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Outline of CMC for vaccines
Here's a breakdown of CMC specifically for vaccines:
Chemistry:
- Drug substance - the antigen component itself, which can be:
- Inactivated or attenuated viruses or bacteria
- Purified proteins or carbohydrates derived from pathogens.
- Recombinant proteins expressed in cell cultures.
- Nucleic acids (DNA or RNA) encoding antigens.
- Conjugates of antigens with carrier molecules.
- Drug product - the final, injectable form of the vaccine, containing the drug substance formulated with:
- Adjuvants: Enhance immune response.
- Preservatives: Maintain sterility.
- Stabilizers: Prevent degradation.
- Excipients: Fillers, buffers, etc.
- Analytical methods - specific methods are established to characterize and quantify the antigen, impurities, and excipients.
- Raw materials and excipients - selection and qualification to ensure purity, consistency, and suitability for vaccine production.
Manufacturing:
- Process development: Designing a scalable and reproducible process for antigen production, purification, formulation, and filling.
- Process validation: Demonstrating the consistency and control of the manufacturing process through extensive testing.
- Quality control: Implementing measures throughout the process to ensure product quality and adherence to specifications.
Controls:
- Stability studies: Evaluating the vaccine's shelf life under various storage conditions.
- Packaging and storage: Defining appropriate packaging and storage protocols to maintain potency and sterility.
- Batch release testing: Each batch undergoes rigorous testing to ensure it meets all quality standards before release.
Additional considerations for vaccine CMC:
- Highly sensitive materials: Many vaccine components require careful handling and processing to avoid degradation or contamination.
- Aseptic processing: Ensuring sterility throughout the manufacturing process is crucial for vaccine safety.
- Regulatory requirements: Stringent regulations govern vaccine development, manufacturing, and testing, demanding detailed documentation and compliance.
Resources:
- FDA Guidance: Content & Format CMC for Vaccine & Related Product. Accessed on Feb 07, 2024.
- Maria Monica Castellanos, CMC Strategies and Advanced Technologies for Vaccine Development to Boost Acceleration and Pandemic Preparedness, Vaccines (Basel). 2023 Jul; 11(7): 1153
Outline of CMC for Biologics
CMC (Chemistry, Manufacturing, and Controls) is a critical aspect of bringing biologics, such as vaccines, blood products, and gene therapies, to market. It ensures that the biologics are safe, pure, potent, and consistent between batches.
Here are the key steps involved in CMC for biologics:
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Chemistry:
- Characterization of the biologic drug substance and drug product, including its structure, purity, and stability.
- Development of analytical methods to measure these attributes.
- Selection and qualification of raw materials and excipients.
-
Manufacturing:
- Development of a robust and scalable manufacturing process that consistently produces a high-quality product.
- Validation of the manufacturing process to ensure it meets all regulatory requirements.
- Implementation of quality control measures throughout the manufacturing process.
-
Controls:
- Development of stability studies to determine the shelf life of the biologic.
- Development of packaging and storage specifications to protect the biologic from degradation.
- Ongoing monitoring of the manufacturing process and product quality.
CMC documentation:
All of the CMC activities are documented in a comprehensive set of reports that are submitted to regulatory agencies, such as the FDA, for approval. This documentation is essential for ensuring the safety and efficacy of the biologic.
CMC considerations for biologics:
- Biologics are complex molecules that can be difficult to characterize and manufacture.
- The manufacturing process for biologics can be very sensitive to changes, so it is important to have a robust and well-controlled process.
- Biologics can be very potent, so it is important to ensure that they are sterile and free of impurities.