In Europe, the Falsified Medicines Directive (FMD) and the changes to EU Part 1 GMP Section 5 have been designed to improve product quality entering the supply chain by placing new and more detailed requirements on the qualification and supervision expected of pharmaceutical excipient manufacturers and distributors. This includes the expectation that there will be a risk-based approach to defining the excipient GMPs and more demands on distributors via GDP. These new regulatory requirements have taken more than a decade to evolve following regulatory false starts and evidence of deliberately adulterated excipients in medicines, exposing patients to harm.
Given the inevitable increase in the number of audits needed to satisfy the regulators, a cost-efficient approach would be needed to maintain the quality and safety of excipients. One way is to use the EXCiPACT Certification Scheme for pharmaceutical excipients, which is based upon the EXCiPACT GMP/GDP standards. This new third-party scheme has been expressly designed to help qualify suppliers of excipients. EXCiPACT certificate holders will provide their certificate, audit report(s), plus any corrective and preventive action plans to their customers.
With audits occurring at least annually, in a short period of time, a comprehensive picture of the supplier’s compliance to the EXCiPACT GMP and/or GDP standards can be built up. This auditing frequency is greater than most excipient users could perform, even for their critical excipients. Thus, users of excipients will be able to ascertain in some detail the GMP and/or GDP applied by their suppliers and so fully meet the new requirements in the FMD and revised EU Part 1 GMPs.
But as a third-party Certification Scheme, how can the excipient user have confidence in the audits? There are three key components in the scheme, all of which have to be present to assure the quality of the audits:
GMP and GDP standards. The scheme development took the existing, well-accepted and widely used IPEC-PQG GMP and IPEC GDP guides for pharmaceutical excipients and converted them into EXCiPACT auditable standards as annexes to ISO 9001. This approach made their adoption and assessment more consistent and simpler for all ISO-registered suppliers. For excipient suppliers without ISO 9001, the GMP audit can be performed by the same certifying body and auditors to the forthcoming ANSI NSF 363 US National Standard, which is equivalent to the EXCiPACT standard. Either way, the GMP requirements will be the same.
Auditor competency. To maintain the scheme’s high quality and service provision, and to be formally approved and listed, all auditors used by the EXCiPACT asbl registered third-party certifying body must first undergo a rigorous and formal two-day training course, pass the end-of-course exam, and be witnessed during a live audit to verify their competence and understanding of the scheme’s requirements.
Third-party certifying bodies. The EXCiPACT asbl registered certifying bodies are audited by EXCiPACT asbl to confirm their quality management system meets the requirements set out in the ISO 17021 annex in the EXCiPACT standards book. Key among these requirements is that the certification decision is not made by the auditor but by an independent review board.
To verify the authenticity of an EXCiPACT certificate holder, the EXCiPACT asbl website lists the EXCiPACT asbl registered certifying bodies; the independently registered auditors; and the name of each excipient supplier with an EXCIPACT certificate, its scope and status.
The EXCiPACT certification scheme has received excellent support from the regulatory authorities on both sides of the Atlantic who see it as “ticking the right boxes” and providing confidence that patient safety will be enhanced. Its use allows users of pharmaceutical excipients to maximise the benefits and minimise the risks of their choice of an excipient supplier.
About the Author
Iain Moore, PhD, is head of global quality assurance at Croda and president of EXCiPACT asbl.