Validating a method
In considering the purpose of methods in early versus late development, the authors advocate that the same amount of rigorous and extensive method-validation experiments, as described in ICH Q2 , which advocates the use of scientifically sound (rather than validated) laboratory controls for API in clinical trials (6).Additionally, an FDA draft guidance on analytical procedures and method validation advocates that the amount of information on analytical procedures and methods validation necessary will vary with the phase of the investigation (7).Although not used for GMP release of clinical materials, qualified methods are reliable experimental methods that may be used for characterization work, such as reference standards and the scientific prediction of shelf-life.A perspective on some recent analytical method challenges and strategies, such as genotoxic impurity methods, use of generic methods, and methods used for testing toxicology materials or stability samples to determine labeled storage conditions, retest periods and shelf life of APIs and drug products are also presented.The authors, part of the International Consortium on Innovation and Quality in Pharmaceutical Development (IQ Consortium), explore and define common industry approaches and practices when applying GMPs in early development.A working group of the consortium aims to develop a set of recommendations that can help the industry identify opportunities to improve lead time to first-in-human studies and reduce development costs while maintaining required quality standards and ensuring patient safety.
In addition, this approach contains some aspects which represent new scientifically sound and appropriate approaches that could enable development scientists to be more efficient without compromising product quality or patient safety.In the June 2012 issue of , a paper was presented which described an overview of IQs consolidated recommendations from the Good Manufacturing Practices (GMPs) in Early Development working group (WG) (1).The focus of this IQ WG has been to develop recommended approaches on how to apply GMPs in early phase CMC development activities covering Phase I through Phase IIa.The initial scope of these efforts has been limited to small-molecule drug development which supports First in Human (FIH) through Phase IIa (Proof-of-Concept) clinical studies.
A series of papers describing a recommended approach to applying GMPs in each of these areas is being published within this journal in the coming months.
In early development, one of the major purposes of analytical methods is to determine the potency of APIs and drug products to ensure that the correct dose is delivered in the clinic.