More transparency on guidelines

Linda Horton and Hector Armengot from the Brussels office of Hogan & Hartson cast light on the new procedure for EU pharmaceutical guidelines.

On 30 June 2005, the European Medicines Agency (EMEA) published a 'Procedure for EU guidelines and related documents within the pharmaceutical legislative framework' - the EMEA Guidelines Procedure for short.¹With this document the EMEA introduces a transparent and open procedure for the drafting, consultation, adoption and implementation of pharmaceutical guidelines.

Importantly, the public is given an earlier input on whether guidelines are needed and on the impact of guidance on industry and others. The EMEA and European Commission (EC) also announced their intent to update and consolidate the rules governing medicinal products in the EU, described as 'the vehicle for publication of guidelines and legislation within the pharmaceutical legislative framework.'

A draft of the EMEA Guidelines Procedure was published for consultation in September 2004.² The new procedure replaces current guidance on the subject, in particular an EC paper on a 'Procedure for EU Guidelines.'

EU guidelines are documents that help to explain EU laws and would typically elaborate on an obligation contained in an EU directive, regulation or decision, or provide advice to market participants and public authorities on the best way to comply with requirements and obligations contained in EU laws.

With some exceptions,³ guidelines do not have legal status and are not legally binding. Alternative approaches may be taken, but only if justified by the authorities. This approach sounds similar to a US Food & Drug Administration (FDA) 'guidance document', but many believe it may be more difficult to justify deviation from an EU guideline. These guidelines are highly influential because they reflect the EC's position on the implementation of EU legislation.

Guidelines are an indispensable tool for those wishing to understand the rather complex EU pharmaceutical legislative framework and to adjust their conduct to the requirements and obligations contained in the law. They also provide legal certainty on the authorities' interpretation of the relevant laws to market authorisation applicants and holders, sponsors and manufacturers.

If followed, guidelines can facilitate the approval, control and assessment of medicinal products by the relevant authorities. Given the significance of guidelines, it is essential that the procedure for their adoption is open and transparent, allowing interested parties to express their views and participate in the decision-making process. After all, guidelines can have a significant impact on the research and commercialisation practices and policies of pharmaceutical companies. Some guidelines are followed by the industry as if they were requirements.

Guidelines have different sources - e.g. the EMEA or the EC - and are sometimes the result of the International Conference on Harmonisation (ICH) efforts among the EU, the US, Japan and other international partners. ICH guidelines are now expressly given the same status as EC and EMEA guidelines. They can also play a role in reducing global product development costs and thus in facilitating international trade in medicines. The EMEA has also stated that a procedure is in place so that issues that arise from scientific advice applications can be progressed to guidelines on question and answer (Q and A) documents (which are not guidelines) 'in a suitably and organised manner'.

clearer definition

The EMEA Guidelines Procedure proposes the term 'guideline' for all pharmaceutical guidance documents. Currently, different names are used, such as 'note for guidance', 'guideline', 'position paper', etc. The choice of a unique name is intended to avoid confusion concerning the nature and legal status of the various forms of guidance.

The EMEA Guidelines Procedure lists and describes the different types of pharmaceutical guidelines with 13 examples, including Regulatory Guidelines, such as those contained in the EC's Notice to Applicants, Scientific Guidelines related to Quality, Safety and Efficacy, Good Manufacturing Practice Guidelines, Good Clinical Practice Guidelines and Orphan Medicinal Products Designation Guidelines. The Procedure also lists documents not considered guidelines reflection papers, and Q & A documents.

The EMEA Guidelines Procedure spells out a series of steps to be followed when adopting guidelines and largely codifies the standard practice of the EC and EMEA. Some steps can be omitted under special circumstances, such as when changes in previous documents are minor or when the adoption of the guideline is urgent.

The EMEA Guidelines Procedure sets out the following 12 steps:

1. Selection of a topic and inclusion in the EMEA work programme. The selection of topics will be carried out mainly within the EMEA, including its scientific committees and other groups comprised of EU member state experts. Input on guideline topics can also be received from the member states as well as interested parties. The procedure does not specify one single mechanism for suggesting new initiatives. Suggestions may be made spontaneously to the EMEA or member state officials on EMEA committees. Input can be given spontaneously or in response to an EMEA request.

2. Appointment of a rapporteur to reflect the views of the relevant committee. Once a topic has been selected, a rapporteur will be appointed who will be in charge of drafting the concept paper and the subsequent guideline with the support of others in the EMEA and its committees. There is no barrier to interested persons contacting guideline rapporteurs directly but this is generally considered not appropriate.4

3. Development of a concept paper. A concept paper is meant to communicate the need for a specific guideline. It is short (e.g. two pages), outlining the issues to be covered and possibly some options, but without elaborating on the solutions. Importantly, the concept paper stage gives the public a chance to comment before EMEA or EC positions are set.

4. Adoption and release for consultation of concept paper. Following adoption, concept papers are published on the EMEA's website and open to comments for two to three months. The EMEA says it is developing improved mechanisms for hearing views from groups representing patients or healthcare professionals.

5. Preparation of initial draft guideline. The draft should include references to existing EU directives and guidelines, and related guidelines in other regions, e.g. FDA guidance. It should take into account comments received during the consultation period on the concept paper. Before publication the draft will be discussed internally within the EMEA and its relevant committees.

6. Release for consultation of draft guideline. Draft guidelines are published on the website of the EMEA, the EC or the European Pharmacopoeia and will normally be open for consultation for three to six months.

7. Collection and treatment of comments. Comments received by the rapporteur, member states, other regulatory authorities, European industry associations, scientific societies, patient groups and other interested parties will be carefully considered by the rapporteur and/or the drafting group in charge of the guideline. All comments will be published on the relevant website unless they contain commercially confidential information or the author has objected to their publication. In response to 'specific justified concerns', the EMEA may convene a meeting with interested persons on a concept paper. Also, more details on the criteria for a meeting would improve the procedure.

8. Preparation of final version. Comments received will be considered.

9. Adoption of final guideline. Depending on the type of guideline, the relevant EMEA committee and/or the EC adopts the final guideline and publishes it on the relevant website.

10. Implementation. Generally, a guideline will be effective six months after its adoption. Guidelines are rarely retroactive; when they apply to medicines already on the market, this coverage will be explained and justified.

11. Training. The EMEA will provide training to member states' officials to ensure uniform application. In some cases other interested parties could be allowed to participate in the training.

12. Maintenance and revision of adopted guidelines. As a general rule, guidelines will be reviewed after five years, and in some cases earlier, depending on available experience and knowledge. The EMEA welcomes suggestions on this issue.

The adoption of the EMEA Guidelines Procedure is part of an effort by the agency to increase transparency in its procedures. With their adoption the EMEA acknowledges the indispensability of the pharmaceutical sector's involvement in its decision-making procedures. For these reasons, the pharmaceutical industry appears to welcome the adoption of the EMEA Guidelines Procedure, but would also welcome an increase in face-to-face meetings as part of the improved transparency.

The EMEA will apply the Guidelines Procedure to all draft and final guidelines published after 1 September 2005.