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  1. Science & Research (Biologics)

FDA developing improved methodology for determining purity of probiotic products

Scientists at the US Food and Drug Administration (FDA) provided “proof-of-concept” for a technique that identifies the presence of potentially harmful contaminants in probiotics.

The technique eliminates a product’s beneficial bacteria and allows any potentially harmful contaminants in the product to grow unimpeded, allowing detection of potentially harmful contaminants using standard laboratory methods.

Probiotics, also referred to as live biotherapeutic products (LBP), are products that contain live organisms, such as bacteria, that are found naturally in humans. The most common are bacteria that belong to groups called Lactobacillus and Bifidobacterium. If a probiotic is intended to diagnose, cure, mitigate, treat or prevent a human disease, it is regulated as a drug and a biological product by the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research and an Investigational New Drug application is required to pursue clinical studies in human volunteers.

While over-the-counter probiotics are generally viewed as safe, at least in healthy individuals, clinical studies to assess these products may be conducted in individuals whose defenses are compromised, such as through a disease process, immunosuppressive clinical treatment, or an immature or aging immune system.

Over-the-counter probiotics used in clinical trials to investigate their potential use for various disease conditions require more stringent quality controls to ensure purity and potency of the product. One of the major safety criteria for LBP’s used in clinical trials is microbial purity, i.e., the absence of extraneous, undesirable microorganisms. However, a challenge of detecting unwanted microbial contaminants is that the sensitivity of detection may be reduced in the presence of the desired probiotic microbial organisms. One strategy that is being investigated to increase the sensitivity of detecting the contaminating microbes is to reduce or eliminate growth of the product bacteria. The FDA scientists developed and used recombinant phage lysins as reagents for improved purity assays for LBPs. The development of rapid and accurate tests for determination of harmful contaminants that may be introduced during various stages of manufacture or product handling in LBPs is critical.

In the study, the FDA scientists used “mock” purity assays (“test-tube” studies) where Lactobacillus jensenii represented the probiotic’s product strain, and developed a recombinantly expressed type of enzyme called a lysin. The lysin is similar to one made by certain viruses called bacteriophages, which use lysins to break open infected bacteria so that new viruses made within that microorganism can escape. The scientists used a lysin against Lactobacillus jensenii cells and developed it as a reagent to eliminate these cells from a culture that had been “spiked” with low numbers of organisms representing potential contaminating bacterial pathogens (either Escherichia coli or Staphylococcus aureus).

Reducing or eliminating the L. jensenii enabled growth and thus detection of the lower numbers of contaminating E coli or Staph aureus, which otherwise would not be easily detected. When testing an actual LBP, the goal would be to eliminate the large numbers of a probiotic product’s beneficial bacteria so that any contaminating bacteria present could grow and be detected.

The FDA study forms the basis of a strategy for further development of lysins as tools and reagents to improve purity testing of LBPs, which could help advance product development.

“Development of Phage Lysin LysA2 for Use in Improved Purity Assays for Live
Biotherapeutic Products”

Viruses 2015, 7, 6675-6688


Sheila M. Dreher-Lesnick *, Jeremy E. Schreier and Scott Stibitz

Office of Vaccines Research and Review, Division of Bacterial, Parasitic and Allergenic Products,
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring,
MD 20993, USA

* Correspondence: Sheila.Dreher-Lesnick@fda.hhs.gov

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