Comments from Merck come two months after the US Food and Drug Administration (FDA) released draft guidance to prevent a reoccurrence of the 2008 contamination. While welcoming FDA efforts to tighten the heparin supply chain, Merck wants the Agency to clarify certain points and definitions.
“A clear and unambiguous definition of crude heparin is of the utmost importance”, Ekopima Ibia, US regulatory policy lead at Merck, wrote in feedback to the FDA. The problem, as Ibia sees it, stems from “inconsistent and confusing” use of the term ‘crude heparin’ by the FDA in its draft guidance.
Clear definitions are needed to make sure testing is effective and efficient. If the FDA defines crude heparin as the intermediate in the production process of the unfractionated active, additional tests for oversulfated chondroitin sulfate (OCSC) may fail to cut the risk of contamination, Ibia wrote.
Heparin-specialist Celsus Laboratories also picks up on the confusion. In feedback to the FDA Daniel Reed, general counsel at Celsus, highlights a section of the draft guidance that says crude heparin is “often intended for use as a component of other drugs”.
In contrast, a FDA letter, shared by Celsus, about detention of crude heparin said it “is considered to be a drug; not a component of a drug or a chemical intermediate”. Citing other FDA regulations, Reed writes that crude heparin fails to meet the requirements for either a component or a drug.
“Crude heparin is the starting material intended for further processing by FDA drug establishments into heparin sodium USP API (active pharmaceutical ingredient), not a finished drug product,…or into heparin derivatives”, Reed wrote.