MLR Review: Getting Promotional Material Cleared

MLR is the review a promotional piece passes before it can be used: medical, legal and regulatory, usually sitting together in one committee.

It exists because prescription drug promotion is regulated speech. A claim that outruns the label is a violation, not a marketing decision, and the company is responsible for every piece it distributes.

What each reviewer is actually checking

They are not doing the same job, and treating MLR as one opinion is why cycles repeat.

Medical. Is the claim scientifically accurate and supported by the data cited? Is the citation the right one, and does it say what the piece says it says? Is the presentation of efficacy fair, including the comparator?

Legal. Intellectual property, competitive claims, contractual constraints, and litigation exposure. Comparative claims attract the most attention.

Regulatory. Is every claim within the approved labelling? Is risk information presented with appropriate prominence? Is the indication stated completely, and is anything implying an unapproved use?

The requirements underneath

Consistency with the label. A claim not supported by the approved labelling is off-label promotion. This is the single most common finding.

Fair balance. Risk information has to be presented with comparable prominence to benefit information. Not merely present, comparably prominent.

Substantiation. Every claim needs support, and for a comparative claim the standard is substantial evidence, usually head-to-head data.

Form FDA 2253. Promotional materials are submitted to FDA at the time of first use. This is a submission obligation, not a pre-approval: FDA does not clear your piece in advance, unless you request advisory comments.

Where OPDP comes in

The Office of Prescription Drug Promotion (OPDP), in CDER, oversees prescription drug promotion. It reviews 2253 submissions, responds to complaints, issues untitled and warning letters on promotional communications it considers false or misleading, and monitors exhibits at medical meetings.

Sponsors may request advisory comments on a proposed piece before use, particularly for launch materials and direct-to-consumer campaigns. That is voluntary and takes time.

One thing worth knowing: OPDP's capacity has been reduced by FDA staffing changes, and the number of enforcement letters it issues has varied considerably year to year. A quiet year is not evidence that a claim is acceptable, and the underlying rules have not changed.

Why cycles repeat

• The claim was written before the data was checked. Medical then rejects it, and the concept goes back to the start.
• Reviewers see the piece without the references attached, so verification becomes a separate round of email.
• The same claim is re-litigated on every piece, because no record exists of the version already agreed.
• Fair balance is treated as a footnote, and regulatory sends it back for prominence rather than content.