Excipient Supplier Qualification - IPEC Europe

Excipient Certification: 

Schemes and Auditable Standards 

- the role in Supplier Qualification 

European Compliance Academy 

Hamburg 26th 27th April 2010 

Dr Iain Moore 

Certification Committee IPEC Europe 

ECA GMP for Excipients Hamburg 2010

Excipient Certification 

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1. Supplier Qualification 

2. Role of 3 rd Party Audits and Certification 

3. Limitations of existing Schemes 

4. New scheme principles and design 

5. New scheme implementation benefits 


Excipient Supplier Qualification 

• Drug product manufacturers (users) have to 

qualify their suppliers 

• A comprehensive assessment of 

– Excipient quality 

– The manufacturing process to make the 

excipient 

– The distribution controls used to deliver the 

excipient to the drug product manufacturer 

• The latter 2 aspects require a detailed 

assessment of the suppliers systems and 

capability 

• A physical audit is the ideal way to achieve 

this 


Excipient Supplier Qualification 

• The purpose of this qualification is to ensure 

that the safety of the drug product is not 

compromised by the excipient 

• Both manufacturing (GMP) and distribution 

(GDP) aspects need to be covered 

• Failures at any point in manufacture or in the 

supply chain may put patients at risk 

• Those excipients posing the greatest risks 

require the most thorough controls 

• Significant effort required for both the user 

and the supplier 

• How can we reduce that burden and allow 

both parties to focus on the critical aspects? 

• How can we Minimise the Risks - Maximise the 

Benefits ? 



• And now legislators intend to further enhance these 

requirements in law on both sides of the Atlantic 

– In the EU the Pharmaceutical Package as amended by 

the European Parliament requires: 

– GMP and GDP for Excipients 

– Registration of excipient manufacturers and 

distributors/traders/brokers (??) 

– Inspection of excipient manufacturing sites 

• In the US the draft legislation would require similar 

registration of excipient suppliers who export to the 

USA 

• Overall an expectation of routine physical audits 

from all users on all their suppliers 



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• So we need a physical audit…. 

• 1000s of excipients (1200 in IID) 

• 1000s of suppliers globally? 

• Could the Inspectorates or Regulators perform the basic 

Audits of all these manufacturers AND distributors? 

• Do users have the resources? 

– Only a fraction of suppliers are audited 

– Standards are inconsistent from one User to another 

• Suppliers are at risk of “death by audit” 

– Some sites could receive 100 or more per year 

– Even today it is common to find suppliers with 1 person solely 

employed to deal with audits 



• Some Suppliers are refusing audits on top of all of these 

– Insufficient business justification 

– Less than minimum order levels 

– Complexities of purchasing through a distributor 

– A few 100Kg per year with all this? 

• Some suppliers are charging for audits 

– Up to €10,000 per audit 

• The chemical industry is traditionally reluctant to share 

intellectual property 

– Restrictions to view batch records 

• Can we find another way around these issues? 



• What if excipients could be qualified by another 

method? 

• What if there was an Internationally and 

regulatory acceptable Excipient certification 

system? 

• Covering the Quality Management Systems in 

manufacture (GMP) and the supply chain (GDP)? 

• Users would then be able to focus qualification 

resources on the technical aspects and higher 

risk excipients 

– Reducing the audit burden for both parties 



• Indeed, the FDA and EU have indicated very 

positively that: 

– 3 rd Part Excipient Audits and Certification have 

a role to play 

– The FDA has a system to approve 3 rd party 

auditing organizations 

– For APIs, The December 2008 Pharmaceutical 

Package from the EU indicated that 3 rd party 

audits from accredited organisations would be 

acceptable 

• The key components are in place then for the 

Excipient industry to implement a valuable 

Excipient Certification Programme 


Who can Provide Auditors? 

• With 1000s of excipient and 1000s of audits 

where do we find all the auditors? 

– Could ISO auditors contribute? 

– Pharmaceutical Packaging (ISO 15378) ? 

– Medical Device (ISO 13485) ? 

– ISO 9001 – chemical / pharmaceutical sector? 

– Existing 3 rd Party Audit 

• BUT 

• FDA and EU have indicated this is viable if 

and only if the auditors are competent 

• So if auditors are deemed competent then we 

can use 3 rd parties with confidence 


Certification 

• The regulatory environment is changing and 

the signals are very clear 

– It’s not a matter of what 

– But of when 

• The need for a viable and effective Excipient 

Certification Scheme has never been greater if 

assurance of excipient quality is to be 

enhanced without disproportionate costs 

• And so EXCIPACT is being developed to 

address these issues 



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Do we need another Excipient 

Certification Scheme? 

PQG PS 9100:2002 

• Audit runs concurrently and 

seamlessly with an ISO 9001 audit 

• ISO 9001 audits are lengthened by 

around 50% 

• So 2 audit days a year becomes 3 

typically 

– As based around ISO 9001 audit – 

there is an audit every 6 months 

– Costs are “insignificant” in 

comparison to the overall business 

costs 

• www.pqg.org 




EFfCI GMP Guide for Cosmetic Ingredients 

• Scheme launched November 2008 – ISO 

9001 type certification 

• 3 ISO style 3 rd party audit bodies have 

signed up, one with global reach 

• NB EFfCI GMP Guide is based on the 

IPEC-PQG GMP Guide and is 80% 

identical 

• Interest in certification reported from 

outside Europe - Asia and US 

www.effci.org 




IPEA 

• International Pharmaceutical Excipients Auditing 

• Independent subsidiary of IPEC-Americas 

• Contract to generate an audit report which is then offered to 

users to demonstrate GMP Compliance against USP 

• Able to audit in 90 countries worldwide 

• Higher investment costs, but overall similar over 3 year 

cycle to PS 9100, and much less than some “expert audit” 

options – e.g. USP Verification Scheme 

• www.ipeainc.org 




• Why there has not been widespread uptake of these 

schemes? 

– Is it because Users are uncertain of the value of 

these certificates to the regulatory authorities? 

– Are they too expensive? 

– Not enough transparency on auditor competency? 

• Project is researching these reasons and believes 

all are true and need to be addressed if the scheme 

is to be successful 



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Project Principles 

Evolve existing best practices 

• Base on the IPEC-PQG GMP Guide 2006 

• Base on IPEC GDP Guide 2006 & SQAS 

Distributor ESAD Scheme 

• Align to ISO 9001 

– Many excipient suppliers are already ISO 

certified or familiar with this quality 

management system standard 

International in scope 

Excipients are a worldwide commodity 

Be valuable and acceptable to Suppliers, Users 

and regulators 



Project Principles 

Include as many Excipients as possible 

• Set standards that are achievable 

• Set standards that are auditable 

Address the definition of and policing of auditor competency 

Be accessible to existing 3 rd party audit organisations 

Consult with all Stakeholders throughout the project 

One session held in Europe in May 2009 

Sessions held with FDA in July 2009 and February 2010 



‣ Preparation: 

• Manufacturers 

• Perform gap analysis on GMP Annex 

• The GMP Audit guide is a useful aid 

• Distributors, repackers etc 

• Perform gap analysis on GDP Annex 

• The GDP Audit guide is a useful aid 


Excipient Classification 

• When Excipient Certification (EXCIPACT) may 

not be suitable as part of Excipient 

qualification… 

– Excipients have many diverse uses, functions, 

manufacturing processes and origins 

– The risks posed to the patient are also very 

variable 

– A one size fits all definition of GMP is not going 

to be appropriate, as PS 9100 first defined in 

2002 

• So can we use a classification system to 

identify “higher risk” excipients? – YES! 


Excipient Classification 

• So EXCIPACT is developing a Guide for Users to identify when 

the Scheme would not be suitable as the only means of 

Excipient Qualification 

• When these excipients are identified Users could still use 

EXCIPACT as the base qualification but would then know 

which areas and activities required additional knowledge 

– Supplier aware of additional activities to address risks 

– Focussed audits by user 

• Equally true that some excipients could be supplied which do 

not meet the IPEC-PQG GMP Guide requirements 

• In this case the User would need to use other methods to help 

qualify the supplier 


Excipient GMP 

• Certification will be against the core 

requirements in the IPEC-PQG GMP Guide 

2006 – as converted to “ISO speak” 

• Suppliers with ISO 9001 will only require 

additional audit time to cover GMP 

– Excipact 

• Suppliers without ISO 9001 will require an 

audit covering GMP and the Quality 

Management System 

– NSF-ANSI United States National Standard 

• Two definitions of Excipient GMP 

containing the same requirements 


Excipient GDP 

• Certification will be against the 

core requirements in the IPEC 

GDP Guide 2006 – as converted to 

“ISO speak” 

• IPEC GDP Guide 2006 

Provides additional explanation 

to the “Good Trade And 

Distribution Practices For 

Pharmaceutical Starting 

Materials” , World Health 

Organization, WHO Technical 

Report Series, No. 917, 2003 


Excipient GDP 

• The GDP Standard will include key elements 

of existing best practices 

• The NACD (National Association of Chemical 

Distributors) Responsible Distribution 

Process (SM) 

• The European SQAS ESAD II assessment 

scheme Section F&G (www.sqas.org) is 

• aligned to the IPEC GDP Guide 

• subject to independent assessment 

• has a defined auditor training 

programme 


Excipient GMP and GDP 

• Both GMP and GDP can therefore be 

certified 

• Common GMP and GDP elements have 

been synchronised 

• Scheme allows organisations to attain GMP 

certification alone or in combination with 

GDP depending on their business model 

• Both GMP and GDP standards are in first 

draft form and a public review is planned 

for later this year 



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Excipient GMP & GDP 

Certification Scheme 

How will 3 rd Party Certification Work? i 

• “IPEC” signs an agreement with 3 rd Party Organisations to 

audit organisations which commits them to 

– Utilise the auditor training and meet the auditor competency 

criteria 

– Perform audits using the scheme rules 

• These 3 rd party audit organisations should meet the criteria 

for a certification body as defined by the “competent national 

authorities” 

– e.g. hold ISO Guide 65. ISO 17021 certification 

– Which means the bodies will have a suitable and independently 

assessed quality management system in place 




How will 3 rd Party Certification Work? ii 

• Supplier selects 3 rd Party Audit organisation to provide 

certification or User(s) select 3 rd Party Audit organisation to 

qualify supplier 

• The 3 rd party certification body will indicate to “IPEC” the 

audit outcome (pass/fail) and IPEC will publish the result on 

the website 

• 3 rd party provides detailed audit report at conclusion of audit 

for access by Users 

• Once certified a user can access the audit report and then 

use a risk assessment to determine if the certification is 

suitable for their use of the excipient (supplier qualification) 

• Certificates used to advertise participation in the scheme 


Certification Plans 

• Supplier or User 

commissions 3 rd Party 

• Who is accredited by 

national competent 

authority known to 

regulatory body 

• Supplier passes 

evidence of GMP and 

GDP to User 

• User passes details to 

regulators at 

inspection or in 

dossiers 

• Virtuous circle 



CERTIFICATE OF 

GMP COMPLIANCE 

USERS 

ECA GMP for Excipients Hamburg 2010 

SUPPLIERS & 

MANUFACTURERS 

CERTIFICATION 

ASSURED EXCIPIENT USE 

AUDIT 

REGULATORS 

3rd PARTY 

ACCREDITATION



Current Project Status 

• GMP Annexes 

– 1 st Draft documented reviewed and revised 

• GDP 

– 1 st Draft documented and sent for review to 

membership of partner organisations & Selected 

stakeholders – undergoing review 

• Auditor Competency 

– 1 st Draft documented including a Study Guide 

– Ready for membership review 

• Certification Scheme 

– Requirements defined and ready for review 

– Website being prepared 

• Scheme Delivery? 

Certified 


Excipient GMP GDP 

Certification 

None of this is realisable without the 

commitment and contribution of all the 

volunteers to the various working parties 

and the Steering Committee 

I thank them for all their efforts 

Thank you for your attention

Excipient Supplier Qualification - IPEC Europe

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