ANNUAL REPORT 2006

1. 2006 was another year of successful expansion with two additional

pharmaceutical inspectorates accepted as PIC/S Participating Authorities.

2. Poland’s Main Pharmaceutical Inspectorate (MPI) became PIC/S’ 29th

Participating Authority on 1 January 2006. MPI has been admitted following a
successful evaluation of the Polish GMP system (including an assessment visit by a
PIC/S Delegation in Poland).

3. Estonia’s State Agency of Medicines (SAM) was admitted at the autumn

meeting of the PIC/S Committee to become PIC/S’ 30th Participating Authority with
effect from 1 January 2007. SAM, which has been an Observer in PIC/S since 2001,
has been admitted after a long but successful evaluation, which also included an on-site
assessment visit.

Pharmaceutical Inspection Co-operation Scheme

The Pharmaceutical Inspection Co-operation Scheme (PIC Scheme) is an informal and

flexible arrangement between GMP inspectorates. It entered into force in November
1995. It is run in parallel with the Pharmaceutical Inspection Convention (see
Annex II). The common logo for both is PIC/S.

The Scheme retains and improves the Convention’s main features, i.e. the networking
and confidence building between the national inspection authorities, the development of
quality systems, the training of inspectors and other related experts and its work towards
global harmonisation of GMP. It is open to the participation of the inspectorates of
other countries.

The main decision-making body is the PIC/S Committee in which all Members are
represented and which meets at least once a year. The Committee is assisted in its task
by an Executive Bureau and a Secretariat.

The PIC/S Executive Bureau’s task is to prepare meetings of the Committee, implement
the latter’s decisions and recommendations, monitor the Scheme’s activities and prepare
the annual budget. The Bureau is composed of the Chairperson, two Deputies as well as
two Members of the Committee.
Annual Report 2006
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Operation of the Scheme

4. The PIC/S Committee, the PIC/S Executive Bureau and the PIC/S Working
Group on the Training of Inspectors met twice in the course of 2006.

5. The PIC/S Committee met under the chairmanship of Mr. Jacques Morénas
(France / French Health Products Safety Agency) in Düsseldorf (Germany) on 29-
30 May 2006 and in Geneva (Switzerland) on 21-22 November 2006.

6. During these two meetings, the Committee approved the 2005 accounts; it
discharged the Chairman for the financial year 2005; and it adopted a budget for 2007.
It also reviewed the operation of the Scheme, the assessment of new Applicants and the
reassessment of older Members. It noted that Latvia’s State Agency of Medicines
(ZVA) had succeeded to the State Pharmaceutical Inspection (SPI) and that Austria’s
AGES PharmMed would take over the PIC/S membership of the Federal Ministry for
Health and Women (BMGF) on 1 January 2007.

7. The Committee discussed and adopted a number of guidance documents and

monitored the activities carried out by the Working on Training and the Executive
Bureau. It re-elected Ms. Eija Pelkonen (Finland / National Agency for Medicines) as
Member of the Executive Bureau for the period 2007-2008.

8. The Executive Bureau met in Düsseldorf (28 May 2006) and Geneva
(20 November 2006): during the first meeting, the Bureau adopted Rules of Procedures;
at the second meeting, it carried out a salary review and performance evaluation of the
Secretariat staff.

9. The Working Group on the Training of Inspectors met under the chairmanship
of the PIC/S First Deputy Chairman, Dr. Johann Kurz (Austria / BMGF), in Düsseldorf
on 29 May 2006 (morning) and in Geneva (Switzerland) on 21 November 2006
(morning). During these two meetings it discussed various training events for PIC/S
inspectors (see “Training of Inspectors”).

10. As in the past, the PIC/S Secretariat continued to provide secretariat services to
the various PIC/S bodies (Committee, Bureau, Working Group on Training.). On
6 February 2006, the Secretariat moved to new offices located in the centre of Geneva
(Switzerland).

The Participating Authorities of the PIC/S

(Convention and Scheme taken together)
By the end of 2006, PIC/S comprised 29 inspectorates from Australia, Austria,
Belgium, Canada, Czech Republic (human & veterinary), Denmark, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein,
Malaysia, Netherlands, Norway, Poland, Portugal, Romania, Singapore, Slovak
Republic, Spain, Sweden, Switzerland and the United Kingdom (see also
Annex I).
 Annual Report 2006
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Membership Applications: Thailand, Malta and French Veterinary Agency apply

11. Three Agencies applied for PIC/S membership in 2006.

12. A first membership application was received from Thailand’s Food and Drug
Administration (Thai FDA) on 24 February 2006. At its spring meeting in Düsseldorf,
the Committee reviewed the evaluation report (based on documentation) made by the
Rapporteur and Co-Rapporteurs. At the same meeting, representatives from the Thai
FDA made a presentation on the Thai GMP system. At its autumn meeting, the
Committee mandated the PIC/S Chairman to visit – in connection with a WHO
assessment on vaccines – the Thai FDA in order to discuss the membership application.
This visit took place on 2 December 2006.

13. The second application was from Malta’s Medicines Authority, which officially
applied for PIC/S Membership on 2 October 2006. At its autumn meeting the
Committee appointed a Rapporteur in order to assess the application.

14. The third membership application was lodged on 11 December 2006 by the
French Agency for Veterinary Medicinal Products (AFSSA - ANMV). The French
Health Products Safety Agency (AFSSAPS), responsible for medicinal products for
human use, is already a PIC/S Participating Authority.

15. The following progress was made with regard to other membership applications:
♦ Assessment visits took place in both South Africa and Argentina: the visit to the
South African Medicines Control Council was from 3 to 9 September 2006
while the visit to Argentina’s “Instituto Nacional de Medicamentos” (INAME)
took place from 27 November to 1 December 2006. Both visits aimed at
assessing the local GMP inspection system.

♦ Presentations were made on the GMP inspection systems of the Lithuania’s State
Medicines Control Agency (SMCA) and the USA’s Food and Drug
Administration (US FDA). A list of questions in connection with the US FDA’s
application, prepared by the Rapporteur, was also discussed.
♦ The membership application by Israel’s Ministry of Health was reviewed and an
on-site assessment was agreed in principle but only once a licensing system has
been introduced in Israel.

16. No progress at all was reported on the membership application of Ukraine’s

Ministry of Health.

Joint Reassessment Programme

17. The Joint Reassessment Programme (JRP) aims at ensuring that older Members
of PIC/S still comply with the PIC/S requirements, as demanded from new Applicants.
It is run in parallel with the EU’s Joint Audit Programme (JAP) and uses basically the
same tools.
Annual Report 2006
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18. In the course of 2006, the reassessment of the Greece’s National Organization
for Medicines (EOF) was successfully closed while a reassessment visit took place at
the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) from 24 to
28 April 2006. The report was still pending by the end of the year.

19. The reassessments of Iceland’s Medicines Control Agency (IMCA),

Switzerland’s Agency for Therapeutic Products (Swissmedic) and Liechtenstein’s
“Kontrollstelle für Arzneimittel” (KA), based on already existing Canadian assessment
reports, were successfully launched in 2006.

20. The Committee decided to reassess Austria’s AGES PharmMed and established
a team composed of German, Italian and Swiss inspectors. It also agreed to reassess
Australia’s Therapeutic Goods Administration (TGA) once its merger with New
Zealand’s Medicines and Medical Devices Safety Authority (Medsafe) will become
effective (1 July 2007).

Training of Inspectors

21. In 2006 the Working Group on the Training of Inspectors reviewed (i) the
operation of the Joint Visits Programme; (ii) past and future Expert Circles meetings
(notably objectives for 2007); (iii) the preparations for the 2006 Seminar (see below)
and the 2007 Seminar on “The Inspection of the Manufacture of Solid Dosage Forms”;
and (iv) the evaluations of the 2005 and 2006 Seminars.

22. It decided to revise the PIC/S Guideline for Expert Circles (PI 022-1) and
discussed the organisation of the 2008 Seminar on “Good Distribution Practices”, which
Poland’s Main Pharmaceutical Inspectorate (MPI) has generously offered to organise in
Krakow. It also agreed that the 2009 Seminar would be on Herbal Medicines (venue to
be decided).

23. Based on a proposal made by the Working Group on Training, the Committee
decided to create a Working Group on Good Distribution Practices (GDP). Based on
another proposal made by the PIC/S Chairman, the Committee agreed to set up a new
Expert Circle on Quality Risk Management in order to train Inspectorates. It also
decided to open up the Joint Visits Programme to GCP inspectors on a trial basis
following a request by EU GCP inspectors to benefit from this training tool.

Joint Visits Programme

24. At the end of 2006, there were 23 joint visit groups under the Joint Visits
Programme representing around 70 inspectors from 27 different nationalities.
 Annual Report 2006
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PIC/S Joint Visit Groups

Another means of training inspectors of the PIC/S countries has been devised in
the form of joint visits to manufacturers by inspectors of different countries.
Groups of three inspectors are set up on the basis of applications sent to the PIC/S
Secretariat. Each inspector is assigned within his/her group to act in turn as host
for one year and guest for the other two years.

Visits are carried out in English or in a language commonly agreed by inspectors.

Joint reports are drafted after each visit and sent to the Committee for evaluation.

The organisation of the joint visits has proved an excellent means for the further
training of inspectors through mutual exchange of experience and a useful
contribution to the maintenance of mutual confidence between competent
authorities. Participants have also the possibility to discuss and compare their
inspection methods and their interpretation of GMP rules.

2006 PIC/S seminar in Düsseldorf

25. The topic of the 2006 PIC/S Seminar was “Quality Risk Management and
related ICH topics”. The Seminar took place in Düsseldorf (Germany) from 31 May to
2 June 2006. It was organised by the German Central Authority of the Laender for
Health Protection regarding Medicinal Products and Medical Devices (ZLG).

26. The Seminar was attended by around 110 participants from 39 countries. This
number includes inspectors from a number of non-Member agencies coming from
Argentina, Cyprus, Croatia, the European Medicines Agency (EMEA*), Israel, Japan,
Lithuania, New Zealand, NIS**, Taipei, Thailand, Serbia, South Africa, and USA.

27. Among the 110 seminar participants were also a number of speakers, session
chairpersons and workshop leaders. Speakers were provided by PIC/S Participating
Authorities, the EMEA, the European Commission, the German Federal Institute for
Drugs and Medical Devices (BfArM) and industry.

28. The Seminar focused on:

(i) the presentation of the ICH process;
(ii) ICH Q8 “Pharmaceutical Development” from both regulators’ and
industry’s perspective;
(iii) ICH Q9 “Quality Risk Management” from both regulators’ and industry’s
perspective;
(iv) the progress made in the development of ICH Q10 “Quality Systems” and
its future use by industry;

* Observer to PIC/S Committee

** New Independent States’ Interstate Commission on Standardisation, Registration and Quality Control of
Medicines and Medical Devices
Annual Report 2006
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(v) the interaction and the complementarity of these 3 topics as a common

framework.

Expert Circles & Working Groups

Expert Circle on Human Blood and Tissue
29. The 13th meeting of the Expert Circle on Human Blood and Tissue was held in
Utrecht (Netherlands) on 19-22 September 2006. It was organised by the Dutch
Inspectorate of Health Care (IGZ) and attended by 50 participants from 25 countries (of
which 5 non-Members). The meeting mainly focused on the inspection of tissue. It
included an overview on legislative changes and projects in PIC/S and non-PIC/S
countries as well as presentations on the practical aspects of procurement (donation of
tissues), risk management and future developments. Practical workshops were
organised on procurement, donor testing, processing, bacterial contamination and
documentation. There was also a visit of a cell therapy products manufacturer. A
number of recommendations were addressed to the PIC/S Committee for consideration.

Expert Circle on Hospital Pharmacy

30. The 9th meeting of the Expert Circle on Hospital Pharmacy was held in Lisbon
(Portugal) on 6-7 June 2006. It was organised by Portugal’s “Instituto Nacional da
Farmácia e do Medicamento” (INFARMED) and attended by 17 participants from 16
countries. The meeting focused on discussing comments from PIC/S Participating
Authorities on the draft guide on “Good Manufacturing Practices for Medicinal
Products in Pharmacies”.

Expert Circle on Computerised Systems

31. The 5th meeting of the Expert Circle on Computerised Systems, organised by
ZLG, took place in Düsseldorf (Germany) from 29-30 May 2006. It was attended by 25
inspectors from 18 countries (including Cyprus, Israel, Japan, and South Africa). The
meeting was split up into two parts: a one-day experts meeting focusing on an update to
inspecting computer validation followed by one-day basic course on “how to inspect
Computerised Systems during GxP-inspections”.

Expert Circle on Medicinal Gases

Following the completion of its work plan, the Expert Circle on Medicinal Gases was
suspended until further notice.

Expert Circle on Active Pharmaceutical Ingredients

32. The second meeting of the Expert Circle on Active Pharmaceutical Ingredients
(APIs), which was originally scheduled to take place in the United Kingdom in the last
quarter 2006, was postponed to 2007.
 Annual Report 2006
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Why Expert Circles?

PIC/S Expert Circles have been set up by the PIC/S Joint Committee to facilitate the
discussions and the exchange of information among inspectors specialised in a specific
area of GMP such as blood, hospital pharmacy, computerised systems, active
pharmaceutical ingredients, etc. Expert Circles meet regularly to develop draft
guidance, recommendations, etc. and offer training in their respective fields of
specialisation.

Harmonisation of guidance documents

33. The following PIC/S documents were adopted in the course of 2006:
- the PIC/S Aide-Memoire on Medicinal Gases (PI 025-1);
- the revised PIC/S GMP Guide (PE 009-5) including additions to Chapters 1, 6
and 8.

34. The Committee also agreed to revise the format of the PIC/S GMP Guide (PE
009-5) in line with the EU GMP Guide: Chapter 1 to 9 will become Part I while the
Guide on APIs (PE 007-2) will become Part II of the revised PIC/S GMP Guide.

35. It further agreed to release the second draft of the PIC/S Guide to Good Practices
for Preparation of Medicinal Products in Pharmacies (PE 010-1, Draft 2) for
consultation to national and international hospital and pharmacy associations.

36. The list of PIC/S publications is available on the PIC/S web site:
http://www.picscheme.org

Relations with other organisations

37. The Committee adopted new Guidelines on Partnership replacing the Guidelines
on PIC/S Observer Status. The Guidelines introduce the status of “Associated Partner”
(replacing the current status of “Observer”) and the concept of “Non-Binding
Partnership”, which aims at defining areas of co-operation between PIC/S and the
Associated Partner.

38. In September and October 2006, the PIC/S Chairman, accompanied by the
Secretary, visited the European Medicines Agency (EMEA), the European
Commission’s Health and Consumer Protection Directorate-General (DG SANCO), the
European Commission’s Enterprise and Industry Directorate-General (DG Enterprise)
and the European Directorate for Quality Medicines EDQM (PIC/S Chairman only).

39. It was the first time that a PIC/S Chairman initiated such visits to these
European Institutions. The outcome of these visits was generally positive, especially in
terms of co-ordination of training activities with the EMEA and EDQM. The
Committee decided to initiate an informal exchange of letters with all these
organisations on the development of future co-operation. It also decided to exchange
Annual Report 2006
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letters with WHO’s Immunization, Vaccines & Biologicals (IVB) Department in order
to co-operate in the fields of training, assessment of Drug Regulatory Authorities, etc.

40. At its autumn meeting in Geneva, the Committee also discussed a project
developed by DG SANCO on “European Standards and Training for the Inspection of
Tissue Establishments” (EUSTITE) as well as a new training and standards programme
on human blood. It noted that both projects were led by tissue and blood banks,
respectively, and agreed to involve PIC/S in these programmes. An official
representative from PIC/S was nominated as Liaison Officer for EUSTITE.

First PIC/S – Industry Forum

41. On 23 November 2006 PIC/S met for the first time with representatives of
international industry and professional associations, i.e.
- EFPIA: European Federation of Pharmaceutical Industry Associations;
- FIP: International Pharmaceutical Federation;
- IFPMA: International Federation of Pharmaceutical Manufacturers &
Associations;
- ISPE: International Society of Pharmaceutical Engineers;
- PDA: Parenteral Drug Association.

42. The meeting aimed at exchanging information and identifying possible areas of
co-operation in terms of GMP (e.g. training).

43. The main operational conclusions from the meeting were the following:

On GMP training, both parties agreed to exchange information on training
programmes. Pharmaceutical manufacturers were encouraged to provide
training material to PIC/S (e.g. short videos or photos) and facilitate visits
("walk around") of manufacturing sites by PIC/S Inspectorates. Both parties
also agreed to explore the possibility to organise back-to-back meetings and
develop common training workshops. The first such joint workshop will be
organised by PIC/S and ISPE in November 2007. The workshop will be on
Quality Risk Management and take place after the 2007 PIC/S Seminar in
Singapore.

On GMP inspections, pharmaceutical companies were encouraged to be more
pro-active by (i) informing PIC/S Inspectorates on the last / forthcoming
inspection by another Inspectorate; (ii) spontaneously submitting the last
inspection report; (iii) fixing across the board deficiencies noted by an
Inspector in one particular spot; (iv) ensuring the commitment of the
company's top management to GMP; and (v) encouraging non-PIC/S
Authorities to join PIC/S. PIC/S agreed to consider better ways to share / use
information on inspections as well as discuss the possibility of "team
inspections".
 Annex I to
Annual Report 2006

LIST OF PIC/S
PARTICIPATING AUTHORITIES & OBSERVERS
(as of 31 December 2006)

I - PARTICIPATING AUTHORITIES

(in the alphabetical order of the country in which they are located)

PARTICIPATING AUTHORITY ACRONYM

Australia Therapeutic Goods Administration TGA
Austria Bundesministerium für Gesundheit und Frauen BMGF
(Federal Ministry for Health and Women)
Belgium Direction Générale de la Protection de la Santé Publique: DGM
Médicaments
Canada Health Products and Food Branch Inspectorate HPFBI
Czech Státní Ústav pro Kontrolu Léčiv SÚKL
Republic (State Institute for Drug Control)
Ústav pro Státní Kontrolu Veterinárních Biopreparátů a ÚSKVBL
Léčiv
(Czech Institute for State Control of Veterinary
Medicaments and Biologicals)
Denmark Danish Medicines Agency DMA
Finland National Agency for Medicines NAM
France Agence Française de Sécurité Sanitaire des Produits de AFSSAPS
Santé (French Health Products Safety Agency)
Germany Bundesministerium für Gesundheit BMG
(Federal Ministry for Health)
Zentralstelle der Länder für Gesundheitsschutz bei ZLG
Arzneimitteln und Medizinprodukten
(Central Authority of the Laender for Health Protection
regarding Medicinal Products and Medical Devices)
Greece Εθνικός Οργανισµός Φαρµάκων EOF
(National Organization for Medicines)
Hungary National Institute of Pharmacy NIP
Iceland The Icelandic Medicines Control Agency IMCA
Ireland Irish Medicines Board IMB
Italy Agenzia Italiana del Fármaco AIFA
Latvia ZāĜu Valsts Aăentūra ZVA
(State Agency of Medicines)
Liechtenstein Kontrollstelle für Arzneimittel KA
Malaysia National Pharmaceutical Control Bureau NPCB
Annex I to
Annual Report 2006
-2-

Netherlands Inspectie voor de Gezondheidszorg IGZ

(Inspectorate of Health Care)
Norway Norwegian Medicines Agency NOMA
Poland Main Pharmaceutical Inspectorate MPI
Portugal Instituto Nacional da Farmácia e do Medicamento INFARMED
Romania National Medicines Agency NMA
Singapore Health Sciences Authority HSA
Slovak State Institute for Drug Control SIDC
Republic
Spain Agencia Española del Medicamento y Productos Sanitarios AEMPS
Sweden Medical Products Agency MPA
Switzerland Swiss Agency for Therapeutic Products Swissmedic
United Medicines and Healthcare Products Regulatory Agency MHRA
Kingdom

II - OBSERVERS

(in the alphabetical order of their acronyms)

OBSERVERS ACRONYM
European Medicines Agency EMEA
Estonia State Agency of Medicines SAM
United Nations International Children’s Emergency Fund UNICEF
World Health Organization WHO
 Annex II to
Annual Report 2006

From the Pharmaceutical Inspection Convention

to the Pharmaceutical Inspection Co-operation Scheme

The Convention for the Mutual Recognition of Inspections in respect of the

Manufacture of Pharmaceutical Products (Pharmaceutical Inspection Convention)
entered into force in 1971.

The Convention applies to inspection of the manufacture of medicinal and

related products intended for human use, which are subject to control under health
legislation. It provides that the Contracting States will exchange, on the basis of
inspections, such information as is necessary for the health authorities in an importing
Contracting State to be able to recognise inspections carried out in the Contracting State
of the manufacturer.

In 2000 the Convention was operating between eighteen countries, namely,

Australia, Austria, Belgium, Denmark, Finland, France, Germany, Hungary, Iceland,
Ireland, Italy, Liechtenstein, Norway, Portugal, Romania, Sweden, Switzerland and the
United Kingdom

Due to some incompatibility for the Member States of the European Union (and
for the States parties to the European Economic Area) between their obligations under
the Convention and under the EU, the conclusion of another type of agreement than the
Convention was agreed upon. This is an arrangement between the inspectorates of the
present Contracting States to the Convention but also open to the participation of the
inspectorates of other countries. The new arrangement called "Pharmaceutical
Inspection Co-operation Scheme" (or PIC Scheme) " was put into force in November
1995.

The Pharmaceutical Inspection Convention and the Pharmaceutical Inspection

Co-operation Scheme are run concurrently by one joint Committee and one Secretariat.
The common logo for both is PIC/S.