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3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 1
Traded Pharma Raw Materials – Compliance and EU Market Situation:
View from a Trading Company with Q7 GMP focus
Mr. Erol Thomas Isim, Pharma Action, Germany
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008Strategies for Compliant Pharma Sourcing
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 2
Aim of today’s Presentation
This presentation is intended to provide information on how the implementation of current regulations affect the supply chain of traded APIs.
Furthermore it will provide insight views on the compliance situation through an actual example.
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 3
Introduction (I)
Implementation of EU guidelines into national
law of EU member states "Basic requirements for active substances as starting
materials": EU GMP Part II (curr. ed.) of the EU guidelines to good manufacturing practice for medicinal products for human and veterinary use (directive 2004/27/EC and 2004/28/EC)
in Germany via: Arzneimittel- und Wirkstoffherstellungsverordnung/ decree for manufacturing of medicinal products and active ingredients: AMWHV (in force since 10th Nov. 06, amended on 26.03.08, amendment in force since 4th April 08)
Germany was the first state to implement the changes
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 4
Introduction (II)
Implementation of a Quality ManagementSystem
including: clean room concept for sample taking, repacking
and relabeling enterprise resource planning system (ERP)
Establishment of a surveillance andinformation network
in no. 1 and 2 API producing third countriesIndia & China
market intelligence, auditing, pre-shipment inspections, registrations, screening of API and intermediate factories/ suppliers
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 5
Q7 GMP Target for Traders
Traders must
know and control the GMP relevant processes of the API supply chain
increase level of trading part up to legal and industry GMP requirements in regulated markets
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 6
Differences in Q7 GMP Implementation (I)
• different interpretationsof the EU directives in the different member states: Germany implemented strict regulations
(i.e. identification test, GMP certificates for transit material)
Italy imposed almost prohibitive measures(compulsory third-country GMP inspections for all APIs / factories via Italian MoH, valid from: 01.01.09)
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 7
Differences in Q7 GMP Implementation (II)
• different speedof the implementation processes into national law
• different enforcementof national law by official bodies within member states
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 8
Current GMP Compliance Situation in Europe• Costs and implementation necessities of
different GMP compliant systems are prohibitive to small and medium sized trading companies.
• Q7 standards are not 100% suitable for trading activities (size, human resources).
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 9
Consequences only a few small and medium sized trading
companies have invested into a QM-System most API trading activities do not comply
with the EU GMP GMP compliant traders lack
competitiveness due to higher process costs
parallel imports: loopholes remain open and are being used
finished dosage form manufacturers accept non-GMP compliant processes and as a consequence non-GMP compliant API sourcing activities, f.e. “old registrations”
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 10
GMP Trading: Review and Previewbefore GMP after GMP
(current state)outlook
many traders small, medium and big size traders many APIs and intermediates intransparent processes along the supply chain
general consolidation of traders (“survival of the fittest”) only medium and big size traders have the opportunities to full fill GMP requirements elimination of small business movement towards transparent processes
few “big” traders gain market shares and act as GMP compliance partners remaining “small/ medium” traders specialise on certain aspects of API supply chains or will be integrated by “big” traders transparent processes
transparencycompetition
GMP compliance (Q7, Q8, Q9, Q10, GAMP5, REACH ...)
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 13
Excursion Heparin: “The B-Case” (I)
• “unknown impurities” led to adverse reactions and possible deaths
• detection methods published on March, 6th 2008
• after starting of testing, product recalls in US and Germany, followed by further product recalls in CH, FR, DK, AUS, ... (regulated markets)
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 14
Excursion Heparin: “The B-Case” (II)
• root cause according to official reading: “oversulfated chondroitin sulfate” (OSCS) inside from China made Heparin (crude / purified Heparin)
• fractioned Heparin (low molecular weight) is affected too
• ongoing US-FDA investigation(s) in China• insufficient inspection routines by industry
and authorities most commonly the big players are being
inspected intra-supply-chain trade, relabeling, commingling
of batches remain un-inspected
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 15
Chinese Heparin Supply Chain (numbers)crude Heparin workshops
small purifiers
medium purifiers
big purifiers
to EU authorities knownHeparin sites
approx. 150 - 200 family owned/ small businesses crude work shops, 2 big crude work shops, > 5 big crude Heparin traders, few medium sized purifiers and 4 big sized purifiers
the unkown Heparin sites
unkown to authorities: approx. 1‘000 to more than 2‘000 family owned/ small businesses crude work shops, many small crude brokers many small sized and medium sized purifiers
number of inspected crude workshops and purifiers by EU-authorities ???number of inspected crude workshops and purifiers by EU-authorities ???
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 16
Chinese Heparin Supply Chain (compliance)crude Heparin workshops
small purifiers
medium purifiers
big purifiers
non-GMP-compliant/ no production license
Chinese GMP
eGMP
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 17
Chinese HeparinSupply Chain (linkages)
Chinese GMP
eGMP
regulated un-regulated
case 2: non-compliance
case 1: compliance
case 4: linkages
case 3: “Baxter“
crude Heparin workshops
small purifiers
medium purifiers
big purifiers
marketsnon-GMP-compliant/ no production license
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 18
crude Heparin workshops
small purifiers
medium purifiers
big purifiers
markets
Chinese Heparin Supply Chain (reality)
non-GMP-compliant/ no production licenseChinese GMPeGMP
Chinese Traders
transparent
intransparent
regulated un-regulated
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 20
Heparin without Contamination
SSpectral Service
Laboratoriumfür Auftragsanalytik GmbH
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 21
Heparin with Low Level of Contamination
SSpectral Service
Laboratoriumfür Auftragsanalytik GmbH
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 22
Heparin with Medium Level of Contamination
SSpectral Service
Laboratoriumfür Auftragsanalytik GmbH
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 23
Heparin with High Level of Contamination
SSpectral Service
Laboratoriumfür Auftragsanalytik GmbH
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 24
Pharma Action‘sIntegrated API Management System
Pharma Action is specialised on GMP compliant API supply chain management.
Benefit from our system, which:
releases bound capacities reduces costs and redundancies bundles suppliers and information creates transparency outsources threshold concentrates on core competence
3rd EFCG Congress, Lisbon, Portugal, 29. - 30. May 2008 25
Thank You!TRADE ACTION-PHARMA ACTION eK
Kurfuerstendamm 13310711 Berlin - Germany
phone 0049 30 - 890 44 99 -0fax 0049 30 - 890 44 99 -99eMail [email protected] www.pharma-action.com