Registering Your API in Japan via a Drug Master File (DMF)

This article was also published on PharmaPhorum

The active pharmaceutical ingredient (API) market in Asia is growing at an increasingly rapid pace. From 2007 to 2011, it went from 24.5 to 28.5 percent of the world market. From now through 2017, it should expand at a rate of 8.2 percent annually. This puts Asia’s API market — worth $33 billion currently — at more than $50 billion by 2017.

Japan has long led the rest of Asia in demand for APIs. In 2012, the market for APIs in Japan was the largest in Asia, at $15.5 billion. Many foreign API firms from India, Europe and the US are actively selling their APIs on the Japanese market.

Japan’s share of innovator APIs is high, and demand is growing especially in the biotech drug sector. But API generics are also starting to gain ground in Japan. Chinese and Indian firms have recently flooded Japan’s market with inexpensive APIs. The accompanying price competition has forced some Japanese API manufacturers out of their own domestic market.


In order to register an API with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), manufacturers must first apply through Japan’s Drug Master File (DMF) system.

The Japanese DMF system is similar to the one run by the US Food and Drug Administration (FDA). The Japanese DMF system makes it possible for API manufacturers to register their products with the PMDA directly. In this way, API manufacturers avoid having to turn over sensitive information when finished drug manufacturers use their product. For each finished drug application involving the API, the PMDA simply pulls the information it needs from the DMF.

DMF registration is a voluntary process in Japan. Items such as APIs and new excipients (those that have different composition ratios from existing excipients) can be registered. According to the PMDA, drug substances, intermediaries and materials in OTC drugs do not need to be registered.

In Japan, the API or excipient manufacturer is in charge of DMF registration. If the manufacturer lacks its own office in Japan, it must appoint a person or a business entity called an In-Country Caretaker (ICC) to apply for them. The ICC must fill out the DMF application and answer all PMDA questions, both during and after API registration.

Registration materials should be submitted in Japanese and must include:

  • The name of the API or drug substance
  • The name and location of the manufacturing site
  • The manufacturing license number and type
  • The name and address of the ICC
  • Drug ingredients
  • Manufacturing methods
  • Manufacturing process controls
  • Specifications and test methods
  • Non-clinical studies (in the case of new excipients)
  • Quality control tests
  • Stability tests
  • Storage methods
  • Safety information
  • The dates of expiration

DMF registration is free. There are no additional government fees. The PMDA suggests that applicants submit all materials prior to the submission of finished drug applications that use their product.

Finished drug manufacturers must cite all relevant DMFs during their own drug registration. They are encouraged to attach DMF registration certificate copies to their own applications. In the course of the PMDA review for the finished drug product, all questions about the DMF products are directed to either the DMF license holder or to the ICC.

If any changes are made to the production process of DMF products, a “minor change notification” or an “application for change in registration” should be filed with the PMDA. The API manufacturer also needs to discuss any such changes with the manufacturer of the finished drug product, as the finished drug manufacturer also needs to file a “partial change notification” or a “partial change approval application” for any changes in the API production process.

The PMDA provides simple consultation sessions for matters relating to DMF registration.


An increasing number of foreign pharmaceutical companies are selling APIs on the Japanese market. Sometimes they sell to domestic drug manufacturers and sometimes they sell to foreign drug companies manufacturing products in Japan.

In April 2013, India’s Dishman Pharmaceuticals and Chemicals announced the company was on track to post an almost fivefold growth in revenue for APIs sold in Japan through the end of 2013. Revenue from Japanese sales reached $2 million in 2012, and 2013 revenue is expected to increase to $10 million. The company currently supplies APIs to more than 10 Japanese companies.

In February 2012, Pfizer Japan launched two new APIs in Japan. One was part of the diabetes treatment glimepiride (Amaryl), while another was part of the antiarrhythmic agent pilsicainide (Sunrythum). Aside from these two APIs, Pfizer Japan launched another 16 APIs in Japan in 2012.


If foreign API manufacturers pay attention to the Japanese API market, they will find excellent sales opportunities, especially in the innovative and generic API segments.