EXCiPACT GMP Certification of pharmaceutical excipients has been providing trustworthy demonstration of the supplier’s commitment to the industry for over 10 years. With over 220 certificates issued to suppliers worldwide there has been growing international acceptance of the value and contribution EXCiPACT Certification makes to securing the excipient supply chain. Proactive feedback from users, compendia and regulators makes EXCiPACT GMP Certification a valuable way to reduce audit burdens. The flexibility in applying a suitable GMP which is a cornerstone of the EXCiPACT standards can also be applied to non-excipient materials that need to be manufactured to GMP principles. EXCiPACT also includes Good Distribution Practice (GDP) and a Good Warehouse Practice (GWP) for unopened packs. Collectively these are known as GxP.
What is EXCiPACT Certification?
Only a few countries in the world legally define GMPs for excipient suppliers. In the remainder it is the responsibility of pharmaceutical customers to define their GxP requirements and to audit their suppliers to obtain evidence of compliance. This poses a major problem for many excipient suppliers, as they may have large numbers of customers, all with potentially different GxP requirements for the same excipient. Additionally, there is an associated audit burden, where large numbers of requests have to be satisfied. It is to address these two points that the EXCiPACT GxP Certification Scheme for pharmaceutical excipients was created. By having a trustworthy and reliable 3rd party certification of the excipient supplier, based on a globally accepted GxP standard, audit requests can be satisfied by providing the Certificate and associated audit reports to customers.
The original idea for EXCiPACT GxP Certification was developed by excipient suppliers, their customers the pharmaceutical drug product manufacturers and the certification bodies which deliver the audits and issue the EXCiPACT Certificates. This multi-dimensional design team delivered a robust and business friendly scheme which also provided the high degree of assurance about supplier capability that the pharmaceutical industry and regulatory authorities require.
How a supplier obtains EXCiPACT Certification and uses it with their customers
EXCiPACT certification of a supplier requires ISO 9001 certification for the manufacture and or supply of excipients. This foundational quality management system is enhanced with the EXCiPACT GxP requirements. The key step is to completion of the quality risk assessments in EXCiPACT GxP, which are then used to determine the additional controls necessary to assure excipient quality. This approach makes EXCiPACT Certification very flexible and agile, relevant and easy for excipient suppliers to perform a comprehensive gap analysis. It is also very adaptive to all the different manufacturing processes used in excipient manufacture, being applicable to all chemical, physical and biological based manufacturing processes.
Once fully prepared, the excipient supplier identifies a suitable EXCiPACT registered certification body from the EXCiPACT website and contracts them to perform the audit to the EXCiPACT GxP standards. Upon successful completion of the audit process, an EXCiPACT Certificate is issued and this, together with the associated audit reports is shared with their customers. The Certification Body can be the same one providing ISO 9001, in which case there can be some economies in the audit process.
Feedback from EXCiPACT certified excipient suppliers shows that over 50% of customers now accept EXCiPACT Certificates and audit reports in place of performing their own audits.
How pharmaceutical customers can use their suppliers’ EXCiPACT certificates and meet regulatory expectations
A key question from all pharmaceutical customers is “do the authorities accept EXCiPACT?”. In the case of the Nigerian NFDAC (1) then the answer is “yes”. Following the latest glycerine/propylene glycol adulteration with ethylene glycol tragedy, the authority expressly mandated that all excipients have to be made in a factory certified to ISO 9001 or EXCiPACT. Elsewhere in the world the authorities cannot directly endorse EXCiPACT as it would imply that it is mandatory.
EXCiPACT recently asked the European Authorities for feedback and whether there are concerns about EXCiPACT Certification, as they will see it in use during inspections of drug product manufacturers quality systems. They explained that the two steps below have to be taken by the pharmaceutical company to enable them to use a suppliers 3rd party audit report (and any associated Certificate) in place of performing their own audits.
Firstly, the pharmaceutical company must determine the GMP required for each excipient in each drug product formulation. The European Guideline for ascertaining the required GMP for excipients (2) explains how do to this and is mandatory for all pharmaceutical companies in Europe. In many cases the output of that risk-based approach is that EXCiPACT GMP is a suitable standard for that excipient in a drug product formulation. Clearly the risk assessment must be completed before the required GMP is matched to the supplier and not the other way round! The power of the approach is that it directly aligns the risk to patient safety with the GMP required. For example, for a low-risk excipient, such as a colorant used in a tablet coating the required GMP could be Food GMP.
Secondly, the pharmaceutical company must also follow the GMP rules on outsourcing (Chapter 7 in European GMP Part 1). In this case they need to approve EXCiPACT as a provider of 3rd party audits and audit reports.
To facilitate this approval, EXCiPACT and its registered Certification Bodies have adopted and made available the templates in the IPEC Federation’s “GMP Certification Scheme and Certification Body Qualification Guide”. These also explain how EXCiPACT ensures auditor competency and further explain how the risks of impartiality and freedom from conflicts of interest which may impact auditor judgements are addressed. These documents align perfectly with the requirements set out in the recent EMA Q&A (3) which highlighted these risks need assessment for all 3rd party audit processes. Although this Q&A was listed as applicable to APIs the principle and requirements are equally applicable to excipients, and compliance would therefore be best practice.
Once these two steps have been completed then the pharmaceutical company can readily justify the use of a suppliers EXCiPACT Certificate and audit report as part of the overall qualification of that supplier.
Other benefits of certification
Recently, both the European Pharmacopoeia and the US Pharmacopoeia have stated that a supplier may use its EXCiPACT GMP Certification to fulfil the requirements in their Certificate of Suitability (CEP) and excipient verification schemes. In the case of the USP the EXCiPACT Certificate means the supplier would be exempt from a USP GMP audit. This is clear acceptance that EXCiPACT GMP provides a foundational level of GMP for excipients and therefore can be applied to most well-established excipients.
Recently, WHO issued a white paper concerning the development of their Starting Materials Certification Scheme (SMACs). In this paper they note it is globally known as a clear and established Certification process and propose discussions to strengthen trust, alignments and the relationship with national regulatory authorities, with an aim to see what role EXCiPACT can play in facilitating SMACS implementation. Again, a clear indication that EXCiPACT GMP is suitable for many excipients.
Conclusions
EXCiPACT has developed a comprehensive GMP/GDP standard suitable for the manufacture and supply of the majority of excipients.
Only those with the most critical roles in the delivery of the active to the patient require a more demanding level of GMP. EXCiPACT Certification has found acceptance from across the pharmaceutical industry, including regulatory authorities who have clearly stipulated how it can be properly used within existing pharmaceutical GMP frameworks.
EXCiPACT Certification reduces audit burden for both suppliers and users of excipients. With over 220 Certificates worldwide EXCiPACT is playing a key role in securing the excipient supply chain and both suppliers and users of excipients are leveraging its value to their relationship and to assuring patient safety.
References and notes
- Sources of API’s and Excipients – NAFDAC
- Formalised risk assessment to ascertain GMP for excipients
- EMA Q&A on 3rd Party Audit providers Questions 3and 9 in Part II for APIs
* EXCiPACT asbl is a not-for-profit organisation set up in Belgium and only comprises full members who are themselves associations. We are proud that IPEC India is now a key part of our membership and look forward to their contributions to the further development of EXCiPACT Certification.
