Manufacturing is one of the biggest bottlenecks faced by microbiome companies. Despite decades of experience growing bacteria to produce biologics, there is actual very limited experience in manufacturing live bacterial therapies within GMP environments, which is essential for pharmaceutical products.
For example, when Lonza formed a Joint Venture with Chr Hansen to accelerate development in the microbiome space, they quickly acquired microbiome expertise and capacity that might have taken them a lot of time to build organically; unfortunately, Chr Hansen’s experience is not in GMP environments but rather in manufacturing agricultural products, where being cGMP compliant was not necessary. This means Lonza and Chr Hansen will have to invest considerable sums to upgrade cGMP-compliant pharma production capabilities.v
This shortage of manufacturing capacity is especially important for companies working on intestinal microbiome strains, which represent the majority of companies in space. As gut microbes require low-oxygen culture conditions and produce spores that can contaminate other cultures, high standards must be applicated during production.
Developing manufacturing standards will be key in this space, as they will be highly scrutinised by regulatory authorities, especially when one considers the batch-to-batch variations that are implicit with living organisms. Live culture compositions will need to be standardised to demonstrate to regulatory bodies that reproducibility is possible. Other key concerns will likely include potency (the quantity of product require to obtain desired efficacy); purity (no detectable pathogens); and identity (the presence of certain organisms, especially when those being responsible for therapeutic effect are not identified).
Further requirements will most likely include additional containment areas to ensure “clean” areas remain sterile: as M. John Aunins, from Seres Therapeutics mentioned his presentation on manufacturing considerations for microbiome -based productsvi: “you really have to make sure that you've got unique facility designs that have appropriate classifications, that have appropriate pressure gradients, so that you can both keep bugs you don't want out, keep your bugs in.” Final considerations will have to be made to demonstrate that beneficial effects are still present when the product gets to the consumer and through to the expiration date of the product.
Going forward, some other ideas manufacturers can explore include minimizing the use of reusable equipment (to limit the chance of cross contamination), use extensive decontamination procedures to make sure that they address concerns of cross-contamination and making sure the environmental testing will actually address the microbes being produced.
Australia Therapeutic Goods Administration (TGA) has proposed a framework for regulating faecal microbiota transplant (FMT) products by suggesting a risk-based approach to regulating FMT products. Under the proposal, the TGA will treat minimally manipulated FMT products as Class 1 or Class 2 biologicals, depending on whether they are manufactured in the treating hospital or remotely for shipping to a healthcare facility. These regulations will form the basis of key, general requirements, such as the standards the TGA will require of hospital-based manufacturing facilities. As producers of Class 1 biologicals, hospitals will be exempt from good manufacturing practices, since it is believed that proximity and immediacy of the biological production unit to where it is used addresses key concerns around long-term stability of microbiotic therapeutics.vii
The microbiome therapeutic space presents both major opportunities and challenges for the coming years. While it is easy to measure the markets growth and the growing costumers’ interest in microbiome therapeutics, important challenges around regulatory approval and manufacturing practices need to be solved.
As big pharma gets increasingly interested in this market, devoting some of its considerable resources to this space, we can expect a more structured industry going forward and, in collaboration with regulatory agencies, the necessary frameworks which enable the growth of this once very niche industry.
i Newman, Tim. “How 'good' viruses may influence health”, January 6th, 2020, https://www.medicalnewstoday.com/articles/327167 (Last Visited 18th of February 2020).
ii Forbes and al. A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease? Frontiers in Microbiology, January 9th, 2019. https://www.frontiersin.org/articles/10.3389/fmicb.2018.03249/full (Last Visited 18th of February 2020).
iii Burrows, Andrew. The state of manufacturing and commercialization of microbiome therapeutics - Data report analysis, November 2019. https://informaconnect.com/manufacturing-commercialization-microbiome-therapeutics/ (Last Visited 18th of February 2020)
iv Moodley, Thunicia and Mistry, Erin. Could the Gut Microbiome Revolutionize Medical Care? Current Status and Initial Considerations for Successful Development and Commercialization of Microbiome Therapies. Syneos Health, April 2019. https://www.syneoshealth.com/sites/default/files/documents/Syneos_Health_Consulting_Microbiome_1_April_2019.pdf (Last Visited 18th of February 2020).
v Press Release, Bloomberg. “Lonza and Chr. Hansen in Joint Venture to Accelerate Momentum in Microbiome”, Bloomberg, Aril 2nd 2019. (Last Visited 10th of February 2020).
vi United States Food and Drug Administration / National Institute of Allergy and Infectious Diseases. “Science and regulation of Live Microbiome-Based Products used to Prevent, Treat and Cure diseases in humans”, Rockville, Maryland, Friday, April 19, 2019 Website: https://www.fda.gov/media/128302/download (Last Visited 10th of February 2020).
vii Taylor, Nick. “Australia proposes manufacturing standards for faecal transplant products” 28th of November, 2019. Website: https://www.biopharma-reporter.com/Article/2019/11/28/Australia-proposes-manufacturing-standards-for-faecal-transplants (Last Visited 10th of February 2020).
