ANSI NSF/IPEC 363 and EXCiPACT GMP Standards –

Need for Global Harmonization

Ann Van MeterBusiness Quality Leader – Dow Pharma & Food

SolutionsChair – GMP Committee – IPEC-Americas

vanmetma@dow.com

www.ipecamericas.org 1

Excipient Maker Example

•Typical “Excipient Manufacturer” produces products for a variety of markets• Majority of production supplies industrial markets – customers buy on price •Profit margins are typically low•Personal Care, Food Additives, Excipients and Atypical Actives represent increasingly smaller percentages of production•Increasing and differing regulations and expectations in regulated markets make it difficult to develop and maintain a sustainable quality system•Geographic differences in regulations and customer expectations add another layer of complexity

Industrial ProductsISO Quality

Excipient MakerPersonal Care Increasing

Food regulations

Excipients and

Atypical Actives Expectations

One Manufacturer:Many Quality Management

Systems • Industrial Customers

– ISO highest quality system expected– Biggest volume, buy on price, speed and availability of supply

• Personal Care– Differing quality standards globally– Customer expectations in many cases greater than for food or pharmaceuticals– Expect multi-day audits

• Food– Country specific registrations and requirements– FSC 22000 not satisfying many customers– Customer specific questionnaires, quality manuals, agreements– Expect on-site audits

• Excipients– IPEC PQG GMPs generally accepted– Country specific requests cause additional, non-sustainable work– Monographs different for same material, additional testing, country specific COAs– Customer specific quality agreements– Expect on-site audits

• Atypical Actives – ICH Q7 concepts expected but not economically supportable.– Expectations vary greatly by country and by customers– Makers often do not know their products are used as atypical actives– Expect on-site audits

Number of customers can be hundreds!

Concept of Harmonization

• Number and complexity of regulatory requirements and customer expectations is no longer manageable

• Number of customer audit requests is no longer manageable

• Mutually accepted standards are the only viable option

• Mutually accepted third party audits are critical to success across all regulated markets

• SOLUTION: Harmonized Excipient GMP Standards – ANSI/IPEC 363 and EXCiPACT

Common Basis and Goals

• We can all agree on the following:– Patient safety is paramount– Verifiable compliance schemes – Sustainable Quality systems

• IPEC PQG GMP Guide has been broadly accepted for many years as the “Gold Standard” of excipient GMPs

• Consensus-based and mutually accepted guides and standards

Guide vs. Standard• The current GMP documents for excipients are “guides”

– A guide is perceived as voluntary– Guides use words such as “should” and “may”

• A standard is perceived as requirements– Standards use words such as “shall” and “must”

• A GMP certification to a standard is desired since it is verified compliance to requirements

• Two standards for Excipient GMPs– ANSI /IPEC 363 (Non-ISO based GMP certification standard)– EXCiPACT (Annex to ISO Quality Management System Standard)

• Both standards used the IPEC PQG GMP Guide as the basis document

ANSI/IPEC 363 Features

• A voluntary initiative of the IPEC Americas and ANSI/NSF Standard setting organization

• Committee representation across all stakeholders including pharmaceutical excipient manufacturers, distributors, regulators, academia, etc.

• Ensures relevant GMP requirements are applied to pharmaceutical excipients through a recognized auditing and certification process

• Certification provides a cost-effective method of ensuring GMP are applied throughout the pharmaceutical supply chain by reducing the audit burden

• Standard issuance is imminent

EXCiPACT Features• EXCiPACT is a voluntary self regulated initiative of the global

pharmaceutical excipient manufacturing, distributing and processing industry supported by excipient users

• Ensures contemporary GMP and GDP requirements are applied to pharmaceutical excipients through a recognized auditing and certification process thereby increasing safety and reliability as well as transparency, of the pharmaceutical supply chain

• Accepted by all major stakeholders including relevant authorities globally

• Certification provides a cost-effective method of ensuring GMP and GDP are applied throughout the pharmaceutical supply chain by reducing the audit burden

IPEC PQG Guide: Update and Harmonization

• Steering team formed to lead update and harmonization of IPEC PQG GMP guide

• Membership from IPEC Americas, IPEC Europe, PQG

• Update needed for the guide to remain current and to ensure alignment with ANSI/IPEC 363 and EXCiPACT standards

• Provide supporting guidance for implementation of the standards, particularly those areas requiring risk assessments

• Will include an annex on risk assessment concepts and techniques

Harmonization• IPEC Americas and EXCiPACT collaborated closely during the

development of each standard

• The IPEC PQG GMP guide was the basis document for both initiatives

• Some common membership to ensure that the standards were as similar as possible

• Both utilize the concept of documented risk assessment to ensure that the implementation of the standards provide appropriate controls in manufacturing to produce excipients that are:– Safe– Of appropriate quality– Consistent composition

• The mutual recognition of these standards goes a long way toward the goal of harmonization

Harmonization: Monitoring Emerging

Regulations• China: new regulations for excipients by SFDA

• China: Pharmacopeia revision

• US: FDASIA Legislation

• EU: Falsified Medicines Directive makes GMP applicable to excipients, using a risk based approach

• Brazil: Excipient GMPs

Other Harmonization Needs

• Monographs– Lack of consistency leads to increased testing and costs for non-

value added activities– Documentation issues across countries and geographies

• Risk Management/assessment of excipients– Increasing regulatory focus on risk based approaches– Excipient Risk management guides currently being

discussed/developed

• ICH Q3D Elemental analysis– More on this topic later today

• Appropriate GMPs for atypical actives– More on this topic later today

Conclusions• Globalization of sourcing will require increased movement to harmonization

• Harmonization doesn’t just happen, it must be deliberate • Countries, Geographies, Regulators need to look at how they can be more

alike than how they can be different

• Patient safety is patient safety – no matter where in the world that patient is

• Sustainable quality management systems at excipient makers are based on ONE standard

• Mutually accepted standards, monographs, etc. are better than hundreds of different requirements when it comes to compliance AND patient safety

• REMEMBER - We all have the same goals

Thank You!