FDA has released a draft guidance on analytical procedures and methods validation, which supersedes the 2000 draft guidance and will also replace the 1987 guidance, Submitting Samples and Analytical Data for Methods Validation. The draft guidance provides recommendations for submitting analytical procedures and methods validation data to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. The revised draft guidance complements International Conference on Harmonization (ICH) Q2(R1) Validation of Analytical Procedures: Text and Methodology.
The guidance is written to help with the assembly of information and presentation of data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and supplements to these applications. The principles in the revised draft guidance also apply to drug substances and drug products covered in Type II drug master files (DMFs). This revised draft guidance does not address investigational new drug application (IND) methods validation, but sponsors preparing INDs may want to consider the recommendations in the guidance.
According to the draft guidance, INDs require sufficient information at each phase of an investigation to ensure proper identity, quality, purity, strength, and/or potency. The amount of information on analytical procedures and methods validation will vary with the phase of the investigation. For general guidance on analytical procedures and methods validation information to be submitted for phase one studies, FDA recommends sponsors refer to Guidance for Industry, Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products. General considerations for analytical procedures and method validation (e.g., bioassay) before conduct of phase three studies are discussed in Guidance for Industry, IND Meetings for Human Drugs and Biologics, Chemistry, Manufacturing, and Controls Information.
The revised analytical validation draft guidance does not address specific method validation recommendations for biological and immunochemical assays for characterization and quality control of many drug substances and drug products. Some bioassays, for example, are based on animal challenge models, and immunogenicity assessments or other immunoassays have unique features that should be considered during development and validation. In addition, the need for revalidation of existing analytical methods may need to be considered when the manufacturing process changes during the product’s lifecycle.