Critical Path Initiative for Generics - AAPS 3

In May of 2007, the FDA added the Critical Path Initiative (CPI) for generic drug development. Still in its infancy, the framework hopes to eventually clear some of the roadblocks in the generic development process.


Speaking at the AAPS show, Robert Lionberger, from the FDA Office of Generic Drugs, explained FDA's role of challenge identifier, input gatherer and collaborative participant in the process. The goal is to smooth the process for faster approval of future generic drugs.


"Since 50-60% of prescriptions are being filled with generics, it was time to look at the impediments to their development," said Lionberger.


The agency has identified roadblocks in characterization, design, bio-equivalency tests and scale up/manufacturing. "To make a copy, an ANDA sponsor might need better characterization than the original," said Lionberger.


In the design phase, it is hard to identify the quality attributes of new/complex dosage forms. For example, inhalers, transdermal patches and modified release mechanisms have limited dissolution IVIVC tests to evaluate the proposed formulations and processes.


According to Lionberger, problems in scale up have led to wasted commercial batches and process variability. In addition, many times it may require the sponsor to reformulate the product or revise the process.


Therefore, the FDA has identified four areas of opportunity in the CPI for generic drugs: "¢ Improve the science underlying quality by design for the development and manufacture of generic drug products. "¢ Improve the efficiency of current methods for assessment of bioequivalence of systemically acting drugs. "¢ Develop methods for the assessment of bioequivalence of locally acting drugs. "¢ Develop methods for characterizing complex drug substances and products.


"Quality by Design tools will help in the design and manufacture of generic products," said Lionberger. "Formulation and absorption modeling, as well as dissolution tests will be critical."


According to Lionberger, the bio-equivalence of locally acting drugs (e.g., nasal, skin, GI tract) will have the biggest impact on generic competition. However, these also have the most challenging scientific issues. New methods sought for locally acting drugs include: in vitro tests for product equivalence; imaging techniques; target tissue sampling; new biomarkers; and new designs for clinical endpoint studies.


"The goal of bio-equivalence is finding a biomarker for local delivery," said Lionberger. "These could help companies identify sooner those product candidates that are likely to fail, while directing more resources to develop promising candidates."