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A further 30 days is set aside in which any difficulties that arise may be resolved. The total application duration is 300 days. If one or more states refuse to grant the marketing authorization (i.e. mutual recognition breaks down), the difficulties are referred back to the EMEA. The CPMP will then make a decision (‘opinion’), which is sent to the European Commission. The Commission, taking into account the CPMP opinion, will make a final decision, which is a binding one.
Drug registration in Japan
The Japanese are the greatest consumers of pharmaceutical products per capita in the world. The Ministry of Health and Welfare in Japan has overall responsibility to implement Japanese pharmaceutical law. Within the department is the Pharmaceutical Affairs Bureau (PAB), which exercises this authority.
There are three basic steps in the Japanese regulatory process:
• approval (‘shonin’) must be obtained to manufacture or import a drug;
• a licence (‘kyoka’) must also be obtained;
• an official price for the drug must be set.
The PAB undertakes drug dossier evaluations, a process which normally takes 18 months. The approval requirements/process for pharmaceuticals (including biopharmaceuticals) are, in
broad terms, quite similar to those in the USA. PAB have issued specific requirements
(Notification 243) for submission of recombinant protein drugs.
Applications are initially carefully checked by a single regulatory examiner to ensure conformance to guidelines. Subsequently, the application is reviewed in detail by a sub-committee of specialists. Clear evidence of safety, quality and efficacy are required prior to approval.
In addition, the Japanese normally insist that at least some clinical trials be carried out in Japan itself. This position is adopted due, for example, to differences in the body size and metabolism of the Japanese compared to US or European citizens. Also, the quantity of active ingredient present in Japanese drugs is lower than in many other world regions. Hence, trials must be undertaken to prove product efficacy under intended Japanese usage conditions.
THE DRUG DEVELOPMENT PROCESS 89
World harmonization of drug approvals
There is a growing trend in the global pharmaceutical industry towards internationalization. Increasingly, mergers and other strategic alliances are a feature of world pharmaceutical activity. Many companies are developing drugs which they aim to register in several world regions. Differences in regulatory practices and requirements in these different regions considerably complicates this process.
Development of harmonized requirements for world drug registrations would be of considerable benefit to pharmaceutical companies and to patients for whom many drugs would be available much more quickly.
The ICH process (International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use) brings together experts from both the regulatory authorities and pharmaceutical industries based in the EU, USA and Japan. The aim is to achieve greater harmonization of technical/guidelines relating to product registration in these world regions, and considerable progress has been made in this regard over the last decade. The ‘members’ comprising ICH are experts from the European Commission, the European Federation of Pharmaceutical Industries Association (EFPIA), the Japanese Ministry of Health and Welfare, the Japanese Pharmaceutical Manufacturers Assocaition (JPMA), the FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA). The ICH process is supported by an ICH secretariat, based in Geneva, Switzerland.
The drug discovery and development process is a long and expensive one. A wide range of strategies may be adopted in the quest for identifying new therapeutic substances. Most biopharmaceuticals, however, have been discovered directly as a consequence of an increased understanding of the molecular mechanisms underlining how the body functions, in both health and disease.
Before any newly discovered drug is placed on the market, it must undergo extensive testing in order to assure that it is both safe and effective in achieving its claimed therapeutic effect. The data generated by these tests (i.e. pre-clinical and clinical trials), are then appraised by independent, government-appointed regulatory agencies, who ultimately decide whether a drug should gain a marketing license. While the drug development process may seem cumbersome and protracted, the cautious attitude adopted by regulatory authorities has served the public well in ensuring that only drugs of the highest quality finally come onto the market.
Adjei, H. (1997). Inhalation Delivery of Therapeutic Peptides and Proteins. J.A. Majors Co., Atlanta, GA.
Ansel, H. (1999). Pharmaceutical Dosage Forms and Drug Delivery Systems. Lippincott Williams & Wilkins, Philadelphia, PA.