Investments in new microbiome therapies as medicinal products continue to be on the rise and are attracting large Consumer Health giants such as Nestle Health Science, as well as Big Pharma.  While the pipeline continues to grow, the FDA and other regulatory bodies are struggling to define guidance and enforce safety for this growing therapeutic area.  Concerns regarding the safety of microbiome therapies have caused the FDA to pause a number of clinical trials. In June 2019, two patients became severely ill after receiving a transplant from the same contaminated donor sample, resulting in one fatality. Microbiome therapies are designed to restore gut health for people with severe health issues, but faulty samples have demonstrated an increased risk of severely endangering patients.

Manufacturers are also having difficulties finding ways to scale-up production while maintaining sample safety. Furthermore, the FDA has yet to finalize its guidance for FMTs (fecal microbiota transplants). However, biotech companies can prepare for future legislative action and prepare to resume clinical trials by ensuring their screening and manufacturing methods are optimized for patient safety.

Despite setbacks, the field of microbiome therapies has enormous potential to treat various diseases and generate revenue. The global market is expected to have a CAGR of 14 percent, with applications ranging from treatments for C. Diff infections, Crohn’s disease and IBS to diabetes and post-chemo treatments. Treating persistent C. Diff infections is the most common use of FMTs, with the therapy demonstrating an effectivness rate of 90 percent. Since these infections affect half a million Americans yearly and cost the US $5 billion in healthcare, reducing the disease burden has significant impacts.

State of FDA Regulations

Whether the FDA will choose to regulate FMTs as pharmaceutical drugs or tissue transplants will affect how therapeutics companies structure their quality and regulatory operations. A group of leaders in GI medicine petitioned the agency to regulate the therapy as a transplant, while others in the industry would rather see it treated like a pharmaceutical product to ensure that long-term monitoring and rigorous clinical trials are being conducted. Draft guidance released in 2016 by the FDA allows manufacturers to use organ transplant protocols for therapies aimed at C. Diff infections, since early research indicates the treatment is promising. However, any other uses of FMTs require applying for IND status.

Manufacturing Best Practices for Microbiome Therapies

Without current guidelines for the screening, preparation, and storage of samples, the biotech industry has the opportunity to be proactive and form their own best practices for manufacturing at a level of excellence. The more types of bacteria used for a single therapy, the more manufacturing processes companies will have to design. For example, Vendanta Biosciences had to create eight-to-twelve processes in order to target various bacterium according to the individual thicknesses of their walls.

While not as expensive to make as cell therapies, microbiome therapies still cost more to manufacture than other traditional types of treatments.  As clinical trials start moving into Phase II and III, biotech companies will need to decide if a CMO would be equipped to handle these kinds of orders or whether to invest in building their own facilities. CMOs often excel at creating sterile environments, which is ironically counter-intuitive to microbiome therapy production, which requires bacterial growth. By lowering oxygen levels to cater to FMT products, CMOs could be putting their other products at risk.

Screening Protocol Best Practices

Due to the enormous biodiversity of microorganisms found in each person’s GI system, the world of gut health is complex and only partially understood. Bacterial strain typing is continuously improving, and researchers are continuing to look for tools to identify bacterium in inexpensive and accurate ways. As research progresses, biotech companies will want to consider changing their screening metrics to reflect the most up-to-date understandings. By investing in metagenomics studies, manufacturers may be able to better understand potential risk factors to screen for.

One of the most important factors involved in patient safety is the institution of rigorous, evidence-based screening methods. Banks operated by organizations such as OpenBiome provide many of the samples that hospitals use to fight C. Diff infections. Since research proves that samples from “unknown” donors are just as effective as samples from biological relatives, screening for contaminates should take precedence.

According to current protocols, donors undergo blood and stool tests before receiving clearance. In addition to basic-level tests, manufacturers should consider screening for viral infections to ensure their product is safe for immuno-compromised patients. Screening the donor again sixty days after they give a sample is another way to prevent the accidental use of a contaminated sample.

Like with any new drug or therapy, manufacturers realize that they must manage patient risk factors with the potential benefits of a treatment. By staying up-to-date on the best screening methods and crafting specialized manufacturing processes, biotech companies have the best shot at meeting the FDA’s current standards and moving their microbiome therapies down the pipeline.

Contributions by Sabrina Zirkle and Courtney Loughran.