Issue link: https://www.e-digitaleditions.com/i/1492687
24 Pharmaceutical Technology ® Bio/Pharma Outsourcing Innovation eBook 2023 PharmTech.com Manufacturing technologies like mRNA tech and other complex new biologics can present unique challenges some devel- opers and manufacturers haven't experienced before, particularly as the project scales. The success of delivering these ground-breaking prod- ucts from discovery to market will be underpinned by dedicated scientists performing diligent experimenta- tion with detailed documentation to ensure clarity and understanding for all those involved in tech transfer. Ercoli (BIOVECTRA): The processes for manufac- turing small molecules have been well established over decades, which means that there aren't many surprises when it comes to transferring technology. With biolog- ics, however, there are new techniques arising weekly across the industry. It requires diligence to keep up with these technological advancements while developing new methods ourselves to stay ahead of the curve. Given the constantly evolving nature of biologics, CDMOs [con- tract development and manufacturing organizations] typically exercise more caution when it comes to pro- tecting [their] client's proprietary process information compared to the techniques and processes for manufac- turing small molecules. Patki (Catalent): One key difference is in the com- plexity of the manufacturing process. mRNA vaccines involve several steps, such as synthesis, formulation, and fill/finish. These can be more complex and harder to replicate than the process for small-molecule products. Additionally, mRNA vaccines may require specialized equipment and facilities, which can also add complexity when it comes to tech transfer. Regulatory requirements also differ because mRNA vaccines are a relatively new technology, and the regulatory requirements are still evolving, unlike for most small-molecule products where regulatory pathways are well established. Thassu (LGM Pharma): There are many differ- ences—in fact, you can't really compare small-mole- cule tech transfer with that of complex products, like biologics, in the same breath. It is a completely differ- ent development plan and supply chain for biologics because of their complexity of structure and biolog- ical origin. The processes and technologies for small molecules have been established for decades; a lot of the chemistry is known. Biologics and other complex products like mRNA vaccines are relatively new, so that's not the case—the experience and expertise is limited as we are still learning. Generally, if the prod- uct is complex, then automatically, the tech transfer becomes complex because many different teams and thought processes are involved in the development. Hanenberg (Recipharm) and Powell (Arranta Bio, a Recipharm Company): The tech transfer of mRNA vac- cines and other complex products is more challenging than that of conventional small-molecule drug products. This is because the treatments themselves and the pro- cesses involved in their development and manufacture are more complicated and specialized. Moreover, they are subject to different and stringent regulatory require- ments. Dedicated scientific knowledge and expert tech- nical support are required to ensure that these transfers run smoothly with minimal unnecessary delays. PharmTech: Are there differences between tech transfer from contract manufacturing organization (CMO) to CMO compared to sponsor to CMO? Ercoli (BIOVECTRA): The most important thing for us, as a CDMO, is having access to the drug innovator. This allows us to understand the context in which the development happened and get any answers we need. When we're dealing directly with a sponsor and have access to the innovator, we can work with them to make process improvements, if necessary. When the tech transfer comes from a CMO, we may be unsure of the intention and have to interpret it. It can be like playing the Telephone Game, where somebody transfers infor- mation to the CMO, then they transfer it to us, but the message becomes distorted. Schemel (Catalent): It is often the case that when [changing] from one CMO to another, many of the con- versations revolve around risk assessment of site-spe- cific platform operations. One site may only be able to pack a column to ±1 cm, while another can pack to ±0.5 cm. It is common for sponsors and CMOs to have an open dialogue with sponsors evaluating the risk to the process performance against nonconformity to a site's platform approach to operations, which often results in compromises for both CMOs. York (Catalent): Facility fit analyses between CMOs are the most critical parts of a transfer. Some CMOs use them to mimic transferred processes, while other CMOs focus only on using their existing platforms, regardless of the process. Thassu (LGM Pharma): Yes—and they're significant. Typically, a sponsor chooses a partner CMO that is like an extension of their company with whom they share their knowledge directly. So, tech transfer between sponsor and CMO is smoother, with minimal failures, because the CMO has direct access to the sponsor. When the transfer happens from CMO to CMO, it be- comes more complicated as both are business units that sometimes compete for the same opportunity. Often, information is not transferred satisfactorily because the sponsors are not involved. So, it would be best for the sponsor to have supervision or technical leadership over a CMO-to-CMO tech transfer as either CMO may not know what is critical to the process. Rhodes (Sterling Pharma Solutions): The major difference is the amount of information that is typ- ically shared, and the level of cooperation received from the other party. A sponsor should see a CMO as a partner and will usually treat the relationship as a col- laboration, with open dialogue and regular commu- nication/progress reporting. Conversely, CMOs may