Fears expressed that API manufacturing could be driven out of Europe
The European Commission’s proposal to extend good manufacturing practice (GMP) guidelines for drugs to include active pharmaceutical ingredients (APIs) has met with a mixed response from industry groups and drug manufacturers, some of whom have been heavily critical.
Twenty-eight groups responded publicly to the Commission’s concept paper, published earlier this year, which proposes extending the scope of Directive 2003/94/EC.
Several claim the proposals might create more confusion than coherence. For example, Swiss multinational DSM Nutritional Products expressed concern at the proposal’s statement that ‘the principles and guidelines would be the same during the manufacturing of active substances as well as medicinal products’.
This would create disharmony within the International Conference on Harmonisation initiative involving the EU, Japan and the US, and would increase manufacturing costs for APIs, DSM argued. The consequence would be to ‘provide more incentive to unscrupulous manufacturers to avoid the higher costs of compliance, and penetrate aggressively into a higher cost market’, the company claimed.
The Bulk Pharmaceuticals Task Force (BPTF) of the US Society of Chemical Manufacturers and Affiliates (SOCMA) warned that, because the generic API industry is highly price competitive, the cost of ensuring API facilities comply with this new standard ‘may force some API producers to choose to exit the European market’.
BPTF also suggested that implementation of drug product GMPs for APIs will ‘further accelerate the relocation of API manufacturing to low-wage, third-world jurisdictions…[which have] poor regulatory oversight’ and could potentially let lower-quality APIs into the European market.
PDA Europe, a German-based subsidiary of the American non-profit Parenteral Drug Association, which promotes r&d, said medicinal products and active substances can have fundamentally different characteristics, formulations and manufacturing processes. Consequently, PDA argued, principles and guidelines for GMP aspects of medicinal products are frequently very different than those for active substances.
PDA recommended instead that the directive should be modified by creating a new, separate section dedicated to GMP expectations for drug substances or APIs. ‘Having separate statements of guidance…will benefit the authorities and the industry by mitigating future confusion or grey areas in GMP interpretation and compliance,’ PDA maintained.
Comments from Germany’s Federal Ministry for Health and from Bogin, the Association of the Dutch Generic Medicines Industry, echoed support for laying down the principles of GMP for active substances in a separate Directive.