Implications for APIs in the European Falsified Medicines Directive - Pharmaceutical Technology

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Implications for APIs in the European Falsified Medicines Directive
Two industry groups offer perspectives on The European Falsified Medicines Directive.

Pharmaceutical Technology
pp. s44-s49

FMD sparks concerns
PharmTech: Do you think the measures contained in the FMD are sufficient to ensure the quality of pharmaceutical ingredients coming into the EU or are there other measures that need to be taken?

APIC and EFCG: No, the FMD does not sufficiently ensure the quality of APIs entering the EU. We have been very close to this topic since the FMD concept was born, and we remain concerned that, despite its objectives, it fails to fully meet the needs of EU patients with respect to product quality. Its effectiveness is still too dependent on industry’s supply chain self-evaluation and open to corrupt practices. Other measures that are needed include:

  • Stricter enforcement of existing laws by all member state regulatory authorities, plus tough sanctions to punish the violators
  • A consistent approach of member states when transposing the FMD into national law throughout the EU
  • A change in the existing laws to include mandatory inspections by competent authorities of all API manufacturers with the industry paying for extra regulatory resources if needed similar to the Generic Drug User Fee Act (GDUFA) in the United States
  • APIs contained in imported finished and semifinished drug products, mixtures of API with excipient(s) and semifinished (crude, moist) APIs should be included in the scope of the FMD.

The EC should have rigorously tested its assumption that there are 15,000-20,000 API manufacturers selling APIs into Europe before they decided not to propose the mandatory inspection of all API producers. In fact, the Heads of Medicines Agencies survey of medicine manufacturers in Europe, published on Mar. 27, 2013, showed that the top 18 third-country manufacturers/exporters of APIs to Europe had only 1479 manufacturing sites (9). It is, however, never too late for the EC to re-consider mandatory inspections to better protect EU citizens and patients.

Inspection process
PharmTech: One concern raised by the FMD is the adequacy of enforcement measures, particularly the inspection process with the new directive lacking a provision requiring mandatory inspections of API producers in third countries (i.e., countries outside the EU). From an industry perspective, what are the advantages/disadvantages of the current inspection process of API producers in third countries? In what areas can the process be improved and at what level/jurisdiction should it be made?

APIC and EFCG: The advantage of the current inspection process eases the continuity of supply of APIs from third countries for EU patients and, hence, avoids major product shortages. The disadvantage is the continued risk of substandard APIs/products entering the EU due to a lack of adequate enforcement and tough sanctions to punish individuals and companies. We suggest the following process improvements:

  • Ideally, change the FMD to provide for mandatory inspections by EU authorities of API producers in third countries with industry helping to pay, or
  • Achieve the same end result by providing for mandatory inspections of third-country API producers by European authorities together with other country authorities applying the same EU GMP standards to share the inspection responsibility via mutual recognition agreements (e.g., US, Australia, and Japan)
  • Inspectors should be trained to detect falsification or fraud, for example, facade constructions, ghost plants, and falsified official papers.

GDP guidelines
PharmTech: Earlier this year, the EU finalized a guideline on GDP for medicinal products in the EU. Although it addresses the distribution of medicinal products from an end-market perspective, the intent of the guideline is to further ensure the quality of medicines coming into the EU. From an industry perspective, what are the implications for suppliers of APIs and other pharmaceutical ingredients?

APIC and EFCG: The industry must ensure transparency of sources and intermediaries (brokers and traders) and a register of evidence of compliance at each step along the entire supply chain from raw-material suppliers to the final medicine. Additionally, the EC published in February 2013 a draft guideline on the principles of Good Distribution Practices for Active Substances as part of the implementation of the FMD. Although this guideline only lays down the “principles” of GDP, it will be a step in the right direction.


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