How important are bioanalytical studies for new biologics?
When creating new biologic molecules, careful analysis is needed to determine factors like dosage, safety, toxicology, and efficacy. Without bioanalytics, crucial data points could be missing from new drug development, leading to lost money and time down the line. Beyond the function of the drug itself, bioanalytics offers key information to regulatory bodies that can also speed up development or kill potentially harmful drugs faster, allowing researchers to move on or modify their drug.
We spoke with Charles River employees Keith Sutton, Scientific Advisor, Immunobiology, and Iain Love, Director, Chromatographic Bioanalysis. Their combined experience working with many clients in this field helps shed light on the importance of bioanalytics.
Why is it so important to conduct bioanalytical studies during the development process of a new biological therapeutic?
KS: Compared to new chemical entities (NCEs) timely delivery of the nonclinical programs to support first in-human (FiH) studies for Biologics and Advanced Therapies requires a much closer interaction between toxicology and bioanalytical teams. So, an early understanding of the bioanalytical endpoints required is important, as these often impact the design of toxicology studies.
IL: The intelligent design of bioanalytical studies is of critical importance in the development of biologic therapies. The bioanalytical phases of a development program help define and shape pivotal safety studies and decision making. As the analytical support for biologic development is often platform diverse or more nuanced than a typical NCE development it is important to engage with the bioanalyst as early as possible and throughout the development program.
What type of data/information in particular does the FDA require from bioanalytical studies?
KS: All bioanalytical methods must be fit for purpose. For chromatography and ligand binding assays, the published guidance clarifies expectations for method validation. A challenge for Biologics and Advanced Therapeutics programs is that there is often a requirement to use bioanalytical approaches not covered by this guidance; flow cytometry, PCR, or ex vivo/in vitro culture systems. The clear documentation of the development phase is often of increased importance as key data that informs the validation approach is often derived from this phase.
IL: All regulatory bodies require bioanalysis to robustly answer the challenging questions posed by drug development. In 2018 the FDA published refreshed guidance concerning bioanlytical method validation for chromatographic and ligand binding assays. Though this serves as a great set of instructions to support routine bioanalysis, challenges remain for other contributing bioanalytical disciplines such as immunology or molecular biology. In these cases, regulatory authorities expect to see robust program decision making underpinned by data that is of appropriately high quality. In this respect early engagement with regulatory authorities and bioanalytical personnel versed in current best-practice is invaluable in developing strategies for in biologic therapy development.
What types of approaches or strategies are best to plan out early on in the drug development process?
KS: For any bioanalytical method, be it classified as pharmacokinetics (PK), pharmacodynamics (PD) or biomarkers, the earlier in the process the criteria for each assay is determined the better. This includes the identification of the analytes, availability of reference standards, and the experimental platform to be used for each. Even when internal capacity exists, early feedback from external partners can facilitate decision making.
IL: Drug development is a long and complex process. Early consultation with bioanalytical personnel in the design of the analytical support is crucial to ensuring programs can be delivered in an efficient and effective manner. The program design, the analyte itself, the analytical platform, and sourcing of reference standards are all examples where a partnership between drug developers and bioanalysts will yield program benefits.
Are there any “best practices” procedures you can recommend for beginning a bioanalytical study program for a new therapeutic?
KS: A few things stand out. Firstly, consider bioanalysis within the context of toxicology study design – a common mis-step is to assume that bioanalysis is secondary and can just ‘fit-in’ around the in vivo phase. Secondly, don’t over complicate the analysis; for any bioanalytical endpoint the key question is translatability; differentiate between need to know and want to know. Finally, be prepared for the challenges when applying novel bioanalytical platforms or pushing techniques to their technical limits; good communication with the bioanalytical team is vital.
IL: In the development of biologic therapies it is “best practice” to consider the bioanalytical program in parallel with the supported study. It follows that the bioanalysis involved in support of an in vivo toxicology study should be discussed at the point where the in vivo study is being planned. The inter-dependency of the in vivo design and the analytics sensitivity requirements, for example, may influence the sampling process, or the capture of appropriate biomarker data may impact the sampling timings. Study deliverables should also be carefully considered due to the complexities involved with biologic modalities. While it may be beneficial to capture many endpoints within a single study protocol the veracity of the critical endpoints should not be compromised in the pursuit of value adding data.
Why is it important for some biopharma companies to partner with an outsourcing partner for the purpose of bioanalytic studies?
KS: An experienced bioanalytical partner consulted early can save both time and money. They can help forward planning: what assays will you need and when. They can provide input and guidance on choices of technical platform and assay validation criteria for methods outside regulatory guidance.
IL: Partnership with a bioanalytical provider can bring about a number of tangible advantages from simple access to appropriate analytical platforms to receiving advice on planning the development program. Outsourcing partners are also likely to be able to apply experience gathered from across a broad portfolio of modalities and biologic development scenarios that can inform program decision making. More than ever bioanalytical science is involved in shaping programs, so careful selection of an expert outsourcing partner is an activity that can bring about the significant benefits involved with an accelerated drug development program.