MLR review is the process pharma companies use to approve promotional and medical content before it's used. Medical, Legal, and Regulatory reviewers each check the material: Medical for scientific accuracy, Legal for legal risk, and Regulatory for compliance with advertising rules and the approved product labeling. For a short definition, see the MLR review glossary entry.
For agencies, MLR review is where the work is judged. Every piece of content an agency produces for a pharma or medical device client, from a detail aid to a social post, has to get through it. Each round of feedback costs time, budget, and client confidence.
Most guides to MLR review are written for the pharma teams running it. This one is written for the agencies submitting to it: how the MLR review process works, what reviewers are looking for in 2026, why content gets sent back, and how to build a process that gets it approved sooner.
The MLR Review Process, Step by Step
The exact steps differ by client, but most MLR review processes follow the same sequence. Knowing it helps an agency plan submissions and predict where comments will come from.
- Submission. The piece is submitted in the client's review system with its references and an annotated list of claims.
- Medical review. Reviewers check that the content is scientifically accurate and that each claim is supported by evidence.
- Legal review. Reviewers check for legal risk, such as misleading, unsupported or comparative claims.
- Regulatory review. Reviewers check the content against advertising rules and against the approved product labeling.
- Reconciliation. Comments from all three functions are consolidated and any conflicts are resolved. The agency makes the changes and resubmits a new, identified version.
- Approval. Each function signs off on the same, identified version, and the approval is recorded.
- Release and filing. The approved version is the one that is used. In the US, most prescription drug promotional materials are also submitted to FDA on Form FDA 2253 at first use, and the approved files and review history are archived.
Steps 5 and 6 are where most time is lost. Reconciliation repeats every time a version changes, and an approval is only meaningful if every reviewer approved the same version. The sections below cover how to avoid both problems.
Why MLR Is Harder for Agencies
Every client runs it differently. Each client has its own review platform, SOPs, reference requirements, and reviewer preferences. An agency with six pharma clients is working with six versions of MLR.
You don't control the timeline. Reviewers work to their own schedules, often across several rounds per piece, while campaign dates stay fixed.
Late feedback lands on you. A late comment means rework, a new version, and another submission, usually on a compressed timeline.
Rejections are costly. They erode margins on fixed-fee projects and, repeated often enough, the client's trust in the agency's regulatory awareness. (See how one healthcare agency handled the time pressure in Real Answers, Not a Ticket Queue.)
We've written about how version confusion drives a lot of this in The MLR Bottleneck Nobody Talks About and The MLR Delay Nobody Budgets For.
What's Changed in the US: FDA's 2026 Enforcement Focus
The US is where MLR review carries the most weight, and 2026 has made it more demanding.
The September 2025 crackdown. In September 2025, FDA and HHS announced a coordinated crackdown on direct-to-consumer (DTC) prescription drug advertising. It included over 100 cease-and-desist and warning letters, thousands of compliance letters to drug and biologic sponsors, and expanded oversight of advertising on social media platforms.
A steady pace of enforcement since. FDA's Office of Prescription Drug Promotion (OPDP) has kept issuing untitled letters through 2026 at a pace of at least two a month. The letters show recurring themes: unsupported superiority implications, overstated quality-of-life claims, and inadequate risk disclosures.
FDA is using AI to find issues. FDA has said it will keep using AI and other tech-enabled tools to monitor promotion, which means more content gets screened, faster, across every channel.
Every channel is in scope. Enforcement has covered DTC television, HCP websites, corporate webpages, influencer content, earned media, and patient testimonials, and has explicitly extended to influencers, online pharmacies, telehealth providers, and compounders. HCP emails have drawn letters too.
Broadcast ads may change next. FDA's 2026 Unified Agenda lists a proposed rule to revise 21 CFR 202.1 and eliminate the "adequate provision" option for broadcast DTC ads, with a proposal expected in December 2026. It would require the full brief summary within the broadcast ad itself, which could make many current TV formats impractical.
What this means for agencies: reviewers at client companies are under more scrutiny, so they're reviewing more conservatively. Content that would have passed with minor comments two years ago may now come back with major ones.
The US Basics Reviewers Check Against
- Consistency with the approved labeling. Promotional claims must be consistent with the FDA-approved prescribing information. Anything beyond it is a risk.
- Fair balance. Risk information must be presented with comparable prominence to benefit claims, in content and in presentation. Burying risks in small type, fast-scrolling text, or distracting visuals is a common letter theme.
- Substantiation. Claims, especially comparative or superiority claims, need adequate evidence behind them.
- Form FDA 2253. Most promotional materials must be submitted to FDA on Form 2253 at the time of first use. One recent untitled letter cited a company for failing to submit a webpage before it was published. The version submitted must match the version used.
What's Changing in the EU
If you work on EU campaigns, the EU Pharma Package will change the advertising rules once it's adopted: a broader definition of advertising that includes disease awareness campaigns, a broader definition of healthcare professionals, and stricter rules on comparative claims. We cover the details in EU Pharma Package: What Changes for Labels and Promotion.
Why Content Gets Sent Back
These are the issues that cause the most MLR rework, and most can be caught before submission:
Claims that don't trace to the source. A claim with no reference, a reference that doesn't support the exact wording, or wording that drifted from the approved source during copy edits. A qualifier dropped or a number rounded changes the claim.
Risk information that's been minimized. Reviewers look at how risk information is presented, not just whether it's there: size, placement, contrast, timing in video, and competition from other visuals.
Different versions in the same review. Reviewers comment on a version that has since changed, or approve a version that isn't the one being released. We cover this in Promotional Review Has a Version Problem Nobody Is Fixing.
Derivatives that drift from the master. A banner, email, or social cut adapted from an approved detail aid, with a claim shortened or a safety statement trimmed in the process.
Changes after approval. A "small" edit made after MLR sign-off, without going back through review.
Outdated labeling. Content based on a previous version of the prescribing information after a safety update.
Building an MLR-Ready Process
1. Start from an approved source pack. Before creative work begins, agree the approved claims, references, and current labeling with the client. Every claim in the piece should trace back to this pack, word for word where required.
2. Check claims against the source before submission. Compare the claims in the draft against the approved source and references. This is where most first-round comments can be avoided.
3. Build derivatives from the approved master. Adapt each format from the approved master, then check each one back against it, so shortened versions don't lose required wording or safety information.
4. Lock the version before submission. Every reviewer should review the same identified version, and any change should create a new version that's re-reviewed. Our Document Version Control guide covers how.
5. Compare the final file with the approved version. Before release, and before the Form 2253 submission in the US, confirm the file going live is exactly the version that was approved.
6. Keep a profile for each client. Record each client's review platform, SOPs, reference style, and reviewer preferences, so every team working on the account starts from the same expectations.
7. Work inside the client's review platform. Most pharma clients run MLR in a platform such as Veeva PromoMats. Verification that works inside it, rather than alongside it, keeps everything in one audit trail. See Content Compare in Veeva PromoMats.
A Pre-Submission Checklist for Agencies
☐ Every claim traces to the approved source pack
☐ Wording matches the source exactly where required
☐ References are current and support the exact claim
☐ Content is consistent with the current approved labeling
☐ Risk information has appropriate prominence in content and presentation
☐ Every derivative has been checked against the approved master
☐ The submitted version is clearly identified and locked
☐ The final release file matches the approved version exactly
☐ (US) The Form 2253 package matches the version being used
Frequently Asked Questions
What is MLR review?
It's the review process pharma and medical device companies use to approve promotional and scientific content. Medical, Legal, and Regulatory reviewers check content for accuracy, legal risk, and regulatory compliance before it's used.
What are the steps in the MLR review process?
Most processes run from submission through medical, legal and regulatory review, then reconciliation of comments, approval of an identified version, and release and filing. The exact steps differ by client. See the step-by-step section above.
What is the purpose of MLR review?
To make sure promotional content is accurate, balanced, supported by evidence, consistent with the approved labeling, and compliant with advertising rules, protecting both patients and the company.
What are MLR submissions?
Content packages submitted for review: the draft material, the references supporting each claim, and any supporting information the reviewers need.
What is Form FDA 2253?
The form companies use to submit promotional materials for prescription drugs and biologics to FDA at the time of first use.
Content Compare checks promotional content against its approved source and every derivative against the approved master, inside Veeva PromoMats or on its own, so agencies catch what MLR would send back before they submit. See how it works on your own content.