Expedited approval system for regenerative medicine products – Is it unusual?

We read with great interest the excellent editorial titled “Stem the tide” on the newly implementation of the conditional and time-limited authorization system for regenerative medicine products in Japan (see Nature 528, 163–164, 2015 [1]). The editor highlighted the introduction of unproven system or the overhaul of drug regulation to create a fast track to bring regenerative therapy to market in Japan. That system may have several problems in the efficacy and cost allocation of regenerative medicine products, and raise a concern about floods of unsuccessful treatments in the country. The author also mentioned that the strategy for establishing the fastest way to meet the patient's needs is working. Because the first regenerative medicine product, HeartSheet was approved by Japanese regulatory authority (Ministry of Health, Labour and Welfare) on September 18, 2015 [2] under the new act. Finally, the editor argues that regulatory agencies around the world should resist pressure from biotech companies to create such fast-track system.

However, there exist similar expedited approval systems such as “accelerated approval” of drugs and biologics for serious or life-threatening illnesses in the US (21 CFR314 subpart E and 21CFR601 subpart E), “conditional market authorization” of drugs for serious and life-threating diseases, in emergency situation, and orphan diseases (Commission Regulation (EC) No 507/2006), and “market authorization under exceptional circumstance” of drugs in the EU (Regulation (EC) No 726/2004). The most of approved therapeutic products are intended to treat a variety of cancers and human immunodeficiency virus disease.

Just focused on regenerative medicine products, Carticel™ which was derived from autologous chondrocytes was approved by the accelerated approval of biological products for serious or life-threating illness on August 22, 1997 in the US [3]. Then, a conditional marketing authorization was granted to Holoclar, which was derived from autologous limbal stem cells advanced-therapy medicinal product (ATMP) on February 17, 2015 [4]. Furthermore, a marketing authorization under exceptional circumstance was granted to Glybera on October 25, 2012, which became the first gene therapy product approved in developed countries [5].

In principle, the benefit and risk of any therapeutic products, including products called “regenerative medicine products” in Japan, “human cells, tissues, and cellular and tissue-based products (HCT/Ps)” in the US, or “ATMP” in the EU, have to be sufficiently evaluated at the stage of marketing authorization application. However, the benefit of some products for rare, severe, degenerating or life-threatening diseases may not be able to be proven enough, because of a limited number of patients during a limited period of clinical trials, or limited scientific knowledge for relevant diseases. Expedited approval pathways are expected to provide patients suffered from serious, debilitating and currently untreatable diseases with new opportunities of treatment. Of course, follow-up has to be conducted for all patients treated with regenerative medicine products that are approved under Japan's new regulation, to monitor not only their adverse events, but also their efficacy.

Conflict of interest

The authors have no conflict of interest to declare.