New Drug Marketing Authorization Compared: FDA, Health Canada, MHRA and EMA

New-drug marketing authorisation compared: FDA, Health Canada, MHRA and EMA

All four regulators take the same basic approach to a new active substance. The sponsor files a full quality, nonclinical and clinical dossier in the ICH Common Technical Document (CTD) format, and each agency offers expedited or conditional routes for serious conditions with unmet need. The differences that matter for global filing strategy are the legal pathway structure, how the review clock is counted, the target durations, and the expedited tools each agency provides.

At a glance

Pathway architecture

FDA

In the US the pathway depends on how the application is supported rather than on who reviews it. A 505(b)(1) NDA contains full reports of safety and effectiveness investigations conducted by or for the applicant, or for which the applicant has a right of reference ⁵². A 505(b)(2) NDA relies at least in part on studies the applicant did not conduct and has no right of reference to, such as published literature or FDA's prior findings for a listed drug. It requires a scientific bridge to that listed drug ⁴⁷⁴³. Biologics are licensed through a BLA under section 351 of the PHS Act, which requires full reports showing the product is safe, pure and potent ⁴². A 351(a) BLA cannot rely on FDA's prior findings for another licensed biologic. The abbreviated route for biologics is 351(k) ⁴⁸⁵⁵.

Health Canada

A new drug is filed as an NDS. Supplements are filed as SNDS, and generics as ANDS referencing a Canadian Reference Product ^9377102. Health Canada may use foreign reviews and decisions as inputs, from critical assessment of the foreign review to using it as a reference alongside a Canadian assessment. A full Canadian data package is still required, and the Canadian benefit-risk decision remains Health Canada's own ^384385389. A 2026 draft guidance on a Ministerial Reliance Order describes a route where, for specified drug classes and listed foreign authorities, certain examination requirements can be deemed met on the basis of foreign decisions. The sponsor must file a complete Canadian submission, and Canadian-specific matters such as labelling and risk management plans are still examined ³⁹⁵⁴⁰³.

MHRA

Since leaving the EU framework, the UK runs its own national procedure for innovative medicines. It uses fixed monthly submission and assessment timetables built around consultation with the Commission on Human Medicines (CHM) ¹²⁵. Alongside it, the International Recognition Procedure (IRP) lets applicants use approvals from reference regulators in Australia, Canada, the EU, Japan, Switzerland, Singapore and the United States. The IRP started alongside the national procedures on 1 January 2024 ³⁴⁵. IRP applications must concern the same product as the reference regulator approved, and must include all iterations of that regulator's assessment reports ²²⁴²²⁵. UK paediatric requirements still apply under every route, including the IRP ²²⁸. The IRP has its own requirements and timelines, separate from national assessment ²²⁹. Recognition B submission dates line up with CHM dates for new active substances ³⁴⁷. Recognition A is a 60-day timetable with no clock-stop. Recognition B is a 110-day timetable with a clock-stop at day 70; the applicant generally has up to 60 days to respond.

EU

A product listed in the Annex to Regulation 726/2004 cannot be placed on the EU market without a Union authorisation granted through the centralised procedure ³⁶³. Products outside the Annex can opt in if they contain an active substance not authorised in the Union on 20 May 2004. They can also opt in if the applicant shows significant therapeutic, scientific or technical innovation, or that Union authorisation is in the interest of patients' health at Union level ³⁶³. Other products go through national procedures or two multi-state routes under Directive 2001/83/EC:

• Mutual recognition (MRP), for products already authorised in a Member State. The reference Member State has 90 days to prepare or update its assessment report, and concerned Member States then have 90 days to approve ²²¹.
• Decentralised procedure (DCP), for products not yet authorised anywhere. The reference Member State has 120 days to prepare draft documents, followed by 90 days for concerned Member States ²²¹.

In both cases, national decisions follow within 30 days of agreement ²²¹.

Data requirements

Common structure

All four agencies use the five-module CTD. Module 1 is regional and administrative. Modules 2 to 5 hold the summaries, quality data, nonclinical reports and clinical study reports, and are meant to be common across regions ^26426562125. The EU's Annex I applies the CTD to all application types, full or abridged, under any procedure ². Region-specific content goes in Module 1. Canada, for example, requires Health Canada summaries, an environmental assessment statement and electronic review documents there, and puts a product's status in other jurisdictions in Module 1.2.7 ⁶²⁵.

Evidentiary standard for effectiveness

• FDA: The statute requires "substantial evidence of effectiveness" from adequate and well-controlled investigations ³⁰⁶. FDA has generally read this as two independently convincing trials. It may accept one adequate and well-controlled trial plus confirmatory evidence, decided case by case based on the persuasiveness of the trial, the strength of the confirmatory evidence, and the disease context ²⁹⁵²⁹². Substantial evidence is necessary but not sufficient for approval: FDA must also find the drug safe and its benefits greater than its risks ³⁰⁶. A June 2026 draft guidance consolidates these approaches ³⁰⁰.
• Health Canada: Under the Priority Review policy, substantial evidence of clinical effectiveness usually means at least two adequate, well-controlled studies. One large study, or one pivotal study plus additional clinical evidence, may be considered in some cases ⁶⁷.
• EU: Article 8(3) of Directive 2001/83/EC requires results of pharmaceutical, pre-clinical and clinical trials with detailed summaries ²²². It also requires a pharmacovigilance system summary, a risk management plan, a statement that non-EU trials met EU ethical requirements, and copies of other marketing authorisations and any refusals ²²²³⁸². The active-substance manufacturer must also have been audited for GMP compliance, with written confirmation ²²².
• MHRA: MHRA refuses applications at technical-completeness stage if the data required by HMR 2012 regulations 49 to 55 and Schedule 8 are missing ¹²⁵. Every MAA must include a risk management plan. The finished-product manufacturer must hold a valid manufacturing authorisation and GMP certificate before grant ¹¹⁵.

Abridged routes and regulatory protection

Each system separates full-dossier applications from reliance-based ones:

• FDA: 505(b)(2) and ANDA routes for drugs, and 351(k) for biosimilars ⁴⁷⁵⁵. New chemical entities receive 5 years of exclusivity. Certain NDA approvals can receive 3 years, and orphan-designated indications 7 years ³⁷⁸³⁷⁹.
• Health Canada: An innovative drug receives 8 years of data protection from its first NOC. This includes a 6-year no-file period for comparative submissions, and can be extended by 6 months for qualifying paediatric studies ³⁶⁵³⁶⁶.
• EU: Generic, hybrid and similar-biological routes exist under Article 10 ¹. Centrally authorised products get 8 years of data exclusivity and 10 years of market protection. Market protection extends to 11 years if a new indication with significant clinical benefit is approved within the first 8 years ²⁰³¹.
• UK: Generic (reg. 51B), biosimilar (reg. 53B) and well-established-use (reg. 54) bases are available alongside the full-dossier reg. 50(5) route ¹¹⁹¹²⁹.

Review timelines

Headline numbers are not directly comparable, because each agency starts and stops its clock differently.

• FDA: Under PDUFA the goal is to review and act on 90% of standard NME NDAs and original BLAs within 10 months of the 60-day filing date, and priority ones within 6 months of it ²³⁶. For non-NME NDAs the clock runs from receipt ²³⁶. "Act" means an approval letter or a complete response letter; meeting the goal does not mean approval ²³⁶. Priority designation is decided within 60 days of receipt and assigned at filing ²³⁴.
• Health Canada: The standard NDS target is 10 days processing, 45 days screening and 300 days review ⁹³. Priority Review cuts these to 25 days screening and 180 days review, for a 215-day total. Responses to a priority Notice of Non-compliance have a 125-day target ⁶⁰. All targets are in calendar days ⁶⁰.
• MHRA: For innovative medicines, MHRA completes its initial assessment by Day 90 and then issues a consolidated request for information (RFI), which stops the clock. Applicants normally have up to 6 months to respond ¹²⁵. MHRA assesses the response by Day 150. If all issues are resolved, a positive decision is possible within 150 clock-on days. Otherwise MHRA aims for a final decision within 210 clock-on days ¹²⁵²²⁹. Timetables are in calendar days excluding clock-stops ²²⁹. MHRA refuses an MA only after final CHM advice, unless the applicant has failed to respond to an RFI in time ¹²⁵.
• EU: The CHMP must give its opinion within 210 days of a valid application. Scientific analysis normally takes at least 80 days ²⁰². The Commission then prepares a draft decision within 15 days of the opinion and adopts the final decision within 15 days of the Standing Committee's opinion ²⁵⁷.

Expedited and conditional mechanisms

Development-stage designations

FDA's fast track requires data showing potential to address an unmet need in a serious condition. Breakthrough therapy requires preliminary clinical evidence of substantial improvement over available therapy. Both include rolling review, and FDA generally responds to designation requests within 60 days ³¹⁸²³⁴. EMA's PRIME is a voluntary scheme based on early clinical data showing potential benefit in unmet need. It provides an early CHMP or CAT rapporteur, a kick-off meeting and scientific advice at key milestones ²⁰⁴. The UK's ILAP is open to developers of potentially transformative medicines that have evidence of safe use in humans but have not yet started confirmatory trials. It brings in MHRA, HTA bodies and the NHS ¹⁶⁸¹⁶⁷. MHRA's rolling review assesses dossier modules iteratively. Each module is assessed within 60 days of validation, and the final phase is structured as 100 days (60 + 40 days) ¹⁸¹²⁸⁸.

Shortened standard review

Examples are FDA priority review (6 months versus 10) ²³⁴, Health Canada Priority Review (180 days versus 300) ⁶⁰ and EU accelerated assessment (150 days versus 210) ²⁰³. Their criteria are similar but not the same:

• FDA: A significant improvement in safety or effectiveness for a serious condition ³¹⁸.
• Health Canada: A serious, life-threatening or severely debilitating condition, plus either no drug therapy marketed in Canada or a clinically relevant improvement in benefit-risk over marketed therapies ⁶⁰⁶². The request, with a Clinical Assessment Package, must be filed before the submission. Health Canada decides within 30 days, and the NDS must then be filed within 60 days ⁶⁶⁷³.
• EU: Major public-health interest, particularly therapeutic innovation ²⁰³.

Approval on less-than-complete evidence

• FDA accelerated approval: Based on a surrogate or intermediate clinical endpoint reasonably likely to predict clinical benefit. Confirmatory trials are required, and the approval can be withdrawn on an expedited basis ³¹⁸.
• Health Canada NOC/c: Based on promising evidence of clinical effectiveness for serious conditions, and applies to the specific indication ¹⁴⁴¹⁵¹. Before authorisation the sponsor signs a Letter of Undertaking committing to confirmatory trials, enhanced surveillance and advertising disclosures ^142146155. The advance-consideration pathway has a 200-day review target. After an NOC/c Qualifying Notice, the sponsor has 30 days to respond and Health Canada has 30 days to finalise the conditions ⁹⁸. SNDS-C filings with confirmatory results get no reduced review target ¹⁴³.
• EU conditional MA (Article 14a): For seriously debilitating or life-threatening diseases where immediate availability outweighs the risk of outstanding data. It carries specific obligations reviewed annually, and is valid for one year and renewable. It can convert to a standard five-year authorisation once the obligations are fulfilled ²⁵⁵.
• UK conditional MA: Mirrors the EU concept. It requires unmet medical need, a positive benefit-risk balance and a one-year renewable validity, and can convert to a standard MA once obligations are met ¹⁷¹¹⁷³.
• Exceptional circumstances (EU and UK): For cases where comprehensive data cannot be provided, for example because the condition is rare. The EU route requires objective, verifiable reasons and annual reassessment ²⁰³. In the UK this route normally does not lead to a standard MA, and applicants must discuss it with MHRA before applying ¹⁷¹¹⁷⁶.

Practical implications for global filing strategy

• One core dossier, four Module 1s. CTD Modules 2 to 5 carry over across all four agencies. Regional effort goes into Module 1, labelling, and region-specific items such as UK paediatric documentation and Canadian environmental assessment statements ^2646228.
• Normalise the clocks before comparing. FDA's clock for NMEs starts after a 60-day filing period ²³⁶. Health Canada adds a screening phase before review ⁹³. MHRA and the EU count days of active assessment, and elapsed time also depends on how quickly the sponsor answers RFIs ¹²⁵²⁰².
• Sequencing can be used deliberately. An FDA or EU approval can later support filings through MHRA's IRP ³⁴⁵ and Health Canada's use of foreign reviews ³⁸⁵³⁹⁰. Health Canada notes that foreign reviews may sometimes allow a faster-than-typical review, but Canadian standards still apply ³⁹⁰.
• Line up expedited requests early. Health Canada requires the priority request before filing ⁶⁶. FDA designations are requested during development ²³⁴. PRIME and ILAP are entered before confirmatory trials ²⁰⁴¹⁶⁸.

The Annex to Regulation 726/2004 makes the centralised procedure mandatory for specified classes, including certain biotechnology products, orphan medicines and advanced-therapy products.