Regulatory Systems in Japan: Process for Regulatory Approval for New Drug in Japan
Japan’s pharmaceutical regulatory system has several standards and comprehensive review processes, overseen primarily by the Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labour and Welfare (MHLW). The regulations emphasize safety, efficacy, and quality, requiring detailed documentation and rigorous clinical trial data. Navigating this complex regulatory landscape can be challenging for overseas sponsors unfamiliar with local requirements and procedures. CMIC Group can offer expertise in understanding the Japanese regulatory frameworks, facilitating smooth communication with regulatory bodies, and ensuring compliance with all local laws. Our team’s expertise helps expedite the approval process, reduces the risk of costly delays, and enhances the overall strategy for entering the Japanese market.
1. Regulatory Authorities for NDA Approval
- PMDA (Pharmaceuticals and Medical Devices Agency): Conducts review of application dossier and conducts compliance investigations
- MHLW (Ministry of Health Labour and Welfare)：Approval Authority
- Expert Advisory Meeting
- Drugs Committee
2. Process for Regulatory Approval
Alongside the review of application documents, reliability document inspection, GCP compliance inspection, and GMP compliance inspection are conducted by PMDA. After approval, the “Review Result Report” is published on the PMDA website.
3. Review Period (Standard Schedule for New Drugs)
- Priority Review
- Orphan Drugs : 9 months (median)
- Specific-purpose drugs
- Drugs designated as “Sakigake”: 6 months (with pre-review)
- Others: 12 months
4. Approval Timing
Generally, four times a year: March, June, September, December
In the year of drug price revision, December approval becomes January approval.
5. Orphan designation and facilitated regulatory pathways (See below)
[Applicant of New Drug Application]
- General Regulatory Approval: Companies with pharmaceutical business license
- Foreign Exceptional Approval: Overseas pharmaceutical companies *However, it is necessary to appoint a domestic company with pharmaceutical business license in Japan.
In order to obtain pharmaceutical business license, it is necessary:
- To have “TRIAD” (General Marketing Compliance Officer, Quality Assurance Officer, Safety Officer) in a Japanese corporation (see Figure).
- To establish GVP (Good Vigilance Practice) and GQP (Good Quality Practice) systems, and to have necessary Standard Operating Procedures (SOPs) to be compliant with regulations.
Under the Japanese laws and regulations, Marketing Authorization of a drug is granted to the pharmaceutical company which maintains Japanese pharmaceutical business licenses. However, even if a foreign company does not establish a Japanese company with pharmaceutical business license, it can apply for marketing approval using the foreign exceptional approval system by appointing Japanese pharmaceutical company as Appointed Marketing Authorization Holder (AMAH). AMAH is responsible to MHLW and PMDA on behalf of foreign pharma.
- There is a system (In-country clinical care taker: ICCC) in place that allows overseas pharmaceutical companies without a Japan entity to conduct clinical trials.
- In general, clinical trial data from Japanese subjects is required. There may be cases where diagnostic criteria and standard treatments differ from those overseas, making it difficult to participate in global trials.
- By receiving ODD, there are benefits such as priority review (median 9 months of review period), extension of re-examination period (market exclusive period, up to 10 years), and price premium (marketability premium I: 10-20%).
- Conducting Orphan Drug Designation (ODD) consultations and discussing with the Ministry of Health, Labour and Welfare (MHLW) is required to determine eligibility for ODD.
- It takes approximately 10 months from application to designation.
- For more info on the Orphan Drug Designation System and designation criteria > Access MHLW HP
LEARN MORE about CMIC Group’s Orphan Drug Development
SAKIGAKE Designation System aims to designate innovative drugs and other medical products that are developed ahead of the world to be commercialized in Japan at an early stage, with notable efficacy expected during early clinical trials, and to achieve early practical use through various support.
[Designation Criteria]
- Innovativeness of the treatment
- Severity of the target disease
- Extremely high efficacy for the target disease
- Intention and infrastructure to develop and apply early in Japan, ahead of the world (including simultaneous application)
[Benefits]
- Priority consultation
- Expedited pre-submission review (Rolling review)
- Priority review (12 months → 6 months)
- Examination Partner System (concierge service by PMDA)
- Enhancement of post-marketing safety measures (extension of re-examination period: up to 10 years)
- For more info about Sakigake > Access MHLW HP
“Conditional Early Approval System” is a system to put highly useful and effective drugs for treating serious diseases into practical use as early as possible.
[Candidate product]
- Drugs that treat serious diseases for which there are limited treatment options and,
- Drugs that it is difficult to conduct clinical trials or it takes long period because the number of patients is small
[Requirement]
MHLW/PMDA needs to:
- Confirm a certain degree of efficacy and safety through clinical trials other than confirmatory clinical trials at the time of submission
- Clarify management of conditions for approval such as imposing to conduct research which is necessary for reconfirmation of post-marketing efficacy and safety
[Benefits]
- Early application through confirmation of a certain degree of efficacy and safety through clinical trials other than confirmatory clinical trials.
- Shorten overall review times for priority review products
