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3- Exercise & Discussion
The document summarizes regulatory reports from sterile manufacturing facilities in Japan, the US, and the UK from 2009-2017. The reports identified issues like failure to perform personnel and environmental monitoring, inadequate cleaning and airflow studies, temporary fixes with tape, delays in investigating mold findings, and penicillin cross-contamination between product areas without comprehensive corrective actions. The take home messages are that failures in sterility assurance or cross-contamination can seriously impact patient safety, and facilities must prioritize design, operations, training, and microbiological testing.
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3- Exercise & Discussion
- 1. Regulatory Science ofSterile Manufacturing Process RSSMP- Week – Two (3/4) Roohi B. Obaid & Obaid Ali 29 July 2018 at Karachi
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- 3. Background Sterile manufacturing facility Workingw/o terminal sterilization Aseptic manufacturing was approved Product was coming in market There was no complaint Regular inspection revealed ...
- 4. Report Company failed toperform routine personnel monitoring during sterile manufacturing Routine Personnel Monitoring
- 5. Report SOP doesn’t sufficientlyaddress the appropriate response to be taken when personnel monitoring yields results outside of action & alert limits Understand word appropriate
- 6. Report Alert & Actionlimit was not supported by an appropriate scientific rationale Unclear & unspeaking is a ?
- 7. Report Company failed toperform routine sampling of clean room environment Justify sampling locations
- 8. Report Justify alert &action limits Ensure all locations are sampled Justify frequency … investigation circumstances
- 9. Report There was noappropriate proof to demonstrate the air flow pattern over the exposed sterile product during processing
- 10. Report There was noappropriate proof to demonstrate the air flow pattern over the exposed sterile product during processing Smoke study
- 11. Report Why a productmanufactured in this environment should not be pulled from market? Risk assessment describing process failure modes, sterility history & action taken to evaluate the acceptability of the product
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- 13. Report Failed to followSOP regarding time & temperature of MF vials Discrepancy in the batch record when 3 MF vials couldn’t be accounted for
- 14. Report The design ofpersonnel entry into the facility doesn’t protect against microbial contamination because The locker rooms do not adequately segregate the area of street cloth & facility uniform/shoes
- 15. Report The design ofpersonnel entry into the facility doesn’t protect against microbial contamination because Shelving is made of wood & is not claen and sanitized … build up of dirt & dust was visible
- 16. Report The design ofpersonnel entry into the facility doesn’t protect against microbial contamination because Sanitizing, cleaning of afctory shoe is not conducted & recorded on a routine schedule
- 17. Report Gram + veBacillus specie were identified in the facility but neither investigation nor root cause was done Reoccurrence not protected … opportunity of learning lost
- 18. Report Gowning rooms arenot included in EM program. Alert is based on historical data though action limits are not based on historical data Science and justification missing
- 19. Report Nonviable particle monitoringprobe is positioned above the work area Without justification of positioning it remains a deficiency observation
- 20. Report Smoke study didn’tadequately demonstrated unidirectional flow Smoke Study Assessment is mandatory
- 21. Report EM sampling sitewas not scientifically justified Science, science & science
- 22. Report Aseptic processingareas are not adequately clan or disinfected The top area of curtain in Class 100 filling areas are not sprayed or wiped Scientific justification for this practice was not available
- 23. Report Sterile filling roomwas left at rest in excess of duration identified in the company SOP Disposition of rejected components was not recorded
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- 25. Report Anaerobic MF werenot performed under anaerobic condition to mimic the drug product fills that are over led with nitrogen Ananerobic MF
- 26. Report Equipment require adhoc modificationsthat include adhesive tape to secure items Undocumented Temporary interventions
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- 28. Report Same facility isused for penicillin processing and non-penicillin products Cross contamination
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- 30. Report Mold was repeatedlyrecovered both in aseptic processing area & support area Several roof leaks in 2013 & 14 were not considered an investigation How long leak … ? There was no document
- 31. Report Surveillance sampling toidentify possible entry of mold was deficient in terms of its process & method of analysis
- 32. Report Investigations associated withmolds recovery were open for extended period of time without resolution
- 33. Report The firm doesn’thave procedure to evaluate potential for adsorption of compounds from contact filling components such as silicon tubing etc.
- 34. Report Firm doesn’t havedocumentation to ensure that they reviewed the disinfectant effectiveness studies
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- 36. Report Contamination of penicillinon the surface of non-penicillin processing areas 187 times
- 37. Report Corrective action didnot include a comprehensive cleaning and decontamination of the associated area and equipment
- 38. Report The cleaning methodused to remove penicillin on surfaces have not been adequately validated Methods used to test the presence of penicillin were not adequate
- 39. Report A variety ofpossible causes for the presence of penicillin in non-penicillin area were identified, but the corrective action didn’t fully correct the findings
- 40. Report Investigations into microbialalert & action level findings in the water system didn’t establish a root cause. Any conclusion not supported by data is not acceptable, it is an assumption It would have been a sampling error
- 41. Failure either insterility assurance or potential cross- contamination can have a serious impact on patient safety Don’t let it go as such Take Home Messages
- 42. Facility design, operational issue,staff training and deficiencies in MF tests are front burner priorities Take Home Messages