As Europe and North America currently contribute to approximately 75 per cent of the global excipients market - and Europe accounts for about half of this share - European pharmaceutical excipients manufacturers are concerned about any regulations that could increase their costs in the face of increasing competition from Asia.
India and China in particular are poised to enter the excipients market in the next four to five years, having already become formidable forces in the production of active pharmaceutical ingredients (APIs).
What worries European manufacturers most is that these countries are likely to have the advantage of low-cost manufacturing capabilities without compromising on product quality.
Making things gloomier for them is the issue of continuous commoditisation, particularly for bulky excipients such as microcrystalline cellulose and lactose.
In these conditions of increased price pressure and shrinking profitability, the last thing European manufacturers say they need is the burden of expensive regulation, particularly when the excipients used come to Europe from parts of the world where this regulation will not apply.
Whether such regulation comes to pass depends on how the EC chooses to interpret directive 2004/27/EC, which states that "this point [on GMP] shall also be applicable to certain excipients, the list of which as well as the specific conditions of application shall be established by a directive adopted by the Commission."
Dr Atzor is keen to point out that this directive will make a distinction between the GMP of APIs and excipients, so there is no intention to simply apply the existing GMP requirements for active substances used as starting materials.
"The need for legislation follows directly from the last paragraph ofArticle 46 of Directive 2001/83/EC as amended by Directive 2004/27/EC," she said.
"This new provision obliges the Commission to establish, in the form of a Commission directive, a list of certain excipients to which principles and guidelines of good manufacturing practices shall apply, as well as the specific conditions of application."
But what are those "certain" excipients? Those are yet to be elaborated and Dr Atzor, without going into specifics, says they will comprise a list according to a "risk-based approach."
In its consultations with the industry, the EC is currently focusing on the following categories of excipients: those derived from human and animal materials with a potential viral contamination risk, especially blood products, those of animal origin subject to transmissible spongiform encephalopathy (TSE) risks, those claiming to be sterile and are used with no further sterilisation, those which are pyrogen/endotoxin controlled, propylene glycol and glycerin.
Several trade bodies and agencies are working with the EC to ensure the resulting directive does not prove too costly for excipient manufacturers.
"In the worst case scenario you could have a large number of pharmaceutical excipients included in this list, it may be very expensive to comply with the guidelines, and many companies, particularly those whose products are not made primarily as excipients, may decide to withdraw from the market," Chris Dafforn, CMC regulatory affairs director at Astrazeneca, who sits in a working group on manufacturing issues of the European Federation of Pharmaceutical Industries and Associations (EFPIA), told In-PharmaTechnologist.com.
Still Dr Atzor insists the EC is not insensitive to such fears.
"This situation will be taken into account in the draft directive and an impact assessment," she said.
"The Commission's proposal will be based on a thorough impact assessment that will look into the different options and their respective burden and benefit for public health and economic operators."
The EC also says that it will launch a major publicity initiative, focused on its Europa server, to ensure all relevant stakeholders take part in the upcoming consultation and complete a questionnaire.
Two versions of the questionnaire will be available; one for excipients manufacturers to probe 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.
"Experience from past consultation via our web site confirms that small and medium-sized businesses (SMEs) contribute," Dr Atzor said.
"In addition, we are actively contacting European industry associations that are representing not only big pharmaceutical companies, but also SMEs."
But even if SMEs, the companies most vulnerable to regulation, are properly consulted, many believe the premise of the legislative exercise is ill-informed.
"The Commission is trying to go it alone here in a move precipitated by earlier proposals in France," said Mr Dafforn.
"What we need is to have GMP for excipients within the framework of the International Conference on Harmonisation (ICH), since the pharma infustry is global in nature."
Nevertheless, it took ten years for ICH Q7 on the GMP of APIs to be put in place, so the EC argues consumers should not have to wait for the ICH to act on this.
"At an international level the Pharmaceutical Inspection Cooperation Scheme (PIC/S) is working on harmonisation of GMPs while considering EU standards," pointed out Dr Atzor.
"Current activities at the level of the ICH relate to elements in the EU GMP guide and the recently adopted ICH Q9 guideline on risk management and the planned Q10 guideline on quality systems relate to GMP and will have to be implemented into the GMP guide."
The EFPIA, the International Pharmaceutical Excipients Council (IPEC) and other trade organisations remain apprehensive, claiming the impact of the new directive could range from minimal to colossal - it all depends on which excipients the EC picks and how different GMP for them will be from GMP for APIs.