CEP, DMF or Written Confirmation: Which One You Need
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Ask an API supplier for "the DMF" and you may get back a certificate, a letter, or a polite question about which market you mean. All three are reasonable responses, because a CEP, a US Drug Master File and an EU written confirmation are not three versions of the same document. They are three different instruments, issued by three different bodies, doing three different jobs.
The practical consequence is the part most buyers miss. Once a product is destined for more than one market, satisfying one of them does not reduce the requirement for the others. A supplier bound for the United States and the European Union from a site in China needs both a Type II DMF for the US and either a CEP or an ASMF for the EU, plus the written confirmation for the EU import. Three filings, one product.
What each document is for
| Document | Issued by | What it does | What unlocks it |
|---|---|---|---|
| CEP | EDQM | Confirms the substance made at a named site is suitably controlled by the European Pharmacopoeia monograph | A pharmacopoeial monograph must exist for the substance |
| US DMF (Type II) | Filed with the FDA by the holder | Holds confidential manufacturing detail that the FDA reviews only when a finished-product application refers to it | Fee paid, completeness check passed, and a letter of authorization issued |
| ASMF | Submitted with the applicant's dossier | The European route when no CEP is available; split into an applicant's part and a restricted part | An EU registration the applicant controls |
| Written confirmation | Competent authority of the exporting country | Attests that the site is supervised and operates to GMP equivalent to EU requirements | Destination is the EU and the exporting country is not on the equivalence list |
The CEP, and the constraint people forget
The Certificate of Suitability is issued by the EDQM, part of the Council of Europe. It certifies that a substance produced at a specific site complies with the European Pharmacopoeia monograph, together with any additional tests needed for that maker's specific impurity profile. It is assessed once, centrally, and regulators can rely on that assessment instead of reviewing the API data themselves.
Three details matter more than the headline.
No monograph, no CEP. If the substance is not described in the European Pharmacopoeia, this route does not exist and a master file is the only option. Ursodeoxycholic acid has a monograph, so the route is open. Tauroursodeoxycholic acid does not, which changes the conversation entirely — we cover that separately in the note on writing a specification where no monograph exists.
The holder is the site, not the seller. A CEP is issued against a specific manufacturing site and is not transferable to a distributor's name. If you buy through an intermediary, the certificate still names the site, and the question to ask is whether the intermediary can demonstrate a continuing supply relationship with that site rather than a one-off purchase.
The certificate alone is not the whole document. Since the CEP 2.0 format came in during 2023, certificates are electronically signed, the holder's own specification is attached, and the letter of access is issued as a separate document. If you receive only the certificate, ask for the letter as well.
Worth knowing also that a CEP travels beyond Europe. Regulators in a number of countries outside the EU accept an EDQM assessment, which is why a supplier holding one often leads with it.
The US DMF, and the two questions that follow the claim
The FDA's own position is the thing to hold on to here: a Drug Master File is never approved or disapproved. The holder files it; the FDA reviews it only when a finished-product application refers to it. For an API, the relevant type is Type II.
So "we have a US DMF" is a statement with very little content on its own. Two follow-up questions turn it into something meaningful:
- Is it on the available-for-reference list? A DMF appears there only after the fee has been paid and the completeness check has passed.
- Will the holder issue a letter of authorization? Without it, the FDA will not look at the file on your behalf, and the DMF may as well not exist for your registration.
There is also a maintenance question. Holders are expected to file an annual report and to notify customers of changes. A dormant DMF that nobody has updated for several years creates its own risk in an inspection or a variation.
Written confirmation, and where it comes from
This one has nothing to do with the quality of the material and everything to do with the origin of the shipment. Under Article 46b of Directive 2001/83/EC, as amended by the Falsified Medicines Directive 2011/62/EU, active substances imported into the EU must be accompanied by a written confirmation from the competent authority of the exporting country. The requirement has applied since 2 July 2013. It only falls away where the exporting country is on the EU's list of countries with equivalent GMP systems. China is not on that list, so the document is required.
Practically, that means a separate administrative track that runs in parallel with the CEP. Both can be in place and you still need to check that the two documents name the same site, because a mismatch between the certificate and the confirmation is a common cause of a shipment being held.
Sorting by market
| Destination | What the API file normally has to be |
|---|---|
| United States | Type II DMF, on the available-for-reference list, with a letter of authorization |
| European Union | CEP, or an ASMF where no monograph exists; plus the Article 46b written confirmation for the import |
| Markets that accept a CEP | A current CEP will often serve, subject to national requirements; check the specific regulator's position before assuming |
| Other national markets | Usually a CTD Module 3.2.S technical package, a GMP certificate and batch data; specific national dossier procedures vary |
What this means when you buy through a partner
This is where the conversation usually gets muddled, so it is worth being direct. The certificates and filings described above are held by the manufacturing site, in its own name, for a named substance. A trading partner does not hold a CEP, and anyone who says otherwise is describing something that does not exist.
What a partner can genuinely do is different, and it is not nothing. It can tell you which filing exists for the substance you actually want to buy, whether it is current, whether the site will issue a letter of authorization, and what the gap is between where you are and where your target market needs you to be. That is a documentary and coordination job, and in a market where the top few sites hold most of the capacity, knowing which filing belongs to which site is most of the work. Our supply-chain page describes how we work, and the supplier verification checklist sets out what to verify independently of anything a supplier tells you.
One more structural note, because it is moving. EU policy on critical medicines has been pushing supply resilience into tender scoring, which means diversification evidence can carry weight alongside the filing itself. The companion article on dual sourcing and supply concentration looks at what that changes for a buyer.
Frequently asked questions
Is a CEP the same as a DMF?
No. A CEP is issued by the EDQM and certifies compliance with the European Pharmacopoeia monograph at a named site. A US DMF is a confidential filing with the FDA that is never approved or disapproved. A supplier selling into both markets will normally need both.
Does a CEP mean the API is approved?
No. A CEP supports your own registration. It does not authorise anyone to sell a medicine, and it is not a marketing authorisation.
What is a written confirmation and who issues it?
Under Article 46b of Directive 2001/83/EC, APIs imported into the EU need a written confirmation from the competent authority of the exporting country, attesting to equivalent GMP supervision. It applies where the exporting country is not on the EU equivalence list.
Can a distributor hold a CEP?
No. A CEP is issued against a specific manufacturing site for a specific substance. A distributor can supply material covered by a site's CEP, but the certificate remains in the site's name.
What is an ASMF and when is it used?
The Active Substance Master File is the European route when no CEP is possible, typically because the substance has no pharmacopoeial monograph. It has an applicant's part and a restricted part the regulator sees.
Is a US DMF ever approved?
No. The FDA reviews a DMF only when a finished-product application refers to it. What matters practically is whether it is on the available-for-reference list and whether the holder will issue a letter of authorization.
The question that sorts it out
Before any of this, ask one thing: which market is this material actually going into? The document set follows from that answer, and almost every confusion in this area comes from a conversation that never asked it.
For the underlying documents, see the EDQM certification of suitability programme, the FDA pages on drug master files and the EudraGMDP database. Always work from the version in force when you read this.
This article describes regulatory documentation routes for active substances, written for regulatory, quality and procurement professionals. It states no therapeutic use, dose or indication for any substance, and no order quantity or lead time. It makes no claim that any particular company holds any particular certificate or filing. Regulatory requirements change; verify the current position with the relevant authority before relying on any of the above.