The European Commission (EC) plans to extend GMP (good manufacturing practice) requirements to cover APIs (active pharmaceutical ingredients) as part of adoption of the falsified medicine directive. To make the finished product GMP directive more API-centric the EC is proposing new requirements,
“In particular, an obligation could be placed on the manufacturer of the active substance to make ensure that the starting material is sourced from the premises claimed by the manufacturer of the starting material”, the EC wrote in a concept paper .
The measure could tackle ‘shadow factories’. In the wake of the heparin contamination cases in 2008 US Food and Drug Administration (FDA) attempts to find the source of the problem revealed the presence of unregulated ‘shadow factories’ in China.
A 2009 FDA warning letter to Shanghai No 1 Biochemical & Pharmaceutical said: “The investigators determined that, contrary to your firm’s claims, manufacturing of heparin sodium was conducted at facilities other than the one identified in your DMF (drug master file).”
The Shanghai No 1 facility “was not manufacturing, and did not appear to have ever manufactured, heparin sodium USP”, the FDA wrote, and was instead sourcing material from an unapproved plant. An inspection of the subcontractor, Qingdao Jiulong, led to another FDA GMP warning letter .
If adopted the EC’s proposal would place the onus on API manufacturers to verify the source of their starting materials. It is unclear from the concept paper how European regulators would enforce the requirement.
The EC only proposes adding the starting material requirements to the GMP directive but other areas will be revised or removed. Most of the changes relate to requirements that are irrelevant to APIs.
For example, the EC proposes to remove rules relating to qualified persons, as well as marketing and manufacturing authorisations. The EC also proposes amending the scope of the document and definitions to include APIs.
Comments must be sent to the EC by 20 April 2012. The EC plans to adopt the act in 2013.