The 33 cases spanning 2016 to 2024 share one common thread: information beyond the approved scope reached prescribers. Some involved direct statements; others used indirect language — 'speaking generally,' 'insurance audits will not flag it,' or 'overseas data shows this indication.' Some were deliberate; others reflected insufficient knowledge of the package insert and approval content. Intent and phrasing are secondary. If the information received by healthcare professionals exceeded what regulatory approval authorized, the violation occurred.

Mio"Yui, you've gone through more than 30 cases in this category. What stood out to you?"

Yui"There were cases with direct statements about unapproved indications, but more common were the ones that seemed to go around it — phrases like 'generally speaking' or 'in some countries this use is recognized.' More indirect, but still pushing toward the same point."

Mio"Right. Some reps seem to think the wording provides cover. How would you assess that as a reviewer?"

Yui"If a healthcare professional walks away with an understanding of an off-label indication or dosage, the phrasing doesn't matter. The outcome is the issue."

Mio"Exactly. Now, what other pattern caught your attention?"

Yui"Several cases used insurance audit outcomes as justification — 'prescriptions like this don't get rejected by insurers.' The argument was that if it passes reimbursement checks, it must be acceptable use."

Mio"And what's wrong with that reasoning?"

Yui"Insurance coverage decisions and regulatory approval are separate systems. A claim being reimbursed doesn't mean the use falls within the approved indication."

Mio"Good. One more: cases 01-25 and 01-26 involved providing information about unapproved or pre-approval products without anyone asking for it. What regulatory issues does that raise?"

Yui"PMD Act Article 68 prohibits advertising unapproved products. Article 68-2 on information provision duties is also relevant — proactively offering information on unapproved uses goes beyond the appropriate scope. Neither article makes an exception for 'it wasn't really advertising, just information.'"

Mio"That distinction between responding to a legitimate inquiry and proactively inserting off-label content into a promotion is exactly what reviewers need to identify. Start there when materials reference indications or dosing — ask whether it stays within the approved label."

33 real cases from the reports

01-01FY2016高リン血症治療剤MR による口頭説明
What happenedAn MR from Company A promoted a known adverse effect—excess accumulation of a nutritional component—as a supplementation benefit, suggesting that existing replacement therapies would become unnecessary. The issue was that the MR pivoted from the approved indication (phosphorus suppression) to repositioning an adverse effect as a therapeutic effect.
MHLW viewA side effect is being actively promoted as an indication (an efficacy/indication claim beyond the approved scope is being made).
Competency lostKnowledge, Risk Detection
Next moveCross-check the adverse effects section of the package insert against the approved indication in the review report, then identify and challenge any statement that frames an adverse effect as a therapeutic benefit.
01-02FY2016統合失調症薬MR によるプレゼンテーション（口頭説明・スライド）
What happenedAn MR from Company B included '** function improvement' in slides at a hospital adoption presentation and highlighted it as a differentiator from competing drugs. The PMDA review report contained no evidence of this improvement in humans, and the claim did not appear in the product information summary.
MHLW viewAn unapproved indication is being actively presented using non-clinical data (an efficacy/indication claim beyond the approved scope is being made).
Competency lostKnowledge, Intelligence
Next moveMap each efficacy and mechanism claim in the slides to the PMDA review report, and verify before each product presentation that unapproved properties are not being used as differentiating claims.
01-03FY2016糖尿病治療薬製品情報概要の臨床試験結果紹介
What happenedCompany C's website displayed graphs showing blood pressure-lowering effects under the label 'reference information' in small text, while presenting them in the same layout and scale as primary and secondary endpoints. The data had not been subject to PMDA review.
MHLW viewData within the scope of regulatory review and data outside that scope are presented side by side, creating a risk that the unapproved effect will be mistaken for an approved indication (an efficacy/indication claim beyond the approved scope is being made).
Competency lostRisk Detection, Intelligence
Next moveReview web-based materials to confirm that non-PMDA-reviewed data is not presented at the same visual weight as primary endpoints—check layout, font size, and order of presentation.
01-04FY2016抗リウマチ薬医療関係者向け情報提供サイトでの企業配信動画
What happenedA video published by Company D on a healthcare professional website recommended an initial daily dose of 100 mg instead of the package insert's 300 mg, and used color changes and flashing effects on bar graphs to emphasize differences versus comparator drugs.
MHLW viewAn unapproved dosage regimen is being recommended. In addition, promotional activity that emphasizes comparisons with a comparator drug is being conducted. (The JPMA Code 'Guidelines for Preparation of Product Information Compendium for Prescription Drugs' states: 'In figures and tables showing comparisons with a comparator drug (including placebo) or pre-/post-treatment differences, arrows or similar devices shall not be used to emphasize the difference, nor shall font size or color be used to emphasize the difference.') Healthcare professionals receiving promotional activities from pharmaceutical companies should, in light of cases such as this involving unapproved indications or dosage regimens, pay attention to the following points: Confirm via the package insert and other sources that the efficacy/indications and dosage/administration fall within the approved scope. In particular, for secondary effects and similar matters, it is advisable to verify the evaluation results of the regulatory review in the PMDA Review Report.
Competency lostKnowledge, Communication
Next moveVerify word-for-word that dosage information in videos and slides matches the package insert, and check whether visual emphasis in comparative graphs—color shifts, flashing, arrows—conflicts with the product information guidelines.
01-05FY2017便秘関連治療薬MR による口頭説明
What happenedMRs from Company A made statements across multiple monitored medical institutions suggesting broader use than the approved indication—including 'can be used widely for patients complaining of constipation' and 'the overseas indication is broader than in Japan.' Multiple facilities reported similar explanations, indicating systematic activity.
MHLW viewUnapproved indications are being actively presented.
Competency lostKnowledge, Risk Detection
Next moveCompare the approved indication wording against actual verbal explanations, and flag statement patterns that use future expansion plans or overseas comparisons to imply currently unapproved indications.
01-06FY2017ホルモン剤MR による口頭説明
What happenedAn MR from Company B cited the drug's absence from insurance pricing as justification for stating 'it is rarely used as written in the package insert,' then introduced off-label timing of administration as a matter of physician discretion—without presenting any supporting evidence.
MHLW viewUnapproved dosage/administration is being presented on the grounds that reimbursement review does not apply.
Competency lostKnowledge, Intelligence
Next moveConfirm that the obligation to follow approved dosage instructions under the PMD Act does not change for self-pay or uninsured products, then explicitly challenge the logic of presenting off-label use on the grounds of avoiding insurance review.
01-07FY2017潰瘍性大腸炎治療薬MR によるプレゼンテーション（口頭説明・パンフレット）
What happenedIn Company C's product information summary, the order of data in a subgroup analysis graph was altered from the interview form, placing whole-colon colitis results first. The original paper stated that this subgroup had insufficient sample size and no statistical analysis, but that caveat was absent from the summary.
MHLW viewBy changing the order in which data are presented within a graph, unapproved indications are being implied.
Competency lostIntelligence, Risk Detection
Next moveCross-reference graphs in the product information summary against the interview form and the original paper, checking for intentional guidance through reordering, omissions, or emphasis.
01-08FY2018抗真菌薬企業担当者による口頭説明
What happenedDuring a new drug hearing, a company representative stated that transition cases from an off-label disease were not uncommon, then suggested effectiveness in that indication without any supporting evidence, saying 'it is probably effective.'
MHLW viewEfficacy for indications other than the approved indication was described without supporting evidence.
Competency lostKnowledge, Intuition
Next moveWhen speculative phrases such as 'probably' or 'likely' appear without evidence, immediately ask the representative to provide supporting data and confirm the approval status.
01-09FY2018糖尿病治療薬企業担当者による口頭説明
What happenedDuring a combination drug hearing, a company representative described the two components as 'compatible,' then cited the drug's effect on body weight as 'reference information,' creating an impression of an off-label weight-loss benefit.
MHLW viewAn effect outside the approved scope — specifically, a weight-reduction effect — was implied.
Competency lostRisk Detection, Intelligence
Next moveAssess whether data presented as 'reference information' implies off-label efficacy by evaluating it in the context of the surrounding explanation. Pay particular attention to patient-appealing metrics such as body weight.
01-10FY2018抗血栓薬企業担当者による口頭説明
What happenedAfter a hospital declined to adopt the new formulation, a company representative proposed crushing the already-adopted 3.75 mg tablets for dose adjustment—a method of off-label use not described in the package insert.
MHLW viewOff-label use via crushing of tablets was recommended.
Competency lostKnowledge, Intuition
Next moveWhen crushing, suspension, or other modified administration methods are proposed during adoption negotiations, immediately check the package insert's pharmaceutical precautions and document the proposal as an off-label use recommendation.
01-11FY2018鎮痛薬企業担当者による口頭説明
What happenedAt a product information meeting, a company representative prefaced the comment with 'this is off-label,' then stated 'there are physicians at other hospitals using it for respiratory suppression,' using the citation of other practitioners' off-label use to implicitly encourage the same.
MHLW viewCases of off-label use were introduced, implicitly recommending such use.
Competency lostRisk Detection, Intuition
Next moveRecognize the pattern of using 'this is off-label, but...' as a disclaimer while still encouraging off-label use indirectly through third-party practice citations, and flag it explicitly.
01-12FY2018脂質異常症治療薬プレゼンテーション用スライド、企業担当者による口頭説明
What happenedAt a hospital study session, a slide labeled 'general information' was inserted between efficacy data slides, creating a narrative that implied off-label use in diabetic patients. At another facility, an off-label glycemic effect was described using the phrase 'a substance very close to this drug.' Similar reports came from multiple institutions.
MHLW viewDespite the absence of data linking the product to the claims made, explanations were given under the guise of 'general information' or 'a substance closely resembling this product,' thereby implying efficacy/indications beyond the approved scope of the drug.
Competency lostIntelligence, Risk Detection
Next moveRead the presentation as a whole to assess placement intent, and check structurally whether indirect expressions such as 'general information' or 'similar substance' function as pathways to off-label efficacy claims.
01-13FY2018パーキンソン病治療薬企業担当者による口頭説明
What happenedA company representative explained that the dosing interval specified in the package insert for a Parkinson's disease drug lacked clear evidence and that shortening it would not trigger insurance rejection, effectively implying that the contraindicated interval requirement could be disregarded. The same explanation was being delivered at multiple medical institutions in the region.
MHLW viewThe company representative implicitly encouraged prescribing contrary to the package insert by informing the physician that doing so would not be subject to insurance claim review.
Competency lostRisk detection, Knowledge
Next moveVerify in writing the package insert's dosing interval requirement and its safety rationale, then submit a written request for correction to both the representative and their manager.
01-14FY2018慢性便秘症治療薬医療関係者向け情報サイト上の Web 講習会
What happenedA web seminar titled 'Preventing Drug-Induced Constipation' featured a chronic constipation drug, but the fact that drug-induced constipation falls outside its approved indications was noted only in a footnote. The main content included no statement discouraging off-label use, leaving attendees with the impression that such use was being promoted.
MHLW viewThe presentation implied efficacy for an indication outside the approved scope.
Competency lostRisk detection, Knowledge
Next movePoint out the specific gap between the seminar title and the drug's approved indication, and request in writing that the main body of the content explicitly state that drug-induced constipation is an off-label use.
01-15FY2018脂質異常症治療薬企業担当者による口頭説明
What happenedA representative for a dyslipidemia drug stated that prescribing an inexpensive generic of a companion drug and instructing patients not to take it would allow monotherapy without triggering insurance rejection, and that some physicians were already doing so. This directly steered physicians toward off-label monotherapy.
MHLW viewThe company representative promoted off-label use of the product as monotherapy.
Competency lostKnowledge, Trust density
Next moveDocument the statement in detail and report it to the pharmacy compliance division and hospital administration as a case of insurance fraud inducement and off-label promotion.
01-16FY2019抗がん剤企業担当者による口頭説明
What happenedWith no efficacy data available for the drug after treatment with agent B, a company representative verbally recommended using it as second-line therapy for such patients, reasoning that other drugs also lacked supporting data for that setting.
MHLW viewThe company representative recommended use of the product as second-line therapy without supporting evidence.
Competency lostKnowledge, Intelligence
Next moveClarify explicitly that the absence of data for other drugs does not justify recommending this drug, and submit a written request that the representative limit information provision to evidence-supported approved uses.
01-17FY2019慢性便秘症治療薬企業担当者による口頭説明（企業の製品説明会の場において）
What happenedAt a product information meeting for a chronic constipation drug, a representative repeatedly described dosing patterns deviating from the package insert's 'once daily before meals' instruction—including post-meal administration, as-needed use, and split morning/evening dosing—implicitly recommending off-label use.
MHLW viewThe company representative introduced off-label uses and implicitly promoted them.
Competency lostKnowledge, Risk detection
Next moveRecord the specific statements made at the meeting and submit a written complaint to the company's compliance division, noting that promotion of dosing deviating from the approved method constitutes off-label promotion.
01-18FY2019腎性貧血治療薬企業担当者による口頭説明
What happenedWhen explaining the switch to a generic version of a renal anemia drug, the representative described only the drug's new pricing status and provided no explanation of the differences in approved indications between the originator and the generic.
MHLW viewThe company representative provided no explanation whatsoever regarding differences in approved indications between the originator product and the generic.
Competency lostKnowledge, Communication
Next moveRequest from the company a written document detailing the indication differences between the originator and the generic, and verify on a per-prescription basis that switch candidates do not have conditions outside the generic's approved indications.
01-19FY2019組織接着剤企業担当者（医療材料企業）による口頭説明
What happenedAt a joint information session held by a pharmaceutical company and a medical device company, the device company's representative gave a detailed explanation—with photographic materials—of off-label use of a tissue adhesive after tongue cancer resection where suturing was feasible. The pharmaceutical company's representative did not dispute this explanation, effectively allowing the off-label content to stand.
MHLW viewAt a joint product information meeting held by a pharmaceutical company and a medical device company, the medical device company provided a detailed explanation of off-label use of the product, and the pharmaceutical company did not deny or otherwise object to the content of that explanation.
Competency lostRisk detection, Relationship building
Next moveNotify the pharmaceutical company in writing of their shared responsibility as co-host, and request both a correction of the failure to refute the off-label content and a written policy for handling off-label explanations at future joint sessions.
01-20FY2019うつ症状治療薬企業の製品説明会
What happenedAt a product information meeting for a drug treating depressive symptoms, a representative described physicians who split the approved once-nightly dose into two half-doses morning and evening to reduce drowsiness, implying an off-label dosing regimen contrary to the package insert.
MHLW viewThe company representative introduced an example of off-label use and implicitly promoted it.
Competency lostKnowledge, Risk detection
Next moveRecord the statement and submit a written request to the representative for a correction, specifying that introducing dosing examples that deviate from the approved method constitutes off-label promotion.
01-21FY2019鎮痛剤企業担当者による口頭説明
What happenedAt a pharmacy department information session for an analgesic, a representative prefaced remarks with 'this is off-label' and 'overseas guidelines suggest,' but then spontaneously—without any question from the audience—provided detailed explanations of the drug's expected effects on dyspnea and cough and its potential as a first-choice agent for patients with renal impairment.
MHLW viewThe company representative promoted off-label use without any inquiry from healthcare professionals.
Competency lostRisk detection, Professional intuition
Next movePoint out that a self-initiated detailed explanation constitutes promotion regardless of an 'off-label' disclaimer, and submit a written complaint to the representative's supervisor.
01-22FY2019慢性便秘症治療薬企業担当者による口頭説明
What happenedA representative's claim that the chronic constipation drug had the fastest onset among laxatives led a medical department to adopt it as an as-needed pre-procedure medication in a clinical pathway—an off-label use. A hospital pharmacist identified the problem and worked to have it removed from the pathway.
MHLW viewAn explanation that led to the promotion of a dosing method (as-needed use) differing from the approved dosing regimen ultimately resulted in off-label use being promoted at the medical institution.
Competency lostRisk detection, Behavior change facilitation
Next moveEstablish an institutional process to alert the pharmacy and therapeutics committee whenever off-label use is suspected, and standardize an indication check before any drug is incorporated into a clinical pathway.
01-23FY2019抗菌薬ウェブセミナー
What happenedA webinar on an antibacterial drug presented clinical trial data from studies that excluded diabetic foot lesion patients, yet concluded that the drug 'can be expected to be effective for diabetic foot lesions as well.' The presentation implied efficacy for a population specifically excluded from the supporting trials.
MHLW viewUsing data from clinical trials in which the target disease had been excluded, the company implied efficacy for an indication outside the approved scope.
Competency lostKnowledge, Intelligence
Next moveReview the exclusion criteria of the cited trials, then formally notify the company in writing that implying efficacy for excluded populations falls outside the approved indication and request correction of the webinar content.
01-24FY2019抗精神病薬企業担当者による口頭説明
What happenedWhen asked by a healthcare professional about usage trends just before an in-house study session, a representative replied that the antipsychotic drug was commonly used not for its approved indication A but for off-label conditions B and C in patients unable to take oral medication—an answer that went beyond the scope of the question and implied that off-label use was standard practice.
MHLW viewThe company representative exceeded the scope of the healthcare professional's question and explained that administration to patients with diseases other than the approved indications was common practice.
Competency lostRisk detection, Communication
Next moveDocument the specific way the representative's answer exceeded the scope of the question and normalized off-label use, then submit a written request that future responses be confined to approved indications.
01-25FY2019抗がん剤企業担当者による口頭説明
What happenedA pharmaceutical company representative requested a meeting and provided information about a combination therapy involving anticancer drug A and B the day before regulatory approval was granted. Despite the pharmacist's request to conduct the meeting in the drug information management room, the company insisted on a private room.
MHLW viewInformation was provided regarding the combination therapy despite the fact that regulatory approval had not yet been granted.
Competency lostRisk detection, Knowledge
Next moveWhen a meeting request involves product information, confirm the approval status before accepting. If the product is pre-approval, decline immediately; treat unusual venue requests as a situational risk signal.
01-26FY2019認知症治療薬企業担当者による口頭説明
What happenedAn MR initiated a conversation about a generic product and, when the pharmacist mentioned the product name, used that moment as a pretext for providing promotional information about a pre-approval dementia drug. The pharmacist perceived the exchange as having been deliberately steered by the MR.
MHLW viewInformation was provided on a pre-approval product by acting as though the request had come from a healthcare professional.
Competency lostIntuition, Risk detection
Next moveIf the conversation appears to be steered by the MR, pause immediately and verify the product's approval status before proceeding. Document whether the inquiry was self-initiated or prompted.
01-27FY2020アルコール依存症治療薬企業担当者による口頭説明
What happenedWhen a healthcare professional inquired about the prescribing conditions for an alcohol dependence drug—which require training by both physicians and nurses—the company's medical information contact verbally suggested that prescribing examples exist where only the physician completed the training, implying the conditions could be disregarded.
MHLW viewAn explanation was given implying that there would be no problem in disregarding the conditions required for prescribing.
Competency lostKnowledge, Communication
Next movePrescribing conditions stated in the package insert cannot be waived by verbal explanation. Request written documentation for any claimed exception; if doubt remains, escalate to the regulatory authority.
01-28FY2020抗精神病薬オンライン面談にて、企業担当者による説明
What happenedFor an antipsychotic whose new indication had been approved only for the injectable form, a company representative verbally stated that the same indication also applied to the oral form—an inaccurate claim, as no such approval had been granted for the oral formulation.
MHLW viewAlthough the additional indication had been approved only for the injectable formulation, an explanation was given implying that the same indication also applied to the oral formulation.
Competency lostKnowledge, Risk detection
Next moveVerify the approved indications separately for each dosage form using the package insert. Cross-check verbal explanations against the product summary on the spot; flag and document any discrepancy immediately.
01-29FY2020抗インフルエンザ薬医薬品卸の営業担当者による説明
What happenedA pharmaceutical wholesaler's sales representative described an unapproved indication as expected to be approved, and used that claim to encourage the healthcare facility to stock the influenza drug.
MHLW viewAn unapproved efficacy/indication was presented.
Competency lostRisk detection, Knowledge
Next moveTreat any claim of anticipated approval as equivalent to unapproved information. If a purchasing recommendation is based on an unapproved indication, separate the purchase decision from that claim and act only after confirmed approval.
01-30FY2021SGLT2 阻害剤企業担当者による説明
What happenedWithout being asked, a company representative for an SGLT2 inhibitor relayed that a physician had suggested attaching a chronic kidney disease diagnosis to HFpEF patients to facilitate prescribing—implying off-label use. The study cited to support efficacy was data from a competing company's product.
MHLW viewTaking advantage of a newly approved additional indication, the company representative gave an explanation that could be construed as encouraging off-label use.
Competency lostRisk detection, Intuition
Next moveTreat a representative's indirect suggestion of off-label use—framed as a physician's anecdote—as equivalent to a direct recommendation. Record the details and report to the appropriate off-label use compliance officer.
01-31FY2022モノクローナル抗体製剤企業担当者による説明
What happenedDuring a pre-approval briefing for in-hospital advertising, a company representative stated that a monoclonal antibody product had demonstrated efficacy for rash following pruritus—an effect not included in the approved indication. Subsequent inquiry revealed this was based on a secondary endpoint from a domestic Phase III trial.
MHLW viewWhile providing information on secondary endpoints is not in itself problematic, using those results to explain an unapproved efficacy or indication constitutes promotion of off-label use and is therefore inappropriate.
Competency lostKnowledge, Risk detection
Next moveSecondary endpoint data may serve as useful reference, but cannot be used to describe an unapproved indication. If an off-label claim is found during the in-hospital advertising review, withhold approval and request written evidence.
01-32FY2023皮膚炎治療剤企業担当者による説明（直接対面）
What happenedDuring a hospital pharmacy interview, an MR stated that the dermatitis drug was being used for pruritus in dialysis patients. The indication was not approved, and when supporting data was requested, the MR acknowledged there were none.
MHLW viewExplaining an unapproved efficacy or indication is inappropriate, as it could amount to recommending off-label use.
Competency lostKnowledge, Communication
Next moveStating that a drug 'is being used' off-label creates risk of misunderstanding even without an explicit recommendation. Request data immediately; if none exists, document the case and prompt referral to the company's compliance team.
01-33FY2024抗悪性腫瘍剤企業担当者による説明（直接対面）
What happenedAt an in-hospital product presentation for an antineoplastic agent, a medical affairs representative—without being asked—stated that the drug would eventually be usable for all solid tumors and described both this product and a competing product as having planned indication expansions.
MHLW viewDespite the absence of any request from healthcare professionals, reference was made to unapproved efficacy or indications.
Competency lostRisk detection, Knowledge
Next moveStatements about anticipated future approvals by medical affairs staff carry the same concern as unapproved promotional claims. If noticed during a presentation, interrupt the statement, and document that out-of-scope claims were made.

The Anatomy of Failure ── All 8 categories

  1. 01. Promotion of Unapproved or Off-Label Indications and Dosage (33 cases) (this category)
  2. 02. Claims Lacking Evidence or Scientific Basis (69 cases)
  3. 03. Cherry-Picking, Data Manipulation, and Selective Presentation (33 cases)
  4. 04. Exaggerated and Misleading Expressions (28 cases)
  5. 05. Emphasizing Efficacy While Downplaying Safety (22 cases)
  6. 06. Disparagement and Defamation of Competitors' Products (28 cases)
  7. 07. Undisclosed Conflicts of Interest and Improper Conduct in Lectures and Prescribing Guidance (10 cases)
  8. 08. Cross-Category Violations Rooted in Process Failures (4 cases)
Key points
  1. Indirect phrasing — 'generally speaking,' 'based on overseas indications,' 'insurance won't reject it' — does not avoid a violation. If a healthcare professional receives and understands off-label information, the result is the same as a direct statement.
  2. A prescription being reimbursed by insurers does not confirm that it falls within the approved indication. The two systems operate independently; 'no audit rejection' does not equal 'approved use.'
  3. Proactively providing information about unapproved or pre-approval products without being asked can constitute a violation of PMD Act Article 68 (prohibition of advertising unapproved products) and Article 68-2 (information provision duties).
Sources
  1. MHLW, "Monitoring Project on Promotional Information for Prescription Drugs — Annual Reports" (FY2016–2024).
  2. Promotional Activity Guidelines, Section 1-3, Principle (2), Prohibited Act (1) — prohibition on providing information relating to unapproved indications, efficacy, or dosage
  3. PMD Act Article 66 — prohibition of false or exaggerated advertising
  4. PMD Act Article 68 — prohibition of advertising drugs and medical devices prior to approval
  5. PMD Act Article 68-2 — obligation to provide information on prescription drugs within the appropriate scope of inquiry