Issue link: https://www.e-digitaleditions.com/i/1499694
30 BioPharm International ® Partnerships for Outsourcing eBook May 2023 www.biopharminternational.com Fill/Finish In response to the pandemic, CDMOs began to adapt and expand their capacities and broaden their capabil- ities. Achieving this was no simple task and presented many difficulties. With careful organization, exper- tise, and applying the right strategies, many compa- nies are now well placed for the future. mRNA paves way for future technologies Wit h relat ively si mple ed it i ng, m R NA ca n of fer "plug-and-play" applications. This characteristic has opened the door to their use in various therapeutic areas. mRNA technologies currently in the develop- ment pipeline include those targeting rare diseases, autoimmune disorders, and various cancers (3). Con- sequently, the global market for mRNA therapeutics is predicted to continue to rise—increasing f rom $46.7 billion in 2021 to $101.3 billion by 2026, at a compound annual growth rate of 16.8% (4). As a result, those organizations that responded to meet rising f i l l/f in ish and cold chain capabi l- it y dem a nd s a re we l l-posit ioned to h a nd le t he predicted r ise in m R NA product ion needs in t he f ut u re. CDMOs w it h t hese ad apted capabi l it ies will also be aligned to support another area in bio- pharma expected to see expansion: the cell and gene therapy (CGT) space. Strategies for new drug modalities The flexibility and adaptations manufacturers had to offer in response to the demand for vaccines during the pandemic were not easy to achieve. Tack ling the challenge of global vaccine production relied on strategies incorporating three key areas. Firstly, man- ufacturers had to solve the challenges of implement- ing and/or expanding vital cold chain and fill/finish capabilities. While doing so, CDMOs had to maintain a transparent relationship with their sponsor to help build an understanding of a novel technology. Considering cold chain capabilities. As the types of cold chain capabilities required for each individ- ual biotherapeutic project can vary greatly, manufac- turers embracing the challenge of producing mRNA technologies had to carefully determine how certain factors could impact cold chain processes. Selecting the right primary packaging. There are many types of containers that are used during cold chain processes, from bottles and vials to bags and cryovials. When determining the right container, the decision will primarily rely on the product owner's platform. How- ever, the chosen container must also align with the oper- ations of the CDMO partner. When working with mRNA technologies, manufacturers had to offer flexibility to their clients, potentially offering the use of an array of different containers to ensure the success of the project. Another impor tant consideration was how the container materials could inf luence the product. Whether containers were made from plastics or glass, manufacturers had to determine the extractables and leachables that could be expected and anticipate how they could be removed. Handling multiple types of freezing and storage. In biologics production, there are typical ranges for freez- ing products. However, being able to handle multiple types of storage capabilities and having the necessary standard operating procedures (SOPs) for each is often key to success when working with new technologies. Despite generally standardized freezing tempera- tures, the rate of freezing required can vary depending on the product. For some biologics, it has been reported that slower freezing rates can cause high levels of cryo- concentration, leading to molecular structures becom- ing damaged. Cryoconcentration is a particular problem when using blast rate freezers, which tend to have slow freezing rates throughout the bulk of liquid products. As a result of compression of the core volume by a slowly advancing solid-frozen phase, the stability of sensitive products within the bulk can be affected. Alternatively, control-rate freezers can minimize po- tential damage by controlling the cooling rate at specific points of freezing. Although these types of freezers can offer consistency between batches in certain parame- ters (including the degree of supercooling), control-rate freezers can be difficult to work with, requiring the ma- nipulation of various probes and containers. Validating cold chain capabilities. The global nature of the pandemic meant that it was vital that manufac- turers considered both static and dynamic handling validations of cold chain capabilities during storage and transport. The US Pharmacopeia (USP) <1079> "Good Storage and Shipping Practices for Qualification" offers guidance in this area, describing best-practice proce- dures for maintaining storage environments to safe- guard a preparation's integrity. Static validations are required for the handling of the drug substance (DS) on-site. In these environments, temperature excursions are typically less likely due to more robust temperature controls. On the other hand, dynamic validations, which are associated with off-site In response to the pandemic, CDMOs began to adapt and expand their capacities and broaden their capabilities.