NSF International A Global Leader in Public Health and Safety

EXCiPACTTM and (Draft) ANSI/NSF 363 : Perspective on a Global Excipient Certification

Koen Bontinck Corporate Vice President

San Juan – April 25, 2012

www.nsf.org

Presentation items

Who is NSF International ?

Excipients Standards– Context

The EXCiPACTTM Scheme

(Draft) ANSI/NSF 363

Certification process

Cost reduction

Questions

NSF is a Global Leader in Public Health and Safety

• Developer of over 75 US national consensus standards.

• Steadfast ties with key associations and govt. agencies.

• A Collaborating Centre for the World Health Organization.

• Testing/Inspection/Certification service provider to over 50,000 organizations in 120 countries.

Bringing Industry, Regulatory and Consumers Together

USDA, EPA, FDA, HC, State, Local

Food, Water, Consumer Goods Media, Educators, Consumer Groups

Consumers

Regulators

Industry

NSF Certified Products: 276,836 and Counting

NSF Health Sciences Unit (Dietary Supplements and Pharma)

NSF developed the only American

National Standard for for Dietary

Supplements in 2001 (NSF/ANSI Standard

173).

• Dietary Supplement Certification Program – GMP audits; Toxicology, Label & Contaminant Reviews

• Athletic Banned Substance Certification Program: – Adds screening for 160 banned substances to the above – MLB, NFL,NHL, PGA, LPGA, NYPD, and Canadian Centre for Ethics in Sport

• NSF Pharmalytica – GLP and GMP Lab • analytical testing, consulting, training, registration and research and development

• NSF-DBA (David Begg Associates) - Pharma Training & Consulting • DBA Analytical – biotech, toxicology, GMP training

NSF International - Around the Globe

Americas EMEA Asia United States Belgium Poland China Brazil Czech Republic South Africa India Canada France Spain Japan Chile Germany Switzerland South Korea Costa Rica Greece United Kingdom Taiwan Mexico Israel Thailand Peru Italy Turkey

Netherlands Vietnam

NSF International Offices

Global Partners

NSF International Offices

Global Partners

Laboratories

• Regulations/Guidelines on GMP for medicinal products updated to address challenges globalisation pharmaceutical industry (supply) chain…

• Medicinal product manufacturers need to demonstrate control of their starting material supply

chains, and that purchased excipients are suitable for use in medicinal products

• Excipient suppliers will need to operate to appropriate levels of GMP and be able to demonstrate they meet required standard(s).

The context…

Amendment to Article 46(f) of Dir 2001/83/EC •“…The holder of the manufacturing authorisation shall verify such compliance (with GMP for APIs) either by himself or, without prejudice to his responsibility as provided for in this Directive, through an entity on his behalf under a contract…” • Already accepted for active substance manufacturers by Regulators.

Falsified Medicines Directive 2011/62/EU, the Holder of the Marketing Authorisation (MAH) shall ensure that ...

The excipients are suitable for use Good Manufacturing Practices (GMP) is applied

Excipient is defined as drug in US statute

• Subject to statutory CGMP adulteration provisions [section 501]

The context (nxt)…

Harmonized references…

Assist medicinal product manufacturers (and their suppliers) in achieving :

• Overall compliance… • Effective QC/QA throughout supply chain to build “upstream” quality

and GMP • At reduced cost/impact on time/resource. • (Higher) Supply chain integrity through clarity and agreement about

R&R and expectations Third party certification adds:

• Auditing at appropriate frequency • Assurance of intention for pharmaceutical use • Assurance of secure supply chain • Credibility and consistency, provided the audit organization is

capable Overall “consumer” safety should be enhanced…

Future ISO document (TS ?)

(Draft) AINSI/NSF 363 cGMP for Pharmaceutical Excipient

Global ANSI Certifiable Standard

cGMP Annex (in ISO 9001:2008)

Global ISO Certifiable Standard

Rx-360 consortium EXIPACT

IPEC-PQG GMP Guide

IPEA Excipient

GMP Auditing

Relationship between various industry group initiatives to harmonize…

The EXCiPACTTM scheme…

EXCiPACTTM is a new voluntary international pharmaceutical excipient cGMP and cGDP certification scheme, designed to help enhance patient safety and supplier quality, as well as minimising overall supply chain costs through the sharing of available information.

EXCiPACT is an independent, non-profit legal entity, registered in Brussels (governing the scheme)

Since 2008 developed as a project via a consortium of industry experts from European Fine Chemical Group (EFCG), European Association of Chemical Distributors (FECC), International Pharmaceutical Excipients Council (IPEC) Europe, IPEC-Americas, and UK Pharmaceutical Quality Group (PQG).

The EXCiPACTTM scheme… (nxt)

EXCiPACT requires 3rd Party Audit Organisations to have QMS suitable for delivering EXCiPACT Certification Specific Annex to ISO/IEC 17021:2006, Conformity assessment requirements for bodies

providing audit and certification of management systems used as the basis; EXCiPACT will check/audit implementation of these requirements – thereby taking on some

duties of accreditation bodies (eg UKAS, ANAB, RvA)

Draft EXCiPACT cGMP and cGDP standards got public and stakeholder review between March and June 2011: based on IPEC-PQG GMP and IPEC GDP Guides; act as Annexes to ISO standards 9001:2008, 19011 and 17021;

Official launching final standard in Barcelona 25th January 2012 Initially targeting both the European and North American market

Japan, China, India, Korea, Singapore; and Brazil, Mexico, Argentina and other interested countries following

The EXCiPACTTM scheme… (nxt)

EXCiPACT’s scope of activities include:

Oversight of pharmaceutical excipient manufacture and distribution certification

Excipient cGMP or cGMD Annex to ISO 9001 and/or (draft) ANSI/NSF 363

Approval/qualification of third party audit companies issuing the EXCiPACTTM certificate

Requirements for auditor competency and third party audit organisations providing the above certification.

Auditor competency development and qualification

Website (ww.excipact.org) with certification status

Certification Process – EXCiPACTTM

A pharmaceutical excipient supplier is certified upon completion of a satisfactory audit and a positive certification decision from a qualified third party certification body (eg NSF).

Certification bodies shall have been assessed and judged as competent by an

accreditation body (eg ANAB, UKAS) and approved and licensed by EXCiPACT.

Certification Process – EXCiPACTTM (nxt)

Supplier identifies if GMP and or GDP parts are needed. Preliminary self assessment (optional) Selection 3rd party audit organization

EXCiPACT™GMP/GDP standards are annexes to ISO 9001:2008

simultaneous audit against ISO 9001 and selected EXCiPACT™ standards is possible

Convential “Two-stage” initial audit (pre-audit, full audit, Corrective and Preventive Action (CAPA), Certification).

At least annual surveillance audits and triennial re-certification

Duration of audits (mandays) shall be adjusted according to the scope and complexity of the

GMP / GDP system and excipients produced

Audit Report, available to the pharmaceutical customer from the excipient supplier, may be redacted to show that confidential information has been hidden – but the substance of report will not be altered.

Certification Process – EXCiPACTTM (nxt)

Source EXCiPACT Version 1 – Edtion 2012 – Page 89 : Clause 9 – Requirements for bodies providing certification of excipient management systems).

Potential cost savings - EXCiPACTTM scheme

EXCiPACT provided an estimation on the potential cost savings…

Costs (financial & time) are comparable to an overall ISO 9001 third party certification.

To be added : license/certification fee payable to EXCiPACT™ currently €5,500 for 3 year period.

Totals are estimates and not guaranteed !

(Draft) ANSI/NSF 363 Standard

• Starting in 2009, IPEC contacted NSF to help draft the National Standard for Pharmaceutical Excipients, based on the IPEC GMP guidelines.

• Goal : formalize the requirements for GMP compliance for the pharmaceutical industry.

• NSF creates specific certification policies for on site audits to verify compliance with Std NSF 363.

– Certificate of GMP compliance will be issued

– Company will be listed on NSF website

– Subsequent yearly requalification to maintain the certification.

• Only ANSI accredited certification bodies will be able to certify to this standard (eg NSF, IPEA)

(Draft) ANSI/NSF 363 Standard (nxt)

• NSF Standards department created a specific “joint committee”.

• This joint committee includes representatives of regulators, US FDA, industry and other consultants and third party certifiers.

• Final completion Standard 363 foreseen in 2012…

USDA, EPA, FDA, HC, State, Local

Food, Water, Consumer Goods Media, Educators, Consumer Groups

Consumers

Regulators

Industry

• ANSI NSF 363 Certification is similar to EXCiPACTTM certification as it relates to the GMP portion…

• ANSI/NSF 363 is only GMP certification, EXCiPACT requires GMP and ISO 9001:2008 certification.

• Certification for EXCiPACTTM requires auditing company to be accredited to certify to ISO 9001-2008 and licensed/accepted by EXCiPACTTM.

• Certification for ANSI/NSF 363 will require the auditing company to be accredited by ANSI.

(Draft) ANSI/NSF 363 Standard (nxt)

Why an (additional) audit to EXCiPACT or AINSI/NSF ?

In Europe the Falsified Medicines Directive in Europe places express requirements on your customers to assess the GMP used in the manufacture and GDP used in the distribution of your excipients. This applies to ALL your European customers. Proportion existing pharmaceutical customer base currently audits you? All those who do not currently audit you will be able to use your audit report instead of

commencing their own audit program.

FDA has indicated in their strategy document that they need to work in partnership with 3rd parties to secure the pharmaceutical supply chain. Quoted EXCiPACT or draft NSF 363 several times in public meetings as being a

suitable scheme to meet this intent: to aid security of the supply chain. Both initiatives ensure all customers of an audited organization have

access to a base audit and the continuing surveillance audits, which will be performed on an annual basis. This is (often) more frequent than your customers could audit you

ExcipactTM and/or ANSI/NSF 363 do not and could not possibly establish all

user/product technical requirements

A Third party certificate is NOT a substitute for a regulatory inspection

An audit is not the only issue an excipient user has to address when qualifying

a new supplier

It is not a requirement that an excipient user can show the excipient supplier

has a GMP Certificate. Nor are excipient users allowed to use GMP Certificates of excipient suppliers as a

substitute for their own (or commissioned) audits.

Some myths…