Uncertainties facing excipients suppliers as European Commission deliberates Excipients Directive; just-published GMP Guide provides a new harmonised, up-to-date guidance for industry
Companies who manufacture excipients for use by pharmaceutical finished dose manufacturers are facing an uncertain regulatory environment as the European Commission draws up its Good Manufacturing Practice Directive for 'certain' excipient products.
But a new guide - developed by the International Pharmaceutical Excipients Council (Ipec) and Pharmaceutical Quality Group (PQG) - provides a widely accepted GMP guidance that will not only help excipient suppliers meet the increasingly stringent demands of the pharmaceutical industry, but also make it easier for pharma companies to ensure their suppliers are meeting acceptable quality levels.
And because the GMP guide has been developed with close consultation between industry, regulators and other stakeholders, on both sides of the Atlantic, the hope is that it will help the European Commission develop workable, pragmatic legislation on excipients, striking the right balance between avoiding risks to public health from quality-impaired products, and avoiding excessive regulation that could affect the ability of suppliers to supply the market.
European legislative environment The overhaul of pharmaceutical legislation by the European Commission in 2004 has brought in GMP requirements for active ingredients and made the development of a Directive on GMP for excipients inevitable.
"There is a clear mandate in the legislation for a Directive on GMP for certain excipients," said Sabine Atzor of the European Commission's EG Industry and Enterprise, at an IPEC seminar in Cannes, France, to launch the new guide to the industry body's membership.
But she stressed that the Commission is determined to avoid 'gold-plating' legislation, and assured delegates that the intention was not simply to apply the existing GMP requirements for active substances used as starting materials - Part II of the Human Medicinal Products Directive (2004/27/EC).
"GMP principles will be adapted for excipients - we will not work with existing requirements," said Dr Atzor, noting that one possibility is that excipients are dealt with in a separate document - perhaps to be called Part III - that will cover those excipients selected for inclusion in the Directive.
Questionnaire.
A critical stage in the consultation period for the Excipients Directive is just about to get underway with the publication of a questionnaire - developed by the Commission with the help of industry - that will try to establish what quality systems are already being used by companies manufacturing and supplying pharmaceutical excipients in the absence of a legislative framework.
This questionnaire will help the Commission develop its GMP guidance for excipients, and crucially will help it assess the impact of legislation on suppliers and the pharmaceutical finished dose manufacturers.
Two versions of the questionnaire will be available: one for excipients manufacturers to gauge what quality standards they are using and what proportion of sales goes to pharmaceutical uses, and another for finished dosage form manufacturers that will examine the qualification and audit systems they operate for excipients manufacturers and distributors.
Atzor made a particular plea at the meeting for word of the questionnaire to be spread to small and medium-size enterprises, as these have been hard to reach in the consultation process to date and their input is critical.
GMP Guide.
"The GMP Guide provides a single, authoritative document that - for the first time - provides a harmonised guidance for excipients that is set at an appropriate level and up to date," according to the Pharmaceutical Quality Group's Steve Moss, who works as manager, new product supply and business development at GlaxoSmithKline.
The new Guide draws together and improves upon all the existing guidances that have been applied to pharmaceutical excipients.
"Manufacturers of pharmaceutical excipients have had to contend with pharmaceutical companies proffering as range of existing guidances and quality requirements".
"The new Guide should eliminate this situation and make it clear what quality systems should be incorporated in everyday controls and delivered at audit," according to Kevin McGlue, operations director at Colorcon, who chairs the GMP committee at IPEC Europe.
It creates a common baseline standard that should be achievable by for all suppliers, even those for whom pharma represents only a fraction of their total business, and is written in a language that all parties can understand, added McGlue.
Moreover, the Guide plugs some crucial gaps in earlier guidance documents.
Perhaps most importantly, for the first time it includes recommendations for companies making excipients by continuous processing, which is commonly used in the chemical industry but less often in the pharmaceutical sector, which tends to manufacture using batch processes.
Up to 50% of pharmaceutical excipient manufacturers are using continuous rather than batch processing.
It also sets out new recommendations on difficult issues such as validation, stability testing, change control and impurity profiling that have been lacking from earlier guidance, which has forced companies to default to guidance on active ingredients that is inappropriate for excipients.
"What we have to do now is take the guidance out to the hundreds and thousands of people who are producing excipients for the pharmaceutical industry and make sure that they use it," concluded McGlue.
"It will be of benefit to them, we just need to demonstrate what that benefit is."
