Historically, in order to meet pharmaceutical GMP expectations, excipient manufacturers have relied on the International Pharmaceutical Excipients Council (IPEC) and Pharmaceutical Quality Group’s (PQG’s) Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients1. The two organizations issued this guidance in 2006, and it was the product of a significant amount of work by IPEC’s members. While the guide provides a great baseline, in the 12 years since its release, the industry has moved on.
Excipient manufacturers should now reference either ExciPact’s Certification Standards for Pharmaceutical Excipient Suppliers 20172 or NSF International (NSF), IPEC, and American National Standards Institute’s (ANSI’s) NSF/ IPEC/ANSI-363-2016 Good Manufacturing Practices (GMP) for Pharmaceutical Excipients3. Both are contemporary standards and are closely aligned because the organizations based them on the IPEC-PQG’s joint standard and recognized the importance of not imposing certain pharmaceutical GMP expectations, such as those relating to process validation, on the pharmaceutical excipient manufacturer. Two separate excipient GMP standards really aren’t necessary, however, so over time, it’s likely that IPEC membership will steer the industry in the direction of adopting a single, globally recognized standard for pharmaceutical excipient GMPs.
Qualification of Excipient Suppliers
The traditional means to determine whether an excipient supplier meets appropriate GMP is to conduct an on-site audit. Most companies resort to paper audits or questionnaires, which are of limited value. In some cases, the excipient supplier won’t permit an on-site audit or will limit the audit’s duration to a single day, which is also of limited value. In most cases, the pharmaceutical company focuses its auditing resources on the APIs and elects to forego on-site audits for some or all of its excipient suppliers. This also isn’t necessarily a good outcome.
More recently, due to the development of GMP-certification schemes, pharmaceutical companies can ensure that their excipient suppliers have received certification to a recognized excipient GMP standard. This provides the pharmaceutical company with the assurance that the supplier’s GMP program and quality- management system meet an established standard. Several certification programs are available. NSF runs the Excipient Certification Program (NSF-ECP), an ANSIaccredited program that has been active for a number of years.
Excipient GMPs and Product Lifecycle
Excipients must adhere to basic GMP requirements irrespective of the developmental stage of the pharmaceutical product. The GMP standards referenced earlier provide good baseline guidance, and the developmental success of a solid-dose product greatly depends on the consistency of the excipient supplied.
Suppose, for example, that the supplier of an excipient intended for use in a manufacturing process for solid oral tablets varies the particle- size characteristics through any number of process changes. The impact on the tablet manufacturing process can be significant, such as variations in mixing uniformity, tableting flowability, or tablet compression.
Furthermore, it’s important to recognize that regulatory approval of pharmaceutical products is a complicated process, and regulatory agencies expect companies to understand the critical process parameters (CPPs) and critical quality attributes (CQAs) of their products. The CPPs often link to excipient properties. A proactive excipient manufacturer will not only consider meeting GMP expectations but will also provide a comprehensive data set that characterizes the excipient and a description of the control measures in place to ensure the excipient’s quality and consistency.
Expectations After Commercialization
After a regulatory agency approves a drug product, it’s incumbent on the excipient manufacturer to be extremely proactive in managing its relationship with the customer. Drug product manufacturers with robust quality systems will monitor a variety of factors. For instance, they will track out-of-specification results, non-conformances, and/or validation issues that could potentially be associated with the quality of the purchased excipient. They will also monitor the supply-chain performance, reliability, and certification status of their suppliers. If the drug product manufacturer is distributing products in the European Union, they will regularly update their suppliers’ risk profiles to ensure that the suppliers continue to meet appropriate GMPs.
The Supplier-Customer Relationship
Pharmaceutical companies are risk averse and highly quality-minded. Excipient suppliers that pay attention to the consistency of the excipients they manufacture and, through GMP certification, demonstrate that they consistently meet a recognized GMP standard, will undoubtedly set themselves up for long lasting, win-win relationships with their pharmaceutical customers.
References
1. http://ipec-europe.org/ UPLOADS/IPEC_PQG_GMP_ Guide_2006(1).pdf.
2. https://www.excipact.org/files/ EXCiPACT/Downloads/2018 0123%20EXC%20Standard_Finalwebversion. pdf.
3. Available at: https://webstore. ansi.org/RecordDetail.aspx?sku=NSF% 2FIPEC%2FANSI%20363-2016 &source=blog.
Jim Morris is executive director, pharma biotech consulting, at NSF Health Sciences, a division of NSF International (734 769 8010, www.nsf.org). A version of this article originally appeared in T&C’s Solid Dose Digest on July 9, 2018.