The final risk assessment guide is stricter and more detailed than the draft form published in February 2013. It requires manufacturing authorization holders to risk assess their entire supply chain, from raw material sources, to stability, cold chain management, and suitability of packaging. They also need to put in place “systems for coding and identifying starting materials, intermediates and excipients to allow full traceability.”
Under the new rules, drugmakers should identify risks to the safety and stability of excipients, from their source (animal, mineral, vegetable, or synthetic) all the way through to their incorporation in the finished dose form.
The guidance draws particular attention to the risks of transmissible spongiform encephalopathy; microbiological, endotoxin or pyrogen contamination from raw materials; aflatoxins; pesticides; and residual solvents and catalysts.
It also says manufacturing authorization holders should beware the potential for impurities to carry over from other processes performed with the same equipment or facilities.
Environmental control and storage and transportation conditions, including cold chain management and packaging integrity are another part of excipient risk profiles.
According to the document, manufacturers should consider an excipient’s function in the finished formulation, including its ratio to API within the medicine and daily patient intake of the excipient. Drugmakers must educate themselves about known quality problems, including “fraudulent adulterations” within involved companies and the pharma industry worldwide.
Quality control: traceability
Once they have performed risk assessments, authorization holders will need to document the steps they take to maintain excipient quality.
These include excipient firms having competent staff with defined job descriptions and up-to-date training and well-maintained premises and equipment.
Facilities need comprehensive documentation systems covering all the manufacturing and quality processes and specifications. These include the ability to code and trace raw materials, intermediates and excipients.
The guidance also requires a quality control expert, independent from the production line, to assess excipients and release batches. Samples from batches must be retained, and any work contracted out must be done under a written contract.
Companies will have to maintain a system for complaints, recalls, and deviations from standard procedure.
The guidelines do not consider stabilisers for APIs that cannot exist on their own to be excipients.
The risk assessment for pharmaceutical excipients: the supply chain including cold chain management, the stability of the excipient and the suitability of the packaging have to be evaluated was published in the official journal of the European Union on March 21, 2015.
Our panel of global experts will be discussing the pharmaceutical excipients market at Excipients Innovation 2015 on March 31. Register here for our free online event.