ANSI NSF/IPEC 363 and EXCiPACT GMP Standards – Need for Global Harmonization Ann Van Meter Business Quality Leader – Dow Pharma & Food Solutions Chair – GMP Committee – IPEC-Americas vanmetma@dow.com www.ipecamericas.org

Excipient Maker Example Personal Care Increasing Food regulations Excipients and Atypical Actives Expectations Industrial Products ISO Quality Excipient Maker 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

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 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 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

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!