CROs, Strategy, and Sustainable Testing: Navigating Formulation Development for Biologics
Manoj Pal is a Senior Principal Scientist at Ambrx, a company working on creating a novel technology for site-specific antibody–drug conjugates optimized for safety, efficacy, quality, and biophysical properties. At Formulation US 2022, Pal moderated the panel discussion Formulation Development for Biologics. He mentioned that the DS and DP (drug substances & drug product) and intermediates used in all their clinical programs were manufactured using contract research organizations (CROs), whose relationship to pharma companies is critical for formulation development.
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Pal said that biologics encompass a huge area of molecules, from polysaccharides, to proteins, to nucleotides. The FDA defines them as anything that can be obtained or produced in an organism. Therefore, the landscape of the formulation of biologics, its excipients and process, are huge and diverse.
Present Day Challenges of Biologics Formulation Development
The first topic that the panellists discussed was what they considered to be the main challenges for the formulation development of biologics. Kejin Zhou, Founder and CEO of Reinvigoron TheraTech, was first to speak on this issue and stressed the importance of understanding the prospective product and the indication that it sets out to treat.
Also significant, said Zhou, was the way in which stability is monitored in the development process: “this is dependent on the assays that you have developed, can these assays give you exact results?” For instance, with antibodies, aggregation causes big problems with immune response. Therefore, the formulation team must be particular about the excipients that they use to avoid aggregation.
Pal added that another issue was that biologics often have products which are not homogeneous, and so there can be components within a formulation which are unknown. He stated that this was a very different predicament to small molecule drugs, and therefore different approaches were needed.
Strategies for Managing Biologics Formulation Development
Synergistic Strategising
Pal then asked what strategies our panel felt were useful when managing formulation development. He offered that the syndication of strategy between formulation team and CRO was critical for development. “The innovator will usually work on the formulation for an extended period of time,” he explained. “When it is decided to move ahead with a formulation, the strategy is transferred to the CRO where the formulation can be finally verified before adoption.”
Knowledge from the formulation team is transferred from the pharma company for the CRO to then build upon. As CROs typically have their own expertise in biologics formulation development, their own thoughts and conceptions of these strategies come with it. Pal said that it often emerges that the findings of the CRO are slightly different than what the team initially evaluated. “Therefore, challenges can emerge in trying to figure out what is right.”
Promoting Partnership
In Zhou’s experience with CROs, he has found it helpful to think about CROs as a partnership. Therefore, choosing a CRO to partner with is an important process. “I like to choose maybe ten CROs to start with and then narrow them down based on interviews and their specifications,” he said. Zhou recommended taking note of the ways that a CRO can help development of the product and what assays are available.
Collaboration between pharma company and CRO sees its strongest benefits once a CRO has been chosen and fruitful communication has been established. Zhou said that the question after that is “how you can solve the problem together and take on board their concerns as well as your own. The key is communication and expectation.”
Pal added that timing is also an important aspect to include in planning partnerships with CROs — “we are always short of time to push through with the project.” Suggestions from CROs regarding modifications and optimisations to the project, may actually speed up the timeline into the clinic. Furthermore, at later stages such as phase II and III, Pal recommended considering very deeply the need to make compromises to speed up the process versus the quality of the product.
Licencing Issues When Working with CROs Across Continents
The final topic introduced by Pal was the impact of licencing issues when working with CROs that are accountable to other regulatory bodies. “If we have a cell-based assay and our CRO is in India, China, or the UK performing those assays, we need to comply with the licencing agreements in transferring cell-lines, reagents, et cetera.”
Due to the discrepancy of regulatory bodies, delays, and disturbances with obtaining licences or transferring cell lines may be incurred. In some cases, there can also be issues with transferring material back to the pharma company for in-house activities like clinical compatibility and comparability studies for different lots.
Formulation & Delivery 2023 will welcome key leaders across two cutting edge programmes highlighting new strategies for optimising biologic and chemical formulations, the latest developments in drug delivery and combination products, and the novel developmental strategies and technologies for a range of innovative new therapeutic modalities.
