Drug Master File (DMF) registration and In-Country Caretaker (ICC) services for your DMFs Comprehensive regulatory related assistance for DMF registration for foreign manufacturers of APIs, and In-Country Caretaker services

Drug Master File (DMF) registration and In-Country Caretaker (ICC) services for your DMFs

ICC Services for Drug Master Files

Cobridge has been serving clients as an ICC practically from the company’s inception in the 1990s. Today, since the changes in the Japanese Pharmaceutical Affairs Law (PAL) has formalized the DMF system and rendered greater flexibility for overseas pharmaceutical firms, the role of the ICC has become more prominent for firms either licensing drug products to Japanese distributors or producing active pharmaceutical ingredients (APIs) for Japanese pharmaceutical manufacturers. Nevertheless, some background can prove helpful to orient a prospective overseas supplier.
For new drugs, an approval application in Japan follows the common technical document (CTD) format of the International Conference on Harmonization (ICH), as with other participants in the ICH. What is peculiar to Japan, however, is the unique contents and role of Module 2 for the Quality sections. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) allows Module 3 to be submitted in English, and as a consequence relies to a large extent for its high-level review on Module 2 (which is in Japanese only).

As in other regions that have retained aspects of their familiar local approval dossier formats, in Japan, Module 2 keeps many features of the former Japanese approval dossier’s gaiyo. A Japanese Module 2 is much more voluminous than a corresponding non-Japanese version—much more of the data, tables and figures from Module 3 are contained in a Japanese Module 2. Thus, simply translating a foreign Module 2 will not work well for submission to the Japanese health authorities. Over and beyond the fact that the applicant must write Module 2 in professional Japanese (regulatory style, in formatting familiar to PMDA reviewers) that might be missed in a conventional translation, there is a need to pay particular attention to details with respect to Module 2’s handling of process limits, compendial matters, and the like.

How well written Module 2 is with regard to the handling of process limits and the like determines degree of flexibility that the applicant will have to introduce process changes, that is, the manner in which process limits are presented in Module 2 determines to a significant extent whether process changes may be implemented by simple notification to the Japanese health authorities or will require prior approval. Simple translation is a recipe for disaster, and an applicant can inadvertently close avenues to smooth process improvements here if the firm is not wise to this and to how to present descriptions of process limits in the most flexible manner.

Cobridge’s capabilities as an ICC include preparation of the DMF in a manner most capable of preserving the vital flexibility that the overseas manufacturer needs, and a high level of husbanding of the DMF during PMDA review and approval of the NDA that references the DMF, and beyond to include maintenance and updates of the DMF for process changes and improvements. Cobridge is able to provide clients an English text version of the prepared Module 2 for confirmation.
Over the past 15 years, Cobridge has gained experience with DMFs for new drugs (which follow the CTD) as well as generic drugs (which in Japan do not follow the CTD at all, but rather that of the conventional Japanese gaiyo). Cobridge has prepared and managed DMFs for APIs and new excipients that have included multiple sourcing, and Cobridge’s clients have ranged geographically from South Asia, Europe, and North America.

Services provided by Cobridge

  1. Preparation of documents for master file to the health authority
  2. Preparation of foreign manufacturer accreditation applications
  3. Preparation of Quality Overall Summary (QOS) for both small-molecule pharmaceuticals and biologics
  4. ICC services post-submission
    • Preparation of response to queries from health authority
    • Services related to registration
    • Maintenance services for DMFs
    • Communication with Japanese MAH(s)
    • Translation services