Development of Complex Generics and Similar Biological Products: An Industrial Perspective of Reverse Engineering.

Generic drugs are developed to be bioequivalent to innovator formulation, matching them in dosage form, safety, strength, quality and efficacy. Known as "interchangeable multi-source pharmaceutical products," generics play a crucial role in reducing therapeutic costs and enhancing patient compliance. Over the past decade, generics have accounted for more than 90% of prescriptions in the U.S., which has driven down the average price of these drugs to nearly match production costs once market competition grows. Simple generics of small-molecule drugs are often produced through trial and error based on existing data, but complex generics require advanced techniques like reverse engineering to replicate the brand drug's release profile. These complex generics include sophisticated drug delivery forms that ensure the therapeutic agent is released gradually, maximizing effectiveness. Conversely, similar biological products highly similar to approved biologics-undergo rigorous analytical and clinical evaluations due to their complexity and the nature of biologic production. The increased demand for similar biological products is driven by expiring biologic patents, economic incentives, and regulatory advancements, with the market expected to grow significantly by 2026. The Biologic Price Competition and Innovation Act (BPCIA) enable abbreviated approvals for similar biological products, promoting affordability. Despite minor differences from original biologics, similar biological products undergo extensive testing to ensure safety and efficacy, following global regulatory guidelines that emphasize strict quality standards. This framework is essential for expanding patient access to effective therapies for conditions like cancer and autoimmune diseases while supporting healthcare sustainability.