Japan Clinical Trials and CRO Services for Medical Device and Pharmaceutical Products

To qualify for the Sakigake pathway, the premarket application must firstly be submitted or simultaneously submitted in Japan as in other countries. If a medical device, IVD, or drug is designated, the applicant will receive these benefits in Japan – 1. priority consultation with the PMDA, 2. substantive review of the pre-application, 3. faster review, and 4. someone at the PMDA will be assigned to work with you and your product. Normally, such products if required to do clinical studies in Japan are able to reduce local Japanese studies and get into the market quicker with a conditional approval – but oftentimes need to do more post market studies.

In Japan, some medical device products need local clinical trials for product approval, whereas other products may be approved using foreign clinical data or via an already approved predicate device. If the device is implantable or risky, a local clinical study in Japan will almost always be required.

To better answer this question, we recommend that you attend one or more formal PMDA consultation sessions. These PMDA consultation sessions require PBM to put together a Japanese dossier with the key facts of your product and also foreign clinical data. We will then submit this dossier and set up the PMDA meeting which our client can attend too. These formal PMDA sessions require the applicant to pay the PMDA consultation fees ranging from $5,000 to $20,000 depending on which consultation session you apply to. PBM can do this work and represent you at each consultation session.

Before conducting Japan clinical trials, the applicant must first submit a dossier containing operating procedures, protocol, Investigator’s Brochure (IB), clinical trial contracts, and compensation outline, among other information. If the applicant plans on outsourcing the clinical trial, a contract must detail the agreement on duties for sponsoring and managing the trial.

Good Clinical Practices (GCP) for medical device clinical trials are enforced by the PMDA and MHLW. Applicants should use PMDA’s clinical trial consulting services to help determine necessary documents, protocol, etc. for their Japan clinical trials.

Conducting clinical trials in Japan requires compliance with certain pre-determined standards. Some of these procedures and rules are outlined below.

Institutional Review Board (IRB)

A Japanese Institutional Review Board (IRB) assesses ethical and scientific processes prior to and during clinical trials. The IRB may be established by a variety of different healthcare institutions, ranging from non-profit organizations to national universities. It is made up of at least five experts in medicine, dentistry, pharmaceutical science, healthcare, or clinical trials. The IRB members are all independent of both the medical institution supervising the trial and the sponsor of the IRB. The IRB board holds meetings to review and comment on the progress of the trial.

Clinical Trial Medical Institution

In order to be considered for clinical trials, Japanese medical institutions must meet four requirements. They must be well equipped, have sufficient personnel, be capable of handling emergencies, and employ competent workers for a seamless and acceptable clinical trial. The head of the medical institution will name a record keeping manager who, similar to the IRB’s founder, will retain all materials regarding operating procedures until receiving marketing approval and notification.

 Investigators

A Japanese clinical trial investigator must be educated, trained, experienced, familiar with the medical device, and have sufficient time to conduct the trial. Investigators will discuss clinical trial developments with sub-investigators.

Japanese investigators are responsible for choosing clinical trial participants with appropriate health conditions, symptoms, and age. All participants must willingly consent and sign an Informed Consent Form. The trial investigator then describes and explains all medical devices to the trial participants, confirms that the participants are using the device properly, and notifies the primary physician that his/her patient is using the device. They must also provide adequate medical care to those suffering from adverse events. Additionally, investigators prepare, change, correct, and inspect Case Report Forms (CRFs). Finally, upon the completion or termination of the study, investigators submit a clinical trial report (CTR) to the head of the medical institution.

Informed Consent of Subjects

The informed consent forms must include the trial’s objective, design, and duration. Informed consent must be given before participating in a clinical trial. After giving consent, participants receive a signed and sealed copy of the form. Participants may only partake in a trial without consent if they face life-threatening emergencies in which current treatments are unlikely to help and the new device has a high probability of saving the patient’s life with minimal complications, or legal representatives are not immediately available to give consent.

To register most drugs in Japan, a local clinical study or Bioequivalence Evaluation (BE) study is required.

To better answer this question, we recommend that you attend one or more formal PMDA consultation sessions. These PMDA consultation sessions require PBM to put together a Japanese dossier with the key facts of your product and also foreign clinical data. We will then submit this dossier and set up the PMDA meeting which our client can attend too. These formal PMDA sessions require the applicant to pay the PMDA consultation fees ranging from $15,000 to $100,000 depending on which cosultation session you apply to. PBM can do this work and represent you at each consultation session.

Japanese clinical trials for pharmaceuticals begin with completing an Investigational New Drug (IND) application, incorporating operating procedures and protocol agreement, the written reason to do a clinical trial, approval from the Institutional Review Board (IRB), etc.

During the clinical trial, a case report form (CRF) must be completed using data collected from the investigation, which will be analyzed in the clinical study report (CSR).

Japanese Good Clinical Practices (GCP)

Japan clinical trials are governed by Japanese Good Clinical Practices (J-GCP) and give investigational KOL doctors much more oversight than internationally recognized ICH standards. Japanese site heads have many responsibilities, which include signing financial contracts, ensuring site qualifications, overseeing compliance with confidentiality laws and standard operating procedures (SOPs), and determining the provisions of Investigational Medicinal Products (IMPs), among others. Furthermore, each site must have its own Institutional Review Board (IRB).