The Pharmaceutical Microbiology Manual, authored by Angele C. Smith, provides comprehensive guidelines and procedures for microbiological testing in pharmaceuticals. This document covers key topics such as antimicrobial effectiveness testing, sterility testing, and environmental monitoring. It serves as a vital resource for ensuring the safety and efficacy of pharmaceutical products.
FOOD AND DRUG ADMINISTRATION
OFFICE OF REGULATORY AFFAIRS
Office of Regulatory Science
Document Number:
ORA.007
Revision #: 02
Revised:
25 Aug 2020
Title:
Pharmaceutical Microbiology Manual
Page 1 of 92
For the most current and official copy, check QMiS.
Sections in This Document
1. Purpose ................................................................................................................................. 1
2. Introduction ............................................................................................................................ 2
3. Current Editorial Board .......................................................................................................... 3
4. Original Authors ..................................................................................................................... 3
5. Chapter 1: Antimicrobial Effectiveness Testing ..................................................................... 4
6. Chapter 2: Microbial Examination of Non-Sterile Products ..................................................... 8
7. Chapter 3: Sterility Testing ................................................................................................. 14
8. Chapter 4: Investigating USP Sterility Testing Failure ......................................................... 28
9. Chapter 5: Bacterial Endotoxin Testing ................................................................................ 30
10. Chapter 6: Particulate Matter .............................................................................................. 40
11. Chapter 7: Antibiotic Potency Testing .................................................................................. 44
12. Chapter 8: Bioburden Estimation for Medical Devices......................................................... 59
13. Chapter 9: Environmental Monitoring .................................................................................. 61
14. Chapter 10: Inspectional Guidance ..................................................................................... 70
15. Glossary/Definitions ............................................................................................................. 90
16. Records ............................................................................................................................... 91
17. Supporting Documents ........................................................................................................ 91
18. Document History ................................................................................................................ 91
19. Change History .................................................................................................................... 92
20. Attachments ......................................................................................................................... 92
1. Purpose
The purpose of this Pharmaceutical Microbiology Manual (PMM) is to
collectively clarify, standardize, and communicate useful analytical procedures
that are not specifically addressed in the microbiology methods chapters in the
United States Pharmacopeia. In addition, some sections of this manual can
serve as a technical reference when conducting microbiological inspections of
drug, biotechnology and medical device manufacturers. The contents of this
PMM were collaboration between ORS and CDER in order to maximize the
efficiency of our analytical results to support CDER’s goal to assure the safety
and reliability of commercially distributed medical products.
FOOD AND DRUG ADMINISTRATION
OFFICE OF REGULATORY AFFAIRS
Office of Regulatory Science
Document Number:
ORA.007
Revision #: 02
Revised:
25 Aug 2020
Title:
Pharmaceutical Microbiology Manual
Page 2 of 92
For the most current and official copy, check QMiS.
2. Introduction
The Pharmaceutical Microbiology Manual (PMM) evolved from the Sterility
Analytical Manual and is a supplement to the United States Pharmacopeia
(USP) for pharmaceutical microbiology testing, including antimicrobial
effectiveness testing, microbial examination of non-sterile products, sterility
testing, bacterial endotoxin testing, particulate matter, device bioburden and
environmental monitoring testing. The goal of this manual is to provide an
ORS/CDER harmonized framework on the knowledge, methods and tools
needed, and to apply the appropriate scientific standards required to assess
the safety and efficacy of medical products within ORS testing laboratories.
The PMM has expanded to include some rapid screening techniques along
with a new section that covers inspectional guidance for microbiologists that
conduct team inspections.
This manual was developed by members of the Pharmaceutical Microbiology
Editorial Board and includes individuals with specialized experience and
training.
The instructions in this document are guidelines for ORS analysts. When
available, analysts should use procedures and worksheets that are
standardized and harmonized across all ORS labs, along with the PMM, when
performing analyses related to product testing of pharmaceuticals and medical
devices. When changes or deviations are necessary, documentation should be
completed per the laboratory’s Quality Management System. Generally, these
changes should originate from situations such as new products, unusual
products, or unique situations.
This manual was written to reduce compendia method ambiguity and increase
standardization between ORS laboratories. By providing clearer instructions to
ORS labs, greater transparency can be provided to both industry and the
public.
However, it should be emphasized that this manual is a supplement and does
not replace any information in USP or applicable FDA official guidance
references. The PMM does not relieve any person or laboratory from the
responsibility of ensuring that the methods being employed from the manual
are fit for use, and that all testing is validated and/or verified by the user.
The PMM will continually be revised as newer products, platforms and
technologies emerge or any significant scientific gaps are identified with
product testing.
Reference to any commercial materials, equipment, or process in the PMM
does not in any way constitute approval, endorsement, or recommendation by
the U.S. Food and Drug Administration.
FOOD AND DRUG ADMINISTRATION
OFFICE OF REGULATORY AFFAIRS
Office of Regulatory Science
Document Number:
ORA.007
Revision #: 02
Revised:
25 Aug 2020
Title:
Pharmaceutical Microbiology Manual
Page 3 of 92
For the most current and official copy, check QMiS.
U.S. FDA, Office of Regulatory Affairs
Office of Regulatory Science
Office of Medical Products and Specialty Laboratory Operations
3. Current Editorial Board
Editor-In-Chief: Angele Smith, ORS Headquarters
Rick Friedman, Center for Drug Evaluation and Research
Jennifer Gogley, Pacific Southwest Medical Products Laboratory
Kristy Ford, Detroit Medical Products Laboratory
Marilyn Khanna, ORS Headquarters
Mivoyel Jeanpaul, ORS Headquarters
Sammie La, Pacific Southwest Medical Products Laboratory
Matthew Silverman, Winchester Engineering and Analytical Center
Marla Stevens-Riley, Center for Drug Evaluation and Research
Allison Rodriguez, Winchester Engineering and Analytical Center
Radhakrishna Tirumalai, United States Pharmacopeia
Theresa To, Winchester Engineering and Analytical Center
4. Original Authors
Rhonda Alexander, Southeast Food and Feed Laboratory
Jasna Braut-Taormina, Northeast Medical Products Laboratory
Jennifer Brzezinski, Forensic Chemistry Center
Marie B. Buen-Bigornia, Denver Food and Feed Laboratory
Rick Friedman, Center for Drug Evaluation and Research
Jennifer Gogley, Pacific Southwest Medical Products Laboratory
Andrew Gonzales, Denver Food and Feed Laboratory
Dennis Guilfoyle (ret), Northeast Medical Products Laboratory
Lawrence James (ret), Northeast Food and Feed Laboratory
Marilyn Khanna, ORS Headquarters
David Lau, San Francisco Food and Feed Laboratory
Eileen Liu, San Francisco Food and Feed Laboratory
End of Document
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