# CEP or ASMF? How API documentation works in EU generic dossiers

Source: https://gfclinics.pl/insights/cep-vs-asmf-api-documentation/
Updated: 2026-10-17

A CEP is an EDQM certificate confirming that the Ph. Eur. monograph controls one manufacturer's substance. An ASMF is a confidential file the authority assesses with each application. Both support Module 3. Neither replaces the buyer's own checks on GMP, impurities and import papers.

Every active pharmaceutical ingredient (API) in an EU generic medicine must be documented in the quality part of the marketing authorisation dossier. API manufacturers often treat their process details as confidential. The EU offers two routes that document the substance without disclosing those details to every customer: the Certificate of Suitability (CEP), issued by the EDQM, and the Active Substance Master File (ASMF), assessed by the authority with each application.

## What is a CEP?

A CEP is a Certificate of Suitability to the monographs of the European Pharmacopoeia (Ph. Eur.). It is issued by the European Directorate for the Quality of Medicines & HealthCare (EDQM), part of the Council of Europe. It confirms that the Ph. Eur. monograph, together with any additional tests stated on the certificate, can suitably control a substance made by a named manufacturer.

Key points:

- **Scope.** The procedure covers substances with a Ph. Eur. general or individual monograph. It does not apply to most biological substances.
- **Not a GMP certificate.** The EDQM assesses a dossier. The manufacturer commits to GMP, and the EDQM may inspect on a risk basis. A CEP can be granted with or without an inspection.
- **CEP 2.0.** Certificates granted since 1 September 2023 are electronic. The approved specification and production sites are part of the certificate. Access is granted through a separate letter of access.
- **Renewal.** A CEP is renewed once, five years after first issue. CEP 2.0 documents carry no expiry date. The renewal due date is shown in the EDQM Certification database.

## What is an ASMF?

An ASMF is a dossier on the active substance that the holder, normally the manufacturer, submits directly to the competent authority. It can only be submitted in support of a marketing authorisation application (MAA) or a variation. It is not a stand-alone approval. The authority assesses it together with each application that refers to it.

### What goes in the Applicant's Part and the Restricted Part?

- **Applicant's Part (AP):** the information the applicant needs to take responsibility for the substance and its specification. The applicant receives it, but may not pass it to third parties without the holder's consent.
- **Restricted Part (RP):** detailed manufacturing steps, reaction conditions and process controls. Only the authority sees it.

### What is a letter of access?

The letter of access is the holder's written permission for the authority to assess the ASMF for a named product. The holder sends it, with the full ASMF, to every authority involved. The submission must arrive no more than one month before the application, and not after it. The applicant receives the AP, its summary and a copy of the letter.

## How do a CEP and an ASMF compare?

| | CEP | ASMF |
|---|---|---|
| Assessed by | EDQM, centrally | National authority or EMA, within each application |
| Precondition | Ph. Eur. monograph exists | None; also for non-pharmacopoeial substances |
| Holder | Manufacturer (CEP holder) | Manufacturer (ASMF holder) |
| Applicant receives | Copy of current CEP and letter of access | Applicant's Part, summary, letter of access |
| Where in the dossier | CEP copy in 3.2.R; applicant's own data in 3.2.S | AP copy in 3.2.S; Restricted Part to authority only |
| Status check | Public EDQM Certification database | Through the holder and the authority |
| Changes | CEP revision by EDQM; holder informs customers | Holder informs each customer and authority |

## How is each referenced in Module 3?

**With a CEP**, the applicant places a copy of the latest CEP and the letter of access in section 3.2.R. The applicant still writes its own 3.2.S sections:

- S.2.1: every site actually used, including testing sites.
- S.4.1: a specification that includes all monograph tests, all extra tests on the CEP, and product-specific attributes such as particle size or polymorphic form.
- S.4.4: batch results from the finished-product manufacturer.
- S.6 and S.7: container closure and stability data where the CEP does not cover them.

Where a section adds nothing to the CEP, the applicant says so and cites the CEP number and revision.

**With an ASMF**, the applicant includes a copy of the current AP in 3.2.S. It also provides its own specification, batch analyses, justification of specification and reference standards. The AP version in the dossier must match the one the holder filed.

## How are changes handled?

A revised CEP supersedes the previous one. The CEP holder must inform its customers of every change, whether or not the CEP is revised. Each marketing authorisation holder then assesses the impact and files a variation where needed. A suspended or withdrawn CEP triggers an impact assessment and, where quality is affected, the national quality-defect procedure.

An ASMF holder may not change the file without informing each applicant and each authority. Every marketing authorisation holder reports the change through its own variation.

Since 15 January 2026, new Commission guidelines on variation categories apply. They complement the revised Variations Regulation, applicable since 1 January 2025.

## When do both apply?

Normally an applicant refers to either a CEP or an ASMF for one substance in one application, not both. The ASMF guideline allows an exception. Where a CEP lacks information, for example stability data, the authority may accept a reference to both. A second case is an intermediate that is itself covered by a CEP. That CEP then goes into the Applicant's Part of the ASMF.

## What should the buyer verify?

A CEP or an ASMF answers the dossier question. It does not answer every supply question. Before approving a source, procurement and QA usually check:

1. **CEP status.** Search the EDQM Certification database for validity, suspension, withdrawal and the renewal due date.
2. **GMP evidence.** Look for an EU GMP certificate or inspection record in EudraGMDP. EU manufacturing authorisation holders must also audit API manufacturers and distributors (Directive 2001/83/EC, Article 46(f)).
3. **Written Confirmation.** APIs imported from third countries not listed under Article 111b, India among them, need a written confirmation from the exporting authority (Article 46b(2)(b)). Check that it covers the site and the substance.
4. **Nitrosamine risk assessment.** EMA expects applicants to obtain information on impurities with vulnerable amines from the CEP holder, even below identification thresholds.
5. **Elemental impurities and solvents.** Ask for an ICH Q3D risk assessment. Check whether solvent limits on the CEP were set under ICH Q3C option 2, which may need recalculation for your product.
6. **Change notification.** Make sure the quality agreement obliges the holder to report changes promptly.

## How Green Future Clinics uses this

When we qualify an Indian API source, we ask the manufacturer for the CEP or the ASMF details first. We check the CEP status in the EDQM database and look for the site in EudraGMDP. We then request the written confirmation, the nitrosamine risk assessment and the ICH Q3D statement. We compare what we receive against the list above and report gaps to the customer before any quote. The customer's own assessment and the qualified person's decision remain with the customer.

## Sources

- EMA – QWP Q&A: how to use a CEP in a marketing authorisation application or variation (EMA/CHMP/CVMP/QWP/5/2024 Rev.1, 28 January 2026): https://www.ema.europa.eu/system/files/documents/scientific-guideline/questions-answers-how-use-cep-context-marketing-authorisation-application-en.pdf
- EMA – Guideline on Active Substance Master File Procedure (CHMP/QWP/227/02 Rev 4/Corr): https://www.ema.europa.eu/en/documents/report/final-guideline-active-substance-master-file-procedure-revision-4_en.pdf
- EDQM FAQ – Is a certificate of suitability equivalent to a GMP certificate?: https://faq.edqm.eu/pages/viewpage.action?pageId=1377020
- EDQM FAQ – Differences between old CEP, hybrid CEP and CEP 2.0: https://faq.edqm.eu/pages/viewpage.action?pageId=74416142
- EDQM FAQ – Will CEPs 2.0 be renewed?: https://faq.edqm.eu/pages/viewpage.action?pageId=74416158
- EDQM – Certification database (Certificates catalogue): https://extranet.edqm.eu/publications/recherches_CEP.shtml
- EudraGMDP – public database of manufacturing authorisations and GMP certificates: https://eudragmdp.ema.europa.eu/inspections/displayWelcome.do
- Directive 2001/83/EC, consolidated text of 1 January 2025 (Articles 46 and 46b): https://publications.europa.eu/resource/celex/02001L0083-20250101
- EMA – Nitrosamine impurities: https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/referral-procedures-human-medicines/nitrosamine-impurities
- EMA – ICH Q3D Elemental impurities (R2): https://www.ema.europa.eu/en/ich-q3d-elemental-impurities-scientific-guideline
- EMA – Guidance on the application of the revised variations framework: https://www.ema.europa.eu/en/guidance-application-revised-variations-framework