Several groups within the pharmaceutical industry have criticized the EC proposals. Some are particularly concerned that by
bringing together the two sets of guidelines, the Q7 standards for API GMP drawn up by the International Conference on Harmonization
(ICH) will be undermined. ICH Q7 provides a basis for international agreement on GMP standards on active ingredients.
The European Federation of Pharmaceutical Industries and Associations (EFPIA), which represents Europe's research-based drug
companies, said that bringing the two guidelines together would make interpretation of GMP both ambiguous and complicated.
Instead, EFPIA suggested placing the active substances guidelines in a separate section in the 2003 directive or putting these
guidelines into a new directive. EFPIA stated that the obligation on API manufacturers to verify the source of starting materials
was unenforceable, while the European Generic Manufacturers Association (EGA) thought that it was beyond the scope of the
existing EU guidelines for active substance GMP.
Several groups involved in the consultation warned that adapting to the new framework would require a period of more than
nine months after publication, particularly for API producers outside the EU. Some suggested that this period between publication
and enforcement should be as long as two years, which could result in the FMD not being fully implemented until 2015.
Another controversial aspect of the legislation is the need for imports of active substances into the EU to be accompanied
by written confirmation from a national regulatory authority that the plant manufacturing the API complies with GMP standards
equivalent to those in the EU. Proposals on this subject were brought forth by the EC in a public consultation. According
to the EC, "equivalence" to EU standards is defined as adherence to ICH Q7 and the active substances GMP standards of the
World Health Organization (WHO). Under the FMD, written confirmation will have to be provided with API shipments from July
However, the EC is also planning to operate a two-tier system under which some countries will be exempted from having to provide
written confirmation on the grounds that their GMP regulatory and monitoring standards are equivalent to those in the EU.
To date, Switzerland, Israel, Singapore, Brazil, and Australia have requested to be assessed for exemption. Earlier this year,
it was widely reported in the media that India and China, which together account for approximately 80% of API imports into
the EU, considered lodging a complaint with the World Trade Organization (WTO) that the written confirmation requirement was
an unfair barrier to trade. India seemed to be backtracking in September when the country's Pharmaceutical Export Promotion
Council (Pharmexcil) announced that the Indian government would be shortly setting up a competent authority to certify the
quality of API exports to Europe.
In a comment on the EC's concept paper on GMP guidelines for active substance, the China State Food and Drug Administration
(SFDA) said that APIs should be given the same manufacturing authorization as the production of medicines. Furthermore, the
SFDA said that the EU should launch its own compulsory GMP inspections for active substances so that it can issue its own
GMP compliance documents.
SFDA's line on GMP is similar to that being pursued by the EFCG. EFCG has been recently reiterating its stance that the only
sustainable solution to the EU's problems with substandard imports of active substances is the mandatory inspection by EU
regulatory authorities of non-EU active substance plants or by those whose competence is acknowledged through mutual recognition
agreements (MRAs). "The implementation of mandatory inspections, via an MRA approach, is a relatively small price to pay to
guarantee that the quality of APIs meets the EU standard," said Gian Mario Baccalini, chairman of the EFCG pharmaceutical
business committee, in a recent group press conference in Madrid.
EGA estimates the extra costs of a strict regime for vetting GMP standards for imported APIs to be as much as €1 billion (US$1.27
billion). Coupled with possible shortages of active substances if Asian producers cease their exports to Europe, this factor
could decide the outcome of the current discussion about the final implementation of the FMD.
Sean Milmo is a freelance writer based in Essex, UK, firstname.lastname@example.org.