Yoshio Mitsumori10.06.06
With respect to SHONIN (ie, product approval), the new PAL introduced new classifications such as General Medical Device (Class I), which does not require any approval; Controlled Medical Device (Class II), which must be certified by a newly introduced Third Review Body; and Highly Controlled Medical Device (Class III & IV), which must be evaluated by the government’s Pharmaceuticals & Medical Devices Agency (PMDA). This is similar to the approval system in the United States and Europe.
In particular, Highly Controlled Medical Devices are classified into three groups:
(1) standardized/without clinical data,
(2) not standardized/without clinical data and (3) not standardized/with clinical data.
Also noteworthy about the SHONIN program is that the Standard Technical Document (STED), which was developed by the Global Harmonization Task Force, was introduced prior to use in other leading countries. The STED requires detailed declaration regarding how the risk analysis was performed and how the manufacturing validations were conducted at the manufacturing site. To complete the STED, overseas manufacturers now must communicate with the MAH much more closely than ever before.
Another development with the new PAL is that the system’s so-called “In-Country Caretaker” (ICC) regulation, which made a foreign manufacturer eligible to obtain marketing approval under its own name, was discontinued. In its place, a new system called “Designated MAH” (DMAH) was introduced. The old ICC represented the foreign manufacturer in documentation, whereas the DMAH focuses on taking care of import, QA, safety and PMS post-market surveillance on behalf of a foreign manufacturer—in other words, its responsibilities are extremely higher than those of the ICC.
Nevertheless, a foreign manufacturer can directly control the SHONIN and the market as it wishes. If multi-channel sales by region or segment are desirable, or if the manufacturer wants to maintain free hands for the future, the DMAH system might be particularly useful.
The manufacturer’s quality management system (QMS) conformance will be evaluated by either documentation or an on-site audit, if necessary. Even foreign manufacturers are now a critical focus during the evaluation for Japanese approval. Sometimes, there is confusion regarding this QMS conformance inspection and the foreign manufacturer’s accreditation audit—note that these are two completely separate issues. Simply put, the QMS conformance inspection is for product approval and the manufacturer’s accreditation audit is for the business license.
Good Clinical Practice
Another important requirement, Good Clinical Practice (GCP), also was greatly amended by the new PAL. The latest GCP for clinical trials of medical devices became almost identical with those for pharmaceutical products. The former GCP only required a minimum of 60 cases (30 cases each at two sites), whereas the new GCP has no minimum and now requires the number of patients, which statistically proves its efficacy. In addition, the newer GCP requires strict monitoring to ensure that cases are being conducted in a proper manner.
The implementation of these GCPs has added some difficulty to conducting Japanese clinical trials in terms of size, quality, time and cost. However, the new GCP basically conforms to the International Conference on Harmonization standard and is similar to requirements of the US FDA. Therefore, clinical trial data from an investigational device exemption or a premarket approval application may have a good chance for use in Japanese submissions. Since Japanese authorities have their own evaluation standards for checking GCP compliance, it is strongly recommended that a manufacturer perform a gap analysis between foreign clinical data and Japanese GCP requirements before using these data for Japanese submission.
The PMDA offers preliminary consultation, which enables the applicant to ensure that the study design is adequate and the foreign clinical data are acceptable, etc., before commencing actual study or submission. This may cost the applicant about $15,000 per consultation, but it may be useful in avoiding an unnecessary long Q&A process or, even worse, rejection.
The Bottom Line
In the 18 months since the newest PAL was enacted, it has become apparent that several problems remain. For example, standardization for many groups of medical devices have not yet been developed, the shortage of reviewers—particularly engineering experts—at PMDA has not been resolved and so on. However, the situation is steadily improving and, hopefully, will only get better.