Small research organizations ranging from individuals to small corporations are developing drugs to treat diseases more effectively than ever before. These smaller organizations often focus on the medicinal aspects of treatments but they lack the knowledge and capability to move their lead compounds into human trials. One requirement for human trials is manufacturing of testable product according to regulations set forth by the Health Authority where the study is to take place. These regulations are generally called current Good Manufacturing Practices or cGMP. While cGMPs are similar around the world, each country may emphasize different aspects of cGMPs or may require supplemental information. The Chemistry Manufacturing and Controls section of the new drug application (CMC) contains the cGMP related activities.
During drug development, the CMC activities ensure the components and processes of the clinical dose are sufficiently characterized for the purpose of the test and all materials used in the manufacture are traceable to specific grades of materials and specific lots. Phase I trials do not require the same degree of materials and process characterization as Phase III, so the sponsor needs to adjust and continue development as the project progresses. The characterization and traceability efforts allows the sponsor to effectively evaluate the changes and reduce the risk for an unexpected outcome as the project progresses from one phase to the next. These procedures and materials used in drug product development become the standard and define the allowed variations for all future manufacturing of the commercial drug product.
Commercial cGMPs exist to ensure that each batch has been manufactured and tested according to the processes and test procedures that were originally approved. When changes to raw materials, the manufacturing procedure, or the test methods are required, the CMC section is updated to document the changes with the health authority. These CMC section changes include data to demonstrate that the product changes are adequately evaluated with the goal of making sure the patient/health care provider receives a product that will be safe and have the same effectiveness as the originally approved product.
Mesa Science Associates has the expertise to evaluate the active pharmaceutical ingredient (API), characterize the API and design a formulation that meets the medical need, and is manufacturable and tested appropriately on development through commercial scales. In addition to the dosage form design and manufacturing, we have experience with developing tests and recommending specifications that meet the expectations of the reviewing Health Authority for each stage of development. Mesa Science will guide our client to ensure the CMC section is populated with appropriate data to get regulatory approval for the drug investigation or for drug approval. Some of the CMC supporting documents are listed below:
- API and API salt/crystal form selection.
- Process optimization and ruggedness evaluations of the API synthesis route.
- API process impurity and degradation product characterizations.
- API packaging, stability protocols, and stability reports.
- API and Product Test Method Development and Validation and specification limits for test results.
- Product dosage form selection; tablet, oral liquid/suspension, topical, inhalation or parenteral.
- Product formulation studies including solubility, excipient compatibility and stability to stress conditions.
- Product manufacturing process development and scale-up studies along with the required ruggedness and validation requirements.
- Product stability protocols and reports.