Accelerating Biologics Therapeutics with Bioassays: An In-Depth Discussion on the Essence of Bioassays Implemented for Drug Development

Eurofins DiscoverX, in conjunction with Drug Target Review, sponsored and moderated a Bioassay roundtable discussion webinar with group leaders from industry’s leading CROs (Contract Research Organizations) and CDMOs (Contract Development and Manufacturing Organizations). The webinar aimed at discussing the common problems faced with the drug development process, and the usefulness of employing bioassays in drug development programs with tailored solutions to drive programs forward. The discussion focused on answering critical, yet commonly overlooked questions when considering bioassays. Gaurav Agrawal, Ph.D., Associate Director of Market Development at Eurofins DiscoverX, moderated the session, and three experienced group leader panelists from CRO/CDMO’s that have been certified to use Eurofins DiscoverX’s bioassays shared their insights and experiences on using the qualified Eurofins DiscoverX Bioassays during the webinar and summarized in the article.

Roundtable Discussion Panelists

• Ramsey Connor, Senior Scientist, Project Director, RSO, Catalent Pharma Solutions
• Pete Broglie, Ph.D., Cell Based Assay Group Lead, KBI Biopharma
• Markus Roucka, Managing Director, Vela Laboratories

Discussion Highlights

The discussion commenced by highlighting the most common challenges observed when setting up cell-based potency assays for lot-release testing for clients. The insightful conversation brought to light several challenges.

• Defining the most appropriate cell growth conditions for accurate, reliable and consistent data generation, and stability of titration curves
• Meeting rushed timelines and the long-term supply of critical reagents to support bioassays in QC lot-release programs
• Key technical assay criteria such as assay interference and assay plate edge effects

Key Advantages of Bioassays Compared to Cell Lines

The webinar discussed the key advantages of using ready-to-use (RTU) assays versus a continuous culture cell-line format. The panelists shared the following RTU bioassay advantages.

• Reduced time for cell culture characterization, such as generating growth curves, monitoring the viability of cells in continuous culture, and eliminating the time needed for master cell bank generation
• A vital alternative and opportunity to work with highly specific cells that are ready-to-thaw and plate, thereby saving capital invested in raw material purchase and procurement
• Lot-to-lot consistency in assay performance and signal-to-noise values obtained
• Elimination of inherent variability with continuous culture methods as the cells are passaged

The above bioassay advantages lead to high efficiency and reproducibility, which are key aspects that help accelerate the drug development timeline when implementing RTU bioassay kits from characterization to potency testing in QC lot-release.

Important Parameters when Selecting Bioassays

The discussion advanced to reasons that a cell based potency assay fails during validation and the early signs to avoid such assays. The panelists highlighted the following parameters when selecting an assay for a program.

• Performing robustness testing is critical
• Checking for lot-to-lot variability of reagents and proper functioning of instruments being used. As an example, for ADCC (Antibody-Dependent Cellular Cytotoxicity) assays – if using an MOA (mechanism-of-action)-reflective assay, the results must be cross-checked with a reporter gene assay. The panelists went on to discuss the key features of Eurofins DiscoverX’s Bioassays that have proven helpful, with the following points associated with the availability of:
  • Well-written protocols provided with the bioassay kit that make it easy to train analysts and run assays
  • A technical support team to troubleshoot with a quick turnaround time
  • The extensive list of documentation and QC-checked applications, with a great level of development already done

Experience with Bioassays

The webinar included asking the audience poll questions, in which the audience responded to multiple choice questions centered around their experiences in using cell-based assays. The poll questions that were asked included:

1. What has been the most recent experience using a commercially available cell-based assay? The audience and panelists shared that they all had a great experience using easy-to-use and reproducible assays when time was of the essence.
2. What challenges were scientists able to overcome when using a cell-based assay from a commercial provider? The responses shared included saving time in overall assay development process, reproducibility of results, decrease in the number of variables, and the ease of tailoring assays to the target molecule.
3. How soon does one start looking for a cell-based potency assay for a biologic program in their pipeline? Panelists suggested that the pre-clinical stage in the drug development process is the best time to begin finding assays and align on the development timeline. In addition, they pointed out that the regulatory authorities tend to ask for an assay early on, which helps characterize one’s product.

Best Practices and Advice when Using Bioassays

Delving deeper into the specifics of the assays, the panelists also discussed the best practices to report the potency values if using RTU cells assay format; that being, not to rely on a single value assay or the average of triplicate assay values, but rather note the potential variability of assays. However, they added that irrespective of the set-up created, it is critical to perform the development, pre-qualification and pre-validation.

Finally, the panelists concluded by sharing their positive experiences with using cell-based assays and the important features to consider when selecting assays, with a key feature of the assay exhibiting the intended MOA relevant for the target drug molecule that is increasingly required for acceptance by the regulators.

Conclusions

An insightful discussion among an eminent panel representing the CRO/CDMO community provided a great opportunity for those in drug development to gain an in-depth understanding of essential aspects when considering the implementation of bioassays for interrogating the MOA of the target drug molecule.

Eurofins DiscoverX offers a diverse portfolio of bioassays with validated assays for biosimilars and innovator drugs across different target classes and MOAs to support the drug development journey from characterization to potency testing in QC lot release. Implementation of the bioassays enables a customer to reduce their drug development timeline – fast-tracked by at least 6-9 months. These bioassay kits are offered as target-based kits or qualified kits (qualified with marketed drugs) and yield results within a day. They contain RTU target cells that are thawed and plated for use with an easy-to-follow protocol and all the reagents needed to run the assay.

Access the webinar recording via Roundtable Webinar Discussion

Discover more about Eurofins DiscoverX bioassays at discoverX.com/bioassays