Live Biotherapeutic Products & Microbiome Manufacturing Market | Industry Analys

1. Live Biotherapeutic Products & Microbiome Manufacturing Market | Industry Analysis | Market Size, 2022-35 The human body is known to harbor numerous communities of microbes, including both beneficial and harmful species, which are collectively referred to as the microbiota. Likewise, the ecological system of commensal, symbiotic, and perhaps pathogenic microorganisms that reside within a host system is called the microbiome. Given the role of the microbiota in both disease development and pathogenesis, the concept of microbiome-based therapeutics has generated significant enthusiasm within the medical science community, defining a new frontier in the field of medicine. In fact, the last two decades have witnessed several developments in the field of microbiome research and their therapeutic applications. However, there are known unmet needs related to manufacturing and research capabilities, quality of products, and time to market, that have restricted growth of this domain to a certain extent. As a result, outsourcing various aspects of product development is gradually emerging as a popular trend for stakeholders engaged in this field. Currently, several microbiome therapy developers prefer to engage the services of an experienced contract service provider, rather than investing in developing novel capabilities in-house. Manufacturing microbiome therapies (including FMTs) is considerably complex as compared to traditional small molecule drugs. As microbiome therapeutics is still in the early stages of development, availability of well-documented manufacturing practices is currently unavailable.

2. Some of the major considerations that need to be addressed for manufacturing microbiome therapies are listed below: ▪Identification of scalable approaches for separation and purification of microbial strains. ▪Development and optimization of cost-effective and chemically modified media. ▪Establishment of secured logistics / supply chain / tracking systems to ensure proper tracking of patient-specific products (within the manufacturing facility and while the product is en route to the clinic). ▪Availability of cryopreservation and cold chain storage facilities (biological products are usually less stable and need to be stored under a specific set of conditions almost immediately post-production). ▪Availability of specialized aseptic fill / finish capabilities, which are compatible for use with biological products. ▪Development of appropriate quality management systems and high-throughput assays to maintain cell-to-cell consistency, with respect to parameters such as phenotype, functionality, quality, and potency. ▪Necessary accreditations and approvals from the concerned regulatory authorities across various regions, to qualify as a biologic’s manufacturer; this includes cGMP compliance certifications as well.

3. LIVE BIOTHERAPEUTIC PRODUCTS:OVERALL MARKET LANDSCAPE The current market landscape features the presence of over 25 well-established players and new entrants that are engaged in the production of live biotherapeutics products, on contract basis. The microbiome contract manufacturing market is currently dominated by the presence of mid-sized players (63%), followed by small firms (18%). Notable examples of well-established players engaged in this domain include (in alphabetical order) Adare Pharmaceuticals, Capsugel and Unique Biotech. Further, most of the manufacturers are presently headquartered in Europe. Within this region, the Netherlands emerged as the key country, featuring the presence of 3 players. Further, North America featured the second highest number of companies engaged in this domain, with US (8) being the base of operations for most of the players located in the region. List of Live Biotherapeutic Product and Microbiome Contract Manufacturers Type of Product Manufactured Type of Fermentation Required Scale of Operation Company Size1 Facility Location Regulatory Accreditation YoE HQ S. No. Name of CMO Capacity API FDF Preclinical Clinical Commercial Aerobic Anaerobic 20L,300L- 3,500L ANSM, KFDA, Minzdrav FAMI, KFDA, PMDA, Swissmedic, USFDA ANVISA, EMA, Health Canada, KFDA, USFDA 500L 1 Company 1 1951 Mid-sized P P P P P P P 8,000L 2 1976 Mid-sized P P P P P P Company 5 1,750L 5 2018 Very Large P P P P P P P Distribution by Company Size and Location of Headquarters Company 8 8 2006 Mid-sized Distribution by Type of Formulation2,3 P P P P P Company 11 11 1963 Large P P P P P Oral Liquids 70% 74% 1948 Mid-sized 12 P P P P North America P 7% 11% 11% Solids 15 Company 15 2016 Small P P P P P 18 Company 18 2001 Large P P P P Europe P 7% 33% 4% 19 Company 19 1985 Small P P P P P 21 1978 Small P P P P P Injectables 11% 4% 23 Company 23 1987 Mid-sized P Asia- Pacific Others P P P P 4% 19% 4% 25 Company 25 2001 Large P P P P P 27 Company 27 2012 Mid-sized P P Small Mid-sized P Large and Very Large P P Abbreviations: ANSM: French National Agency for Medicines and Health Products Safety, ANVISA: The Brazilian Health Surveillance Agency, EMA: European Medicines Agency, FAMI: Feed Additives and Pre-mixtures, HQ: Headquarters, KFDA: Korea Food & Drug Administration, Minzdrav: Ministry of Health of the Russian Federation, PMDA: Pharmaceuticals and Medical Devices Agency, TFDA: Taiwan Food and Drug Administration, USFDA: United States Food and Drug Administration, YoE: Year of Establishment Note 1: Small companies: Less than 50 employees, mid-sized companies: 51-500 employees; large companies: 501-5,000 employees; very large companies: more than 5,000 employees Note 2: Companies offering more than one type of formulation have been counted multiple times Note 3: Others category includes formulations which could not be categorized in the aforementioned segments In fact, most of the contract manufactures engaged in this domain are currently formulating microbiome therapeutics in liquid form (20). The predominance of this segment can be attributed

4. to the lower cost, ease of manufacturing, and patient’s adherence to such medications. This was followed by players offering microbiome-based therapeutics in solid form (19); examples of such players include Cabrios-Pharma, ProbioFerm and Probiotics Australia. During our research, we came across 27 industry players that claim to be engaged in the manufacturing of microbiome-based biologics for therapeutic purposes. Notable examples of well- established players engaged in this domain include (in alphabetical order) Adare Pharmaceuticals, Capsugel and Unique Biotech. It is evident from the figure that majority of the companies are offering fermentation services (96%), followed by companies offering fill-finish (89%) and analytical services (74%). Considering the cost and time required in these processes, if performed in-house, several microbiome therapeutic developers tend to outsource such operations. It is also worth highlighting that only two players claim to be capable of offering all service; these are (in alphabetical order) Boise and Wacker Biotech. Most of the CMOs (13) have the required capabilities to operate at all scales of operation, followed by those capable of operating at both clinical and commercial scales (7). This can be attributed to the fact that stakeholders engaged in this domain are actively striving to adopt the one-stop-shop model and provide end-to-end services to customers based across the globe.