CMC plays a critical role in the development of a biological product. While it may not be possible for early stage and mid-size biotech companies to have all the necessary CMC resources to steer through the maze and tangle of drug development challenges, there are steps you can take to insure success.
The first step was covered in our previous blog and it was: Have a Clear CMC Strategy. Some of the important components of CMC strategy include defining:
- Critical process parameters (CPPs)
- Critical quality attributes (CQAs)
- Control strategies for genotoxic impurities
- Drug substance and drug product specifications
- Selection of drug substance starting materials
- Analytical method development and validation
- Regulatory compliant stability studies
- Process analytical technology (PAT) and quality by design (QbD) approaches to product and process design
- Selection and management of CDMO, project management
The second necessary component is to have a clear Quality Target Product Profile.
Have a Clear Quality Target Product Profile (QTPP)
The goal of CMC is to apply the state-of-the-art scientific and technical approaches and regulatory compliant quality standards to develop the right quality target product profile (QTPP) for the biopharmaceutical and design the biologic product and process using process analytical technology (PAT) and quality by design (QbD) principles. It is extremely important to understand that the production of biological products is tightly controlled so that the product tested in clinical trials stays consistent as the batch sizes increase during clinical advancement, leading to registration batches followed by commercialization.
Biologic drugs are often complex, demanding exact three-dimensional conformation, often requiring post-translational modification, high purity, and poorly understood mechanism of action. In addition, the source material for biologics can potentially lead to the transmission of adventitious agents that can be difficult to identify and may not be easy to measure. As a result, there is a need for substantial in-process purification, control, and validation. Also, the bio-friendly nature of the fermentation manufacturing process aids the susceptibility of the process to microbial contamination, and it’s simply not possible to employ aseptic processing throughout, especially in the bulk drug substance (BDS) purification processes.
Given the complexity and challenge of CMC development, the best strategy is to anchor it on a “quality target product profile (QTPP)”, which looks holistically at what’s the main objective and what’s to be achieved. In a larger sense, it’s to identify product requirements to meet patient needs and then determine the quality target product profile (QTPP) and the critical quality attributes (CQAs) required to meet those patient needs. Based on this information, the sponsor then designs the biomolecule, the manufacturing process, and the control strategies to ensure that the desired product quality is met consistently. Questions to address include the therapy, patient population, understanding the physical, chemical, and biological characteristics of the drug, dosage form and delivery method, strength, container closure and how all these factors play into the success of drug development.
In addition to QTPP, time, and cost factors, as well as intellectual property (IP) protection, must also be considered. An understanding of not only the basic science and technology of CMC but also how that fits into the preclinical strategy, clinical strategy, and regulatory strategy for successful licensure of the product is essential.
Check out the next step for success in our follow up blog: The Right Technology – A Critical Element in Your CMC Strategy