Q（Question）

When a physician or pharmacist requests information on an unapproved drug, off-label drug, or dosage not approved domestically, what information may be provided?

A（MHLW answer）

There is no objection to providing, in accordance with the conditions of the Guidelines, information that the company has determined complies with the Guidelines and may be provided.

The information provided must be accurate and based on scientific and objective evidence. Treatment guidelines, peer-reviewed original research articles, review reports and adverse event information published by overseas regulatory authorities such as the FDA and EMA, and foreign package inserts have undergone a certain level of evaluation by academic societies and overseas regulatory authorities, and can therefore serve as benchmarks for determining whether information is accurate and based on scientific and objective evidence.

For case reports, when information is requested regarding cases involving a limited number of patients, there is no objection to providing case reports as long as they are not selected arbitrarily and the limited evidence base is clearly communicated.

Negative information must be provided, including case reports.

Items requiring particular attention: (4), (5), (6), (7)

So what (meaning): If a physician or pharmacist requests it, companies may provide off-label/unapproved information that has passed internal review for Guideline compliance. Treatment guidelines, peer-reviewed articles, and FDA/EMA reports serve as evidence benchmarks; case reports may be shared with an explicit caveat on limited evidence. Negative information must always be included.

So why (rationale): A blanket ban on off-label information conflicts with legitimate clinical information needs, so provision in response to requests is permitted, provided scientific accuracy and disclosure of negative data protect patient safety.

Commentary — background, application, practical notes

Section 4-3 relaxes the previously rigid interpretation that companies could not provide any unapproved or off-label information, in recognition that off-label use is unavoidable in clinical practice. The provision makes a 'request from a healthcare professional' a necessary condition and imposes a quality requirement — that information be accurate and based on scientific, objective evidence — to draw a clear line between information provision and promotional activity. The enumeration of treatment guidelines, peer-reviewed articles, FDA/EMA review reports, and foreign package inserts as 'benchmarks for scientific grounding' reflects the intent to relax the evidentiary bar only for materials that have been evaluated by independent bodies; in-house documents not meeting those criteria require more rigorous internal assessment.

The most common scenario involves specialists in rare diseases or pediatrics — fields where domestic approvals are sparse — requesting information based on FDA review reports or international guidelines. In oncology and neurology, where multiple treatment regimens coexist, internationally standard guidelines frequently include therapies not yet approved in Japan. Providing scientifically reliable third-party materials to assist physicians in making autonomous treatment decisions is what the provision is designed to permit.

The most frequent compliance error in practice is mishandling negative information. Selectively providing only data that support efficacy — whether from case reports or journal articles — constitutes the 'arbitrary selection' prohibited by the Guidelines. A typical example is presenting a publication showing efficacy at a specific dose while omitting one that reports safety concerns at the same dose. Additionally, when providing case reports, the limitation of the evidence base must be explicitly communicated, either verbally or in writing; listing facts without stating the evidential limits does not satisfy the requirement.