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Microbial issues in cleaning validation.pptx
- 1. MICROBIAL ISSUES IN CLEANINGVALIDATION Presented by : Chetsi Dalsania Rushali N Shah 1
- 2. CONTENT • Importance ofmicrobial residue control • Changes in microbial residues • Microbial residue reduction • What is measured for acceptance criteria? 2
- 3. IMPORTANCE OF MICROBIAL RESIDUECONTROL The rationale for considering microbiological contamination as part of a cleaning program is that microbiological quality is of concern for all products. At a minimum, the absence of certain enteric organisms in the cleaned equipment is a must for all products. For biotechnology manufacturing involving microbial cells, the presence of species other than the one desired for manufacturing purposes may interfere with productivity and quality. 3
- 4. CONT… The issue ofmicrobiological contamination of cleaned equipment for sterile products may also be related to endotoxin levels in the subsequently manufactured product. Additional concerns are the possible effects of microbes on the stability of the drug product or perhaps on the bioavailability of the drug active. 4
- 5. CHANGES IN MICROBIALRESIDUE • Microbial residues are different from chemical residues. • Chemical residues generally are transferred unchanged to the subsequently manufactured product. • As pointed out in the FDA guidance document, there may be microbial proliferation after the cleaning step (and during storage), which may considerably change the level of microbial residues. 5
- 6. CONT… • On theother hand, there may be microbial death on cleaned, dried equipment that significantly lowers the bioburden transferred to the subsequently manufactured product. • The main issue is that levels of microbial residues present at the end of cleaning are not as relevant as levels of microbial residues that are present at the beginning of manufacture of the next product. • The key point is that microbial residues may change during storage of the cleaned equipment 6
- 7. CONT… • If theproduct is a dry product with a water content of < 0.6 percent, it is generally accepted that microbes will not grow in such products. 7
- 8. MICROBIAL RESIDUE REDUCTION • Effectivecleaning by itself can in most cases produce equipment that will have acceptable microbial residue levels. • Effective cleaning in this case generally means cleaning with a hot solution of a highly alkaline or acidic cleaning agent containing surfactants, which also remove the chemical residues that are present in the system. • The purpose of the acidity or alkalinity is to produce a cleaning environment that is hostile to microorganisms. The same is true for using an elevated temperature (generally above 60°C) to produce an environment hostile to microbes. 8
- 9. CONT… • It isimportant that the cleaning process also remove the chemical residues present; significant amounts of chemical residues left behind may serve as microbial traps, which prevents the destruction or removal of the microorganism during the cleaning process. • A proper design and engineering of the equipment is necessary to eliminate locations where microorganisms can hide and proliferate. These are generally the same locations that may cause problems with chemical residues, including dead legs and crevices. 9
- 10. WHAT IS MEASUREDFOR ACCEPTANCE CRITERIA? • The acceptance criteria preferably include a specification of restricted organisms (that is, those that should not be present at all, such as enteric organisms) and a specification of the maximum number of CFUs per swab or contact plate. • The maximum number acceptable in the cleaned equipment should be based, on the contribution of microbial load to the subsequently manufactured product or to the bioburden for the subsequent sterilization process. • In selecting acceptable limits for cleaning validation acceptance criteria, one possibly could view these numbers as extremely high; in most cases, one would never have equipment contaminated at those levels. 10
- 11. CONT… • The action/alertlimits measured as part of routine monitoring will be significantly below the acceptance criteria for cleaning validation purposes. This is to be expected. • The action/alert limits are initially established as tentative limits based on prequalification testing. As more data are obtained from routine monitoring, these action/alert limits may be revised. • The action/alert levels for monitoring purposes are designed to provide an early warning of possible changes in the system through a review of trend data. 11
- 12. CONT… • This contrastbetween validation acceptance criteria and routine monitoring limits is important for chemical monitoring as well as for microbial monitoring. • It should also be noted that microbial testing for cleaning validation usually focuses on bacterial or mold/yeast contamination. 12
- 13. CONCLUSION • Control measuresin manufacturing may include limiting bioburden: i. In raw materials (and on equipment in direct contact with these). ii. In packaging components iii. In manufacturing environment iv. On product-contact surfaces • The purpose of microbiological consideration in cleaning validation is to control microbial bioburden within an acceptable level. • Cleaning of cleanroom surfaces & cleaning of process equipment – have distinct regulatory and technical focus. 13
- 14. REFERENCES 1. Validated CleaningTechnologies for Pharmaceutical Manufacturing_Destin A. LeBlanc(2000, Informa Healthcare) 2. Microbiological Aspects of Cleaning Validation; Dr. Tim Sandle https://www.pharmig.org.uk/en/wp-content/uploads/2019/05/10.10-10.50- Tim-Sandle-Microbial-Cleaning-Validation-frkkgor55kfiodug.pdf 3. Microbiological Cleaning Method Validation; Fergus O’Connell https://cdnmedia.eurofins.com/apac/media/489871/raci-capsig- microbiological-cleaning-method-validation-16-aug-2017.pdf 14
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