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By Brian R. Moyer, Bakul Bhatnagar, and Adrienne Clements-Egan

Brian Moyer Bakul Bhatnagar - final Adrienne Clements Egan

Hello, Boston, we’re back! After a long hiatus from the East Coast, the AAPS National Biotechnology Conference (NBC) is returning to one of the major biotech hubs in the United States. The NBC Program Committee (NBCPC) has created an incredibly diverse and interesting program this year. AAPS section and focus group representatives met last July and identified four hallmark themes to be covered at this NBC: Formulation and Manufacturing, Biomarkers, Advances in Immunogenicity, and Drug Delivery Innovations. In addition, special courses and workshops before the meeting will cover ligand binding, clinical pharmacology of biotherapeutics, and biosimilar development. A postmeeting scientific forum covering imaging and pharmacometric approaches will also be offered. And a special session providing an update on the Zika pandemic and the world’s biotech response is scheduled.

A broad range of topics related to the four themes will be presented over NBC’s three days. The themes were selected to address biotech product innovation, lessons learned, novel developments, and identified challenges. At the end of the meeting, Brian will be presenting the new session What Have We Learned?, a summary of the major advances and novel concepts in biotechnology, as an integration of what was presented at the meeting. Here are short summaries of two of the four themes and why the Programming Committee considered these topics. Tune in tomorrow to learn about the other two themes: biomarkers and drug delivery.

Theme 1: Formulation and Manufacturing (CMC)

We will offer participants several currently debated CMC technologies. The theme was selected to cover many evolving technologies such as alternate drying technologies for biologics and innovations in flexible manufacturing. Vaccines fall into this topic, as the Ebola, pandemic flu, and Zika events have exposed a need to allow for rapid change in continuous manufacturing lines. Combination products also present significant CMC challenges such as drug product-material interface issues, delivery of large volume or viscous solutions, design history filing, human factors studies, and regulatory considerations, all very relevant to formulators and engineers. Topics of wide interest and debate include:

  • how to characterize impurities and degradation products in biologics,
  • vaccine drug substance and drug product vialing and rapid response manufacturing platforms,
  • container-closure integrity considerations for finished products, and,
  • new discoveries in how the subcutaneous environment can be harnessed for effective absorption of biologics.

Recognizing both the debate and the need, the NBCPC has included programming on the use of surfactants in biopharmaceuticals as these formulations have considerable impact on product quality. In addition, recent insights on the role of ice and the freeze concentrate in the stability of frozen pharmaceuticals and container closure systems integrity have become quite topical. Attendees will have opportunities to participate on considerations that govern the choice between a frozen liquid and freeze-dried cakes as a drug product for use in first-in-human studies.

Theme 2: Immunogenicity

Immunogenicity was a unanimous choice for a theme for this year. The NBCPC selected a variety of immunogenicity highlights such as a multiparametric problem, bioanalytical strategies, predicting safety risks, and understanding clinical relevance.

For example, NBC will address logistical and scientific considerations for determining in-study assay cut-points and overcoming drug and target interferences. Approaches for in-study assay cut-points have been developed in recent years to meet the demands of immunogenicity assessments in less abundant study populations (e.g. samples from populations that cannot be utilized for pre-study cut-point assessments). What are the pros and cons of in-study cut-points? When is pre-study cut-point determination good (or not good) enough? Another topic to be addressed is assay interference. As the need to understand the clinical consequences of immunogenicity has developed, more sophisticated assays are required to overcome drug and target interferences. While there are a few published assay strategies to accomplish this, what other unique approaches have been successful in the industry to get to the correct conclusion of the antidrug antibody (ADA) status in patients?

The clinical relevance of pre-existing antibodies and detection strategies for them are sources of much debate. We focused this year’s immunogenicity programming on perspectives on how to determine the risk of pre-existing antibodies and to design bioanalytical approaches for evaluating these entities. There are outstanding questions in the field. For example, are pre-existing antibodies clinically meaningful? In subjects who have them, do pre-existing antibodies precede hypersensitivity reactions or a more robust anti-drug antibody response? What classes of biologics lend themselves most to pre-existing antibodies? What is the best way to identify pre-existing antibodies during assay development, validation, and study phase bioanalysis?

In several other sessions, the immunogenicity theme will also meet other industry-wide issues, including how to evaluate clinical immunogenicity of biosimilars, ways to dive deeper into assessing clinical relevance of ADAs and neutralizing antidrug antibodies (NAbs), and how to mitigate immune responses.

Please comment on these themes and share your ideas below on what you want to see from the programming. We want the 2016 NBC to be the best of experiences!

And return tomorrow to read about the biomarkers and drug delivery themes.

Brian R. Moyer is president and principal of BRMoyer & Associates in Amherst, N.H., a full-time senior science advisor for the Biomedical Advanced Research and Development Authority, and chair of the 2016 NBC Program Committee.
Bakul Bhatnagar, Ph.D., is a principal scientist in Formulation & Process Development at Pfizer.
Adrienne Clements-Egan, Ph.D., is scientific director at Janssen Biotherapeutics, Johnson and Johnson.