When it comes to creating any form of medication, reputation is everything. Customers expect their medicine to have the correct ingredients, to be safe, and to work as described, with limited side effects. Should a medication fail to live up to those expectations, a company’s reputation could be at stake, and an entire product line might be scrapped due to concerns over efficacy or safety.
However, when working with biologic medicines, creating a quality product can be far more complicated than making small-molecule medicines like aspirin. Biologic medicines require significant testing to determine structure in several dimensions. These include its primary amino acid structures, the three-dimensional structure of the biologic and how it exists in space, and the way the biologic’s molecules interact when in solution. Without these controls, the efficacy and quality of the biologic may be compromised, devastating the product’s status in the marketplace.
Defining Quality Standards for Biologic Through Redundant Testing
Manufacturing a biologic can be tricky. The process requires the growth of living systems, multi-step purification processes designed to generate the active pharmaceutical ingredient (API), and, eventually, the final drug product. Unfortunately, this means that there are many points in the production process when unacceptable variances may develop; these could jeopardize the quality of the final product.
Thus, the quality of the final product relies heavily on a system of thorough and redundant checks of critical quality attributes (CQAs). This data, when combined with a broad enough sampling of multiple batches, helps define the CQAs that make up the unique signature of a biologic medicine. This allows for control of the final product, whether produced in-house or outsourced, by reference to the quality of the presence of the appropriate CQAs.
Because biologics involve living systems, variability is inevitable. Nevertheless, to maintain quality control, these variances must be minimized to the greatest extent possible. Too much variation can result in the biologic falling outside of its specifications and having unintended consequences for anyone who might use it.
Using a single lab for testing may be favorable in some situations to ensure that samples are handled in a uniform manner. Use of multiple testing labs can actually introduce the appearance of undesirable variation thanks to differences in the manner of handling samples, testing criteria, etc. Variations may demonstrate a lack of control, making it difficult to link non-clinical trial materials with late-phase manufacturing. This, in turn, may interfere with making a successful regulatory filing.
How to Establish and Maintain Quality Control
Variations will occur in biologics, so one must simply accept that inevitability. Adopting appropriate analytical methodologies should help to identify the core parameters for a biologic via its CQAs. By using as few testing labs as possible and attempting to achieve sample homogeneity, one can better establish a relationship between early and late stage materials; a critical step to achieving successful approval of the product for commercial sale.