23 September 2010
EMA/607491/2010
Interim report on the International API Inspection Pilot Programme

1. Objective
The objective of this report is to provide an interim update on the achievement of the Pilot Programme
after 18 months and to check if the results so far are in line with the expected deliverables.
2. Background of the pilot programme
In the context of the Transatlantic Administrative Simplification Workshop organised in Brussels
November 2007 and the 2nd International Summit in Dublin in December 2007 it was proposed, as an
initial effort to improve international sharing of information and to facilitate more risk based
approaches to inspection planning, that a small group of interested regulators establish a pilot project
for Active Pharmaceutical Ingredients (API). This would, build on equivalent API GMP standards and
taking into account a risk based approach, foster mutual confidence between regulators.
The pilot phase is restricted to inspections of API manufacturers carried out outside the participating
regions.

3. Activities of the pilot programme
Between December 2007 and May 2008, EMA approached a number of EU Member States active in the
area of inspections of active pharmaceuticals: France, Germany, Ireland, Italy, United Kingdom, as
well as the European Directorate for the Quality of Medicines and Healthcare (EDQM) from the Council
of Europe, the United States of America Food and Drug Administration (US FDA) and the Australian
Therapeutic Goods Administration (TGA).
A start date of the operational phase of December 2008 was marked by the actual sharing by all
parties of their inspection plans according to a previously agreed template and the sharing of
information on inspections carried out in the last 24-36 months. The pilot phase was supposed to last
for 18 months from the date it became operational but as setting up the practical details to implement
the project took some time it was decided in November 2009 during a plenary meeting in Washington
to extend the pilot an additional 6 months. This would have the advantage of two full years of
functioning and it was agreed to publish a final report in December 2010 where the outcomes will be
analysed and a recommendation for future action made.

Nevertheless it was decided to publish after June 2010 the present interim report, the date when the
programme was originally supposed to end.
4. Expected deliverables and key performance indicators
The following items were originally identified as key performance indicators:

• Increased transparency and visibility of inspections performed by participating authorities
• Decrease in “duplicate inspections”, (inspections of the same product or sites carried out by more
  than one participating authority within a similar time period)
• Increase in the number of inspections performed of value to more than one authority
• Overall increase in the number of API sites inspected by participating authorities for all inspections
• Positive assessment of the deliverables by the participating authorities

Increased transparency and visibility of inspections performed by
participating authorities
The key element of increased transparency and visibility is the elaboration, based on the contributions
of all participants, the maintenance and sharing of a Master List which records the sites of interest for
the participants including (when available) the APIs produced at the site, the date and outcome of the
last and the date of the next, planned, inspection.
To date the participants submitted the following into the Master List:
1046 site entries were provided by the participants together, from which:

• Europe submitted 499 sites (France: 44; EDQM: 173; Ireland: 4; Italy: 11;EMA: 112; UK: 51;
  Germany: 104)
• US FDA submitted 352 sites
• Australian TGA submitted 195 sites

In the Master List the sites which are of interest to more than one participant i.e. “shared” are
highlighted in order to identify them easily as they are the starting point for collaboration.
Not all participants have yet submitted all the API manufacturing sites which supply APIs to their
national territories but based on the present information the tables below show the number and
manner in which the sites are shared:

The Master List also contains the inspection dates and outcome of inspections performed during 2009
and 2010, about 250 inspections in total done by the participants of the 3 regions, Australia, Europe,
and US, which were submitted by the participants.
With all those elements organized and easily available to all participants, the Master List has increased
transparency and visibility of the inspection activities.
Decrease in “duplicate inspections”
The number of joint inspections organised so far, thus avoiding duplicate inspections are:

1. Europe (EMA, EDQM) participated in 6 joint inspections: 5 with TGA and 1 with FDA.
2. FDA participated in 2 joint inspections: one with 1 Europe (EMA) and 1 with TGA.
3. TGA participated in 6 joint inspections: 5 with Europe (EMA and EDQM) and 1 with FDA.

In total: 7 joint inspections were performed:
1. Europe (EDQM) / TGA : India
2. Europe (EDQM) / TGA : India
3. Europe (EDQM) / TGA : India
4. Europe (EDQM) / TGA : India
5. Europe (EMA) / FDA : Croatia
6. FDA / TGA : Mexico
7. Europe (EMA) / TGA : Japan

4. 2 planned and confirmed joint FDA/TGA inspections in Japan were ultimately cancelled.

However, it has been noted that a number of duplicate inspections were still performed and the
reasons for this will be explored in the final report:
Country of the
inspected sites
Inspectorates Dates of the duplicate inspections
Japan US / Europe (ZLG) 2009 February / September
China US / Europe (EDQM)
US / Europe (EDQM)
2009 July / October
2009 February / February
India US / Europe (EDQM)
US / Europe (EDQM)
Europe (EMA) / US
US / Europe (AFSSAPS)
Europe (ZLG) / US
US / Europe (EDQM)
US / Europe (EDQM)
2009 March / April
2009 April / June
2009 October / 2010 February
2009 February / September
2009 February / April
2009 April / 2010 February
2009 January / April
Increase in number of inspections performed of value to more than one
authority
The exchange of inspection-related information included in the Master List allows participants to know
about inspections performed by other participants and their outcome. In case they need more
information they can request a copy of the inspection report. Based on the information regarding the
planning of inspections, the participants can also contact each other to ask for an already planned
inspection to have its scope extended so that the shared report covers more products and is therefore
of value for more than one authority.
The number of inspection reports requested is as shown in the below table:

                          Requested by Europe Requested by FDA Requested by TGA
From Europe                      -                               20                     7
From FDA                       47                               -                      8
From TGA                       16                             16                      -

Overall increase in number of sites of API inspected by participating
authorities
It is not possible to be concise about an overall increase in the number of sites inspected, but because
of the sharing of information and inspection reports it is self-evident that resources were freed up for
other priorities including inspection of sites which are not shared by other participants and/or which
were never inspected before.

Region-specific analysis will be developed in the final report based on the feedback of the participants.
Positive assessment of the deliverables by the participant authorities
This will be developed in the final report based on the feedback of the participants and will look at a
wider range of deliverables.
5. Conclusion
There is an unquestionable strong commitment of the participants in the pilot programme and there is
an essential public health incentive to collaborate on the inspections of API manufacturers worldwide.
The achievements of the pilot to date are promising because collaboration has started and palpable
results of team work within the pilot programme are already available. However, a full continuous
collaboration between the participants will certainly need additional effort as there still appears to be
some duplicated inspections.
Still, the tools developed during the pilot programme, especially the Master List and its wide ranging
information on the API manufacturing sites supplying APIs to the three participating regions is a
precious source of information. It is also a model which can be used to design the future Eudra GMP
module for sharing of inspection planning.
To further develop collaboration, tools will have to be adapted and improved to better suit the intended
use and national systems will have to be adapted to make better use of international cooperation
opportunities.
The project is contributing substantially to the better understanding of regional approaches to
inspection and building mutual confidence.
A more comprehensive analysis of learnings will be provided in the final report.