Getting the study drug at the right time is challenging for any clinical trial, and this is more prominent with the multi-regional clinical trials. To have the IMPs and ancillaries at the clinical trial sites in time, the sponsors need to have the right people, processes, facilities, and technology in place.
Generally, the sites require three types of supplies while conducting clinical trials
- IMPs and their supportive products (i.e. Investigational and Non-Investigational medical products).
- Laboratory supplies such as sample collection tubes, laboratory kits.
- Ancillary supplies such as medical devices, equipment, documents, etc.
In this article, we will be focusing on IMPs and their supportive products.
Challenges for IMP importation
Here are some global challenges for IMPs import
- Require experts with knowledge in import regularly and distribution,
- Diversified import regulations for each country,
- Frequent change in the local regulations for import,
- Import and Distribution of shipment within time,
- Maintain the IMP temperature need and shipment tracking,
- Requires seamless integration between manufacturing, logistics, and technology,
- Return and destruction handling after completion.
Regulatory for IMP importation in Japan
- The regulatory authority which regulates the clinical trial approval and the import of IMP’s is the Pharmaceuticals and Medical Devices Agency (PMDA).
- An In-country caretaker (ICC) is required to import IMPs into Japan.
- The ICC represents the importer to the Japanese government and is responsible for
- Recovering the package upon arrival,
- Bringing it to the customs warehouse,
- Presenting the appropriate documents and paperwork to customs, and
- Answering any questions that the Japanese government may have.
- The documents required for the import of IMPs depends on the type of study and the IMP.
- The IMP’s and the supportive products need to be listed in the “Clinical Trial Notification (CTN)”
Import and timely delivery of IMPs and IMP related Products (Supportive products) is crucial for any clinical trial and this process is more complex in the case of multi-regional sites. Understanding the complete regulatory process is very important while planning any clinical trial and this should be thought out well before submitting a clinical trial application.
The IMPs include investigational drugs, comparators, etc while the IMPs supporting Non-Investigational medical products include the devices or instruments used for administering the IMPs such as an aerosol spray in case of asthma drug under investigation. The IMPs most of the time require temperature-controlled storage conditions and this will be challenging for the importation & logistics.
The regulatory requirements for the import of IMPs vary from the clinical ancillary supplies. The requirements and regulations are stringent in the case of IMPs as they are directly involved in the patient's health.
For importation of IMPs into Japan, it's very important to understand
The regulatory approvals required for the import of these products
Since the approval process for import of IMPs is entirely different from the import of clinical ancillary supplies and the planning of IMPs import shall be planned well before making a clinical trial application. The regulatory authority would be the PMDA.
Review & Approval of IMPs
The review and approval of the IMPs depend on various factors such as the approval status of the clinical trial, the Impact of investigational drugs on the patient's health, etc.
Process of importation of ancillary supplies
The process for the importation of IMPs and (Supportive products) Non-Investigational Medical Products is different from the import of clinical ancillary supplies and requires clinical trial approval before making the shipment. The listed IMPs are reviewed by the PMDA before approving their import into Japan.
Responsibility of import for clinical trials
Since the importation is for clinical trial purposes, the responsibility of importation must be defined and authorized in the correct manner. Japan has an extra layer of role known as In-Country Caretaker, along with Importer of Record (IOR). The services provided by these two roles are different. You need to identify who will be the better option for you.
Impact of various factors on the import process
Different aspects such as depot facilities, controlled temperature management, the port of entry & port of shipment may impact the import process in their own way. It's important to understand these nuances.
Timelines for the total importation process
It is crucial to plan the importation of IMPs and IMP Supportive Products well before making a clinical trial application to avoid delays. Having all the documents and necessary approvals for importation on hand necessary and makes a cost-effective and time-saving process.
Get Details on Regulatory Process, Requirements, and Aspects of Importation of IMPs and IMP Supportive Products.
With an increasing number of multi-site trials being conducted in different regions, we at Credevo, receive multiple queries asking for regulations and requirements of such importation along with importation services such as ICC or IOR or clinical trial-related services. This may also be due to the fact that the information found on the internet could be incomplete, outdated, or at times unrelated. The practical scenario of regulatory compliance could have many more aspects to be considered.
Credevo has prepared a report by collecting the relevant information as per the current understanding and awareness of Credevo. Click on the blue button below to download the report.
What would you get by downloading this report?
- Details on the regulations, requirements, and process to import IMPs and IMP Supportive Products into Japan.
- Free assessment of your ancillary products by Credevo to check specific requirements that apply for import.
Note: The details presented in the report are intended to help in creating awareness about the regulatory process and requirements for importing IMPs and IMP Supportive Products into Japan. While the report can be considered as an informative resource, it is not being presented as legal guidance, a binding document, or any authoritative report. The information in this report was prepared on the basis of relevant information from the public domain as of the date, however, the PMDA regulations and requirements may change with time and it is advisable to refer to current regulations at any given time. It is recommended to confirm the specific details, requirements, and processes applicable to your specific products at a given time before initiating any process of importation.
Clinical Trial Notification
To import the IMP’s and its supportive products, the products need to be listed in the clinical trial application, this facilitates the importation process and customs clearance.
The document required for the CTA include
- Statement regarding the reason why the sponsoring of the proposed clinical trial is scientifically justified,
- A protocol of the proposed clinical trial,
- An explanation document used for informed consent and consent form,
- A Sample of Case Report Form, and
- Current investigator’s brochure all the documents in Japanese.
The sponsor, before initiating any clinical trial shall submit a notification and protocol to the PMDA.
PMDA assesses whether a proposed study complies with the requirements for regulatory submission, taking into consideration the science proposed data collection, and analysis techniques, patient safety, and ethics and implements the “Clinical trial consultation system” where the PMDA gives guidance and advice concerning study protocols.
The CTN can be in English however on request a copy in the Japanese language can be submitted. The PMDA evaluates the clinical trial application along with the list of IMP’s products mentioned in the application.
The import of IMP products is approved along with the CTN. Once the CTN and import are approved the sponsor can initiate the clinical trials along with the import of IMPs in coordination with the ICC or the CRO.
In order to import the IMP’s and supporting products, the sponsor requires various documents which may include CTA, data on comparators, commercial invoice, etc. Usually, the import license is not required, however, this may vary with the individual scenario.
The process of importation can be made easier by reviewing the category of products, the status of your clinical trial application, and other factors. If you have downloaded the above referred Report ‘Japan: Clinical Ancillaries Import Requirements’, just fill up the information below to receive a free assessment of your ancillary supply products (up to 4 products) that need to be imported by Credevo experts to identify specific requirements that apply for importation.
Who handles your import?
The expert partner who manages the clinical trial right from making a clinical trial application for conducting clinical trials to conducting clinical trials and providing the study report to the sponsor along with the procurement or the import of IMPs and ancillary supplies for the clinical trials. These are usually referred as In-country caretakers. The CRO who handles all these clinical trials operations also handles the importation and is referred to as the ICC.
The ICC should be an expert in import regulations to avoid glitches and delays during importation for this they may partner with the experts for logistics and the local regulatory service providers that help in better handling of import. Choosing better logistic partners helps in making efficient, safe, and economical importation.
Importer Of Record (IOR)
The IOR – Importer Of Record, in this scenario, is not usually required as the duties of the IOR are limited to only to the import of ancillaries where import of these doesn’t require an import license and need to be listed in the CTN which is usually handled by the CRO.
The role of IOR is required while importing the clinical ancillary supplies and non-medical products which usually do not require listing in the CTN and can be imported by fulfilling certain requirements.
Labeling and packing
To import medicines from overseas is subject to control by the Pharmaceutical Affairs Law and the Customs Law to prevent health hazards caused by defective products. The details such as “For trial use only”, the name and address of the sponsor of the Clinical Trial,
Chemical name or identification code etc have to be mentioned on the label during the importation of products.
The packing is also an important consideration for importation and shall be planets well before. Some of the points that need to be considered.
- How the barcode and labeling will be used for easy tracking
- Whether the packaging fits into the controlled temperature system
- Is the packing as per the Japanese norms
Listing the IMP’s’ in the clinical trial application helps in facilitating the custom clearance. Presenting the CTN is usually sufficient for custom clearance. For custom clearance other than import license (if applicable) or/and the CTN, the importer may require to provide documents such as commercial invoice, freight costs, etc.
Depot & Distribution
Having a depot for moving the shipment from the customs to the depot is very important. Temperature management of IMP’s is critical and challenging for logistic providers.
Choosing an experienced logistic partner having the necessary vehicles that maintain the necessary temperature to handle these IMP’s is very important. These experienced logistics also have a well-structured tracking system that helps in proper monitoring of supplies till they reach the destination.
Once the goods are transferred to the depot, they are distributed to the sites where the clinical trial are being conducted.
Tips for a successful importation
- Advanced planning for importation with the review of the complete list of IMP’s and its support required for import.
- Sorting all the required IMPs and supportive products to listed in the CTN before making a clinical trial application.
- Partner with an efficient ICC who handles all the process of importation with a previous successful track record
- Understand the requirements, segregate, and compile before making the importation.