DMF, ASMF and CEP for API Buyers: Differences and Review

Direct answer

DMF, ASMF and CEP are not interchangeable approvals. A U.S. DMF is a confidential submission to FDA that an applicant may reference through a Letter of Authorization; FDA does not approve or disapprove the DMF itself. An EU ASMF separates an Applicant’s Part from a Restricted Part and is assessed within a marketing-authorisation procedure. A CEP is issued by EDQM after assessing whether the relevant European Pharmacopoeia monograph, together with any stated additional controls, is suitable for controlling the substance. The appropriate route depends on the target market, substance and regulatory strategy.

Overview of DMF, ASMF, and CEP

DMF and ASMF are regulatory file mechanisms used to provide confidential active-substance information to competent authorities, while a CEP is a certificate issued by EDQM following assessment of a CEP dossier. All three can support active-substance documentation, but they differ in regulatory authority, submission procedure, scope and the information that buyers can independently verify.

• DMF (Drug Master File): Primarily used in the United States and some other regions, DMFs are submitted to the FDA or equivalent authorities to support drug product applications without disclosing proprietary manufacturing details to the applicant.
• ASMF (Active Substance Master File): Commonly used in the European Union, ASMFs provide detailed information on the active substance to support marketing authorization applications while protecting confidential information.
• CEP (Certificate of Suitability): Issued by the European Directorate for the Quality of Medicines (EDQM), a CEP confirms that the relevant European Pharmacopoeia monograph, together with any additional controls stated on the certificate, is suitable for controlling the quality of the substance.

Key Differences and Buyer Considerations

Document	Regulatory route / authority	Typical use	What buyers can verify	What it does not prove
DMF	Confidential submission to FDA	Supports applications referencing the DMF in the US	DMF number, holder, subject, type, public status and Letter of Authorization	FDA approval, GMP compliance or batch quality
ASMF	Submitted to an EU competent authority or EMA within a marketing-authorisation procedure	Provides active-substance information while protecting the holder’s confidential know-how	ASMF reference, current Applicant’s Part, version and Letter of Access	Standalone approval, GMP status or batch conformity
CEP	Certificate issued by EDQM following assessment of a CEP dossier	Demonstrates that the Ph. Eur. monograph, with stated additional controls where applicable, is suitable for controlling the substance	CEP number, holder, substance, issue date, validity and regulatory actions	Batch quality, COA equivalence, GMP certification or marketing authorisation

Which Regulatory Route Applies to an API Submission?

For a US application, an applicant may reference an applicable DMF after obtaining a Letter of Authorization from the DMF holder. For an EU marketing-authorisation application, active-substance information may be provided through an ASMF, a CEP where the certification procedure is applicable, or complete active-substance information included directly in the application dossier. These routes are not automatically interchangeable, and the appropriate option should be confirmed with the applicant’s regulatory team and the relevant authority.

How Buyers Can Verify DMF, ASMF and CEP Status

Regulatory documentation should be verified against the relevant authority record and the current documents supplied by the holder. A DMF number, ASMF reference or CEP number should not be treated as sufficient evidence by itself. Buyers should confirm that the document applies to the correct active substance, holder, manufacturing route and intended market.

Verifying a US Drug Master File

For a US DMF, search the official FDA Drug Master File list using the DMF number, holder name or subject. Confirm the following information:

• DMF number and type
• Holder name
• Subject or covered substance
• Active or inactive status
• Consistency between the public record and the supplier’s declaration

For an API, the relevant filing is commonly a Type II DMF. An “active” listing means that the file remains administratively active; it does not by itself confirm that the DMF has been scientifically reviewed or found adequate for a particular application.

The buyer should also request a current Letter of Authorization issued to the relevant applicant. The DMF holder must authorize FDA to reference the file in connection with a specific application. The authorization should identify the DMF number, holder, authorized party and covered product or information.

FDA publishes a DMF list containing the file number, type, holder, subject and active/inactive status. FDA also explains that a Letter of Authorization is required before the file can be referenced for an application. FDA DMF public list, FDA DMF guidance.

Verifying an Active Substance Master File

ASMF verification is based mainly on controlled document review and communication between the ASMF holder, applicant and competent authority. Unlike a CEP, an ASMF does not have an equivalent public certificate database that allows a buyer to confirm its complete status through a simple public search.

Buyers should request and compare:

• The EMEA/EU or national ASMF reference number
• The active substance and ASMF holder
• The current version and submission date
• The Applicant’s Part, also called the Open Part
• Confirmation that the Restricted Part has been submitted to the relevant authority
• A valid Letter of Access naming the applicable applicant
• A summary of changes between the current and previous versions

The reference number, holder, substance and version information should be consistent across the Applicant’s Part, Letter of Access and regulatory application. The existence of an ASMF reference does not alone prove acceptance for every product, applicant or jurisdiction.

EMA describes the ASMF as comprising an Applicant’s Part and a Restricted Part and requires the relevant reference number and Letter of Access in the regulatory procedure. EMA ASMF guidance.

Verifying a Certificate of Suitability

For a CEP, search the official EDQM Certification Database using the complete CEP number, substance name or holder. Confirm:

• Full CEP number
• Substance and certificate type
• Holder name
• Issue date
• Current validity status
• Any suspension, withdrawal, cancellation or restoration action
• Whether the certificate supplied by the seller matches the database record

A partial CEP number or an undated certificate copy is not sufficient for verification. Buyers should confirm the complete number and current status directly in the EDQM database and review EDQM’s published actions on CEPs.

EDQM states that its database provides the substance, full CEP number, issue date and validity status and is updated daily. It also publishes suspension, withdrawal and restoration actions. EDQM actions on CEPs.

What These Records Do Not Replace

DMF, ASMF and CEP verification supports regulatory-document assessment, but none of these records replaces product- and batch-specific quality review. Buyers should separately review:

• Current product specification
• Batch-specific Certificate of Analysis
• HPLC and identity-testing results
• Impurity and microbiological data where applicable
• Manufacturing-site and GMP evidence
• Change-control information
• Supplier qualification and quality agreement
• Storage, packaging and shipment requirements

Regulatory references and batch documentation should be reviewed together before a material is approved for procurement or regulatory use.

Frequently Asked Questions

What is the difference between ASMF and DMF?

A Drug Master File (DMF) is submitted to the US FDA, while an Active Substance Master File (ASMF) is used in European regulatory procedures. Both allow confidential manufacturing and quality information to be reviewed by an authority without disclosing the complete file to the applicant. However, they follow different regulatory systems, submission structures and access procedures. A US DMF generally requires a Letter of Authorization, while an ASMF uses an Applicant’s Part, a Restricted Part and a Letter of Access.

What is the difference between ASMF and CEP?

An ASMF contains detailed information about the manufacture and quality control of a specific active substance. It consists of an Applicant’s Part and a confidential Restricted Part submitted to the competent authority. A CEP is issued by EDQM and confirms that the controls described in the certificate are suitable for addressing the requirements of a relevant European Pharmacopoeia monograph. A CEP has a publicly verifiable certificate status, while an ASMF does not have an equivalent public certificate database.

Can a CEP replace an ASMF?

A valid CEP may be accepted as an alternative way of documenting certain active-substance information covered by the certificate. However, it does not automatically replace every part of an ASMF or all information required in a marketing-authorisation dossier. The applicant may still need to provide information not covered by the CEP, such as stability data, particle-size controls, polymorphism, sterilisation details or additional impurity controls. The applicable requirements depend on the substance, manufacturing process, dosage form and regulatory procedure. EMA active-substance requirements.

Does an active DMF mean FDA approval?

No. An active status generally indicates that the DMF is administratively active. It does not mean that FDA has approved the DMF, the holder, the manufacturing facility or a product associated with the file. FDA states that DMFs are neither approved nor disapproved. Their technical content is reviewed when an authorised applicant references the file in support of an applicable regulatory submission. Buyers should therefore verify the status, holder, subject, DMF type and Letter of Authorization separately. FDA DMF guidance.

Does a CEP replace a COA or GMP certificate?

No. A CEP does not replace a batch-specific Certificate of Analysis or evidence of GMP compliance. The CEP addresses the suitability of the controls described in the certificate in relation to the applicable European Pharmacopoeia monograph. A COA reports results for a specific supplied batch, while GMP evidence relates to the manufacturing site and quality system. Buyers should review the current CEP together with the product specification, batch COA, analytical results and applicable GMP documentation.

Which documents should an API buyer request from the holder?

The required documents depend on the product, market and intended regulatory use. Buyers should normally request the current product specification, batch-specific COA, identity and purity results, applicable impurity data, storage conditions, packaging information and available safety documentation. When regulatory files are relevant, buyers should also request the correct DMF or ASMF reference, Letter of Authorization or Letter of Access, or the complete current CEP number. Manufacturing-site information, GMP evidence and change-control information should be reviewed separately.

Is it necessary to have all three documents for one API?

Not necessarily; the required document depends on the target market and regulatory framework.

Where can buyers find more guidance on API documentation review?

Related insights such as the documents to request before API supplier qualification and checklist for reviewing peptide API documentation provide practical guidance.

Buyers should review regulatory references together with product specifications,  batch-specific COA, HPLC results and other applicable quality documents.

 Learn more about our quality documentation

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