Method Development, validation, & Transfer

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The key elements of any pharmaceutical development program include method development, validation, and transfer. These three elements are interrelated as changes to one method may elicit necessary modifications to a separate existing method.  

Method Development is the process that determines if a specific method is acceptable to measure the concentration of an API in a specific compound dosage form. Accurately deciding on the correct method is based on many considerations such as chemical properties, sample matrix, speed and cost of the analyte, and type of measurements. The most common analytical methods include:

• Identification Tests
• Potency Assays
• Quantitative Tests for Impurities
• Limit Tests for Impurity Control

The most widely used methods for the quantitative determination of drug products and metabolites include chromatography. Chromatographic procedures allow for a substance to be separated based on different migration rates through the column. Some of these techniques include:  

• Gas chromatography (GC)
• High-performance liquid chromatography (HPLC)
• Thin-layer chromatography (TLC) 
• GC-MS, GC-MS-MS
• LC-MS, LC-MS-MS
• NMR (used for structure identification)

Method Validation will verify that the method will deliver reliable measurements of the active ingredient. The validation process is critical for analytical method development and tests for specificity, linearity,  accuracy, precision, range, detection limit, and robustness. A method should be validated when it's necessary to verify that its performance parameters are adequate for a specific problem. ChRi Labs works with our clients to assist in the development of a proper QC plan for routine analysis.

A method can be marked validated once the method and equipment consistently deliver accurate results. As a contract laboratory, our expertise allows us to develop and validate the most complex methods. 

A formal Method Transfer is a required process that allows the receiving laboratory to utilize a method that was developed in the transferring lab.  The stringent ICH and USP protocols ensure that the method performs as intended within the receiving laboratory's environment.    

Not all method transfer techniques are the most efficient and applicable.  ChRi utilizes extensive scientific expertise to define the best strategy. Common method transfer options include:   

• Comparative Testing 
  • Samples are tested from the same lot as the product or substance by both the receiving and sending lab. The transfer protocol states the details of the procedure, acceptance criteria, and acceptance variability.  

• Covalidation Testing 
  • If two or more labs are required for GMP testing, ChRi often suggests covalidation as the more efficient method transfer process. The receiving lab is a part of the validation process assisting and aiding in the overall reproducibility of the method.

• Revalidation
  • If the transferring lab in unavailable for comparative testing, revalidation is the best option. A risk-based approach is used to assess if a partial or complete validation is needed per <1225> Validation of Compendial Procedures by the receiving lab.