#USA #FDA #Providence #EpiVax #Teriparatide

New Insights on Immunogenicity in Generic Drugs

In a significant collaborative effort, EpiVax, Inc. has partnered with scientists from the U.S. Food and Drug Administration (FDA) and CUBRC, Inc. to publish a groundbreaking study concerning the immunogenicity risks associated with peptide-related impurities in generic teriparatide products. This study represents a substantial advancement in our understanding of drug safety related to synthetic generics, particularly for patients undergoing treatment for osteoporosis.

Teriparatide, a recombinant peptide, holds an important position in treating osteoporosis by stimulating bone formation. However, the safety of generic versions of this medication has come under scrutiny, particularly regarding the impurities that may arise during manufacturing processes. This is particularly significant since regulatory guidelines have emphasized the need for generic drug manufacturers to assess the immunogenicity risk associated with these products, especially those submitted through abbreviated new drug applications (ANDAs).

The study titled "Immunogenicity Risk Assessment of Peptide-Related Impurities Identified in Generic Teriparatide Products" employs an innovative approach using a combination of in silico assessments and laboratory experiments. The researchers utilized EpiVax's unique PANDA methodology, which employs T-cell epitope prediction and characterization tools like EpiMatrix® and JanusMatrix®, alongside in vitro assays to assess HLA binding.

Through these methods, the team evaluated different impurities, both theoretical and observed, that could potentially influence unwanted immune responses. Their analyses revealed that several of these impurities exhibited a higher predicted immunogenic potential compared to the reference sequence of teriparatide itself. Moreover, the experimental data supported these predictions, demonstrating that some impurities enhanced HLA binding and provoked stronger T-cell responses than the original drug.

One particularly intriguing discovery was identifying a possibly tolerogenic region within the teriparatide sequence that could mitigate immune response. However, the presence of impurities could disrupt this region, leading to significant variations in the immune response elicited by the drug.

Dr. Vibha Jawa, Chief Science Officer at EpiVax, emphasized, "This collaboration with FDA scientists underscores the power of combining robust computational and wet-lab methods to better understand and mitigate immunogenicity risks in generic peptide development. Our findings offer a practical framework for developers navigating the FDA guidance on impurity assessment and highlight opportunities to strengthen peptide drug safety."

The implications of this research are profound; it aids generic peptide manufacturers in pinpointing which impurities need closer monitoring to prevent potential immunogenicity issues. Addressing these concerns is critical for ensuring the safety of patients relying on these essential medications.

Additional context regarding the support behind this study reveals that it was conducted in collaboration with FDA while receiving backing from FDA contract HHSF223018186C. However, it’s noteworthy that the views expressed in the study do not necessarily reflect the official positions of the FDA or the U.S. Government, reiterating the independent nature of scientific research.

As the pharmaceutical community continues to evolve, such collaborations highlight the importance of rigorous research in maintaining the integrity and safety of generic medications. The findings from EpiVax and the FDA could pave the way for more stringent regulations and practices surrounding the production and evaluation of generic drugs, ultimately safeguarding patient health across the board.

References

• - EpiVax Press Release
• - FDA Guidelines on Generic Drug Approval

This collaboration sets a precedent for future research and regulatory assessments, establishing a vital pathway for ensuring that generic medications not only serve their purpose but do so safely in the ever-expanding pharmaceutical marketplace.