Microbiological safety of biologic products is a critical step throughout development, manufacturing, and batch release. Biologics require a comprehensive testing strategy that verifies the absence of microbial contamination while demonstrating compliance with international pharmacopeial and regulatory requirements.
A comprehensive microbiological control strategy is essential to assess potential contamination risks at different stages of product development and manufacturing. At Kymos Group, our GMP-certified microbiology laboratory supports this strategy with microbiological quality control services for biologics, cell and gene therapies, vaccines, and other sterile and non-sterile pharmaceutical products.
A Complete Approach
Product safety relies on a combination of assays that evaluate contamination risks at different stages of manufacturing and quality control.
These microbiological assessments are often performed alongside physicochemical and analytical quality control testing, providing an integrated approach to product characterization and batch release.
Bioburden
(In accordance with Ph. Eur. 2.6.12; USP <1119>)
Bioburden testing determines the total population of viable microorganisms present in raw materials, APIs or finished products prior to sterilization or aseptic processing. It is a critical quality control measure used to assess the microbiological status of the manufacturing processes. Routine monitoring of bioburden levels provides assurance that the processes remains under control and supports the validation and continued effectiveness of sterilization procedures.
Microbial Limits Testing: TAMC, TYMC and Specified Microorganisms
(In accordance with Ph. Eur. 2.6.12/Ph. Eur. 2.6.13; USP <61>/ USP <62>)
Unlike bioburden testing, microbial limits testing is used for non-sterile pharmaceutical products to evaluate the microbiological quality of the product and verify that the microbial population remains within acceptable limits defined by the relevant pharmacopoeias.
The test include:
- Total Aerobic Microbial Count (TAMC): enumeration of aerobic bacteria.
- Total Yeast and Mold Count (TYMC): enumeration of yeasts and filamentous fungi.
- Detection of specified microorganisms, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella spp., Candida albicans or bile-tolerant Gram-negative bacteria, depending on the product category and route of administration.
Sterility Testing
(In accordance with Ph. Eur. 2.6.1, USP<71>)
Sterility testing confirms the absence of viable microorganisms in products intended to be sterile. Performed under strictly controlled aseptic conditions, it is a critical quality control test and a key requirement for batch release of sterile biologics and injectable products.
For sterile product testing, our microbiology laboratory includes a dedicated clean room equipped with two 4-glove isolators, a Steritest® Symbio® Pump, and an H₂O₂ biodecontamination system. This advanced isolator technology minimizes the risk of external contamination while ensuring reliable sterility testing in accordance with pharmacopeial requirements.
Bacterial Endotoxin Testing
(In accordance with Ph. Eur. 2.6.14; USP <85> and <86>)
Bacterial endotoxins, originating from the outer membrane of Gram-negative bacteria, may remain present even after microorganisms have been eliminated. If administered to patients, endotoxins can induce severe pyrogenic reactions, making their detection essential for medical products, particulary parenteral biologics.
The selection of an appropriate endotoxin detection method depends on the characteristics of the product and applicable requirements. Multiple validated methodologies are available, including:
- Kinetic Chromogenic LAL
- Kinetic Turbidimetric LAL
- Gel- Clot- assay
- Recombinant Cascade Reagent (rCR)
Rapid Mycoplasma Detection by qPCR: Early Detection for Better Decisions
In addition to conventional microbiological methods, molecular approaches can provide faster detection of specific contaminants. Rapid mycoplasma detection by qPCR is particularly valuable for monitoring cell cultures, cell banks, viral vectors and other biologics, enabling early detection of contamination.
At Kymos, GLP-compliant qPCR-based mycoplasma detection is available to support development activities.
Compared with traditional culture-based methods, qPCR offers:
- Results within hours instead of several weeks
- High analytical sensitivity and specificity
- Early detection of contamination
The increasing adoption of nucleic acid amplification techniques (NAT), including qPCR, is reflected in current pharmacopeial guidance. The revised European Pharmacopoeia Chapter “2.6.7 Mycoplasmas” recognizes validated NAT-based methods as part of the regulatory framework for mycoplasma detection, while the new ”USP <77> Mycoplasma Nucleic Acid Amplification Tests” provides guidance for the validation and application of qualitative NAT methods. These revisions highlight the growing acceptance of PCR-based technologies for mycoplasma detection when appropriately validated for their intended use.
Integrated GMP Microbiology Services for Biologics
Ensuring the microbiological safety of biologics requires more than a single test. The appropriate combination of microbiological and molecular methods depends on the product, manufacturing process, stage of development and applicable regulatory requirements.
Our microbiology laboratory combines state-of-the-art facilities, highly specialized personnel and extensive regulatory expertise to support manufacturers throughout the product lifecycle, from process development and technology transfer to method validation, stability studies and commercial batch release.
This integrated approach helps ensure that microbiological risks are effectively assessed, monitored and controlled while supporting compliance with international GMP requirements, reliable product release and, ultimately, patient safety.
