The Commission and the EMEA have recognised that for a small number of medicinal products the primary use of the active substance is not in a medicinal product and the producer may therefore not be aiming to meet the specific requirements of pharmaceutical customers that represent an insignificant volume of business. This issue has been the subject of discussions between the Commission/EMEA and various industry groups for some time. In September 2008 the EMEA issued the following advice on the Q&A section of their website on how to proceed when dealing with an ‘atypical’ active:

“Alternative sources should normally be sought but in exceptional circumstances the manufacturing authorisation holder should assess and document to which extent GMP is complied with and provide a risk-based justification for the acceptance of any derogation. The declaration provided by the Qualified Person should set out in detail the basis for declaring that the standards applied provide the same level of assurance as GMP. EMEA will collect experience with this approach which can be used as a basis for discussion on related amendments to guidelines in the future.”

This is a pragmatic solution that has generally been welcomed by industry.

My article in the last Journal on why EUGMP expectations are now the toughest in the world drew numerous emails from readers – most notably from readers in the US who felt that I was criticising the FDA and USGMP standards!

Let me be perfectly clear. I draw absolutely no pride from my belief that EUGMP requirements are tougher than those of FDA – far from it. I believe that Regulatorsa ll over the world, but particularly in parts of the EU, are in danger of pursuing higher levels of GMP for GMP’s sake, and not for the benefit of the patient. Recent initiatives through ICH represent a welcome attempt to bring everyone’s attention back to what is really important.

Just because GMP requirements are getting tougher, it doesn’t mean that they are getting better or that patients are being better protected.

In March 2008 the EMEA issued a “Reflection Paper” on WFI by RO. Exactly why the EMEA wants to stimulate this discussion at this time is unclear. There does not appear to be a ground swell of opinion among users or suppliers to lobby for a change in the regulations to allow the use of membranes to manufacture WFI water such as there was in the 1990s. Rather, with the progression to hot water sanitisable systems there is probably a trend the other way and some companies are considering using distillation to make both WFI and Purified Water, particularly where the Purified Water volume requirement is relatively low compared with the WFI usage. Putting in a new Purified Water generation and distribution system is now around the same cost as putting in a new WFI generation and distribution system, not because the product quality requirement has changed but because the expectations of inspectors and industry approaches have changed.

All aspects of quality and regulatory requirements for WFI will be discussed in detail in our training course “Sterile Products Manufacture” to be held in Manchester in September.

In March 2008 the Commission launched a public consultation on ideas for amending the regulatory framework governing the manufacture, trading and distribution of active substances and medicines for human use. The Commission is proposing the following new measures to combat counterfeiting:

• Subjecting all parties in the distribution chain to pharmaceutical legislation
• Improving product integrity and traceability
• Sharpening the technical requirements for GMP and GDP
• Tightening inspections and supervision
• Improving transparency

The Commission is also considering making audits of GMP/GDP compliance by qualified auditors (these might include third-party audits by accredited companies) mandatory. This would apply not only to dealings between manufacturers and contract manufacturers but to the relationship between manufacturers and supplying/purchasing wholesalers, where there were grounds for suspicion of non-compliance. The Commission says that “acceptance of third-party audits by accredited companies could be considered”.

Ideas for improving product integrity include requiring a unique seal for the outer packaging of a medicinal product in its journey from the manufacturer to the retailer or wholesaler. The right to open the seal would be restricted to the market authorisation holder and the end-user of the product (i.e. hospital, healthcare professional, patient). This rule would not apply to all medicines but to certain categories of product identified through a risk-based approach, taking into account the potential public health impact of counterfeiting and the profit strategies of counterfeiters. The move would be backed up by a ban on repackaging.

In terms of traceability, the consultation document suggests introducing an obligatory product pedigree, comprising a “unique and centrally accessible record of all past ownerships and transactions”. The supplied retailer/pharmacy would be the final traceable point in the distribution chain.