APR Sept/Oct 2023 - 82

» WHITEPAPER
Microbial Testing for the Pharmaceutical Industry
A straightforward path to regulatory compliance,
data integrity, and computer systems validation
Darryl León, PhD
Senior Product Manager, Thermo Fisher Scientific
Sandi True, PhD
Staff Scientist, Thermo Fisher Scientific
Throughout the drug development and manufacturing processes,
the potential for bacterial and fungal contamination of raw materials,
production facilities, and branded products poses a serious threat to
drug efficacy and patient safety. Regulators expect manufacturers to
have robust environmental monitoring and contamination control
strategies in place as part of current good manufacturing practice
(cGMP). A validated microbial identification system is a key facet of
these programs.
The genotypic method is the gold standard in microbial identification
(ID). This method involves using PCR and DNA sequencing for
environmental monitoring, detection and identification of contamination,
as well as root cause analysis, and ensures the sterility
of raw materials. However, implementation and validation of such a
system in the cGMP environment can be overwhelming. Technical
expertise with the hardware and software of a proven microbial ID
platform, familiarity with regulatory requirements, and the ongoing
support of an experienced team of field service engineers, field
application specialists, and computer system validation (CSV) experts
can be invaluable to any group looking to implement a robust
environmental monitoring system.
This white paper covers what you should consider when implementing
a microbial identification system, including ensuring data integrity
and validating the computer system used for microbial testing in a
bioproduction workflow. Read on to learn about:
* Current regulatory guidance concerning validation of microbial
ID processes in a GMP environment.
* What to look for when implementing a microbial ID system and
various options for validation.
* Real-world examples of companies that used different strategies
for implementation and CSV.
Regulatory Expectations for
Microbial Control and Identification
Microbial contaminants should be identified at the species level
or, where appropriate, at the genus level at frequent intervals to
establish a valid, current database of contaminants present in a
facility during processing.1
82 |
| September/October 2023
The USP <1113> monograph recommends the use of one of the
following methods of verification of a microbial identification system:
* Use an existing system to compare with microbial isolates
obtained from routine testing. The number of isolates can be as
high as 50;
* Test 12-15 referenced stock cultures of different commonly
isolated species, for a total of 50 tests; or,
* Confirm 20-50 organism IDs, including 15-20 species that agree
with the results from a reference laboratory testing of a split sample.
Accuracy and reproducibility are the most important parameters used
to verify the chosen method.
What to Look for in a Microbial
Identification System
The ideal microbial identification platform provides accurate results
quickly, is easy to use, includes a comprehensive sequence library
for bacteria and fungi and is cost effective. It would be invaluable to
assess a new system on the following parameters: technology, cost,
and data quality.
Technology
Choose a system with required throughput, high accuracy, rapid
turnaround time, and simplicity of use. The US Food and Drug
Administration (FDA) recognizes DNA sequencing and the genotypic
method as the most accurate and precise for the phylogenetic
classification of bacteria and fungi.1
An expansive library that includes
validated sequence data for a large number and range of species
ensures accuracy. It should include polymorphism data and be
constantly updated and expanded.
Cost
Assess the relative cost and benefit of in-house microbial testing
versus waiting for results from an external testing lab. Choose a system
that gives accurate results the first time, eliminating wasted resources
to retest unsuccessfully identified samples.
APR Sept/Oct 2023

Table of Contents for the Digital Edition of APR Sept/Oct 2023
