Off-label and the Australian PI — what the ceiling is, and what it isn't.

Ask five people on a pharmaceutical affiliate what "off-label" means and four will say "promoting for an indication the TGA hasn't approved". That is the most visible case and not the definition. In Australia the definition is one sentence of the Code, and it is wider than a disease name: a promotional claim is off-label when it is not consistent with the Australian Product Information as a whole — indication, population, directions, dose, endpoints, safety. A claim can name the right disease and still be off-label. A claim can sit beside the wrong PBS line and not be. This guide is the rule in the Code's own words, the five tests the Tool Kit gives for applying it, the shapes that most often fail them, and the two things that are routinely mistaken for it.

Where the rule sits

The Code puts it in the Overarching Principles — the ten statements in Part A that "govern all activities covered by this Code" § Interpreting this Code. The eighth reads, in full: "All promotional claims are consistent with the Australian Product Information document, including claims about competitor products, irrespective of the source on which the claim is based" § OP 8.

Three words in that sentence carry the weight.

Australian. The reference document is the PI approved by the TGA for this market — in the Glossary, "the current Australian Approved Product Information" § Glossary. Not the FDA label, not the SmPC, not the global core data sheet the master was written to. Where a product's registration predates the current regulatory review, the reference is the registered "Full Product Information", and the document "must comply with the format specified in the TGA Australian Regulatory Guidelines for Prescription Medicines" § Glossary.

Including claims about competitor products. The ceiling applies to what you say about the other company's product as much as your own. Section 1 says the same from the other direction: the responsibility for claims "relates to any information given or claims made about the product being promoted, other products, disease states or conditions" § 1.

Irrespective of the source. A peer-reviewed paper, a guideline, a registry, an overseas approval — none of them lift the ceiling. This is the clause that separates off-label from substantiation. A claim can be true, published and referenced to the Code's standard § 1(a) and still be off-label, because the PI does not carry it.

Section 1 then restates the principle as the operating rule for promotion to healthcare professionals. Companies may promote prescription products "so long as all information, claims and graphical representations are current, accurate, balanced, consistent with the approved product information, and do not mislead directly, by implication, or by omission" § 1. "Consistent with the approved product information" is one of five words a reviewer tests every piece against; the other four are covered in the MLR review guide.

Underneath the Code is the statute. The Code "is underpinned by the Therapeutic Goods Act and Regulations" § Scope, and the Act — not the Code — makes advertising a registered medicine for an indication other than those accepted for its entry in the Register an offence. Two consequences follow. A finding of off-label promotion is a Code breach and a possible breach of the Act, which is why the Code lets Medicines Australia refer an unactioned finding to the TGA § 15.6(d). And the audience does not change the ceiling: promotion of prescription medicines to the general public is prohibited outright, so the only off-label question that arises with consumers is whether the piece was promotion at all § 2.3(a), § 12.

Consistent is not identical — the five tests

The Code does not define "consistent". The Tool Kit does. The Promotional Claims Guidance (published March 2025, revised February 2026) says consistency relates to the PI as a whole, not only the approved indications, and gives five questions to ask of a claim. They are the working definition of off-label in Australia, and a reviewer who runs all five catches what a reviewer who runs the first one misses.

1. Indication. Does the claim relate to a different or broader indication than the PI states? This is the case everyone knows — the second-line product positioned first-line, the adjunct positioned as monotherapy, the disease the trial studied but the TGA did not approve.

2. Patient population. Is the population presented outside the PI's? The PI's indication paragraph is usually narrower than the trial's inclusion criteria: an age band, a severity threshold, a prior-therapy requirement, a biomarker. A claim about "patients with X" that quietly drops the qualifier the PI carries is off-label even though the disease name is right.

3. Limitations and directions for use. Does the claim conflict with a limitation or a direction in the PI? A contraindication, a "not recommended in", a monitoring requirement, a duration cap. A piece that implies use where the PI says do not, or that leaves out a direction the PI makes conditional, fails here.

4. Dose, regimen, administration and strength. Does the information conflict with the approved dose, regimen, route or strength? A loading dose the trial used and the PI did not adopt; an every-eight-weeks interval where the PI says every four; a strength registered overseas and not here. This is also where the wrong PI gets used — a product with several presentations has a PI set, and the claim is held to the PI of the strength or presentation being promoted.

5. Endpoints, outcomes and safety. Are the endpoints, outcomes and safety statements consistent with the PI's? This is the test the Guidance qualifies, and the qualification matters: "consistent" is not necessarily "the same as", because not all data on endpoints, outcomes and safety will be in the PI. A secondary endpoint the PI does not report is not automatically off-label. It is off-label when it contradicts what the PI does say, or when it is deployed to support a use the PI does not — a quality-of-life result used to imply an indication, a safety figure that outruns the PI's adverse-effect profile.

Two further points the Guidance makes. The responsibility extends to claims about other products, disease states and conditions, not only the company's own — which is § OP 8 and § 1 again. And where products used in combination have inconsistent approved PIs, the primary focus is consistency with the PI of the product being promoted.

Run the five in order and the finding names itself: extends beyond the indication, outside the population, conflicts with a direction, conflicts with the dose, inconsistent with the PI's outcomes. A finding that can't be phrased as one of those five is probably not an off-label finding — it is a substantiation, balance or accuracy finding wearing the wrong label, and it should be written up under the clause it actually breaches.

Where it hides

The visible case is rare in reviewed material; nobody sends a reviewer a detail aid for an unapproved disease. The findings that survive to a reviewer are the ones that pass a first read.

The global master. Written to another market's label, localised by find-and-replace. The indication paragraph gets fixed; the population qualifiers, the dosing table and the safety summary keep the source market's numbers. Every one of the five tests can fail in a piece whose headline indication is correct. The Help Desk has made the same point about shared Australian–New Zealand assets: indications can differ, small PI wording differences can support off-label promotion in one country and not the other, and a broader New Zealand indication cannot be promoted to Australian healthcare professionals. Adapting a master to the Australian PI is its own workflow — Global to local — and the Localiser exists because the find-and-replace version of it is where off-label lives.

The trial population. The pivotal study enrolled a wider population than the TGA approved. The efficacy claim quotes the trial; the trial's population is not the PI's. A claim substantiated to the Code's standard § 1(a), § 1.2 and consistent with the body of evidence § 1.2(c) can still fail test 2.

The endpoint that implies a use. The Code lets a claim rest on a pre-specified secondary endpoint, if it is consistent with the body of evidence, reflects the study's conclusion and the reader can see the primary endpoint was not met § 1.2(e); it lets post-hoc analyses in when they are identified and qualified § 1.2(g). Those are substantiation rules. None of them says the endpoint may be used to position the product for something the PI does not carry. The question is not "is this result real?" but "what is this result being deployed to say?"

Dose creep. The regimen in the hero chart is the one the trial optimised, and the PI approved a different one. Or the PI approves a dose range and the piece presents the top of it as the standard. Test 4, and a common one in re-used congress material.

Positioning read as a whole. The Code holds "graphical representations" to the same standard as claims § 1, and defines Graphics to include "photographs, drawings, x-rays, graphs and bar charts" § Glossary. A tagline, a hero statistic and a photograph of a patient who could not be in the approved population together position the product for a use no single sentence claims. A reviewer reads the piece the way the recipient will — as a whole — and tests the positioning, not just the copy.

The pipeline and the unregistered product. Nothing about an unregistered product or an unapproved use can be promoted, but the Code allows both to be discussed in two places: scientific exchange § 7, below, and market research, which "may be undertaken about an approved or unapproved product or unapproved indication" so long as it is not "a means to promote to and/or reward participants" § 8(a), § 8(b). Material for either that reads as promotion is off-label promotion with a different heading.

The reprint. A published paper on an unapproved use is not off-label promotion when it is provided as literature — but the Code forbids highlighting: "no part of a reprint or article should be specifically highlighted to draw the attention of the healthcare professional" § 3(a). A reprint with a paragraph circled is a claim.

What PBS does and doesn't do

This is the confusion that costs reviewers the most time, and the Code's position is short.

A PBS listing does not widen the ceiling. Where the PBS restriction is broader than the TGA indication — it happens — only claims consistent with the approved PI may be made, and the Promotional Claims Guidance records that the TGA has advised Medicines Australia that printing PBS listing details broader than the approved indications may risk breaching Therapeutic Goods legislation. The Guidance's instruction is to limit the material to a statement of PBS listing. That is what § 2.1(e) asks for anyway: "a statement indicating the public funding or reimbursement status of the product, with or without details of listing, or a direction to where the relevant information is available".

The other direction is just as true and less often said. A PBS line that is narrower than the TGA indication, or missing, or stale, does not make a claim off-label. The ceiling is the PI. A product registered for two indications and listed for one may be promoted for both; the second is unfunded, which is a § 2.1(e) accuracy question about the funding statement, not an off-label question. Promoting a TGA-registered indication before its PBS listing — the launch window — is not off-label. And a piece that frames a registered indication the PBS restriction does not name is not off-label either; if the funding statement is wrong or incomplete, that is the finding to write.

It matters because the two findings are different in kind. An off-label finding is the most serious a reviewer makes — a severe breach carries safety implications and up to $200,000 per finding, cumulative to $300,000 per complaint, with withdrawal and corrective advertising on top § 15.6. A funding-statement finding is a wording correction. Writing the second up as the first is the category error a medical director will not forgive, and it happens most often when the PBS restriction is the document a reviewer has to hand and the PI is not.

In practice, then: hold the claim to the PI first; hold the funding statement to the PBS schedule second; never let the second write the first. The Reviewer is built to that rule — its first pass reads the material as a whole against the TGA indication and population, tests one and two, and does not let a PBS statement move that answer. Dose, directions and endpoints follow in the detailed pass, and a listing-statement problem is written up under § 2.1(e) where it belongs. That is our practice, not the Code; the Code prescribes the standard.

The other door — scientific exchange

There is a legitimate way to talk to a healthcare professional about an unapproved use, and the Code gives it a section of its own. Scientific exchange "must be for the purposes of enhancing scientific understanding, improving patient care, improving access to medicines (including compassionate access), supporting quality use of medicines or assisting research and/or stakeholder budgetary planning", and "the intent of such activities must be non-promotional with a focus on exchange being two-way communication" § 7. The Glossary defines it as exchange "in a non-promotional manner, concerning (but not limited to) an unregistered product or use", which "must be without any reasonable likelihood to influence the intent to prescribe or use a product and must not constitute promotion" § Glossary.

The Code sets six conditions.

• Reactive is the easy case. Where healthcare professionals or other stakeholders "are seeking clarity and/or additional information on products not approved in Australia and/or subjects not covered in the Australian Product Information", it is reasonable to provide it § 7(a).
• Proactive is permitted, narrowly. Companies may "anticipate the needs of appropriate stakeholders for scientific and medical information", but only for "those stakeholders whose need for or interest in can reasonably be assumed for the conduct of their role", and "material should be tailored to the audience to whom it is directed" § 7(b). The Tool Kit's Scientific Exchange FAQs are frank that proactive exchange carries a higher perception of promotion, and that wide distribution reads as promotional.
• Who. "The Company Medical Department may engage in scientific exchange regarding unregistered products, uses or other off label topics." Non-promotional roles such as market access and regulatory affairs may be permitted to; the exchange "must be non-promotional in intent, content and nature and must be distinguished from promotional activities" § 7(c). A sales representative — "a person expressly employed by a Company whose main purpose is the promotion of the Company's products" § Glossary — is not a non-promotional role and cannot deliver it. The FAQs add that the Code does not require commercial staff to be excluded from the room, but that their engaging in the Q&A is where the risk of breach sits.
• Oversight. "Scientific Exchange activities must be overseen by the Company Medical Director or their delegate" § 7(d).
• Labelling and approval. "Any information relating to unregistered products or off label topics must be clearly identified as such and must meet the requirements of this Code. Such materials must be approved by the Company Medical Director or their delegate" § 7(e).
• The search gate. In digital medical information applications, information on unapproved products and uses may be provided "when this information is only viewable after the healthcare professional executes a search that includes specific search terms relating to the unapproved product or use" § 7(f).

Two things follow that affiliates get wrong in both directions. Scientific exchange material is not promotional material, so the seven § 2.1 inclusions do not automatically apply to it — the FAQs say so, and say that including them does not turn it into promotion; the Overarching Principles on accurate, balanced and safety-forward information still do § OP 3, § OP 7. And the label on the activity does not decide what it is. A "medical education" evening delivered by the brand team, a "scientific update" e-mailed to a territory list, a symposium whose slides carry the campaign tagline — each is promotion, and if the content is outside the PI, off-label promotion, whatever the invitation said. The Code's own test is the one in the Glossary: any reasonable likelihood of influencing the intent to prescribe.

For the public the doors are narrower still. A company may make the PI and the CMI available to members of the public "providing they appear in their entire form and are not amended, abridged or displayed in a promotional manner" § 12(a); requests for advice on diagnosis or choice of therapy "must always be refused and the inquirer recommended to consult their doctor" § 12(b); and a patient already prescribed the product may have matters clarified "in a non-promotional manner using the Consumer Medicine Information" § 12(c).

Running the test on the desk

What a reviewer actually does with a piece, in the order that avoids the two mistakes above.

1. Get the right PI, and the current one. The Australian Approved PI for the product — and for the strength or presentation the piece promotes, where the PI set has more than one. The TGA's eBusiness Services search is the source of record; a PI pulled from a global system or a previous job is the first thing a competitor's medical director will check.
2. Read the piece as a whole before reading any claim. Note what it positions the product for — headline, hero statistic, imagery, audience. Test that positioning against the PI's indication and population first § OP 8. That is the finding that stops the piece; everything else is a revision.
3. Run the other three tests claim by claim. Directions and limitations; dose, regimen, route and strength; endpoints, outcomes and safety — remembering that on the fifth, consistent is not identical, and the question is what the result is being used to say.
4. Keep substantiation separate. A claim is referenced, current and reflects the body of evidence § 1(a), § 1.2 — and then, separately, is or is not within the PI. Passing the first test is not evidence for the second, and the write-up should cite the clause each finding actually breaches.
5. Hold the funding statement to the PBS schedule, on its own. Is it present, and is it accurate § 2.1(e)? A PBS problem is a § 2.1(e) problem. It does not touch the answer to step 2.
6. Route what isn't promotion. If the material's purpose is to inform a healthcare professional about an unapproved use, it is not a piece to be fixed in review; it is a Section 7 activity, which means Medical, the Medical Director's approval, clear labelling, and a non-promotional role to deliver it § 7(c), § 7(d), § 7(e).

The rule is one sentence and the test is five questions. The work is in the second word — Australian — and in keeping the PI open beside the piece, rather than the PBS schedule, when the questions are asked.