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Xiaobin ZhaoAnne McCasland-KellerRobert GeigerRodney Ho

Xiaobin (Ben) Zhao is a product quality reviewer from CDER, FDA.
Anne McCasland-Keller is a research advisor in global regulatory affairs at Eli Lilly & Co.
Robert Geiger is vice president at Ambiopharm.
Rodney Ho is a presidential entrepreneurial fellow and professor of pharmaceutics at University of Washington. He is the recipient of the 2013 AAPS Biotechnology lifetime achievement award.

Peptides are synthetic or recombinant DNA-derived polymers of amino acids. Historically, therapeutic peptide development has been hampered by scientific barriers and skepticism about their commercial viability. In the past decade, the number of new peptides entering the clinic has doubled according to a report from Peptide Therapeutics Foundation, and many believe that peptide drugs might offer novel solutions for the industry’s weak pipelines. This growth in novel and generic peptide drug has continued even under uncertain regulatory environment.  Unlike for small-molecule drugs, no guidance is available to drug sponsors in bringing their peptide drugs to market. Nevertheless, over twenty therapeutic peptide drugs have been approved in the United States. Among these, seven of them have achieved global sales near or above the $1 billion benchmark. Insulin, glatiramer acetate, leuprolide acetate, goserelin acetate, octreotide acetate, exenatide, and teriparatide are among these.1Generic versions are now available for a few and some are in regulatory review.

Several driving forces fuel growth in peptide drug development. (1) Advances in molecular design and chemical modification improved pharmacokinetics and pharmacodynamics (PK/PD) profile. (2) Innovative delivery/formulation strategies improve bioavilability. (3) The looming patent expiration of peptide therapeutics has attracted near-term investment form generic drug industry.

Chemistry, manufacturing, and controls (CMC) is more complex for peptide drugs, compared to small molecule drugs. The CMC complexity increases exponentially for peptide drugs containing unnatural amino acids, modified structure, and carrier molecules intended to enhance the PK properties. The pharmaceutical industry is investing to ensure that manufacturing processes is robust, high quality, cost-effective, and environmentally friendly for peptide products derived from both chemical synthesis and recombinant cells.

As noted, all these challenges are being addressed in an uncertain regulatory environment. Unlike small molecule drugs, no clear regulatory guidance exists to help peptide drug developers improve peptide quality and smooth the regulatory review pathway. The current ICH guidelines specifically exclude peptides with regard to the testing and quality of pharmaceutical products. The established method validation guidance may not be directly applicable to peptides due to the lack of internal standards and/or reference materials.

This year at the AAPS Annual Meeting and Exposition, the hot topic session Emerging Development and Regulatory Issues Related to Novel and Generic Peptide Drugs will discuss these most sought-after yet challenging areas in peptide drug development. Leading researchers from both innovator and generic industry will discuss approaches that may successfully overcome these challenges, followed by a Q&A session.

We invite you to bring your questions, comments and suggestions on the current issues related to peptide drug development and regulatory paradigms at this hot topic session.