Pharmaceutical Inspection

Co-operation Scheme (PIC/S)

Daniel Brunner*
Pharmaceutical Inspection Co-operation Scheme, P.O. Box 5695, 1211 Geneva, Switzerland

History PIC/S and its Functions

The Pharmaceutical Inspection Co-operation Unlike PIC, which is a legal agreement between
Scheme (PIC Scheme) was established in 1995 as countries with treaty status, PIC/S is an informal
an extension to the Pharmaceutical Inspection co-operative arrangement between regulatory
Convention (PIC). authorities. PIC/S provides for, amongst other
PIC itself was founded in October 1970 by the things, Good Manufacturing Practice (GMP)
European Free Trade Association (EFTA) under inspection reports and GMP certificates to be
the title of ‘The Convention for the Mutual exchanged; but unlike PIC there is no legal obli-
Recognition of Inspections in Respect of the gation that member authorities must accept such
Manufacture of Pharmaceutical Products’. The reports or certificates.
initial members of PIC comprised the 10 EFTA The regulatory authorities of all PIC member
Member States at that time, i.e. Austria, Denmark, countries are also members of PIC/S, with
Finland, Iceland, Liechtenstein, Norway, Portugal, Germany becoming the last PIC member to join
Sweden, Switzerland and United Kingdom. PIC/S in December 2000. Consequently, a deci-
Membership of PIC was subsequently expanded sion will need to be made by the PIC/S Committee
(until 1993) to the following countries: Hungary, on the future of PIC. The PIC/S Committee,
Ireland, Romania, Germany, Italy, Belgium, which comprises one senior representative from
France and Australia. each member regulatory authority, meets at
It was realised in the early 1990s that an approximately six monthly intervals to co-ordi-
incompatibility between PIC and European law nate the activities of PIC/S.
did not permit individual EU countries, which
The PIC/S goal is:
were members of PIC, to sign agreements with
other countries seeking to join PIC. Only the To lead the international development, imple-
European Commission was permitted to sign mentation and maintenance of harmonised
agreements with countries outside Europe, and Good Manufacturing Practice (GMP) stan-
the Commission was not a member of PIC dards and quality systems of inspectorates in
(Australia was the last country that was able to the field of medicinal products.
become a member of PIC in January 1993). If The main functions of PIC/S are:
PIC was to survive and expand, a way had to be
found to overcome this legal impasse while retain- ● To provide a forum for the training of GMP
ing the main functions of PIC. inspectors.
Consequently, the PIC Scheme was formed on ● To facilitate the exchange of information
2 November 1995. The PIC Scheme and PIC, between member authorities.
which currently operate together in parallel, are ● To develop guidance documents on GMP.
jointly referred to as ‘PIC/S’. ● To promote uniform interpretation of
GMP.
● To encourage international harmonisation
of GMP.
*Correspondence to: Pharmaceutical Inspection Co-operation
Scheme, P.O. Box 5695, 1211 Geneva 11, Switzerland. ● To develop and promote Quality Systems for
E-mail:[email protected] GMP Inspectorate.

Copyright © 2004 John Wiley & Sons, Ltd. Qual Assur J 2004; 8, 207–211.
DOI: 10.1002/qaj.281
208 Profile

● To ensure that all Members comply with PIC/S Table 1. Current membership of PIC and
standards (assessment of new applicants and PIC/S
reassessment of older inspectorates).
Country Accession Accession to
● To provide a forum for networking and con- to PIC PIC/S
fidence building amongst inspectors.
Austria May 1971 November 1999
Denmark May 1971 November 1995
Membership Finland May 1971 January 1996
Iceland May 1971 November 1995
Current membership of PIC and PIC/S, as well as Liechtenstein May 1971 November 1995
the accession dates for each member, is sum- Norway May 1971 November 1995
marised in Table 1. Portugal May 1971 January 1999
Other health authorities have shown an inter- Sweden May 1971 February 1996
est in joining PIC/S, in particular Argentina, Switzerland May 1971 February 1996
Brazil, Cyprus, Indonesia, Israel, Philippines, United May 1971 June 1999
Kingdom
Slovenia, Thailand, the United States, and the
Hungary August 1976 December 1995
British Veterinary Medicine Directorate.
Ireland December 1977 February 1996
Romania May 1982 November 1995
Assessment Germany September 1983 December 2000
Italy August 1990 February 2000
Belgium September 1991 February 1997
Before a regulatory authority can become a mem-
France December 1992 February 1997
ber of PIC/S, a detailed assessment is undertaken
Australia January 1993 November 1995
to determine whether the authority has the Netherlands – November 1995
arrangements and competence necessary to apply Czech Republic – January 1997
an inspection system equivalent to that of current Slovak Republic – January 1997
PIC/S members. This assessment involves an Spain – January 1998
examination of the authority’s inspection and Canada – January 1999
licensing system, quality system, legislative Singapore – January 2000
requirements, inspector training, etc., and is fol- Greece – January 2002
lowed by a visit by a PIC/S delegation to observe Malaysia – January 2002
inspectors carrying out routine GMP inspections. Latvia January 2004
Membership may take several years to achieve, The regulatory authorities of the following countries/
during which time various changes and improve- entities have applied to join PIC/S and their applications
ments may be recommended by the PIC/S are currently being assessed:
Committee; if necessary, follow-up visits are
Bulgariaa Poland
undertaken by a PIC/S delegation to verify the Chinese Taipei Omana
suitability of corrective actions. Czech Veterinary Agency Russiaa
In line with a recently adopted programme, Estonia South Africa
existing PIC/S members are now also reassessed Lithuania Ukrainea
for equivalence on a regular basis. This should aThe application will be assessed once all supporting
ensure that both new applicants and older mem-
documents have been submitted.
bers fulfil the same requirements.

Training of Inspectors ferent topic each year. The Training Seminars are
hosted by a different PIC/S member authority
PIC/S arranges an annual Training Seminar for each year. Seminar topics for the past ten years
inspectors, with each Seminar dealing with a dif- are displayed in Table 2.

Copyright © 2004 John Wiley & Sons, Ltd. Qual Assur J 2004; 8, 207–211.
Profile 209

Table 2. PIC/S Seminar Topics

Year Seminar Topic Country

2003 Inspection of QC laboratories Slovak Republic

2002 Interface between GCP and GMP Canada
2001 Utilities Used by the Manufacturer of Pharmaceuticals Czech Republic
2000 Inspection of Products Derived from Biotechnology France
1999 Non-Technical Aspects of Inspection UK
1998 Quality Systems for Inspectorates Netherlands
1997 Inspection of Active Pharmaceutical Ingredients Finland
1996 Inspection of Computer Systems Australia
1995 Inspecting the Manufacture of sterile Products Iceland
1994 Validation in Pharmaceutical Manufacture Ireland

The proceedings of each Seminar are pub- PIC/S Guidance Documents

lished in booklet form or CD-ROM and are avail-
able for purchase from the PIC/S Secretariat The annual PIC/S Seminar usually results in the
([email protected]). formation of a PIC/S Working Group to develop
Another avenue for the training for inspectors GMP guidance documents or new/amended
is the PIC/S Joint Visits Program. Under this pro- Annexes to the PIC/S GMP Guide for Medicinal
gramme three inspectors from three different Products. For example, the 1994 PIC/S Seminar
countries are teamed up to observe typical GMP on Validation resulted in the preparation and
inspections in each country with a view to com- issue of a PIC/S guidance document on Validation
paring inspection procedures and techniques and in Pharmaceutical Manufacture covering valida-
to uniform GMP interpretation. Any differences tion master plan, installation and operational
are reported to a PIC/S Working Group on qualification (IQ, OQ), process validation and
Training for appropriate action. Joint visit cleaning validation.
groups are also encouraged to recommend specif- Other GMP guidance documents prepared and
ic training needs for inspectors, including topics issued by PIC/S have included guidance on
for future PIC/S Seminars. Validation of Aseptic Processing, Sterility Testing
and Quality Systems for Inspectorates. Other
Expert Circles PIC/S guidance documents currently under
preparation include guidance on Parametric
PIC/S has formed several ‘Expert Circle’ groups Release, Inspection of Isolator Technology and
to enable inspectors to discuss and exchange Inspection of Computerised Systems.
information on specific technical areas of GMP. In order to minimise duplication of effort in
Expert Circles on Medicinal Gases, Human the development of GMP guidance documents
Blood & Tissue and Hospital Pharmacy are cur- and GMP Guides, PIC/S works closely and
rently active and meet regularly. A new Expert co-operatively with European Medicines
Circle on Computerised Systems was recently Evaluation Agency (EMEA) and EU through its
created and another Expert Circle on Ad Hoc Working Group of GMP Inspectors.
Biotechnology is in the process of being estab- Under this co-operative arrangement, docu-
lished. One of the aims of Expert Circle groups is ments developed by PIC/S can be adopted by the
to develop draft guidance documents (or draft EU through its Pharmaceutical Committee;
new Annexes to the GMP Guide) and provide for likewise documents developed by EU can be
training opportunities. adopted by PIC/S.
Copyright © 2004 John Wiley & Sons, Ltd. Qual Assur J 2004; 8, 207–211.
210 Profile

The PIC/S GMP Guide for Medicinal Products The IMID constitutes a new option for the
is almost identical to the EC GMP Guide; the sharing of information on the GMP compliance
main differences are: status of manufacturing sites for finished medici-
nal products, active pharmaceutical ingredients
● The PIC/S GMP Guide uses the term ‘autho- (APIs) and investigational medicinal products. It
rised person’ (rather than the term is cost efficient by allowing inspection reports to
‘Qualified Person’ in the EC GMP Guide). be shared among all participating RAs and will
● References to EU Directives have been result in a reduction in the number of inspec-
removed from the PIC/S GMP Guide. tions, in particular of duplicative inspections.
The recently finalised International Confe- The IMID will also strengthen the partnership
rence on Harmonization (ICH) GMP Guide on among the IMID users.
active pharmaceutical ingredients (APIs)
originated from PIC/S, with PIC/S convening a
Benefits of PIC/S
government/industry conference in 1996 in
Membership
Canberra (Australia) to discuss the need for an
internationally harmonised GMP on APIs.
The benefits of PIC/S membership for regulatory
Consensus to proceed was unanimous and PIC/S
authorities are fairly obvious, and include the
utilised the resources of many member authori-
following:
ties to prepare an initial draft GMP Guide. After
further work by PIC/S, the draft was transferred ● More effective use of inspection resources
to ICH in order to allow industry to become through the sharing of the results of GMP
involved in further refinement of the document, inspections.
and its finalisation in November 2000. PIC/S ● Training of inspectors through participation
adopted the ICH GMP Guide as a stand alone in PIC/S Seminars and the PIC/S Joint
PIC/S GMP Guide on APIs. Visits Program.
● Promotion of the harmonisation of GMP
inspections.
● Forces improvements in the inspection sys-
The International Medicinal tems and procedures of authorities seeking
Inspectorates Database to join PIC/S, through the PIC/S assessment
process.
PIC/S recently endorsed the creation – within
● Facilitates the sharing of information and
PIC/S – of a non-profit International Medicinal
experiences amongst inspectors.
Inspectorates Database (IMID). The IMID data-
base includes information on GMP inspections There may also be benefits to industry when
carried out (or to be carried out) by the PIC/S their relevant regulatory authority becomes a
participating Regulatory Authorities (RAs) out- member of PIC/S. These benefits may include the
side of their respective domestic jurisdiction following:
(foreign inspections). The PIC/S website pro- ● Reduced duplication of inspections.
vides a list of all PIC/S Members, which have ● Cost savings.
accepted to participate in the IMID. ● Export facilitation.
Participation is on a voluntary basis. ● Enhanced market access.
The participating RAs use the database to
access information provided on the GMP inspec-
tions of foreign sites for approval purposes. All PIC/S Web Site
participating RAs have committed to use the
database through their acceptance of the Statute The PIC/S web site has been in operation since
of the IMID. June 2000 and provides detailed information on

Copyright © 2004 John Wiley & Sons, Ltd. Qual Assur J 2004; 8, 207–211.
Profile 211

the history, role, membership, publications and The web site address for PIC/S is www.picscheme.
Secretariat of PIC/S. A number of PIC/S publica- org.
tions, including the PIC/S GMP Guide and many
Hans Smallenbroek (Netherlands, Inspectie voor
PIC/S GMP guidance documents, are available
de Gezondheitszorg)
for download from the web site.
PIC/S Chairman

Copyright © 2004 John Wiley & Sons, Ltd. Qual Assur J 2004; 8, 207–211.