Drug development is a long, expensive, and risky process. The drug development process mainly includes: Target identification, Discovery, Preclinical pharmaceutical research (IND), Clinical trials (Phases I, II, and III) , NDA/BLA and comercial Launch. CMC (Chemistry Manufacturing & Control) is a very important part of drug approval. It begins with the identification of a lead compound through drug discovery and continues throughout all stages of drug development. CMC research mainly includes the following: Production process research, Impurity research, Quality research and Stability research.
The focus of CMC research varies at different stages of development.
- In the preclinical and early clinical research stages, CMC research is mainly to provide quality-assured research samples for these studies.
- As clinical research progresses, CMC research focuses on the production process and quality control system.
- CMC research is also used to adjust and optimize the dosage form, specifications, formulation, manufacturing process, analytical methods, and quality standards based on clinical data.
Regulatory agencies’ requirements for CMC research are based on the following:
- The stage of clinical research
- The number of subjects and study duration
- The novelty of the drug’s structure and mechanism of action
- The dosage form and route of administration
- The known and potential risks
The key points of CMC for innovative drugs and generic drugs are different.
Innovative drugs are characterized by uncertainty, so their dosage form, specifications, and formulation may change as toxicity and efficacy data are collected. CMC research for innovative drugs is therefore focused on ensuring the safety and efficacy of the drug.
CMC research for generic drugs is more focused on demonstrating equivalence to the reference product.
Drug development is a phased process, and the key points of CMC research also vary at each stage.
Drug research work can be divided into the following four stages:
- Research stage (preclinical research, Phase I clinical research)
- Full development stage (Phase II clinical research, Phase III clinical research)
- New drug application stage
- Post-market stage
In the preclinical research stage, CMC research is mainly focused on providing quality-assured research samples.
- Provide quality-assured research samples.
- Determine the feasibility of the drug’s synthesis and manufacturing process.
- Identify potential impurities and hazards.
In the Phase I clinical research stage, CMC research is focused on ensuring the safety and quality of the drug.
- Ensure the safety of the drug at the initial dose levels.
- Identify potential toxicity issues.
- Determine the appropriate dosage form and route of administration.
In the Phase II clinical research stage, CMC research is focused on optimizing the dosage form, specifications, formulation, and manufacturing process.
- Optimize the dosage form, specifications, and formulation.
- Confirm the safety and efficacy of the drug at higher dose levels.
In the Phase III clinical research stage, CMC research is focused on confirming the stability of the drug and establishing a quality control system.
- Confirm the safety and efficacy of the drug in a large population.
- Establish a quality control system
In the post-market stage, CMC research is focused on monitoring the stability of the drug and responding to any changes in the manufacturing process or quality control system.
- Monitor the stability of the drug.
- Respond to any changes in the manufacturing process or quality control system.
In conclusion, CMC is a critical part of drug development. CMC research at each stage of development is essential to ensure the safety and efficacy of the drug.