Because the ICH guidelines cover individual aspects of pharmaceutical manufacture, there is no uniform single ICH guideline
for GMP for finished products, according to EMA. That said, "....there is pre-existing broad equivalence in requirements,"
says the EMA spokesperson. "We are in regular contact with our US and Japanese colleagues under different frameworks and do
not believe that the changes proposed are inconsistent with existing or planned requirements of those international partners."
Nonetheless, the divergences are beginning to concern manufacturers of medicines and APIs. "In general, we always advocate
that requirements should be harmonized between geographic areas as much as possible," says Chris Oldenhof, president of the
Active Pharmaceutical Ingredients Committee (APIC), a branch of the European Chemical Industry Council.
API producers in Europe are also worried that the scope of the alterations on starting materials could be too broad to be
effective. "If the required changes are to apply further upstream to include raw and starting materials throughout the synthesis
chain then they will not be realistic," says Oldenhof, who is also manager of external regulatory affairs at DSM (Heerlen,
The Netherlands). "It is well-known that unrealistic requirements usually lead to widespread noncompliance and even fraud."
The European Commission has declined to amend the EU guideline to allow for mandatory GMP inspections by regulatory agencies
of API plants, which has been a long-established demand of European API producers. "Without adequate plant inspections, levels
of compliance will always be quite low," says Oldenhof. "This is the main weakness of the proposals."
For APIC and the European Fine Chemicals Group, which also represents API producers, the Commission's suggested changes are
welcome overall because they tighten up existing GMP controls in an area in which it is notoriously difficult to enforce regulations.
Sean Milmo is a freelance writer based in Essex, UK.