Many complex drug products require sterile capabilities leading to increased demand for aseptic manufacturing. Aseptic processing is uniquely challenging as it requires highly trained personnel and specialized facilities and equipment. The FDA requires that drug products delivered via parenteral, ophthalmic, inhaled, or otic route be supplied as sterile products due to increased risk of infection. As these complex formulations become more common, there is an increased need for sterile manufacturing operations, resulting in outsourcing to contract manufacturers. 

According to a new report by Visiongain: Global Biopharmaceuticals Contract Manufacturing Market Forecast 2022-2032: Market Segment by Source, Service, Product, Company Size, Scale of Operations, By Region, the market was estimated to be valued at $12.9 billion in 2021. The worldwide market is expected to witness a CAGR of 8.53% from 2022 to 2027 and is expected to reach $21.0 billion in 2027 from its previous value of $13.96 billion in 2022. 

According to Visiongain analysis, the biopharmaceutical market’s success is primarily due to contract manufacturers, as CMOs can provide advantages such as reduced total investment necessary to bring products to market, access to advanced technology, and faster product entrance into markets, as well as more flexibility, prompting sponsors to outsource their biopharmaceutical manufacture. Additionally, as the biopharmaceutical business continues to grow, organizations are encountering production challenges, such as a lack of experience and advanced equipment, while performing in-house manufacturing, according to the report. 

Catalent’s Paresh Vadgama, Principal Scientist, Biologics Formulation and Drug Product Development, and Dhaval Patel, Director, Manufacturing Science and Technology, address sterile manufacturing trends, current challenges pharmaceutical companies face, and advances in sterile manufacturing processes. –KB 

Contract Pharma: What are some sterile manufacturing trends and/or R&D trends impacting sterile manufacturing?

Paresh Vadgama: Three areas within sterile biologics R&D are currently seeing rapid growth: next-generation antibody development (e.g., antibody-drug conjugates, bi/tri-specific antibodies); new delivery platforms for complex APIs, such as lipid nanoparticles for mRNAs; and of the switching of drug product delivery methods. These, as well as overcoming molecular instability, extreme solution characteristics such as high-viscosity, and the need for preserving sterility during manufacturing (as opposed to terminal sterilization that is not an option for temperature-sensitive formulations), limit the choice of compatible bioprocessing raw materials. 

In manufacturing, the use of end-to-end single use technologies is increasing, allowing shorter timelines by eliminating laborious and costly validation work, as well as reducing product changeover time. In addition, Catalent is seeing growth in the need to process temperature-sensitive products, which need to be stored and delivered using energy-efficient supply chain solutions, as well as the development of novel, safer and stable excipients and potentially re-purposing previously approved, generally recognized as safe (GRAS)-listed excipients for novel biologics.

Contract Pharma: What are some current sterile manufacturing challenges the industry or pharma companies face?

Dhaval Patel: The pandemic changed the way the pharmaceutical industry operated, and its effects are still being felt today. For example, the supply chain is still heavily constrained by longer lead times for critical excipients, components, and consumables that are necessary for manufacturing. Because of this, sponsor companies are looking to diversify their supply chains with a growing reliance on outsourcing partners. As sponsors identify additional partners, there is pressure for these to assist in reducing time to market. In some scenarios, critical resources, whether a process or a material, can be rate-limiting, but the work that was undertaken during the pandemic demonstrated that the pharmaceutical industry can safely accelerate products to patients when it works collaboratively to find and implement creative solutions. 

Contract Pharma: How can the above manufacturing challenges be overcome? Are there any advances in sterile manufacturing processes to combat those challenges?

Dhaval Patel: As sponsor companies continue to outsource, it is important that they keep three factors in mind: efficiency, technology, and experience. An outsourcing partner should have proven sterile manufacturing experience, and be able to demonstrate how its track record has helped take a product from clinic to multiple global markets. That experience could include working on numerous programs, and being able to streamline processes while standardizing equipment to pass on efficiencies to sponsor companies. Some technologies that outsourcing partners may offer could be new to sponsors, so it is important to highlight any advantages that could ultimately mean that a product reaches patients faster.