3rd efcg congress, lisbon, portugal, 29. - 30. may 20081 traded pharma raw materials – compliance...

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


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.


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


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


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


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)


Differences in Q7 GMP Implementation (II)

• different speedof the implementation processes into national law

• different enforcementof national law by official bodies within member states


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).


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”


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 ...)


Traditional API Supply Chain


Integrated TraderGMP Supply Chain


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)


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


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 ???


Chinese Heparin Supply Chain (compliance)crude Heparin workshops

small purifiers

medium purifiers

big purifiers

non-GMP-compliant/ no production license

Chinese GMP

eGMP


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


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


FDA 1H-NMR Spectroscopy

Source: FDA


Heparin without Contamination

SSpectral Service

Laboratoriumfür Auftragsanalytik GmbH


Heparin with Low Level of Contamination

SSpectral Service



Heparin with Medium Level of Contamination

SSpectral Service



Heparin with High Level of Contamination

SSpectral Service



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


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

3rd efcg congress, lisbon, portugal, 29. - 30. may 20081 traded pharma raw materials – compliance...

Documents

rd efcg congress

eu gmp

q7 gmp implementation

gmp certificates

q7 gmp focus

q7 gmp target

changes slide

country gmp inspections