Raw Materials Control For Biotechs (Part 1): Pre-Clinical Development Considerations

In the realm of pharmaceutical development, the pre-clinical phase that precedes the submission of an Investigational New Drug (IND) application for a phase 1 clinical study is a pivotal juncture. This stage, often referred to as pre-clinical development, brims with critical choices concerning CMC (chemistry, manufacturing, and controls). These decisions wield a profound impact on the quality of both the drug substance (DS) and the drug product (DP) slated for deployment in early-stage biotech companies' phase 1 clinical trials. Key determinations include the design and execution of manufacturing processes, the requisite quality control (QC) tests for in-process, lot release, and stability testing, the establishment of acceptance criteria for lot release and stability, container and closure selection, impurity profile monitoring and refinement, the blueprint for a robust stability program, the material chosen for IND-enabling studies, and more.

Among these pivotal CMC decisions, one of the most critical is the selection of the quality of raw materials used in crafting the DS and DP manufacturing processes. Often, raw material choices are grounded in research conducted early in the developmental process by individuals unfamiliar with the requirements of current Good Manufacturing Practices (cGMP), a cornerstone of a successful clinical development program. Consequently, the use of such raw materials may present regulatory challenges when the company submits its IND application to the U.S. Food and Drug Administration (FDA) for review.

In light of these challenges, this article delves into how early-stage biotechnology companies can navigate these pitfalls and establish a robust cGMP foundation for their raw materials control program. While the primary focus is on cell and gene therapies (CGTs), the insights provided are broadly applicable to other types of early-stage biological therapies.