Generally, for new or unique medical device registration in Japan, a local Japanese clinical trial will be needed. However, in some cases, a separate Japanese trial is not required for device approval. Please keep in mind that the PMDA will normally not accept a foreign study report at face value. For foreign device companies, applicants must demonstrate that their foreign clinical trial data provides the same benefits for Japanese patients (no ethnic differences with Westerners) and that GCP is met. Oftentimes, you need to engage with the PMDA for one or multiple PMDA consultation sessions to know exactly what will be required for product registration in Japan.
When is Clinical Data Required?
First of all, it is important to note that local Japanese clinical studies are not always required. Japan classifies devices into four risk-based classes, which in turn route into one of three regulatory pathways: Notification, Certification (Ninsho), or Approval (Shonin). Only the higher-risk track, Pre-Market Approval, or Shonin applications will require clinical data. Lower-risk devices reviewed through the certification or notification routes typically do not require clinical data. A general consultation with PMDA early in development will help determine whether clinical data is required.
Foreign Data is Generally Acceptable
The PMDA has accepted overseas clinical studies in some instances. The basic principle is that if a company already has solid pivotal clinical data from trials conducted overseas (in the United States, Europe, or other major device markets), that data can sometimes support a Japanese application without a new domestic Japanese trial, provided the applicant can show the product results will apply to the Japanese population.
The most important question is whether there are meaningful ethnic differences between the Western population and the Japanese population. If a company can credibly demonstrate, with data and literature, that these factors do not meaningfully change the device’s efficacy and quality profile, the applicant may be able to proceed without a Japanese local clinical trial. Keep in mind that the foreign clinical trial has to meet Japan’s GCP requirements.
What the PMDA Allows in Place of a New Trial
Where the differences above are manageable, the PMDA may accept one of the following approaches instead of requiring fresh local domestic data:
- Foreign data plus a phased rollout. Approval is granted on the foreign device based on the foreign data, with the applicant agreeing to launch at a limited number of facilities in Japan first, while collecting real-world safety data in Japan.
- A post-market safety plan is in place of a pre-market clinical trial. For incremental upgrades to an already-approved device or for some new devices, the PMDA may accept existing overseas evidence plus a detailed post-market safety monitoring plan, without requiring a new Japanese pre-market trial.
- Literature and performance data. For some devices, existing clinical literature, mechanical performance testing, or a Western CER can sometimes support the registration application without a local clinical study too.
PMDA Consultation
The first PMDA meeting is an early, preliminary informal one. It requires a 10-15 page PowerPoint introducing the company and the device, along with the specific questions the applicant wants PMDA’s feedback on. It typically takes about a month to put together the PowerPoint, and another two months or so before the meeting actually takes place. The PMDA generally will not answer questions in much detail at this stage. Instead, they will recommend the applicant move on to a Formal PMDA Consultation.
The second consultation, either a pre-development consultation or a clinical trial necessity consultation, will be held next. It requires 30-50 pages of material for the PMDA to review, which typically takes about 3 months to prepare and has to be submitted several weeks ahead of the PMDA consultation. From there, it is usually another few weeks to a month before the consultation itself takes place. This time, the PMDA will address the applicant’s questions in detail, though they may come back with additional questions of their own.
If the outcome of this second meeting, or even a third meeting, is that a local Japanese clinical trial will not be waived, there may be a further PMDA consultation to work through the trial protocol, the number of Japanese patients needed, and other related details. Once the PMDA and the applicant reach agreement on the local trial, the applicant can move forward with submitting the CTA.