Pharmaceutical Excipients (Excipients) and the EXCiPACT Certification System

Joel D'Silva - Director, Life Sciences and International Trade / European Chemical Distributors Association (FECC)

Tony Scott - Operations Manager

Pharmaceutical Excipients and the EXCiPACT Certification System – Overview and Current Status

Introduction

Regulatory authorities in the European Union and the USA have recently encountered and documented cases in which counterfeit medicines and substandard materials have entered the supply chain, resulting in tragic consequences. Users of pharmaceutical excipients are subject to increasingly stringent compliance standards imposed by regulatory authorities and are pressured to strengthen their supply chains by sourcing products from reliable suppliers that meet these standards. This article is prepared for pharmaceutical excipient manufacturers, suppliers and their customers – marketing authorization holders (MAHs) that produce and are authorized to manufacture medicinal products. The article addresses new regulatory requirements in Europe and the USA and how the EXCiPACT Certification System resolves these issues and enhances patient safety while reducing supplier quality verification costs, total costs and audit burden. All organizations within the pharmaceutical supply chain, from raw material suppliers to final dosage forms, will find information relevant to their operations in this article.

What is the EXCiPACT Certification System?

The EXCiPACT Certification System is an independently designed certification system for pharmaceutical excipient manufacturers, suppliers and distributors. The system is managed by EXCiPACT asbl, a non-profit association based in Brussels, and third-party certifications approved by EXCiPACT are issued by inspectors who are EXCiPACT staff members. The system, developed by pharmaceutical excipient users and suppliers, covers the following: • Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) Standards for ISO 9001-certified excipients, • Certification System Quality Determination and Quality Registration Procedures, • Inspector Competence Determination, Training, Examination and Registration Procedures. EXCiPACT Standards and Quality/Registration procedures are available for download on the EXCiPACT website. Certification of these standards requires that the supplier/distributor hold a valid ISO 9001 certificate. In the absence of an ISO 9001 certificate (common in the USA), NSF/IPEC/ANSI 363-2014 GMP Standards may apply. These standards were developed with contributions from pharmaceutical excipient manufacturers, health ministries and pharmaceutical excipient distributors. ISO 9001/EXCiPACT GMP/GDP Standards are equivalent. While NSF/IPEC/ANSI 363-2014 is only a quality standard, the EXCiPACT Certification System also measures the quality of the certification body and inspection mechanism. Therefore, when NSF/IPEC/ANSI 363-2014 certification is carried out, users should verify whether the certification body and inspection mechanism meet accepted standards of reliability.

Regulatory Need

Pharmaceutical excipients are base materials not primarily designed for medical use. GMPs used for excipients considered safe and used in sectors such as food and cosmetics may vary by industry. Pharmaceutical excipients are substances added to a medicinal dosage form to assist in the manufacturing process – as preservatives, stabilizers or for patient acceptance – or provide additional benefits such as product differentiation, safety or extended shelf life. Excipients include many substances such as anti-adherents, adhesives, colorants, dispersants, sweeteners and preservatives. Therefore, the use of GMP and GDP is critical for excipients used in pharmaceutical manufacturing. Prior to the launch of the EXCiPACT Certification System in 2012, regulatory authorities in Europe and the USA were required to oversee the quality levels of excipient manufacturers. In 2011, the European Union Falsified Medicines Directive (FMD) 2011/62/EU established benchmarks for the quality of excipient manufacturers. In 2014, the revision of EU GMP Part 1 Chapter 5 was issued for excipient manufacture. In March 2015, guidance principles were published to ensure appropriate use conditions for excipients used in medicinal products and to eliminate formulation risks, with implementation planned from 21 March 2016.

European Union principles further require pharmaceutical excipients to undergo various risk assessments. After confirming that appropriate GMP is in use, a gap analysis must be performed to measure manufacturer competence.

Data supporting the gap analysis must come from inspections or information provided by the excipient manufacturer. Any certifications or quality systems held by the manufacturer should be considered and verification that these certifications meet the requirements should be ensured. Similarly, in the USA, FDASIA requires pharmaceutical manufacturers to verify the excipients they use and confirm that they are manufactured in accordance with Good Manufacturing Practice (GMP) standards. The EXCiPACT Certification System makes these requirements applicable in both the European Union and the USA. Strategically, the FDA works in partnership with third-party organizations to secure the supply chain. The EXCiPACT Certification System is widely used publicly to secure the supply chain. Similarly, in Europe, the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) stated in a statement that it anticipated that no third-party organization other than the EXCiPACT Certification System would be effective.

Current Status

EXCiPACT Certification has been in use since 2013, with 6 accredited bodies certified to date. More than 42 site certifications have been achieved in over 14 countries worldwide, including Canada, the USA, Europe, the Middle East, India and China. For excipient manufacturers and suppliers seeking information on the use of EXCiPACT and solutions it can recommend to secure the supply chain, as well as for inspectors overseeing the EXCiPACT Certification program, regular EXCiPACT Certification courses are held. As the use of EXCiPACT becomes more widespread, increased awareness among qualified individuals about the system plays an important role in meeting the requirements of manufacturing to European standards.

Advantages of the EXCiPACT Certification System

One of the positive outcomes of the European Union's regulatory requirements regarding GMP use in excipient manufacturing is that the inspection mechanism in manufacturing and the supply chain is provided from outside the manufacturing party. This challenging task for the pharmaceutical industry and the manufacturing party is facilitated by the EXCiPACT Certification System, which enables safer inspection of medicinal products in low and medium risk groups. While certain inspections remain necessary for some excipients in the high-risk group, the use of EXCiPACT Certification makes these inspections possible without additional resource allocation. EXCiPACT Certification thus reduces audit costs for both suppliers and manufacturers without compromising quality and patient safety.

Conclusion

We are witnessing increasingly stringent inspections and regulatory requirements for quality excipient production. While the use of the EXCiPACT Certification System does not eliminate all audit costs, it significantly reduces audit costs on users and suppliers, enabling these resources to be directed toward reducing high risks. Through the international EXCiPACT approach, the quality and safety of pharmaceutical excipients will be better ensured within the supply chain, and this chain will expand worldwide.