Q&A Part 3 (MHLW administrative notice, Sep 6, 2019). Topic: Crushing / simple-suspension data in the interview form (1 Q). Each question below reproduces the official Q&A faithfully and adds so-what (what the answer means in practice) and so-why (the underlying rationale).
FAQ on this page (click to jump)
Q1 May stability data for simple suspension/crushing be included in the Interview Form for provision?
Part 1-2 Scope of Application / Part 4-3 Information Provision on Unapproved/Off-label Drugs
Q（Question）
Is it permissible to include information on drug stability during simple suspension, crushing, and similar procedures in the Interview Form and provide it to healthcare professionals, when such procedures are performed at the discretion of clinical staff based on the patient's condition?
A（MHLW answer）
The MSA Guidelines permit marketing authorization holders to provide information on unapproved or off-label use when requested by healthcare professionals.
The Interview Form is created at the request of medical associations as an information resource for appropriate drug use, complementing the package insert and supplying information needed for dispensing.
Given the established clinical practice of performing simple suspension, crushing, and similar procedures at the discretion of medical staff for patients with dysphagia and pediatric patients, a marketing authorization holder's inclusion of stability data for such procedures in the Interview Form may be treated as a response to a healthcare professional's request under the Guidelines.
However, because such procedures fall outside approved indications, the entries must follow standardized common rules including explicit description of test methods. When excerpting such information for posting on a website, the content must be reproduced completely and without omission from the Interview Form.
So what (meaning): Stability data for simple suspension and crushing may be included in the Interview Form for dysphagia and pediatric use, but common documentation rules (e.g., explicit test methods) must be followed, and any web posting must reproduce the IF content in full.
So why (rationale): Because simple suspension and crushing are off-label procedures, they are legitimized by framing them as responses to healthcare professional requests, while rules on accuracy and consistency protect patients and ensure fair information provision.
Commentary — background, application, practical notes
Simple suspension and crushing are procedures outside the approved method of administration, which means they fall under the Guidelines' rule that information on off-label use may only be provided 'when requested by a healthcare professional.' However, the Interview Form (IF) is an official information resource created by marketing authorization holders at the request of medical associations to support dispensing decisions; including data in the IF can itself be characterised as a response to the collective request of the medical community. Under this reasoning, the act of including stability data in the IF and distributing it as part of routine information provision is treated as equivalent to a request-driven disclosure, keeping it within the Guidelines.
The most common real-world scenario involves pharmacists in facilities with tube-fed patients or paediatric wards consulting IF stability data — such as residual drug content after suspension or dissolution behaviour after crushing — and sharing this with prescribers. By pre-populating the IF with concrete test results (e.g., percentage of intact drug remaining in a thickened suspension after 30 minutes), manufacturers enable clinical teams to make informed decisions without delay. Proactively building and publishing this data in the IF provides more consistent and reliable support than answering ad hoc queries case by case.
A common compliance error arises when IF content is excerpted and posted to a company website. The Q&A requires that website postings reproduce the IF content 'completely and without omission'; selectively presenting only favourable values is not permitted. Equally, any entry must explicitly state the test method — suspension medium, temperature, time elapsed — in accordance with the common documentation rules. When website content diverges from the full IF entry, healthcare professionals risk interpreting data obtained under different conditions as if they were obtained under the same conditions, and that misunderstanding is precisely what the rule is designed to prevent.
Source: MHLW MSA Guidelines Q&A Part 3, Sep 6 2019, Q1
Case set — the reasoning that exploits "it isn't written down," and the verdict
Recording stability data on simple suspension or crushing in the Interview Form (IF) is permitted under the guidelines as a conditional exception. However, the logic that 'anything written in the IF is allowed' represents a classic misappropriation: converting a conditional allowance into unconditional permission. The following four-tier cases illustrate escalating degrees of non-compliance.
GRAY 1 — Spirit deviation (touches no wording but violates the spirit of the guideline)
Improper reasoning: [GRAY1: Spirit Violation] An MR repeatedly visited physicians with proactive explanatory materials, stating: 'Since it is documented in the IF, I am free to explain stability data on simple suspension.'
Verdict: The guideline's framing of 'IF documentation as equivalent to a healthcare professional's request' is not a license for proactive promotion. The structure requires that a request precedes the provision of information; an MR who initiates visits and announces freedom to explain inverts that premise. The correct approach is to present IF content only when a physician asks or specifically requests the information.
GRAY 2 — Gap-exploitation (deliberately exploits a gap to mislead)
Improper reasoning: [GRAY2: Loophole Exploitation] The IF section showed only quantitative stability data (residual rate, pH change) while omitting test conditions—temperature, humidity, suspension medium, and duration. Internal review was bypassed with the assertion that 'all figures are actual measured values.'
Verdict: The guideline explicitly states that 'descriptions must follow a common set of rules, including clear specification of test methods.' Numerical values without test conditions provide no safety assurance when applied to different clinical settings. The fact that figures are measured values does not justify omitting the conditions. The correct approach is to present measurement conditions, medium, and time points together with the data so clinicians can judge applicability themselves.
GRAY 3 — Higher-norm violation (arguably "not written," but almost certainly out under the Act / Advertising Standards / JPMA Code)
Improper reasoning: [GRAY3: Higher-Norm Violation] When posting an excerpt of IF suspension data on the company website, the disclaimer 'this is not an approved method of administration' was omitted, and the qualifying phrase 'reference data under specific conditions' was removed. The company asserted that 'the excerpt is accurate as drawn from the IF.'
Verdict: The guideline requires that IF content be reproduced 'completely and without omission.' Removing disclaimers or qualifiers constitutes 'omission.' Even if the numerical data are accurate, an excerpt stripped of its contextual conditions and warnings creates a misleading whole. The correct approach is to carry forward disclaimers about unapproved use, test conditions, and qualifying language exactly as they appear in the IF, so clinicians receive the full context.
BLACK — Explicit violation (a plain breach of the provision itself)
Improper reasoning: [BLACK: Express Violation] Without any request from healthcare professionals, the company created a proprietary brochure titled 'Simple Suspension Compatible Product List' (re-editing IF stability data) and distributed it en masse to hospital pharmacists.
Verdict: The guideline permits information provision only 'when requested by healthcare professionals.' Mass distribution entirely lacks this prerequisite and fundamentally abandons the conditional framework. Proactively distributing a proprietary document derived from IF data amounts to de facto advertising of an unapproved method, creating dual exposure under the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals (exaggerated advertising provisions). The correct approach requires an explicit inquiry from a healthcare professional before any IF content is provided or explained.
Improper intent by implication — three ranges of "hinting" without stating
Even without explicit prohibited language, document structure, emphasis, and selective omission can embed a specific impression in the reader. The following three cases illustrate techniques that imply intent at different scopes: localized, adjacent, and holistic.
Implication 1 / Local — packed into a single word or sentence
Construction: [Local Implication] Inserting the phrase 'contributes to improved medication compliance' immediately after the stability data.
Readable intent: This links a causal chain—'using this data makes simple suspension easier, which improves compliance'—without stating it explicitly. The reader automatically completes the narrative: stability data → suspension recommended → improved compliance.
Verdict: Juxtaposing stability data with a product benefit claim generates the same effect as actively recommending an unapproved method. The correct approach is to create a clear contextual separation between data presentation and any product messaging, presenting stability information neutrally as reference material only.
Implication 2 / Adjacent — read through neighbouring phrases
Construction: [Adjacent Implication] Placing a 'Product Characteristics' section immediately after the test conditions page, emphasizing 'high disintegration rate' and 'uniform particle design.'
Readable intent: The reader encounters product physical advantages immediately after viewing suspension stability data. The sequence appears coincidental within the IF structure, but the deliberate placement guides the reader to independently conclude 'this product is well-suited for suspension'—a conclusion the manufacturer cannot state directly.
Verdict: Page placement and section order are part of the 'content' of information provision; intentional juxtaposition can constitute implicit recommendation of an unapproved method. The correct approach is to separate product characteristics from unapproved-use data into independent sections, with each section explicitly stating the purpose and scope of the information presented.
Implication 3 / Whole — raised by the context of the whole document
Construction: [Holistic Implication] Applying uniform color schemes, heading hierarchy, font size, and layout across the 'Approved Dosage' chapter and the 'Simple Suspension' chapter, making both appear visually equivalent.
Readable intent: Visual equivalence between approved and unapproved methods generates an impression across the entire document that 'both are official methods.' Readers are more likely to miss individual disclaimers, effectively neutralizing the legal distinction of 'unapproved.'
Verdict: The visual hierarchy of a document should reflect the regulatory weight of its information. Data relating to unapproved methods must be presented in a format that is clearly distinguishable from approved-use information—through section-level disclaimers, distinct heading styles, or cautionary color coding. When overall design works to erase this distinction, the design itself may be evaluated as an inappropriate inducement.