Q&A Collection 4 — Full Text (14 questions)

Q（Question）

Part 1-3 Principle (2)(iv) prohibits claiming the superiority of one's own product by disparaging or defaming competing products. Is it nonetheless permissible to provide information on competing products or comparative information between one's own and competing products when requested by a physician or pharmacist?

A（MHLW answer）

Providing information on competing products or comparative information in response to a request from a physician or pharmacist does not itself violate that provision. However, all of the following conditions must be met.

• Limit the content of the information provided to what was requested and limit recipients to the requesting party. Confirm with the requesting physician or pharmacist the specific information being sought.

• Do not pretend that a request was made when no request for information was received from healthcare professionals or patients.

• The information provided must not be false or exaggerated; it must be accurate and based on scientific and objective evidence. Do not selectively choose only information unfavorable to competing products.

• When direct comparison is scientifically inappropriate, provide that fact and its reasons, along with any other information necessary to promote accurate understanding.

Because this activity is part of marketing information activities, compliance with the Guidelines and the Standards for Appropriate Pharmaceutical Advertising is a prerequisite.

So what (meaning): Comparative product information is not prohibited when requested, but the scope must be limited to the requester and specific request, and all four conditions of scientific fairness must be satisfied.

So why (rationale): The anti-disparagement rule targets unsolicited attacks on competitors, not neutral responses to requests; the four conditions prevent abuse while enabling legitimate scientific exchange.

Commentary — background, application, practical notes

The prohibition in Part 1-3(2)(iv) — claiming one's own product is superior by disparaging or defaming competing products — is directed at unsolicited attacks on competitors initiated by the manufacturer. Providing comparative information in response to a request from a physician or pharmacist is a categorically different act that lies outside the prohibition's scope. Q&A Part 4 makes this explicit while imposing four conditions to prevent abuse. The framing is not 'an exception that lifts the ban' but rather 'a different activity that was never prohibited in the first place.'

Typical situations include a physician considering switching treatments who asks specifically 'what is the clinical difference between your product and the current drug?' or a pharmacist asking 'do you have any literature comparing the adverse event profiles of both agents?' In these cases, the MR or MSL may respond by satisfying all four conditions: (1) limiting content to what was requested; (2) limiting recipients to the requesting individual; (3) using scientifically and objectively grounded information; and (4) noting where direct comparison is scientifically inappropriate.

Two errors are particularly common in practice. The first is 'fabricating a request': steering a conversation so that an unsolicited comparison appears to have been requested by the healthcare professional is an explicit violation. The second is 'selective information choice': presenting only adverse event data unfavourable to a competing product while omitting unfavourable data about one's own product is prohibited. These two points are frequently overlooked and are among the issues most likely to draw regulatory scrutiny.

Q（Question）

When a physician or pharmacist requests comparative information between one's own and competing products, is it permissible to provide information drawn from package inserts, Interview Forms, treatment guidelines, etc.?

A（MHLW answer）

The handling of information provision is the same as A1.

Regarding cited materials, using content from package inserts or Interview Forms is permissible. For the handling of treatment guidelines, refer to Q&A Part 2, A1.

So what (meaning): Provision of comparative data follows A1's four conditions. Citing package inserts and IFs is allowed; for treatment guidelines, additionally apply the requirements in Q&A Part 2, A1 (source disclosure, off-label information handling, etc.).

So why (rationale): Scientific reliability and usage conditions differ by source type, so the guidance separates references to provide clear rules for each category of material.

Commentary — background, application, practical notes

Q2 clarifies the rules by type of reference material. Package inserts and IFs are official documents whose creation is mandated by the government; their content is either backed by the approval review process or produced under a supervised framework. Using them as the basis for comparative information is unproblematic from the standpoints of scientific objectivity and source transparency.

Treatment guidelines are subject to the additional requirements set out in Q&A Part 2, A1 — including prior notification that the guideline contains off-label or domestically unapproved drug information, explicit source disclosure, and limiting recipients. They are therefore not treated on the same footing as package inserts and IFs; they carry an additional layer of conditions. Even when the underlying material is 'medical evidence,' the applicable rules differ by document type.

A common practical error is extracting only a relevant section from a treatment guideline and presenting it without disclosing that the guideline contains information on domestically unapproved drugs. Another issue arises when the IF is cited for comparative data but the source is not identified, creating an impression that the data comes from the manufacturer's own proprietary research. Source disclosure is an integral part of the four conditions established in A1 and is non-negotiable regardless of the type of reference material used.

Q（Question）

When a physician or pharmacist requests comparative information on the efficacy of one's own product versus a competing product, is it permissible to provide such information?

A（MHLW answer）

The handling of information provision is the same as A1.

Because simply comparing results from clinical trials with different patient backgrounds without adjustment may not constitute a scientifically fair comparison, it is necessary to disclose the sources of comparative information and to clearly indicate the positioning of primary and secondary endpoints, in accordance with the Guidelines.

So what (meaning): Efficacy comparisons must follow A1's four conditions and additionally require source disclosure and clear labeling of primary vs. secondary endpoints; unadjusted cross-trial comparisons are considered scientifically unfair.

So why (rationale): Efficacy data interpretation depends heavily on trial design and patient population, so disclosing limitations and endpoint positioning is required to prevent misunderstanding.

Commentary — background, application, practical notes

Comparative efficacy information has the most direct influence on prescribing decisions, so the scientific fairness requirement is applied with particular rigour. The central point Q3 makes explicit is that 'presenting results from clinical trials with different patient backgrounds side by side without statistical adjustment does not constitute a scientifically fair comparison.' This directly addresses the limitations of naive indirect comparisons — placing unadjusted numerical results from separate trials next to each other without a network meta-analysis.

A typical scenario is a physician asking 'is the improvement rate on the primary endpoint for product A higher than for product B?' Even if the manufacturer's own trial shows a 60% improvement rate on the primary endpoint while a separately conducted trial for a competing product shows 50%, those figures cannot simply be placed side by side if the trials differ in disease severity, patient age, or concomitant medications. What can be provided is information that clearly states each trial's design and conditions and explains that head-to-head evidence is not available.

Particular attention must be paid to the explicit labelling of endpoint positioning. Comparing data that appeared as a secondary endpoint in one trial against the primary endpoint result of another trial is not scientifically fair. When preparing a comparison table, the distinction between primary and secondary endpoints must always be shown, along with the control group design and observation period. A comparison table that omits this context risks being judged by regulators as lacking scientific fairness.

Q（Question）

When a physician or pharmacist requests comparative efficacy information between one's own and competing products, is it permissible to provide information from conference presentations that have not yet been published as papers?

A（MHLW answer）

The handling of information provision is the same as A1.

Regarding cited materials, Guideline Part 1-3(1)(iii) establishes as a principle that 'information provided must be based on scientific and objective evidence and must be accurate enough to demonstrate that evidence. The scientific evidence must be verifiable and objectively evaluable by third parties, including the original data, or must have undergone propriety review by a third party (such as peer review of papers), including evaluation materials and review reports used in approval assessments.' The fact that a conference presentation has not been published as a paper does not alone render it impermissible; however, because conference presentations are not substantively peer-reviewed and evidence cannot be considered fully established, the information must be provided with a clear explanation that it derives from a conference presentation not yet published as a paper and that the evidence is not yet fully established. Additionally, because this activity is part of marketing information activities, compliance with the Guidelines and the Standards for Appropriate Pharmaceutical Advertising is a prerequisite.

So what (meaning): Conference-only data may be shared, but the presenter must explicitly state that the data is unpublished and not peer-reviewed and that the evidence base is not yet established.

So why (rationale): The Guidelines require evidence verifiable by third parties; conference abstracts lack peer review, so mandatory disclosure of this limitation prevents overinterpretation by healthcare professionals.

Commentary — background, application, practical notes

Guideline Part 1-3(1)(iii) requires that the scientific basis for information provided must be 'objectively evaluable and verifiable by third parties, including original data, or must have undergone propriety review by a third party such as peer review of papers.' Although conference presentations go through an abstract selection process, this differs substantially from peer review in both rigour and depth. Q4 does not prohibit the use of conference data, but it imposes an obligation to explicitly disclose the limitations of the evidence in order to prevent healthcare professionals from overvaluing it.

A typical scenario is a physician requesting comparative data — such as efficacy rates shown in an abstract or slides — that exists only as a conference presentation and has not been published as a paper. The provider must clearly communicate two points, both verbally and in writing: that the presentation has not been peer-reviewed, and that the evidence cannot be considered fully established at this time. Documentation of the provision — who received what information, when, and with what explanatory caveats — is also important for audit readiness.

A common practical error is assuming that labelling conference slides as 'reference information' is sufficient. The phrase 'reference information' does not adequately convey the limitations of the evidence. A specific statement that the material has 'not undergone third-party peer review' and that 'the evidence base is not yet established' is required; omitting this constitutes a Guideline violation. Additionally, using conference presentation data to emphasise comparative figures in a promotional context goes beyond the scope of request-driven provision and creates separate compliance problems.

Q（Question）

When a physician or pharmacist requests a comparative table of efficacy information (from head-to-head trials or individual trials) between one's own and competing products, is it permissible to provide it?

A（MHLW answer）

Same as A3.

So what (meaning): Providing a comparative table is handled identically to A3: source disclosure, clear labeling of primary and secondary endpoints, and scientific fairness are all required, with explicit distinction between direct and indirect comparisons.

So why (rationale): The table format does not change the scientific fairness requirements that apply to efficacy comparisons, so A3 applies in full.

Commentary — background, application, practical notes

A comparative table places numerical values side by side visually, which tends to emphasise the impression of comparison more strongly than an individual verbal explanation. Q5 simply applies A3 and neither relaxes nor adds to the rules on the basis that the format is tabular. All information required by scientific fairness principles — source disclosure, trial design, explicit labelling of primary and secondary endpoints, and identification of whether the comparison is direct or indirect — must be included in the table just as it would be in any other format.

A typical scenario is a prescribing physician requesting a table to compare the efficacy rates and adverse event rates of several drugs in the same class at a glance. When preparing a table that lists individual trial results for the manufacturer's own product and competing products, presenting only the numbers without footnotes or annotations showing each trial's patient background (disease stage, study duration, control group design) is considered to lack scientific fairness.

A particularly common error is mixing results from head-to-head trials and results from separate individual trials in the same table without clearly distinguishing them. The question itself in Q5 specifically contemplates information from 'head-to-head trials or individual trials,' implying that the source of each data point must be identified in the table. A table that omits this distinction risks leading physicians to misread indirect comparison data as head-to-head results, and therefore fails to meet the Guideline's requirement to 'promote accurate understanding.'

Q（Question）

When a physician or pharmacist requests comparative safety (adverse event, etc.) information between one's own and competing products, is it permissible to provide such information?

A（MHLW answer）

The handling of information provision is the same as A1.

Because simply comparing results from clinical trials with different patient backgrounds without adjustment may not constitute a scientifically fair comparison, it is necessary to disclose the sources of comparative information in accordance with the Guidelines. Additionally, it is necessary to present the overall safety profile (adverse events, etc.) rather than showing only specific types of adverse events.

So what (meaning): Safety comparisons follow A1's four conditions and additionally require source disclosure and presentation of the complete safety profile; selectively highlighting specific adverse events is considered scientifically unfair.

So why (rationale): Presenting only selected adverse event data creates a biased impression of competing products; requiring a full safety profile prevents such selective use.

Commentary — background, application, practical notes

Safety comparisons must satisfy the same four conditions from A1 as efficacy comparisons, but Q6 adds a specific further requirement: 'the overall safety profile (adverse events, etc.) must be presented.' This addresses the structural asymmetry of adverse event information. Adverse event rates vary substantially by trial and patient population, and selectively extracting a specific adverse event type can readily skew the perceived safety of a competing product.

A typical scenario is a physician asking whether one's own product causes fewer of a specific adverse event (e.g., gastrointestinal symptoms) than a competing product. Even if the manufacturer's own clinical trial showed a low incidence of gastrointestinal symptoms, presenting that single figure and nothing more is not sufficient. The overall safety profile from that trial — including incidence rates for major adverse event categories and the profile of serious adverse events — must be presented alongside, including information on whether a lower gastrointestinal rate corresponds to different rates in other categories.

What is most frequently overlooked in practice is determining the scope of 'presenting the overall picture.' Covering every adverse event exhaustively is not realistic, but at minimum the information should be framed to correspond to the package insert sections on 'important precautions,' 'serious adverse reactions,' and 'other adverse reactions.' Emphasising only a specific adverse event while omitting other safety information creates a one-sided unfavourable impression of the competing product, which can approach the type of conduct the anti-disparagement prohibition is designed to prevent.

Q（Question）

When a physician or pharmacist requests comparative information on contraindications, specific precautions, drug interactions, specific adverse events, or adverse events in specific patient backgrounds between one's own and competing products, is it permissible to provide such information?

A（MHLW answer）

Same as A6.

So what (meaning): Comparative data on contraindications (= the patients or conditions for which the drug must not be used), interactions (= cases where taking the drug together with another drug or food makes it work too strongly or too weakly), and specific adverse events is handled the same way as A6. Even when the question is narrowed to a single item, provide the information without dropping the context of the overall safety profile (= the full picture of a drug's safety information), and state the source.

So why (rationale): Contraindications and specific adverse events are part of that safety picture. The condition required in A6 — show the full picture of safety — does not change here, so the A6 answer is applied directly to this case as well (= applied by analogy).

Commentary — background, application, practical notes

Q7 applies A6 by analogy (= taking an earlier answer with the same intent and applying it directly to this case). It confirms that even when someone requests a comparison of individual safety items — contraindications, precautions, drug interactions, and specific adverse events — the A6 duty to present the full picture (= the duty to show not just part of the safety information but the whole picture) still applies. Even if the request is focused on a specific item, that does not mean the provider may narrow the range of information they give in the same way.

A typical scenario is a physician asking, 'what is the difference in contraindications between your product and the competing product for patients with reduced kidney function?' Showing the contraindication comparison itself is fine, because it stays within the scope of the request. But suppose you show only the fact that favours your own product — your product has no contraindication while the competing product does — and say nothing about points where the competing product's specific adverse event profile (= the body of information on particular adverse events) is more favourable than yours. That way of presenting it picks only the convenient facts, which is arbitrary, selective use of information.

A frequent problem in interaction comparisons is showing only part of the interaction profile (= the body of information on interactions) for an enzyme that breaks drugs down in the body (CYP = a drug-metabolising enzyme found mainly in the liver; when it is involved, interactions with other drugs become more likely). When you stress that your product has little effect on a specific CYP pathway but deliberately leave out how it compares with the competing product on other interactions (e.g., differences in the renal elimination route by which the drug leaves the body in urine, or P-glycoprotein substrate status = how readily the drug is affected by Pgp, a transporter that pumps drugs out of cells), you distort the context of the whole safety profile. Even when the request is narrowed to a specific interaction, showing where that interaction sits within the full interaction information in the package insert is the safe practical move.

Q（Question）

When a physician or pharmacist requests information on the switching dose from a competing product to one's own product, is it permissible to provide information from conference presentations that have not been published as papers?

A（MHLW answer）

Same as A4.

So what (meaning): Switching dose data from conference presentations is handled identically to A4: the provider must explicitly state that the source is unpublished and not peer-reviewed and that the evidence is not yet established.

So why (rationale): Switching dose information directly influences prescribing decisions, making explicit disclosure of evidence level especially important; A4's rules for unpublished conference presentations apply in full.

Commentary — background, application, practical notes

Switching dose information directly drives prescribing change decisions, which makes explicit disclosure of evidence level especially critical. Q8 applies A4, permitting the provision of switching dose data from unpublished conference presentations provided the provider clearly states that the data is unpublished, not peer-reviewed, and that the evidence is not yet established — while strictly maintaining that explanatory obligation.

A typical scenario is a physician who has been prescribing a competing product asking whether any conference data exists on the conversion dose when switching to the manufacturer's own product, since no published literature is available. If an abstract or presentation slides include results from a dose-conversion study, provision is permissible, but it must be accompanied by an explanation to the effect that 'this conversion ratio has not been peer-reviewed and does not represent a dosage approved through regulatory review; use within the dosage range stated in the package insert is the basis for any application.'

A common practical error is handing over conference data on conversion doses without explanation simply because 'the physician asked for it.' Errors in switching doses translate directly into patient overdose or treatment failure, so the risk of omitting a disclosure of evidence limitations is particularly high. When switching dose guidance based on conference data is given repeatedly to multiple physicians, there is also a risk that it qualifies as advertising activity, which would require assessment by the medical information function and prior internal review of the materials.

Q（Question）

When a physician or pharmacist requests comparative drug pricing information between one's own and competing products, is it permissible to provide such information?

A（MHLW answer）

Drug pricing information is not subject to the regulations of the Guidelines as a content matter; however, because such provision is part of marketing information activities, compliance with the Guidelines and the Standards for Appropriate Pharmaceutical Advertising is a prerequisite. When providing such information, it must constitute a fair comparison that does not cause misunderstanding in physicians or pharmacists.

So what (meaning): Drug pricing comparisons fall outside the Guidelines' regulatory scope as content, but as part of promotional activity they must comply with advertising standards and be fair comparisons that do not mislead.

So why (rationale): Drug pricing differs from the scientific information the Guidelines primarily govern, but it influences prescribing and dispensing decisions, so fairness requirements still apply.

Commentary — background, application, practical notes

Drug pricing information does not fall within the 'scientific information about pharmaceuticals' that the Guidelines primarily regulate, so the scientific evidence requirements set out in Part 1-3(1) do not apply. However, because drug pricing information is still provided as part of marketing information activity, it remains subject to the general requirements of the Guidelines and the Standards for Appropriate Pharmaceutical Advertising, including the obligation to ensure fairness.

A typical scenario is a physician or pharmacist asking 'is there a difference in reimbursement points between your product and the competing product?' or 'how does the branded drug price compare to available generics?' Drug prices are publicly set by the Ministry of Health, Labour and Welfare, and presenting accurate figures is unproblematic. However, the impression created by a price comparison can differ significantly depending on whether the comparison uses daily cost, per-course cost, or per-unit cost, so explicitly identifying which calculation basis was used is important for preventing misunderstanding.

A practical caution: layering an assessment of 'pharmacoeconomic superiority' onto a drug price comparison introduces a separate compliance question — comparative advertising under the Standards for Appropriate Pharmaceutical Advertising — distinct from the scientific fairness requirements of the Guidelines. There is a meaningful regulatory distinction between simply stating 'the drug price is X yen' and asserting 'our product is superior in cost-effectiveness.' When providing drug price comparisons, the safest practice is for the medical affairs representative to present only the pricing figures without independently adding economic evaluations.

Q（Question）

Does the fact that Q1 through Q9 address requests mean that comparative information between one's own and competing products cannot be provided at all unless physicians or pharmacists make a request?

A（MHLW answer）

Q1 through Q9 were written assuming situations in which marketing authorization holders are asked by physicians or pharmacists to provide comparative product information as part of marketing information activities; they were not intended to indicate that comparative information may only be provided when a request is made. When providing comparative information without a request from a physician or pharmacist, this must be done appropriately in light of 'On the Applicability of Advertising of Drugs, etc. under the Pharmaceutical Affairs Law' (Notification No. Yakukankan 148, September 29, 1998, Director of Supervisory Guidance Division, Pharmaceutical Safety Bureau, Ministry of Health and Welfare) and Section 2, Part 4-9 of 'Explanation and Considerations for Standards for Appropriate Pharmaceutical Advertising' (Notification No. Yakuseikaнmasa 0929 No. 5, September 29, 2017). Note that providing comparative information on one's own and competing products when the intent is not to attract customers — such as providing information related to promoting appropriate drug use or ensuring stable supply — does not constitute advertising and is permissible.

So what (meaning): Q1-Q9 address the request-driven scenario only; proactive comparative information provision without a request is not automatically prohibited but must be assessed for advertising applicability. Comparative information with no customer-solicitation intent (e.g., appropriate use promotion) is not advertising.

So why (rationale): Whether comparative information is permissible depends on advertising applicability and the absence of disparagement, not on whether a request was made; this clarification prevents unnecessary self-restraint.

Commentary — background, application, practical notes

Q10 makes explicit that Q1 through Q9 were written in the context of request-driven provision, and confirms that proactive comparative information provision without a prior request is not categorically prohibited. The Q&A restates the fundamental framework: whether comparative information may be provided depends on 'advertising applicability' and 'the presence or absence of disparagement,' not on whether a request was made.

When providing comparative information without a request, two branching questions must be assessed. The first is 'is there intent to attract customers?' Information provided without customer-solicitation intent — such as information related to promoting appropriate use or ensuring stable supply — does not qualify as advertising, and comparative information may be included in such communications without issue. The second question is 'does it amount to disparagement?' If comparative information is selective, one-sided, false, or exaggerated, it is prohibited regardless of whether a request was made.

The most common practical misreading is concluding, after reading Q1 to Q9, that proactive comparative information provision is entirely prohibited. This is unnecessary self-restraint, and Q10 was specifically added to correct it. The opposite misreading also exists: 'as long as a request is made, anything goes.' Even when responding to a request, the four conditions of Q1 — prohibiting selective information, requiring scientific objectivity, and so on — must all be satisfied; the existence of a 'request' is only one of the conditions. Avoiding both misreadings is the starting point for sound compliance practice.

Q（Question）

When a physician or pharmacist requests information on off-label use of one's own product, is it permissible to provide the information on the spot, assuming the representative is prepared to give an appropriate answer to the specific request?

A（MHLW answer）

Providing information on the spot when a physician or pharmacist requests information on off-label use of one's own product is not prohibited. However, the handling of off-label use information must comply with Part 4-3 of the Guidelines, including limiting the recipients of the information to the requesting party.

So what (meaning): On-the-spot provision of off-label information is not prohibited; however, the Part 4-3 conditions — especially limiting recipients to the requesting individual — must be met even in real-time interactions.

So why (rationale): The format of providing information immediately in person is not itself a basis for prohibition; the substantive conditions of the Guidelines apply regardless of timing.

Commentary — background, application, practical notes

Part 4-3 of the Guidelines sets conditions for the provision of off-label use information — including that it be provided in response to a request and that recipients be limited to the requester — but places no restriction on the timing or location of provision. Q11 confirms this point, making explicit that providing information on the spot when a physician or pharmacist asks for off-label information during a visit is not prohibited for reasons of form alone.

A typical scenario is a physician asking during a meeting with an MR 'is there any safety data for using this drug off-label for [condition]?' The prerequisite is that the representative is prepared to give an appropriate response at that moment — relevant literature, IF entries, or internally reviewed response materials. If that preparation is not in place, 'I will get back to you on that' is the appropriate response.

A common practical error is blanket self-restraint based on the belief that providing off-label information on the spot is categorically prohibited. Q11 was issued specifically to correct this, but at the same time, the condition to 'limit recipients to the requesting party' must be strictly observed even in real-time settings. If off-label information is conveyed to other physicians, MRs, or company staff present in the room, this may violate the recipient-limitation condition, and the circumstances of the meeting environment must therefore be considered.

Q（Question）

When a physician or pharmacist requests off-label use information on one's own product, is it permissible to provide, in addition to the information indicated in Q1 of Q&A Part 2, the latest conference presentation data?

A（MHLW answer）

The handling of conference presentation information is the same as A4. The handling of information provision on off-label drugs, etc. must also comply with the Guidelines.

So what (meaning): Latest conference data may be added to the Q&A Part 2-Q1 information set for off-label use, but A4's requirement to disclose that the source is unpublished and not peer-reviewed, and that evidence is not established, applies; Part 4-3 conditions must also be met simultaneously.

So why (rationale): Off-label information and conference presentation data each carry distinct requirements; both sets of conditions must be applied together, not selectively.

Commentary — background, application, practical notes

Q12 confirms the simultaneous application of two separate sets of conditions. The first is the basic framework for off-label information provision established in Q&A Part 2, Q1 — responding to a request, limiting recipients, disclosing sources, and so on. The second is the requirement established in Q4 for conference presentation data — explicitly disclosing that the source is unpublished, not peer-reviewed, and that the evidence is not established. The provision of off-label information sourced from conference presentations must satisfy both sets of conditions at the same time.

A typical scenario is a physician asking to be given information on off-label use for a particular condition 'including data from recent conferences.' When adding unpublished conference presentation data to the information already permitted under Part 2 Q1 (such as data from evaluation materials used in approval review or from peer-reviewed papers), the additional data must be accompanied by the explanation that it is 'not peer-reviewed and the evidence base is not yet established.' When presenting both types of information together, it is essential to clearly indicate which information corresponds to which level of evidence.

A common practical error is interpreting Q12 to mean 'conference presentations can be provided because the request was for off-label information' and then omitting the disclosure of unpublished status. The opposite error also occurs: 'conference presentations cannot be provided as off-label information because the evidence is insufficient.' What Q12 actually establishes is 'permissible under conditions' — neither omitting the conditions nor applying blanket self-restraint. The requirement is to apply both sets of conditions accurately and simultaneously.

Q（Question）

When a physician or pharmacist requests information on a treatment guideline, is it permissible to provide that information even if the guideline contains information on domestically unapproved drugs, in addition to the off-label drug and unapproved domestic indication/dosage information indicated in Q10 of Q&A Part 2?

A（MHLW answer）

It is permissible to provide information on the treatment guideline in accordance with the conditions of the Guidelines, provided that it is clearly communicated that the treatment guideline contains information on unapproved drugs.

So what (meaning): Treatment guidelines containing domestically unapproved drug information may be provided if the representative explicitly notifies the recipient upfront that the guideline includes unapproved drug data and complies with the Guidelines' conditions (e.g., recipient limitation).

So why (rationale): Prior notification that unapproved drug information is included is essential to prevent misunderstanding by healthcare professionals; requiring this disclosure enables provision while maintaining safeguards.

Commentary — background, application, practical notes

Q&A Part 2, Q10 had already established the conditions for providing treatment guidelines containing off-label drug information or dosage information not approved domestically. Q13 in Part 4 extends this further, confirming that guidelines containing information on domestically unapproved drugs — drugs whose indications have not been approved within Japan at all — may also be provided under specific conditions. Those conditions reduce to two: clearly communicating that the guideline contains information on unapproved drugs, and complying with the conditions of the Guidelines.

A typical scenario is a physician who references an international treatment guideline (e.g., one issued by a European or US medical society) and requests the full text. Even if that guideline recommends a domestically unapproved drug as a first-line treatment, providing it with the clear upfront statement that 'this guideline contains information on drugs not approved in Japan' is permissible. However, emphasising that section in a manner intended to encourage prescribing of the unapproved drug is a separately prohibited act.

A common practical error is deleting or blacking out the sections of a guideline that reference unapproved drugs before handing it over. This intentionally conceals part of the scientific context and is problematic from the standpoint of information accuracy and completeness. The approach more consistent with the spirit of the Guidelines is to provide the full guideline after explicitly notifying the recipient upfront that it contains unapproved drug information, thereby enabling healthcare professionals to accurately understand both the international clinical evidence and the domestic regulatory situation.

Q（Question）

When a physician or pharmacist requests information on whether insurance reimbursement is available for off-label use of a drug, is it permissible to simply inform them that the drug is listed on the Ministry of Health, Labour and Welfare website 'On Insurance Coverage of Off-label Drugs for Which Prior Evaluation Related to Well-known Application Has Been Completed' or the Social Insurance Medical Fee Payment Fund website 'Review Information Provision Cases (Drugs)'? https://www.mhlw.go.jp/bunya/iryouhoken/topics/110202-01.html https://www.ssk.or.jp/shinryohoshu/teikyojirei/yakuzai/index.html

A（MHLW answer）

This is permissible.

So what (meaning): Informing a physician or pharmacist that a drug is listed on the MHLW or Social Insurance Medical Fee Payment Fund public websites for off-label insurance coverage is permitted. The key is limiting the information to confirming the listing; adding one's own interpretation of coverage eligibility would be a separate matter.

So why (rationale): Directing healthcare professionals to publicly available information from government agencies is an objective statement of fact, fundamentally different from a marketing authorization holder independently asserting or interpreting insurance eligibility.

Commentary — background, application, practical notes

Whether off-label use is reimbursable under public health insurance is not a matter that a marketing authorization holder can independently determine or assert; it is determined by public agencies such as the Ministry of Health, Labour and Welfare and the Social Insurance Medical Fee Payment Fund. What Q14 permits is limited to informing physicians and pharmacists of the fact that the drug is 'listed' on the relevant public website. This is a sharing of objective fact, fundamentally different in character from the manufacturer asserting or guaranteeing insurance coverage.

A typical scenario is a physician asking 'can I submit an insurance claim for this off-label use?' If the off-label use has completed the prior evaluation process related to well-known application, it will be listed on the MHLW website, and providing the URL or describing what the listing states is permitted. The same applies to the Social Insurance Medical Fee Payment Fund's 'Review Information Provision Cases (Drugs)' website: informing the physician or pharmacist that the off-label use is listed as a review information provision case is permissible.

The critical practical boundary is that the permission is specifically limited to informing about the fact of a listing. Adding an interpretation or assertion — such as 'since the well-known application process is complete, you can submit an insurance claim for this' — is not permitted. Insurance coverage determinations are ultimately made by review agencies; a marketing authorization holder independently interpreting and asserting coverage eligibility to physicians or pharmacists carries the risk of inducing erroneous insurance claims. Limiting the communication to directing healthcare professionals to where public information exists is the essential boundary that this Q&A response draws.