February 2014 – Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics
“This revised draft guidance supersedes the 2000 draft guidance for industry on Analytical Procedures and Methods Validation and, when finalized, will also replace the 1987 FDA guidance for industry on Submitting Samples and Analytical Data for Methods Validation.” It is applicable to NDAs, ANDAs, BLAs, DMFs and supplements to them.
The Guidance recommends that the robustness of an analytical method be tested early in the development process, which makes sense since there is no point in validating a method that will not be robust. It also lists the features of the method which should be provided: Principle/Scope, Apparatus/Equipment, Operating Parameters, Reagents/Standards, Sample Preparation, Standards Control Solution Preparation, Procedure, System Suitability, Calculations and Data Reporting. For the standard(s) the Guidance suggests including grade, source, state (e.g. dried or undried), concentration, any needed purity correction factors, storage conditions, directions for safe use as per MSDS and validated shelf life.
The Guidance lists typical validation characteristics: specificity, linearity, accuracy, precision (repeatability, intermediate precision and reproducibility), range, quantitation limit and detection limit. To demonstrate that a method is stability-indicating, the Guidance recommends a combination of spiking samples with the target analyte and all known interferences, sample stressing and testing commercial samples, either aged or subject to accelerated stability storage conditions.
Compendial analytical methods require verification. The characteristics to be verified depend on the parameters for which the method will be used. Robustness does not need to be included if the method is followed without deviation.
Trend analysis of the ease of meeting system suitability requirements should be used to determine whether the method requires adjustment. Laboratories will need to set up systems for collecting the needed information for the trend analysis. You may consider consulting with a statistician, too. The Guidance also recommends saving some samples for use in changing or revalidating methods. Revalidation is only recommended if the method or the manufacturing procedure of the product is changed. You may wish to consider clearly identifying when revalidation is required through a decision tree.
Comparability studies and FDA Methods Verification are also discussed in the Guidance.
Except for the recommendation for trend analysis, the Guidance does not depart much from the previous guidance. It is written more clearly than the Guidances it supersedes. For this reason, it will be welcomed by analytical laboratories.
Have a question for one of our regulatory experts? Contact us.
Author: Akesis Regulatory Department