Welcome to our Press Conference CPhI, Madrid · Summary • EFCG has made a ... • Detailed Guidelines on GMPs for APIs published (ICH Q7a)

EFCG Press ConferenceAt CPHI, Madrid, 2nd November 2005

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Welcome to our Press ConferenceCPhI, Madrid

2nd November 2005


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Programme

1530h Welcome & overview of EFCG’s progress and plans

Dr Heinz SiegerDr Heinz Sieger, CEO,Chemie UetikonPresident EFCG

1540h EFCG’s Action Plans in the API arena in anticipation of the new law on GMP compliance

Mr Guy VillaxMr Guy Villax, CEO, HovioneChairman, EFCG Pharmaceuticals Business Committee

1610h Q&A

1630h Cocktails & light refreshments


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Cefic Organisation

Plastics Chlorine PetrochemistrySpecialtySpecialty

ChemicalsChemicals

EFCG (+70SGs)EFCG (+70SGs)

Int. Trade

Competitiveness

Enlargement

Product

Stewardship

Trust &

Reputation

Science

&

Research

LRIGovernance

&Legal Issues

GENERAL ASSEMBLY AND BOARD

Director General

Leadership Team

7 Programmes


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Vision & Mission

Vision Vision --• To sustain value creation through competitiveness, growth and

environmental performance of our members, and that this is recognised by society

MissionMission --• To be the voicevoice of the European Fine Chemicals Industry


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Progress Report 2005

Since December 2004, we have: -

• Maintained our focus – pharma, agro, innovation, REACH and recruitment

• Formed 4 new committees - each with a mission, objectives and an action plan

• Integrated with APIC – Active Pharmaceutical Ingredients Committee

• Formalised contacts with key stakeholders in the supply chain, government, NGOs and other international trade bodies

• Increased membership from 20 to 37• Raised our brand awareness


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EFCG Organisation

• Board / REACH Committee Chairman: Heinz Sieger, CEO, Chemie Uetikon

• Pharmaceutical Business Committee (PBC)Chairman: Guy Villax, CEO, Hovione

• Active Pharma’ Ingredients Committee (APIC)Chairman: Matt Moran, Director, PharmaChemical Ireland

• Agrochemicals Intermediates Manufacturers inEurope (AIME) CommitteeChairman: Laurent Schmitt, President, Rhodia Organics

• Innovation Committee (IC)Chairman: Brian Murphy, MD, Robinson Brothers


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Membership - 37

CompaniesAlbemarle LanxessAvecia MerckChemial RaschigBorregaard SynkemCaffaro Robinson BroDegussa Rhodia (2)DSM (3) RutgersNovasep SolvayHovione UetikonIsochem ClariantDipharma WackerPCAS KemFineUquifa LonzaPentagon

National AssociationsPCI IRLSICOS FSOCSA UKCASID DAschimfarma ICPA I

International GroupsAPIC B


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Board Members

Dr Heinz Sieger (President) Uetikon DDr Brian Murphy (Vice President) RBL GB Dr Rudolf Hanko Degussa DMr Guy Villax HovioneHovione PTDr Ellen de Brabander DSM NLMr Laurent Schmitt Rhodia FMr Paolo Ferrario Caffaro IMr Matt Moran PCI + APIC EIDr Chris Oldenhof DSM + APIC NLMr Tony Scott Cefic B


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Pharmaceuticals Business Committee (PBC)

Mission -• To be the business voice of the European GMP Fine Chem. Industry to

assure the safety of medicines and enhance business performance

Objectives -• To minimise regulatory bias favouring non-European manufacturers• To protect EU citizens health via better inspections & enforcement• To support the concept of ‘APIC Approved’ manufacturing sites• To promote high quality EU manufacturers’ operational excellence,

added value, and security of supply• To advocate and communicate our positions widely via the press• To inform, train and promote the European API community• To form alliances with other (inter-) national trade bodiesMembership – 12 companies

Guy Villax to report later


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Board / REACH Committee

Mission -• To be the forum and the voice of the European fine chemicals

industry on REACH regulationsObjective -• To achieve workable and affordable regulationsStrategy -• Working with Cefic and the Alliance of SMEs (OBJECT!ON) to

achieve a satisfactory outcomeNext Steps -• SME meetings 7th & 8th November. EP vote 15-16 November.

Council Agreement 28 November.


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Active PharmaceuticalIngredients Committee (APIC)

Mission -• To advance and promote the technical interests of European

companies who manufacture APIs and intermediates for APIs

Main Objectives -• To maintain APIC as recognised technical voice on Good

Manufacturing Practice (GMP), Regulatory Affairs and other related topics

• To be the forum where European manufacturers can discuss these and other technical issues

Membership – 65 companies


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Agrochemical IntermediatesManufacturers in Europe (AIME)

Mission –

• To be the forum and the voice of Agrochemical Intermediates Manufacturers in Europe who supply global customers in non-captive markets

Objectives -

• To sustain the highest standards of business ethics, customer relationships and security of supply on a long-term basis

• To improve business performance through added customer value• To upgrade members knowledge of the global marketplace• To improve AIME brand awareness and identity among all stakeholders• To form alliances with other (inter-) national trade bodies



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Innovation Committee (IC)

Mission –• To sustain and promote growth of the European Fine Chemicals Industry

through enhanced innovationOur Definitions –• Research + € Knowledge. Innovation + Knowledge €Objectives -• To improve advocacy for real innovation• To define the focus for innovation for the Fine Chem. industry sector• To improve business performance by identifying and dealing with the

barriers to innovation• To establish a collaborative innovation work programme • To seek additional government support for innovation• To form alliances with other (inter-) national trade bodies



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Summary

• EFCG has made a good start but still much to do!

• Our Action Agenda: -– Double our membership; get more companies involved– Minimise regulatory bias favouring non-European

manufacturers– Promote EU citizens health through better law enforcement– Promote the high quality added value provided to customers by

European producers– Provide focus and help on innovation– Facilitate communication – www.gmpapi.migg.com then

www.efcg.cefic.org

http://www.efcg.cefic.org/

http://www.efcg.cefic.org/


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Thank youFor more information, please contact:

Heinz [email protected]: +49 (7821) 585 200

Tony [email protected]: +44 (1428) 653 510

Pieter van der [email protected]: +32 (2) 676 7202

mailto:[email protected]




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Press Conference, CPhI, MadridPress Conference, CPhI, Madrid2nd November 2005

Pharmaceutical Business CommitteeGuy Villax - Chairman


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Agenda

• What the New Directives mean for the API industry• What else has happened• What has room for improvement• Next Steps

– By the Health Authorities– By EFCG


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What the New Directives mean for the API

• Human - Directive 2004/27 amending 2001/83• Veterinary - Directive 2004/28 amending 2001/82


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FDA Filings and Inspections

...making sure GMP is met

PharmaCompanies

APIProducers sale

EU authoritiesFilings

EU authoritiesInspections


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Article 111 (a) “…The competent authority may also carry out unannounced inspections at the premises of manufacturers of active substances used as starting materials, …”

Article 47 “…only active substances.. manufactured...to good manufacturing practice”

As from 30th October 2005

PharmaCompanies

APIProducers sale




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It will be up to the QP tomake sure...

APIProducers

PharmaCompaniessale




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Qualified person

Pharmacien Responsible

Sachkundige Person

Director Técnico


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What the New Directives mean for the API industry

• Human - Directive 2004/27 amending 2001/83• Veterinary - Directive 2004/28 amending 2001/82

“APIs must meet GMP requirements”Finally !


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What the New Directives mean for the API industry - general

What is in place in Europe as from 30 Oct 2005? • Inspections of API manufacturers, traders & brokers,

also “non-CEP APIs”• Focus on incoming-API aspects during inspections at

dosage form manufacturer• API fingerprinting also by OMCL Network

(85 authorities’ laboratories)• More focus on possible fraud / counterfeiting• Enforcement, penalties including MAA withdrawals &

Rapid Alerts/Recalls


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What the New Directives mean for the API industry - details

• QP must declare API Q7a compliance in the MAA

• An GMP certificate from Health Authorities not sufficient to evidence that the GMP requirements are met

• Guidelines require that an audit report be on file (<3 years) and available to Regulators

• By implication..– You can no longer “just buy the API from a

trader”– You will obtain a declaration and data to

evidence such compliance from the API producer

• Audits of API producers will occur more frequently:

– Performed by user of API– Performed by a 3rd party

• Audit reports will be available to Regulators, and will cease to be confidential


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What else has happened• Detailed Guidelines on GMPs for APIs published (ICH Q7a)• Q&A on how MAH should fulfill obligations on ensuring API GMP

compliance – clarity needed• GMP certificate and database• GMP inspections and definition of triggers• Compilation of EU procedures (including rapid alert system)• Issues:

– Additional guidance to come (including Revision of GMP Guide Part I)

– National legislations and guidelines (Beware! Differences)


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What can be improved

• Guideline on API inspection triggers• GMP certificate format• GMP inspection format• Sanctions• Q&A on how MAH should fulfill obligations on ensuring API

GMP compliance


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Guideline on API inspection triggers

• There is no provision for a “random” inspection• No random audit, no deterrence

• There are only inspections when there is suspicion...• EDQM’s inspections have focused on “doubtful” API

producers:– Out of 58 inspections 9 led to suspensions of CEPs, all

in Asia most of them held by brokers.


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GMP inspection format – room for improvement

• Are EU inspectors trained to detect fraud ?• US inspectors:

– “The only difference between an FDA investigator and an FBI investigator, is that I don’t carry a gun”.

• EU inspectors:– Technically competent but they assume API producers

are all honest, just as reviewers assume the data in a DMF reflects what is done at the plant...

– They should train with the carabinieri.


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GMP certificate format – room for improvement

• There is no guidance as to whether GMP certificates are general or specific, 1. A general GMP statement as to a company ?2. A general GMP statement about a factory ?3. A general GMP statement about a building in a factory ?4. For a class of drug (oral, injectable, inhaled ?) ?5. For a specific drug (a specific API) ?6. For a specific API made as per DMF description ?

» Only the latter (6) assures quality !


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• Specimen


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Co. Name +Street

Address of

factory

No product definition !

This is only a level 2 inspection. FDA works to a higher standard

One year validity !but

No inspection date...


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• Specimen:


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Company+

Street Address of factory

Products are well defined

What is covered at

that site

Format

Inspection date


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• Specimen:

This is only a level 6 inspection. FDA works to a higher standard


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GMP certificate format – room for improvement

• Format of GMP certificate needs harmonization across Europe• GMP certificates should refer to an inspection and should be

matched (be traceable) to a DMF version that is dated

Same questions apply to audit reportsAudit reports must be of a format such that it addresses the QP’s concerns

his/her concerns are driven by the Health Authorities definitons of what they expect him to check ! ie What they will train the inspectors to ask !

None of this has been clarified / communicated !


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GMP Audit report– room for improvement

• Does it just state facts ?• Does it conclude ?

• Compliant or Not ? • Who takes the view ?• Must it have a corrective action plan ?

• No longer confidential so will it really contain “sensitive aspects”– Will this compromise the constructive nature of a client

audit ?


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Sanctions

• Sanctions are a matter for the member states• EFCG is not aware of precedents of sanctions

– Maybe since there was no law, there was no non-compliance...

– Most likely there was no checking of compliance of:

» Use of a trader supplied API without traceability

» Use of a API source not approved by MA


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Q&A on how MAH should fulfill obligations on ensuring API GMP

compliance

• EMEA aware of lack of clarity• Inviting all major associations (EGA, AESGP, IFAH, EFPIA,

CEFIC, FECC) to a forum later this month• To discuss various issues connected with the obligations

of manufacturing authorisation holders in assuring the active substances they use have been manufactured in accordance with GMP to discuss the matter

» High level of constructive dialogue, » Example to follow by several health

authorities in member states.


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Next Steps

• By EFCG• By the Health Authorities


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Next Steps by EFCG

• Promote the 3rd party audit process– EMEA to lead the way and clarify the process– Industry to provide input and to provide the auditing

resoucres and competences• EFCG’s simple guide to buying APIs that meet GMPs• EFCG benchmarking exercise across EU to assess Member

States’ readiness to enforce the Directives with reference to the APIs


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GMP Audits

• To avoid an avalanche of audits– Third Party Audits acceptable (no conflict of interest,

contractual arrangements etc.)• MAHs may share audit reports on same API• Inspector may review Audit Programmes & Audit Reports (!)• Full transparency back to API manufacturers

Providers of audit services: The APIC audit programeInteractive Consulting


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Next Steps by the Health Authorities

• Enforcement• Enforcement• Enforcement

Benchmarking survey results out in April 2006 at the EFCG Conference “the business of compliance”.


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Thank youFor more information, please contact:

Guy [email protected]: +351 21 982 9381

Tony [email protected]: +44 (1428) 653 510

Pieter van der [email protected]: +32 (2) 676 7202

This presentation can be found at www.gmpapi.migg.com




Documents

Welcome to our Press Conference CPhI, Madrid · Summary • EFCG has made a ... • Detailed Guidelines on GMPs for APIs published (ICH Q7a)