MHW, the Ministry of Health, Labour and Welfare plans and proposes policies for high quality medical services in Japan, in response to the aging of the society in recent years, changes in the disease structure and stronger people's demands for medical services of higher quality. The Ministry of Health, Labour and Welfare sets policies for reforms to medical services, “aiming to realize "high-quality" "efficient" medical services for the new century.“ A company intending to produce and distribute drugs in Japan must obtain approval for manufacture and marketing. Approval is issued by the MHLW after investigation of each product's efficacy, safety, quality, and other properties. A manufacturing/marketing business license and GMP-compliant manufacturing are conditions for drug manufacture/marketing approval. GMP inspection of a factory had to be carried out before issuance of the product manufacturing license for each product. In the future, such inspections will be integrated with the approval investigation. Factories will be inspected at regular intervals, e.g.every 5 years, to ensure continued GMP-compliant manufacturing.
Japan Regulatory Affairs - this document from the Japan Manufacturers Association gives a complete overview of the Japan Regulations.
The Pharmaceutical Affairs Law (PAL) was introduced in 1943 to implement regulations necessary for ensuring the quality, effectiveness, and safety of drugs and medical devices. The PAL has since been revised several times, including the introduction of legislation covering the reevaluation/reexamination system.
Since a recommendation to introduce GMP was issued by the World Health Assembly (WHA), the general meeting of the World Health Organization (WHO) in July 1969, Japan Standards for Manufacturing Control and Quality Control (GMP) were specified in Notification No. 801 of the PAB dated September 14, 1974 and they were enforced from April 1976 with some exceptions. With the partial revision of the Pharmaceutical Affairs Law in October 1979, the GMP became legally binding.
The control part of the GMP is specified in Drug Manufacturing and Quality Control Regulations in MHW Ordinance No. 31, 1980, and the part concerning buildings and facilities is specified in the revision of the Regulations for Buildings and Facilities for Pharmacies, etc. in MHW Ordinance No. 32, 1980 based on Article 13 of the Pharmaceutical Affairs Law.
Thereafter, provisions related to validation, recall, self-inspections, and education and training were added and the revised Regulations for Manufacturing Control and Quality Control of Drugs (MHW Ordinance No.3, January 27, 1994) and Regulations for Buildings and Facilities of Pharmacies, etc. (MHW Ordinance No.4, January 27, 1994) were issued and went into effect from April 1, 1994. Provisions required to assure the quality of biological products, including prevention of contamination by microorganisms, were added to the Regulations for Manufacturing Control and Quality Control of Drugs (Drug GMP) (MHW Ordinance No.71, September 25, 1997) and to the Regulations for Buildings and Facilities of Pharmacies, etc. (MHW Ordinance No. 57, April 30, 1999) since biological products require handling of animals and microorganisms in the manufacturing process, and a high level of control in accordance with the features of individual products such as utilization of biological reactions.
Regulations for Manufacturing Control and Quality Control of Drugs were revised to apply to some quasi-drugs (MHW Ordinance No. 16, March 12, 1999). To eliminate the risk of spreading infections from cell and tissue-derived drugs and medical devices, the regulations for buildings and facilities for biological products have been applied, the period of retention reference substances and records has been extended and donor screening has been added (MHLW Ordinances No. 54, 55, 56, 57, 58 nd 59 dated March 28, 2001).
On July 25, 2002, the Japanese House of Representatives passed and enacted the revised PAL. The latest revisions to the PAL are meant to address the enhancements in the development and safety of new medical products in the 21st century. According to the Ministry of Health, Labor and Welfare (MHLW), the revised PAL is intended to strengthen the safety measures related to medical devices, enhance government regulations with respect to the application of biotechnology and genome technology in developing medical products and fortify post marketing safety measures and the review system for approval and license while taking international conformity into account. The full implementation of the PAL revisions is scheduled for completion by April 2005.
However, regulations related to the biologically derived products were to be implemented from April to July of 2003. Various other enforcement ordinances will also be issued between July 2003 and April of 2005.
For Manufacturing, a factory that produces drugs must have a pharmaceutical manufacturing business license. Separate licenses are required for each class of drug manufactured, eg general or sterile class. Compliance of factory structure and facilities with the GMP standard is a condition for license acquisition. MHLW certification must be obtained for overseas factories that manufacture drugs for export to Japan. Ministry policy is to inspect overseas factories prior to issuing certification subject to the same standards as apply to Japanese factories. Proceedings are underway with the EU for mutual recognition of GMP. Progress in this regard is certainly essential for the smooth operation of the approval system under this amendment. International harmonization on GMP is important since it forms the basis of the system.
Source: Japan Pharmaceutical Manufacturers Association (JPMA)
