Michael Cooke

Excipients should be regulated to manage risk. Although, excipients are an integral part of a finished pharmaceutical product, the issue of regulation is complex. Unlike APIs, which are developed solely for pharmaceutical use, many excipients are found in diverse, other non-pharmaceutical products. As such, compared with other industries, a solvent may be sold in relatively small quantities to pharma and the producer may not see a business case for making expensive changes to the production process for the relatively small volume required by pharma customers.  

I believe that a solid risk-based approach (for example, one which includes cross-contamination risks, meeting the European Pharmacopoeia specifications, traceability, etc.) is needed so that all excipients have to undergo a GMP assessment. However, the controls and manufacturing processes do not necessarily need to be equivalent to those used in the pharma plant, so long as the risks can be properly managed by other means, such as on-site analysis against the specifications set out in Pharmacopoeia. The EU is currently proposing GMP for excipients as part of the draft "Directive on falsified medicinal products".  

One common theme raised in supplier audits is change management. For example, a change in a manufacturing site can be a major issue if the new site does not follow exactly the same production process as the original, or the control measures taken are different. The customer needs to know of any changes to production processes or equipment so that they can assess whether these might impact product quality. This is a key issue for distributors, who may handle thousands of products from many different suppliers and need to keep track of any changes made at any of them.  

Other issues that can arise in audits include stability testing, defined operating procedures for quality control, etc. 

Audits are conducted to ensure a product is fit for purpose. The auditor will generally be looking to ensure that the end product is not exposed to any risk in any part of the supply/manufacturing chain thereby ensuring patient safety. Understanding the GMP requirements as set out by IPEC and implementing these as appropriate will help ensure an audit is favourable.  

The burden of audit requests can be eased by working with distributors who can consolidate audit requests from customers and ensure that the excipients manufacturer is audited only once instead of several times. It is also possible to share audit reports. At Univar, for example, we work in partnership with specific excipient manufacturers to conduct an independent, third party audit of the supplier. The detailed report as far as confidentiality requirements allow and suppliers agree to, is then made available to all customers participating in the scheme. The supplier and customer both benefit in terms of reduced costs and time commitment.  

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Excipients should be regulated to manage risk. Although, excipients are an integral part of a finished pharmaceutical product, the issue of regulation is complex.