1. General context
At the end of February, COFEPRIS released the new version of the Guide for structuring the dossier in accordance with the Common Technical Document (CTD), which is part of a stricter adoption of this document, aligned with the ICH M4 guideline and new national provisions such as:
- Simplification of Procedures Agreement (Official Gazette, August 22, 2025)
- Agreement for the Abbreviated Regulatory Pathway (Official Gazette, July 18, 2025)
- New COFEPRIS guidelines for Modules 2, 3, 4, and 5
The main objective is to standardize submissions, incorporate updates stemming from simplification agreements and the abbreviated regulatory pathway, as well as migrate a large portion of the information to declarations and reference numbers, thereby reducing the physical documentary burden.
One of the most significant changes is the elimination of documents issued by COFEPRIS from application files. That is, simple copies of most administrative documents are no longer required; instead, only the following are requested:
- Reference number / official letter number
- Declaration in the cover letter or corresponding format
- Checklist registration
This includes licenses, notices, GMP certificates (CBPF), certificates, prior official letters, cancellations, extensions, etc.
2. Main changes in the Guide for structuring the dossier in accordance with the Common Technical Document (CTD) for the submission of sanitary registration applications and modifications to registration conditions for medicines and biological products V.3.0 vs. V.2.0
The most relevant changes in version 3.0 of the aforementioned guide are outlined below:
2.1 Structural changes
The CTD Guide now focuses exclusively on Module 1; sections corresponding to Modules 2 through 5 have been eliminated.
These have been replaced by new specific guides published by COFEPRIS:
- CTD Organization Guide
- Quality Guide (Modules 2–3)
- Safety Guide (Modules 2–4)
- Efficacy Guide (Modules 2–5)
2.2 Cover letters
Complete replacement of the previous annexes:
- For Sanitary Registration (SR) applications → now Annex 3
- For applications for Modifications to Registration Conditions (MRC) → now Annex 4
These formats include greater detail and mandatory fields.
2.3 Sanitary Registration (SR) history
- Reference to ICH Q12 (lifecycle management)
- Only the official letter number is declared; no copy is attached
- Converted into Annex 5
2.4 International regulatory status
- Must be declared in tabular format
- Minimum required fields are included
- Important update: adoption of RRAs (Reference Regulatory Authorities)
2.5 Accreditation of legal standing
If the accreditation document was previously submitted via a free-format submission (EL), this requirement is simplified by declaring only:
- Official response letter number or EL submission number
- Registration notice number for the legal representative
2.6 Registration official letters and certificates
Only the reference number will be declared in the cover letter or corresponding annexes.
IMPORTANT: This will be a critical step when assembling the dossier, as an incorrect declaration of any number will result in lack of traceability during assessment and may lead to a request for additional information by the authority.
2.7 “Abbreviated Regulatory Pathway” Agreement
This completely replaces the previous section on equivalency agreements, aligning requirements and information with the Agreement for the application of the Abbreviated Regulatory Pathway published on July 18, 2025.
Another notable update is that, through this pathway, Module 3 will accept the inclusion of the Certificate of Suitability (CEP) issued by the EDQM for chemically synthesized medicines.
2.8 Interchangeability (generic medicines)
- The following documents are no longer required:
- Agreement to determine the type of test
- Reference product webpage
- Protocol authorized by COFEPRIS
- This information will only be declared in the checklist.
3. Main changes in the ANNEXES
- Format for the sanitary registration application dossier and its modifications for medicines and biological products, in accordance with the Common Technical Document (CTD)
Change: Existing document updated to reflect the legal basis for each requirement, incorporating simplification agreements. - ANNEX 2. Checklist for submission of information for the sanitary registration application of medicines and biological products
Change: Inclusion of requirements for submission via the Abbreviated Regulatory Pathway, as well as fields for:- Sanitary Registration history
- Official letters/certificates (number only)
- Marketing Authorization Holder and supply chain
- Previously required documents → no longer physically attached
- ANNEX 3. Cover letter for the Sanitary Registration (SR) application
Change: Previously Annex I. Tables added to declare information on:- Marketing Authorization Holder
- Product characteristics
- Supply chain
- Documents with COFEPRIS reference numbers
- ANNEX 4. Cover letter for the MRC application
Change: Previously Annex II. A table is added to integrate information on:- Marketing Authorization Holder (national or foreign)
- Supply chain
- New Molecules Committee
- Sanitary Registration history
- ANNEX 5. SR history
Change: Previously Annex III. Format change only. - ANNEX 6. Change control formats for labeling, package insert, and prescribing information in full and reduced versions
Change: New format.
4. General conclusions
a) COFEPRIS eliminates physical annexes
Most of the administrative dossier becomes declarative, based solely on reference numbers and links.
b) Restructuring of Module 1
Far more detailed and significantly stricter.
c) Official introduction of CEP usage
Specifically for applications submitted through the Abbreviated Regulatory Pathway.
d) Alignment with new 2025 guidelines and agreements
Establishes a new regulatory basis for all submissions.
e) New guides for Modules 2, 3, 4, and 5
Clear instructions and requirements for the structure of these modules.
Contact our regulatory experts to assess the impact of CTD Guide Version 3.0 on your submissions and ensure full compliance with COFEPRIS requirements.