Welcome to the Virtual Summit: Bioconjugates

The NEW Virtual Summit is a one-day virtual program on different hot topics with four sessions of speaker presentations and panel discussions.

This Virtual Summit on "Tackling Bioconjugate Challenges" aims to discuss two key challenges faced by bioconjugate developers and manufacturers: impurity control strategies and comparability assessments. The Summit will explore the risk-based assessments and enhanced process understanding that could be used to guide the strategy for comparability determinations. View the full Summit abstract below.

The full scientific program will be available soon.

Summit Abstract

Antibody drug conjugates (ADCs) have emerged as an important class of medicines to treat hematologic and solid tumor cancers. Since the first ADC was approved by the FDA in 2000, the success of this therapeutic class has resulted in a burgeoning field with development across many different therapeutic areas. In addition to conjugation of cytotoxic agents to antibodies for oncology, the broader application of conjugating a synthetic moiety (e.g., peptide, oligonucleotide, radionuclide, etc.) to a protein is being explored to expand the therapeutic use of bioconjugates. As the definition of the “drug” portion of an ADC expands to encompass a wide array of molecule types, manufacturing and control challenges can be diverse and labor-intensive to address. This Virtual Summit aims to discuss two key challenges faced by bioconjugate developers and manufacturers: impurity control strategies and comparability assessments.

One of the major challenges, and a key topic of debate for bioconjugate therapeutics, is the impurity control strategy for the synthetic drug-linker portion of the molecule. With the wide array of drug-linker modalities, the complexity of the synthetic molecule portion of the bioconjugate is increasing and may therefore not meet the purity and impurity standards for traditional small molecule drugs. The first part of this Summit will explore different approaches and control strategies for ensuring product quality while safeguarding patient safety. We will discuss risk-based approaches to setting specifications and delve into the applicability of typical ICH Q3A impurity thresholds.

The second half of the Summit will focus on the design of comparability assessments to support manufacturing changes. Comparability protocols have been successfully used for therapeutic proteins for several decades to enable implementation of manufacturing changes to improve capacity and productivity.  ADC manufacturing processes are more complex and less established compared to monoclonal antibodies, which has resulted in more ambiguity in what is needed to ensure comparability after a manufacturing change. Regulations are unclear on whether comparability can be established at the drug substance intermediate (e.g., monoclonal antibody, drug-linker) rather than evaluating one node beyond the point of change (e.g, testing all the way to drug substance for a change in the drug-linker process).  ICH Q5E indicates that the evaluation should be made at the process step most appropriate to detect a change in the quality attributes but indicates that additional evaluation may be needed if downstream impact cannot be ruled out. Summit attendees will explore the risk-based assessments and enhanced process understanding that could be used to guide the strategy for comparability determinations.

The Summit will share case studies for these complex challenges. Both topics will also have panel discussions with industry and regulatory experts to further discuss the considerations needed to ensure patient safety and therapeutic benefit. The panels can discuss if different types of bioconjugates may warrant additional or unique considerations compared to a more traditional oncology ADC. Working through these challenges is paramount to accelerate the development and delivery of this important class of new medicines.