Japan has become the second largest market for in vitro diagnostics (IVD) in the world.
In Japan, the Ministry of Health, Labor, and Welfare (MHLW) and the Pharmaceutical Medical Devices Agency (PMDA) are the two main regulatory authorities that manage pharmaceuticals, medical devices, and IVDs.
There is currently a plan in action to accelerate the review of IVDs in Japan. From 2014 to 2018, in order to shorten and standardize IVD approval periods, Japanese authorities are working to improve collaboration between Japanese regulators and industries by taking measures to improve the quality of the review process, setting standard review periods, increasing the number of reviewers, and closely managing the plan’s progress as it is implemented.
Classification of IVD Reagents in Japan
The classification of IVD reagents in Japan is based on the risk to individuals or public health, and is designated by notification. An applicant cannot determine the class of the product by preference.
The IVD classifications are as follows:
- Class I: Low Risk (i.e. cholesterol, glucose, hemoglobin)
- Class II: Middle Risk (i.e. CD4, CD8, OTC tests, uric acid)
- Class III: High Risk (i.e. CEA, AFP, HIV, gene tests)
Japan IVD Approval Applications and Regulatory Requirements
There are different approval applications for IVD reagents, which are determined by the type of product being categorized. Products fall into these categories:
- New item: the product is intended for determination or detection of a new item
- Conforming to the “approval” standard: the product conforms to the established approval standards
- No “approval” standard: high risk Class III products that are not applicable to the “approval” standard (i.e. HIV, HCV, pathogen and human gene tests)
- Not conforming to the standards: the product does not conform to the established approval, Ninsho, or Seihan Notification standards
IVD approval applications are submitted depending on the product’s classification and submission category:
- Seihan Notification (self-certification by notification, without review)
- Class I products that do not require approval or Ninsho certification
- Ninsho Certification (certification by a 3rd party reviewer)
- Class II products that conform to the Ninsho standard
- PMDA/MHLW Approval
- Class I products that do not conform to the self-certification standard
- Class II products that do not conform to the Ninsho standard
- Class III products that conform to the approval standard
- Class III products that do not conform to the approval standard
- Class III products for which there is no approval standard
- New items
The Class III IVD approval application can require the following details about the product:
- Generic name
- Proprietary name
- Intended use
- Shape, structure, and principle
- Active ingredients
- Kit specification
- Instructions for use
- Manufacturing method
- Storage condition and shelf life
- Origin or history of the product and status of its use in foreign countries
- Setting of product specification
- Stability
- Kit performance
- Risk analysis
- Clinical study
Japanese IVD Change Procedures
In Japan, IVD change procedures vary. Some changes require no action, some require a new registration, others require a partial change application (i.e. shelf life extension, addition of applicable specimen type, change of QC testing methods), and still others require a minor change notification (i.e. change of name of ingredient, change of reagent preparation) within 30 days after executing the change.
Companion Diagnostics in Japan
In Japan, the definition of companion diagnostics is closely aligned with the U.S. FDA’s. Companion diagnostics in Japan correspond to one of the following:
- Medical devices or IVDs that are necessary for judging the withdrawal of specific drugs or optimizing the dosage and administration of specific drugs
- Medical devices or IVDs that identify patients who might show a higher degree of therapeutic efficacy from particular drugs
- Medical devices or IVDs that identify patients who may have high incidences of specific adverse reactions to particular drugs
To further clarify companion diagnostics in Japan, the PMDA offers consultation sessions specifically for companion diagnostic products.