The biopharma landscape is forever changing, and with it, a demand from both patients and investors for the rapid development and progression of drug products to market. Analytical testing is a crucial part of this process and must be carefully considered when striving for a speedy development timeline while maintaining safety for patients.
Well-designed analytical testing of biologics is essential during every stage of biopharmaceutical development to ensure the safety and quality of the drug and provides an important feedback loop during development. The complexity of biologics means meeting the stringent regulations surrounding their approval is often more challenging than small molecule therapeutics, emphasizing the importance of a robust approach to their analysis.
Tactics and Strategies for analytical success
Meeting the specifications and regulatory requirements for biopharmaceuticals can be a challenging task, requiring a high level of knowledge of the pharmaceutical space and practical expertise. Understanding the mechanism of action and the way the medicine is intended to be delivered to the patient can help guide the levels of analytics needed. Often, for similar proteins, such as mAbs or mAb derivatives there is a standard set of analytics applied. However, the details related to delivery can alter the testing strategy along with the knowledge gained by testing from early development through scale up. For example, a molecule showing susceptibility to aggregation at early production in transients or pools can potentially be remediated by different handling and formulation strategies.
The importance of analytics
During biopharmaceutical development, analytical testing is a critical process. Targets are set by developer-defined critical quality attributes (CQAs) based on the biological activity, impurities profile or potency of the drug product (DP) or drug substance (DS).
Analytical testing also plays an important role in biopharmaceutical regulations. Regulatory bodies require drug developers to identify and define the CQAs of their product to ensure the drug is stable throughout development and manufacturing, and again, is safe for patient use. Performing analytical testing is essential to meet regulatory expectations as mandated by the U.S. FDA, EMA, and PDMA. This testing produces the certificate of analysis (COA) of drug substance (DS) and drug product (DP), ensuring they meet target ranges of biological activity/potency, impurities profile, purity and identity. As regulatory requirements of the FDA and GMP requirements for biopharmaceuticals, analytical testing ensures products reach patients safely and efficiently.
To achieve this efficiency, the drug development and manufacturing process is tightly regulated. It is essential to have established stages of analytical testing during this process to control the final drug product. To avoid delays in development and manufacturing, analytics are key to minimizing process changes and keeping the CQAs within set parameters.
Biologic drug developers must consider adopting the following tactics and strategies to enable analytical success.
1. Choosing appropriate bioassays
When considering analytical testing, an appropriate range of physiochemical and functional assays for release, in-process control/monitoring, protein characterization, and stability studies are needed to deliver products to market efficiently.
A selective, physiologically relevant bioassay is essential for biopharmaceuticals. Selecting the appropriate bioassay is not only challenging because of the need to mimic the mechanisms of action (MOA), but also because bioassays can be costly to develop, perform and maintain. Often, a phased approach is adopted. Support based on developing bioassays and binding assays such as enzyme-linked immunosorbent assays (ELISAs), surface plasmon resonance (SPR) techniques, and in particular cell-based bioassays, are needed when planning analytical testing.
2. Consider introducing more sensitive testing
Improvements in analytical technologies have provided increased capabilities to examine proteins, cell lines, raw materials, and pharmaceuticals seamlessly throughout the drug development and manufacturing process. Analytical testing is moving towards a focus on methods that are highly sensitive, with low limits of detection. This will reduce the use of important drug products during analysis, which is beneficial to both patient and manufacturer as it can reduce production costs during analytical analysis. Introducing techniques such as high-performance liquid chromatography (HPLC) into analytical analysis is an excellent example of biopharma companies adapting to more sensitive techniques.
3. Adopting a holistic approach to pre-formulation
Formulation development is often conducted by performing high throughput screening, to evaluate solubility and conformational stability of different formulations. While this approach is standard, sometimes the correlation between thermal stability and conformational stability is not represented. This should be taken into consideration, and if needed, formulation development should be altered appropriately.
A more holistic approach should be by investigating the thermal stability of the product in a designated final drug product container using reliable stability-indicating assays. These are straightforward, and more directly correlated with the conditions encountered in the product life cycle.
4. Transparent communication with specialists
Transparency and open communication are important when planning outsourced analytical testing. It is important to communicate expectations and observed timelines, to ensure that products go through analytics smoothly. Experienced CDMOs prefer to assign dedicated scientists to each project who will lead development from planning execution, all the way to analysis, ensuring that turnaround time is rapid.
Choosing a tailored and personalized service for analytical testing
When performing analytical development, it is important to consider the use of a CDMO offering a full range of technical capabilities. Transparency and open communication are key to maximizing these services during biopharmaceutical development. Working alongside an established CDMO who assigns experienced scientists to projects and understands the upstream and downstream development processes can drive the critical quality of biologics analytics. In turn, these analytics can be used to efficiently drive the development process forward. This is especially important where rapid timelines are needed, with the ability to incorporate pre-formulation analytics into formulation development alongside stability testing highly desirable.
Bora Biologics specializes in a range of processes including formulation development and analytical testing, which can be tailored specifically to the client’s needs. Each project will come with its own unique set of challenges, and we are perfectly suited to deal with this in-house.
For a trusted partner to make success more certain for your breakthrough drug, get in touch with us today.