6 August 2003
the GMP Regulations Be Harmonised Worldwide?
For a long time, the worldwide harmonisation of the GMP requirements
seemed inconceivable. But now, this idea is not so unthinkable any more.
Many will find it astonishing that such
an initiative comes from the FDA. We have already reported several times
about the FDA reform "cGMP for the 21st Century." Some people
may just have seen it as a normal improvement process of an authority.
However, the actual consequences of this initiative will now
also become clear to the last remaining sceptics.
The initiative, about which we reported
in our News of 4 September 2002,
has been established in order to review and revise the now almost
25-year-old GMP regulations fundamentally. The
Risk-based Approach, as it is called, is at the heart of this initiative. By means of this approach, the FDA
intends to coordinate all of its activities, e.g. the creation of
guidelines, but also the conduct of inspections. In the interest of
patient safety, special focus is now to be placed on those processes that
involve a high risk for the patient. This means that the regulations will
certainly place more emphasis e.g. on aseptic processing rather than on
classic solid dosage forms manufacture for a generic drug.
The FDA does not see this initiative as
an isolated activity. The Agency also intends to introduce this approach
into international harmonisation. It aims at harmonising inspections and
regulations and thus at increasing patient safety while reducing costs. To
reach this aim, the FDA intends to harmonise the GMP requirements in
important areas via the International
Conference on Harmonisation (ICH). With ICH Q7A, there are already GMP
regulations (GMP for active pharmaceutical ingredients) that have been
harmonised worldwide. The other harmonised regulations in the triad
consisting of Europe, Japan, and the USA concern mainly the registration
of medicinal products. At the moment, the FDA is investigating whether it
should join the Pharmaceutical Inspection Convention Scheme (PIC/S). Only
few months ago, this would have been absolutely unthinkable. But the first
steps that have been taken leave no room for doubt.
The following paragraphs were taken from the minutes of the FDA meeting
for preparing the participation in ICH6 on 24 June 2003:
Ms Showalter, ICH Coordinator of FDA: "The way we are going to do the meeting today, we are
going to go through some of the big topics for the Brussels meeting. One
of the big items on the agenda is actually the ICH portion of the GMP
Program, the Drug Product Quality, or GMP, Program for the 21st Century."
"When we decided to take the GMP Initiative up in ICH, we had some
concerns about whether ICH would be an appropriate venue for this. As we
went, we reflected on some of the kinds of topics that we had taken in the
past to ICH and we realized that there were some similarities with other
topics in terms of the process that we might use for this one."
"One of the other venues that you will find repeatedly gets mentioned,
and we had a discussion of this at our February meeting, is the PIC/s.
That is something that we are currently investigating as a venue for
further regulatory collaboration on this topic."
The FDA already presented its approach at the preparation meeting in
Brussels for the coming ICH6 Conference, where it fell on sympathetic ears.
In the minutes of the ICH Meeting from 15 to 18 July, it says:
The Steering Committee was pleased to hear
the positive outcome of a brainstorming workshop on initiatives related to
a risk-based approach to Drug Product Quality. This session was attended
by more than 60 designated experts from the six ICH parties, observers and
non-ICH parties. The workshop discussion led to a general agreement on a
high level vision: a harmonized pharmaceutical quality system applicable
across the lifecycle of the product emphasizing an integrated approach to
The Steering Committee agreed that the experts from the six parties
will work further on two areas:
- on Pharmaceutical Development incorporating elements of Risk and
Quality By Design, and covering the product lifecycle.
- on a better definition of the principles by which Risk Management is
integrated into decisions regarding Quality including GMP compliance
both by the regulators and industry.
Industry will, in addition, produce a Quality Systems Scoping Document
including GMP as a subset, which should address areas of perceived
differences in the three regions.
It was also agreed to include a one-hour session of presentations on
these GMP-related discussions and initiatives in the programme of the ICH6
And what does the industry think about it? It is positively
surprised! It considers the new FDA Initiative "cGMP for the 21st
Century" as an extraordinary chance to harmonise the requirements and
to focus them on the risk for the patient. Within the shortest possible time, EFPIA, the
European Federation of Pharmaceutical Industries and Associations, has produced a
separate paper on this subject. Here just a brief excerpt that shows how
positive EFPIA's reaction to this FDA initiative was:
EFPIA welcomes the FDA's initiative to develop regulations and guidelines that would result
in advancing scientifically sound and integrated systems, applicable to
ensuring pharmaceutical product quality. EFPIA also appreciates the chance
to comment on the concept paper and to participate in further discussion at
the ICH meeting in Brussels in July 2003.
So this unique FDA initiative will not only influence the area regulated
and inspected by the FDA, but it will also have a direct impact on the requirements here in
One essential aspect of the FDA's cGMP
Initiative is Process Analytical Technology (PAT). On behalf of the
University of Heidelberg, the European Conference and Workshop
Infrared Spectroscopy and FDA's PAT Initiative
is held in Heidelberg, Germany, on 17-19 September. Dr Ali Afnan from the FDA will be
among the speakers.
The most-discussed GMP requirements that
differ between Europe and the US are those on electronic records and
signatures. Especially for the implementation in the laboratory, both the
EU-GMP and the FDA requirements are examined at the European Conference
Requirements for Laboratory Computers and Records
in Vienna, Austria,
on 17-19 September.
As mentioned above, ICH Q7A (GMP
for active pharmaceutical ingredients) is the first GMP guideline that has
been harmonised. It will be one of the topics of the
APIC/CEFIC European Conference on Active Pharmaceutical Ingredients.
Dr Nasr and Dr Miller from the FDA will be among the 23 speakers.
Since its foundation, the European
Compliance Academy (ECA) has been focusing its activities on imparting
both the EU GMP requirements and the FDA cGMP requirements. Now it turns
out that ECA's decision was, and still is, pointing the way ahead!
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