GMP Harmonisation. Pirkko Puranen Senior Inspector, PhD

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1 GMP Harmonisation Pirkko Puranen Senior Inspector, PhD

2 Why GMP (Good Maunufacturing Practice) was established? Patient safety! All GMP requirements have a reason Prevention of cross contamination, microbial contamination of product, using wrong API, mislabelling To make sure that the medicinal product fulfils the specifications described in the marketing authorisation or clinical trial application Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 2

3 Harmonisation of GMPs in different countries is harmonisation of GMP requirements/guidance GMP inspection procedures Pharmacopoeias Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 3

4 Why we should harmonise GMP? Global market, global manufacturing, global companies Less inspections are needed Saves resources (money) from companies and authorities More efficient prevention of counterfeit medicines Harmonisation is needed for MRA:s Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 4

5 MRAs = Mutual Recognition Agreements Formal agreements of mutual recognision and acceptance of GMP inspection systems Between EU (European Union) and non-eu countries (in EU every country is responsible of GMP inspections of their own manufacturers, there is full mutual recognisition in EU level) GMP inspections carried out by another country are accepted MRAs do not cover inspections in third countries Between EU countries also inspections in third countries are accepted Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 5

6 GMP MRAs between EU and other countries Fully operational: Australia, New Zealand, Switzerland Operational, limited scope: Canada, Japan Not in operation: USA Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 6

7 Present situation between EU and USA USA and EU carry out their own GMP inspections according to their own procedures and requirements If pharmaceutical product is manufactured in USA and exported to EU, EU authority inspects the manufacturing site and vice versa Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 7

8 GMP Guidelines USA: FDA regulations EU: EU Good Manufacturing Practice (GMP) Guidelines + 19 Annexes Guidelines harmonised under PIC/S Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 8

9 Pharmacopoeias Methods for quality control testing of pharmaceutical products and raw materials USP = Unites States Pharmacopoeia Ph.Eur. = EP = European Pharmacopoeia (EDQM = European Directorate for Quality of Medicines and Health Care) (JP = Japanese Pharmacopoeia) Differencies in details Manufacturers have to follow both, if export to USA and EU ICH = International Conference on Harmonisation (between EU, USA and Japan), since 1990, meetings twice a year Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 9

10 EMA = European Medicines Agency Agency of the European Union Located in London, UK Network of 4500 experts Responsible of centralised approval process of medicinal products in Europe (approval of all commercial ATMPs is done according to the centralised process) Co-ordinates inspections in non-eu-member countries in centralised approval processes Practical work (assessments, inspections) are carried out by experts from the national authorities Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 10

11 27 member countries in European Union (EU) (with national legislation and national language) Germany France UK Italy Spain Poland Romania Netherland Greece Belgium Portugal Czech Republic Hungary Sweden Austria Bulgaria Denmark Slovakia Finland Ireland Lithuania Latvia Slovenia Estonia Cyprus Luxemburg Malta Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 11

12 Fimea = Finnish Medicines Agency National authority for pharmaceuticals of Finland Located in Helsinki and Kuopio, Finland EU regulations are implemented in national legislation (Medicines Act) of Finland Medicines Act regulates also items on non -EU level (retail pharmacies, hospital pharmacies ) Fimea is the responsible authority of practical implementation of pharmaceutical legislation and control of medicines in Finland Number of personnel about 220 About 20 persons in the inspectorate, four GMP inspectors OMCL = Official Medicines Control Laboratory, about 20 persons Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 12

13 GMP inspections by Fimea About 50 pharmaceutical manufacturers in Finland About 15 manufacturers located in third countries (= non-eu countries) are also inspected regularly (manufacturing medicines that are imported to Finland under national marketing authorisations) Inspectors of Fimea take part in EMA inspections (for centralised MA-procedure) Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 13

14 National GMP inspections by Fimea Inspections may or may not be preliminary announced 2 inspectors (+ experts if needed) Planning meeting 1 5 days normally Risk based inspection programme, frequency will not exceed 3 years Deficiencies are presented at the closing meeting If critical findings, order to start immediately corrective actions is given at the closing meeting Report in 30 days Manufacturer has 30 days to provide a response When acceptable response has been received, manufacturer will receive a certificate in Eudra GMP database Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 14

15 EMA GMP inspections Co-ordinated by EMA Lead inspector usually from the country where product is imported to EU Supportive inspectors Announced beforehand 3 5 days normally Deficiencies are presented at the closing meeting Preliminary report (at least list of deficiencies) in 7 days Final report in 30 days after the company has provided response Eudra GMP certificate will be provided Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 15

16 PIC/S Pharmaceutical Inspection Convention and Pharmaceutical Cooperation Scheme Mission: To lead the international development, implementation and maintenance of harmonised Good Manufacturing Practice (GMP) standards and quality systems of inspectorates in the fied of medicinal products Harmonisation network, not MRA authority 43 participating authorities, including US FDA Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 16

17 Tools for harmonisation of inspections in PIC/S Harmonisation workshops Joint inspections Informal discussions Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 17

18 Harmonisation workshops PIC/S Annual seminar for inspectors (2012 in Ukraine, 2013 in Canada) PIC/S Expert groups for different fields: APIs, compurized systems, hospital pharmacies, medical gases Worshop between EU and USA planned Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 18

19 Joint inspections PIC/S Joint Inspections Programme: - groups of three inspectors from three different countries carry out three inspections, discuss and report EMA inspections for centrally approved products are usually carried out by a lead inspector and a supporting inspector from different countries Inspections for nationally approved products may be carried out as joint inspections Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 19

20 Informal discussions between inspectors Part of continuous daily work Need to know each other Connections built in seminars and during joint inspections Very important Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 20

21 MRA between USA and EU Need to save resources Timeframe??? Phacilitate Cell & Gene Therapy Forum 2013 Pirkko Puranen 21