5 Best Practices for Managing Clinical Trial Supplies in Japan
Regulators have made significant progress in reducing the time lag for drug development in Japan. The average time for a standard review decreased nearly 50 percent, from 22 months in 2008 to 11.5 months in 2011, according to a report from GBI Research1.
This is a promising development for the fourth largest pharmaceutical market, as defined by IMS Health2. The improvement in review times is largely due to several government initiatives to add new regulatory guidelines and hire more personnel, while expanding their training and education3.
Yes, this is good news. But there is still a sizable gap between the time a new drug is approved in the U.S. or EU and the time it is approved in Japan. The most recent data shows that patients in Japan needed to wait for new therapies more than a year longer than those in the other two markets referenced. This delay is attributed to a clinical development process that is far more arduous in Japan.
Below, I’ve outlined the five best practices to help clinical supply professionals do their part to reduce development delays.
- The first practice involves the importation of investigational medicines into Japan. As I noted in a previous blog, an In-Country Caretaker is required in Japan to manage clinical trials. What’s vital is that the trial Sponsor determines early on how this role will be defined and who will take on the creation and submission of the Clinical Trial Protocol Notification to regulators in Japanese. This document will contain importation quantities and must have descriptions that match those on the proforma invoice.
- The second best practice addresses the challenge of developing a suitable supply strategy to support the study design. The In-Country Caretaker, whether it’s the contract research organization or the Sponsor’s local affiliate, needs to work closely with the site physicians to determine that the study design will work. In general, global study designs are no problem. But often, minor tweaks need to be made. During these consultations with the investigators, consider discussing the label design, packaging type (bottles or blisters, etc.), and any ancillary items. Note that ancillary products present their own set of challenges if you are unable to source them locally. In some cases, the strategy may have to change so that Japanese equivalents can be used.
- Third on this list is how to manage local distribution. Remember that specific appointments – day, time and details – need to be negotiated for each shipment. When I say “details,” I mean small things like when to call before arrival and where to park on site. Obviously, getting these details together and following different protocols for each shipment adds time and cost to the process. In our experience, it takes 2-5 days longer for the investigational product to get to the sites in Japan compared with other markets. There’s one other important note about behavior at the clinical sites: ensure that the drivers show the proper respect for all site personnel, especially the investigator. Meanwhile, make sure to lay out a plan for returning study materials (shipper boxes, gel packs, etc.) and destroying unused drug because Japanese clinical sites traditionally do not handle returns and destruction. The process is lengthened because the driver must wait at the clinical site while the drug is removed from the shipper and material waste is received. Make use of these local distributors to download data from the temperature loggers and perform “fit for use” analysis of the clinical supply when possible because those are two tasks that the clinical sites usually do not get involved with either.
- That leads me to my fourth point: temperature control. To protect sensitive material, ensure that the international transportation route is known well. Though the seasons in Japan are similar to those in the U.S. and EU, the product may come through regions where temperatures differ drastically. Allow enough time to source and approve different shippers and temperature loggers, and to import shippers into Japan when the preferred type is not available here. Reduce the risk of a temperature excursion by making sure all paperwork such as the airway bill and proforma invoice match the Clinical Trial Protocol Notification. Incorrect paperwork at customs could lead to a delay in clearance, possibly resulting in an excursion. Let me return to my point about local distribution. Work with local partners early in the planning stages to determine how to manage temperature control for local shipments.
- The final best practice reviewed here has a silver lining. Ensuring the cosmetic appearance of clinical supplies has been a major challenge in the past—but times have changed. Yes, there are still some companies that demand Japan-specific packaging in compliance with their individual standards, but these situations are less common today. It is best to ask questions early about cosmetic issues when dealing with potential Japanese partners, yet there is much more flexibility than there was 10 years ago. What we’ve seen more lately is that 99% of product packaged overseas is now acceptable. Despite this reassurance, there may still be hesitancy about running afoul of rules for cosmetic appearance. If there is heightened concern about this, it’s always an option to introduce Japan specific inspection criteria into the quality process.
- GBI Research. Japan Pharmaceutical Market Outlook - Deregulation and More Efficient New Drug Approval Process Attract Foreign Investment and Improve the Competitiveness of Japanese Players. April 2013
- IMS Health. Total Unaudited and Audited Global Pharmaceutical Market by Region/2012 – 2017. June 2013
- Conducting Clinical Trials in Japan: A CRO Perspective. Pharmaceutical Product Development Inc. White Paper. October 2013.