 The
annual APIC/CEFIC European Conference on APIs is the leading event for
European Regulatory- and GMP API professionals. This year the conference
was held for the 8th time, this time in Germany's capital
Berlin from 12 to 14 October.
There were more than 200 participants from 25 countries all over the
world. As in previous years, the conference was divided into a GMP- and a
Regulatory Affairs part in order to take the increased attention for
API-related pharmaceutical registration matters into account.
As mentioned in the conference flyer, there indeed probably has never
been a better moment in time for an API Conference than October 2005. The
regulatory systems in the EU and in the US are about to go through
important changes. In the EU a major API milestone will be reached on 30
October 2005. This date is the deadline for the EU Member States to
finalise the transposition of the amendments of the EU Directives
2001/83/EC and 2001/82/EC into national law. From this date on APIs for
the manufacture of both human- and veterinary medicinal products have to
comply with cGMP for APIs as defined in the ICH/Q7A Guideline that has
recently been included as Part II into the EU GMP Guide.
In the meantime major progress has been made in the USA towards
implementation of the elements of FDA's 21st Century
Initiative.
Many of the topics presented and discussed during the 8th
CEFIC/APIC Conference related to these changing regulatory realities in
the EU and the USA.
A total of 21 speakers from the European- and US authorities -
including speakers from the European Commission, EMEA, EDQM, RIVM, BfArM,
FDA - as well as from leading European- and US pharmaceutical and API
companies presented and discussed the latest developments. This year
special attention was also given to the increasingly worrying situation
for API manufacturers in Europe where over the past decade a dramatic
shift towards imports of APIs from especially Asia has taken place.
Matt Moran, President of the APIC, opened the conference with a talk
about the history of API regulations in the EU and the implications for
the market. He emphasized that the playing field for the API industry is
increasingly tilted against the European API industry to the advantage of
Asian competitors, partly due to differences in levels and costs related
to regulatory- and GMP compliance. Meanwhile over 70% of APIs used in
medicines in Europe are imported from India and China compared to
approximately 10% in the early 80s. The lack of oversight over API
manufacture and -trading through inspection and enforcement by EU
authorities implies a risk for European patients' safety in the form of
sub-standard, potentially dangerous APIs. This is the reason why APIC has
joined forces with the newly established European Fine Chemicals Group
(EFCG) to defend the competitiveness of the European API sector, as
vividly presented by Guy Villax, CEO of API manufacturer Hovione SA,
Portugal and Chairman of the Pharmaceutical Business Committee of EFCG.
Mrs Sabine Atzor from the European Commission's DG Enterprise and
Industry, Brussels, gave a comprehensive insight into the new
pharmaceutical legislation and its subsequent implementation. As GMP
audits by dosage form manufacturers are a major tool for evaluating the
GMP compliance status of an API manufacturer or distributor, an important
aspect highlighted by Mrs Atzor was - provided that certain conditions
will be met - the acceptability to the authorities of third party GMP
audits of API manufacturers. This is important news in relation to the
standardized third party audit programme that APIC has developed: the
'APIC Audit Programme', aimed at relieving the industry from excessive
audit burdens. The details of the APIC Audit Programme were presented and
discussed during one of the parallel sessions of the conference.
While on the one hand the direction into which regulatory change is
taking place in the EU is in part different from the US, at the same time
there is a strong drive for harmonisation between the two systems. It was
encouraging to see during the conference how renewed efforts have recently
been started to aim for more alignment between the two areas.
 Dr.
Nicholas Buhay, CDER/FDA, gave a comprehensive insight into the highly
ambitious and challenging 21st Century Initiative from the FDA's point of
view, while Dr. Gerald Migliaccio, Vice President - Global Quality
Operations at Pfizer / US, discussed the new regulatory paradigm from
industry's point of view. An important objective of the new US regulatory
system is to take away unnecessary regulatory barriers to the upgrading of
pharmaceutical including API manufacture towards modern industry
standards, while at the same time protecting the health and safety of the
patient event better than before. One of the central mottos of the new FDA
paradigm is 'to put change back into the hands of industry'; with
the important footnote that this will apply only to manufacturers who can
prove that they are capable of fully controlling their manufacturing- and
other changes in an appropriate, responsible manner. For those companies
it should come down largely to having to file less regulatory submissions
(supplements) while being subject to risk-based and focused inspections
while GMP requirements of course continue to apply fully. Dr. Moheb Nasr,
Director of the Office of New Drug Chemistry, Office of Pharmaceutical
Science, CDER/FDA explained how the new regulatory paradigm is being put
into place and how new thinking and new ways of communicating will be
required both from FDA and from industry.
Particularly regarding the way of handling the filing and authorisation
of manufacturing- and other changes, the EU has been drifting into the
opposite direction with Variation Regulations even having been qualified
by the API industry as being 'draconian'. Still these revised Regulations
that were implemented in 2003 are seen as one of the major reasons for
inhibiting improvement and innovation in API manufacture.
In this context it was welcomed by the API industry that the EMEA/QWP's
current view on Variation No 15 ('Submission of a new or updated CEP'), as
presented by its vice-chair Dr. Susanne Keitel, includes the exclusion of
residual solvents from the scope of its 'Condition 2': Changes in residual
solvent levels on CEPs - provided these remain within ICH/Q3C limits -
should therefore lead to Variations Type I only.
Mrs Diana van Riet-Nales of the RIVM gave an insight into how Dutch
authorities handle Variations with special focus on ASMF amendments.
Another point of major concern for the API industry was also
extensively highlighted: With Directive 2001/83/EC as amended coming into
force, the responsibility for using GMP compliant APIs for the manufacture
of medicinal products for both, human- and veterinary use, rests on the
shoulders of the dosage form manufacturers. API inspections by the
competent authorities will only be considered when there are grounds for
suspecting serious non-compliance with the GMP guidelines or on request of
the manufacturer. This situation differs strongly from that in the US,
where FDA performs worldwide inspections of pharmaceutical- and API
manufacturers on a regular, routine basis.
Another reason why improvement and innovation at compliant API
manufacturers are being blocked is the existence of great differences
between the regulatory requirements in each region of the world. This lack
of harmonisation forms an extreme burden for the API industry in a world
where regulatory requirements are increasing everywhere, as explained by
Dr. Jan Smeets, DSM Anti-Infectives/The Netherlands, who presented
striking examples of different filing requirements worldwide.
Mrs H้l่ne Bruguera / EDQM presented recent experiences with the new
CEP change submission guidelines. She also updated the audience on the
EDQM inspection programme and mentioned that this has thus far resulted in
CEPs of in total seven manufacturers and traders having been suspended,
all relating to API manufacture in China and India.
 Amidst
all the ongoing and coming changes to the regulatory systems the ICH
programme may offer opportunities to build bridges between the systems to
make them more compatible. An important, recent example is the newly
proposed ICH Q10 topic on Quality Systems and its possible implications
for continuous improvement. Dr. Joyce Ramsbotham, Solvay Pharmaceuticals,
presented its history and the current status.
The last two lectures dealt with a topic on which the final speaker -
APIC vice-president Dr. Chris Oldenhof of DSM Anti-Infectives stated
that it 'probably contained a root cause of many of the regulatory
problems we are discussing at this event': Transparency and cooperation in
developing regulatory documents. He concluded that also in the development
of EU- & US regulations and guidelines much earlier and more extensive
industry involvement is needed, as already proven by the successful ICH
procedure. As presented by Ms. Dunja Schumacher of EMEA, the new EMEA
Procedure provides for a first careful step into that direction.
A special feature of this year's APIC conference was the inclusion
during the second conference day of parallel sessions that appeared to be
highly appreciated by the participants. Each delegate could choose to
attend 2 out of 8 different sessions. The sessions on 'PAT Latest
developments' and 'Impurities' attracted by far the most participants with
nearly 90 attendants in each group. Other topics of high interest were the
sessions about 'Vendor qualification', 'Counterfeit in the API supply
chain' and 'The APIC Audit Programme'. Very specialised topics were
covered with the computer-related session on 'SAP and validation', a
session focussing on 'Microbial-, viral and TSE risks of biotech products'
and another one covering the 'Implications of the clinical trials
directive'.
In conclusion: The conference was an ideal arena for open and fruitful
discussions that will hopefully result in a further increase in mutual
understanding and cooperation between the authorities and the API industry
and in an ever stronger basis for the harmonisation of API regulations
worldwide.
Considering the state of change the API regulatory situation is in
today, it will be very interesting to see what the 9th
APIC/CEFIC European Conference on APIs in 2006 will bring.
Conference folders can be ordered from CONCEPT HEIDELBERG the organiser
of the Event. You will find the contact details below
25.10.05,
Dr. Barbara Jentges
CONCEPT HEIDELBERG GmbH
Rischerstrasse 8
69123 Heidelberg
Germany
www.concept-heidelberg.de
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