Streamline Microbial QC Testing in the Pharmaceutical Industry with MicroQuant™

The importance of microbial QC testing

Microbial contamination of drug products is a serious concern in the pharmaceutical industry and is one of the leading reasons why products are recalled by the US Food and Drug Administration.^3,4 The release of contaminated products can significantly affect patient health and safety and may result in permanent disabilities or potentially life-threatening conditions. The subsequent recall of these products is equally damaging for patients that rely on the medication for a chronic condition.³ For the manufacturer, recalls can lead to extensive financial losses, regulatory consequences, brand erosion, and reputational damage.³ To mitigate these risks, the implementation of robust quality control programs is essential.

Global regulatory bodies such as the United States Pharmacopeia (USP), European Pharmacopoeia (EP), and Japanese Pharmacopoeia (JP) have mandated that various quality control tests be performed throughout the development and manufacturing process. These include tests such as environmental monitoring, growth promotion testing, bioburden testing, sterility testing, and suitability testing, among others.^5-9 When properly followed, these procedures can help identify microbial contamination prior to product release, thus helping to avoid the pitfalls of product recalls.

Challenges when using microbial reference materials

The accuracy of any microbial QC test is dependent on the quality of the reference materials used. That’s why each of the pharmacopeia specifies a preselected list of fully authenticated and characterized microbial strains from a national culture collection as control input organisms. The USP, for instance, recommends the use of controls that are maintained by well-renowned culture collections like ATCC. ATCC meets the needs for microbial QC testing by providing reference materials that are not only fully authenticated but also managed under seed-lot culture maintenance techniques.

While identifying which reference materials are needed for testing is straightforward, pharmaceutical manufacturers and testing laboratories often face challenges when it comes to storing, handling, and quantitating the controls. For instance, when performing marketing research, we discovered that many of our customers choose to develop and maintain their own internal control banks of reference materials. Generating these control banks frequently requires complex expansion protocols, well-trained staff, and extensive laboratory space and equipment.

Storage of these internal control banks is also a concern for our customers. In many instances, controls are frozen as it is a simpler preservation method than lyophilization. However, while freezing microbial strains is an optimal storage method, if it is not done correctly the strain can be at risk for damage due to ice crystal formation and osmotic excursion. Further, ultralow and cryogenic freezers can be expensive to purchase, run, and maintain. There are also added uncertainties related to freezer performance and given the high cost associated with maintenance of the freezers, they are frequently considered to be capital investment by the end users.

Precise quantitation of microbial reference materials is another predominant challenge. Several USP chapters specify that reference materials be prepared in either low-titer (10-100 CFU/mL) or high-titer (~10⁵-10⁸ CFU/mL) formats. Meeting these required formats as well as consistently maintaining the correct quantitation between lots can be difficult to achieve.

While there are quantitated single-use products for microbial QC testing available on the market that can help alleviate some of these issues, they are not without their own unique set of challenges. For instance, while the single-use format enables easier handling of microbial reference strains, the controls often can’t be used immediately as they can require up to an hour to process before plating can occur. Consistent quantitation is also a problem; when speaking to our customers and performing our own internal studies, we discovered that several of these products demonstrated poor quantitation accuracy and consistency. Lastly, the single-use products available are derived from strains acquired by culture collections such as NCTC or ATCC; they are not original source materials. This can raise questions regarding passage history and how the materials were handled.

What’s the solution?

The labor, expertise, equipment, and space needed to generate, maintain, store, and quantitate internal control banks can be considerably costly in time and money. While single-use products provide a solution for streamlining microbial QC testing, available controls have demonstrated limitations regarding processing time, consistent quantitation, and passage history. At ATCC, we believe there is a better way.

When time and resources are limited, pharmaceutical manufacturers need full confidence that their reference materials are authenticated, low passage, and precisely quantitated as well as easy to use and store. That’s why we are looking toward the future and incorporating next-generation cryobiology technology to improve the format, usability, and stability of our best-in-class reference materials. Our new MicroQuant™ products enable you to streamline your microbial QC testing with confidence.

Introducing ATCC^® MicroQuant™: A single-use, quantitative format that delivers consistency you can count on

Leveraging an innovative cryopreservation technology, our new MicroQuant™ products come in the form of stable, rapidly rehydrating pellets that deliver consistent quantitation and accurate, reproducible results—addressing the key challenges faced by microbial testing laboratories. This novel product suite enables simplified workflows and quick turnaround times while adhering to strict quality standards. With nearly a century of enabling scientific progress, this new ATCC offering represents the latest step in empowering innovation, collaboration, and trust through industry-leading microbial testing solutions.

References

1. Smith ZP, DiMasi JA, Getz KA. New Estimates on the Cost of a Delay Day in Drug Development. Ther Innov Regul Sci. Online ahead of print, 2024. PubMed: 38773058
2. Phuong JM, et al. The impacts of medication shortages on patient outcomes: A scoping review. PLoS One 14(5): e0215837, 2019.
3. Hock SC, et al. Contamination Trends & Proposed Solutions. Pharmaceutical Engineering April 2023. Accessed online: https://ispe.org/pharmaceutical-engineering/march-april-2023/contamination-trends-proposed-solutions  
4. Patel R, et al. A retrospective regulatory analysis of FDA recalls carried out by pharmaceutical companies from 2012 to 2023. Drug Discov Today 29(6): 103993, 2024.
5. USP General Chapters. <51> Antimicrobial Effectiveness Testing. In: USP-NF. Rockville, MD: United States Pharmacopeia. DOI: https://doi.usp.org/USPNF/USPNF_M98790_03_01.html
6. USP General Chapters. <60> Microbiological Examination of Nonsterile Products Tests for Burkholderia Cepacia Complex. In: USP-NF. Rockville, MD: United States Pharmacopeia. DOI: >https://doi.usp.org/USPNF/USPNF_M12455_02_01.html
7. USP General Chapters. <61> Microbial Examination of Nonsterile Products: Microbial Enumeration Tests. In: USP-NF. Rockville, MD: United States Pharmacopeia. DOI: https://doi.usp.org/USPNF/USPNF_M98800_01_01.html 
8. USP General Chapters. <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms. In: USP-NF. Rockville, MD: United States Pharmacopeia. DOI: https://doi.usp.org/USPNF/USPNF_M98802_01_01.html 
9. USP General Chapters. <71> Sterility Tests. In: USP-NF. Rockville, MD: United States Pharmacopeia. DOI: https://doi.usp.org/USPNF/USPNF_M98810_01_01.html