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This paper will examine the multi-state procedure from the perspective of the critical communication points, who is involved, and what information needs to be communicated. Marion Merrell Dow's experience with the multi-state procedure will be described from a similar perspective, identifying the good and bad communication points, what has been done to improve communications, and how they could be further improved. Finally, whether or not technology can help to facilitate the interface between the regulatory authorities and industry during registration procedures will be discussed.

The United Kingdom has been one of the major rapporteur countries in the multi-state procedure. Viewing the role of the Medicines Control Agency (MCA) as rapporteur as a facilitator, we have seen cooperation among Member States and a great deal of teamwork between the rapporteurs and co-rapporteurs. In the future decentralized system, as we move from a few companies using it for a few products to a large number of companies using it for a large number of products, the role of rapporteur will need to be clearly defined.

Italy has received many applications using the multi-state procedure. To keep up with demand, the Ministry of Health has made many internal adjustments, including increasing staffing and setting up a computer network. The Ministry focuses on early discussions with other Member States, and tries to work closely with them to keep objections relevant. This paper reveals what Italy looks for when reviewing a dossier.

Recently, Scotia Pharmaceuticals submitted Epogam Capsules for registration through the multi-state procedure. A small company, at the time of the application, Scotia had 75 employees and a two-person regulatory department. This paper ex­ plores the decision process Scotia used to decide whether to go with a multi-state procedure, national procedures, or a combination of the two and the results of that choice, faster approval in two Member States and less drain on company resources.

Marion Merrell Dow's (MMD) European regulatory strategy, focusing on the company's experience with the EC multi-state procedure, is summarized here. An overview of MMD's European regulatory strategy to date is presented, detailing how the strategy has been developed, the results achieved, the lessons learned, and finally, how the company can build on this experience in preparation for the introduction of future EC systems.

Although the multi-state procedure with new chemical entities and generics appears to be in the process of being phased out, there are certain advantages that the multi-state procedure has over national registration. These components may be useful in any future European registration system. The effectiveness of multi-state procedures is illustrated with three examples: Theophylline, Salbutamol, and Urapidil.

Procedures recently published for a new European registration system will make a centralized or decentralized multi-state procedure mandatory in most circumstances. Although these changes will not come into being for several years, companies should gain experience with the current multi-state procedure before the new system be­ comes mandatory. This paper discusses the pros and cons of the procedure as it now exists and offers practical advice on using it through Sanofi's experience.

The multi-state procedure, while effective in some ways, has not on the whole met its objective of providing for the free movement of pharmaceutical products within the EC. Flawed legislation and attitude of Member States and industry toward the multi-state procedure have prevented it from leading to a single market. We've learned quite a bit from the multi-state procedure and this knowledge has been applied in developing the proposed decentralized procedure, which will be binding on all Member States.

In 1987, Du Pont Pharma submitted its first multi-state application for a product named Brevibloc. The two-step application began with submission in France for a concentrated dosage form. Two years later, the company applied for a variation on a diluted dosage form. Initially, no common decision was agreed upon, and a quality working party was assembled to sort out the conditions of approval. Du Pont Pharma found that the multi-state procedure can be a fast track in certain countries, but encountered problems with nonbinding CPMP opinions.

In 1990, F. Hoffman-LaRoche used the multi-state procedure for moclobemide, with Denmark as rapporteur. Our experience demonstrated the importance of planning. We developed a custom focused document in reply to questions, which enabled the authorities to evaluate answers easily, and made reference documents available, but not part of the main answers. From our experience, we've seen a trend toward harmonization of the summary of product characteristics and noted the importance of the efficacy working party in facilitating harmonization and shortening approval time.

The multi-state and concertation procedures have generally been successful, but there is room for improvement. Pharmaceutical companies, regulatory agencies, and the European Commission must work together to truly achieve a single European pharmaceutical market. These remarks discuss actions which could be introduced to facilitate the transition from the old regulatory system to the new.

The Drug Information Association holds an annual Euromeeting. Topics for these meetings vary, as do the “tracks” which make up the meetings. It was my pleasure to chair this track which dealt with ...