It looks as if the advanced state of pharmaceutical manufacturing in the U.S. will pave the abbreviated pathway to the making of biosimilars.
The FDA last week issued its highly anticipated draft guidance documents on biosimilar product development. Sprinkled throughout the the document on "Quality Considerations" were references to how advances in manufacturing can shorten the road to commercial production.
The document points out that in the past, the FDA required clinical testing to prove a change in a manufacturing process "does not adversely affect identity, purity, or potency of its FDA-approved product." But since 1996, while additional testing might be required, the agency has approved many changes in manufacturing for licensed biological products based on "quality criteria and analytical testing."
While manufacturing by a biosimilar maker will be different than the original, "[g]reater knowledge due to advances in science and technology, and improvements in manufacturing processes, process controls, materials and product testing, as well as characterization tests and studies, facilitate the use of an abbreviated pathway for the approval of a protein product," the FDA said.
The proposals largely followed the outlines FDA officials have been suggesting for months. Regulators will typically require developers to provide clean animal data on toxicity and compelling PK and PD data from human studies. Additional studies may be required before a developer can win approval for an "interchangeable" therapy, which would allow payers and pharmacists to automatically switch a patient to a less expensive copy.
While manufacturers can rely on much of the discovery and early-stage work of the target drug, regulators made it clear that these new drugs will typically require expensive late-stage human studies.
About the manufacturing process specifically, the draft says: "A comprehensive understanding of all steps in the manufacturing process for the proposed biosimilar product should be established during product development. Characterization tests, process controls, and specifications that will emerge from information gained during process development must be specific for the proposed biosimilar product and manufacturing process. The use of Quality-by-Design approaches to pharmaceutical development, along with quality risk management and effective quality systems, will facilitate the consistent manufacturing of a high-quality product. A type II Drug Master File (DMF) would not be acceptable for a 351(k) application because, as with 351(a) BLAs, the license holder needs to have knowledge of and control over the manufacturing process for the biological product."
Among other things, the guidance document on biosimilars had this to say about manufacturing:
--Advances in manufacturing science and production methods may enhance the likelihood that a product will be highly similar to another product by better targeting the original product's physiochemical and functional properties;
--A scientifically sound characterization that provides a comprehensive understanding of the chemical, physical, and biological characteristics of the proposed biosimilar product is essential to the design of the manufacturing process and to the conduct of development studies; and
--Advances in manufacturing science and Quality-by-Design approaches may facilitate production processes that can better match a reference product's fingerprint. Such a strategy could further quantify the overall similarity between two molecules and may lead to additional bases for a more selective and targeted approach to subsequent animal and/or clinical studies.
Citing data from Datamonitor, Reuters reports that the global market for copies of biotech medicines will grow to $3.7 billion by 2015 from just $243 million in 2010, as more than 30 branded biologics lose patent exclusivity. The Congressional Budget Office has estimated that the U.S. could save $25 billion over 10 years using biosimilars. The FDA made it clear that while it will expect rigorous science and high production standards, saving money is central to the proposal.
"These draft documents are designed to help industry develop biosimilar versions of currently approved biological products, which can enhance competition and may lead to better patient access and lower cost to consumers," Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said upon release of the proposals.
- here's the Reuters story
- here's a copy of the rules (.pdf)
- read the FDA release