MHLW Issues Guidelines on Biosimilars Development and Regulatory Applications

Japan's Ministry of Health, Labour and Welfare (MHLW) has issued guidance on biosimilars, which sets out the policies regarding requests on development and regulatory approval application for biosimilars in Japan, according to a report by Pharma Japan.

Key Guidelines for Biosimilars Regulation in Japan

• Definition: "Biosimilars are drugs which are equivalent and homogeneous to original biopharmaceuticals in terms of quality, efficacy and safety and which are developed by manufacturers different from those of the original biopharmaceuticals".
• Development: Based on the guidance's definition, biosimilars should be developed to be equivalent and homogeneous to original drugs. However, biosimilars are also requested to be developed with updated technologies and knowledge, therefore only need to demonstrate enough similarity to guarantee the safety and efficacy instead of absolute identity.
• Application Filing: Biosimilars' regulatory approval applications will be categorised separately from conventional generic drugs. In general, the applications should be submitted, as in new drug applications, with data on clinical trials, manufacturing methods, long-term stability and information on overseas use. The MHLW will assess the data on absorption, distribution, metabolism and excretion (ADME) on a case-by-case basis. The applicants do not need to provide data on accessory pharmacology, safety pharmacology and genotoxicity.
• Naming: Biosimilars are requested to use brand names and non-proprietary names of the original biopharmaceuticals less the genetic recombination description. The non-proprietary names should also be followed by kozoku-1, meaning follow-on-1 and so on.
• Fee: The regulatory review fee for biosimilars will be ¥23.79 million (US$241,862), the same as new drugs' review fee. Some ¥480,700 should be paid for the approval.

Outlook and Implications

Following Europe, Japan has put forward the biosimilar guidance to give a clear instruction on the definition of this group of drugs, and requests for development and registration. Last September, the MHLW issued draft biosimilar guidelines for public consultation starting from 17 October 2008 (see Japan: 23 September 2008: Japan's MHLW Announces Consultation on Biosimilars).

The key points in the draft guidelines have pretty much remained in the final version, especially the requirements for biosimilar development and regulatory approval data. Although the development of biosimilars is only requested to bear enough similarities to the original drug, the approval data, process and fee are more likely to treat biosimilars as new drugs rather than generic chemical drugs. This reflects the need to assure the public and the prescribers about follow-on biomedicine safety, efficacy and quality. Nevertheless, the pricing and reimbursement of biosimilars are not likely to be put in line with new drugs. On the other hand, to what extent biosimilars' pricing and reimbursement will be set close to conventional generics drugs still remains to be seen as the discussions continue.