drug product Young further found that Greenway had not es tablished written procedures for conducting annual prod uct reviews of its drug products Observation 11 The responsibilities and pro cedures applicable to the quality control unit are not in writing The investigator stated that you have not estab lished procedures detailing
36. za tional unit Greenway failed to established product specifica tions or sampling plans for Acne Relief Gel Acne Cleans er or Day Cream SPF30 the inspector found Release testing for these products includes assay testing and mi crobiological contamination testing Get The COMPLETE Validation Handbook today in a downloadable PDF form More than 600 pages of FDA ICH and other guidance on validation compliance in ONE handbook All FDA Guidance and compliance references on validation including computer and software validation cleaning analytical methods and more ICH guidance Articles from WIS newsletters on how and how not to validate your processes Just 459 plus shipping Order The COMPLETE Validation Handbook today Inspection Monitor Observation 7 The identity of each compo nent of a drug product is not verified by conducting at least one test to verify the identity using specific identity tests if they exist Young observed that the company did not con duct an identity test for received components used during drug manufacturing including certain lots of the active in gredients salicylic acid titanium dioxide and zinc oxide octinoxate and benzoyl peroxide Observation 8 Reports of analysis from com ponent suppliers are accepted in lieu of testing each component for conformity with all appropriate writ ten specifications without establishing the reliability of the s

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