4/1/2018 Overview on DMF/CEP - Need of Regulatory Submission

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Overview on DMF/CEP - Company Resource Center Global Delivery Models Contact Us

Need of Regulatory
Submission ≡

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submission)

Drug Master File (DMF) is one of the important parts of the documents submi ed to the regulatory
authori es including the US Food and Drug Administra on (FDA), the European Medicines Agency (EMA) and
Japan’s Ministry of Health, Labor and Welfare (MHLW).

What is Drug Master File (DMF)

Drug Master File is a type of voluntary submission of confiden al informa on in length to the FDA that
includes data on the facili es, processes, or ar cles used in the developing, processing, packaging, and storing
of drug items.

This document is usually prepared by a pharmaceu cal company that is further submi ed to the concerned
regulatory agency in the intended drug market. DMF usually contains detailed informa on about any Ac ve
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4/1/2018 Overview on DMF/CEP - Need of Regulatory Submission

Pharmaceu cal Ingredient (API), drug substance, medium of drug substance, packaging material etc.

These files are also used to allow the DMF holder to handover the authority to sponsors or applicants who
support a submission to FDA without the DMF holders having to disclose the informa on to them.

Overview of DMF in regulatory submissions

DMF contains complete informa on on an Ac ve Pharmaceu cal Ingredient (API) or Finished Drug substance.
It is referred in the following ways in different countries. For instance in US it is known as US-Drug Master file
(US-DMF) and in Europe it is known as European Drug Master File (EDMF) or Ac ve Substance Master File
(ASMF) in United States and Europe respec vely.

DMFs usually cover the Chemistry, Manufacturing and Controls (CMC) of a component of a drug product e.g.
drug substance, excipient, packaging material. Drug product informa on or non-CMC informa on (e.g.,
facili es, toxicological) may be filed in a DMF.

DMFs have significant importance because they support the NDAs, ANDAs, and INDs which represent mul -
billion dollar poten al profits for drug applicants, and several hundred thousand to several million dollars each
in corresponding investment me and research.

1.1 Parts of DMF

Unlike US-Drug Master file, the scien fic informa on of EDMF or ASMF is physically divided into 2 parts as per
European filing procedures.

A. Restricted part (Closed part) –

Informa on regarded as to be confiden al and to be submi ed only to the Authority.

Manufacture
Manufacturer(s)/site of manufacture
Detailed descrip on of the manufacturing process and process controls
Control of materials (Star ng material of the API, reagents, solvents, other materials used)
Control of cri cal steps and intermediates
Process valida on and/or evalua on
Manufacturing process development

B. Applicant’s part (Open part) – Informa on regarded as to be non-confiden al and to be given to the
applicant. This informa on is also given to the authority as part of DMF services
(h p://www.freyrsolu ons.com/ind-nda-anda-bla-and-dmf-submissions).

These parts include:

General informa on
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4/1/2018 Overview on DMF/CEP - Need of Regulatory Submission

Characteriza on
Control of API
Reference standards or materials
Container closure system
Stability

1.2 DMFs format

DMFs may be submi ed following the format recommended in the “Guidance for Industry M4Q: the CTD –
Quality”. The Common Technical Document (CTD) is a set of specifica on for applica on dossier for the
registra on of Medicines and designed to be used across Europe, Japan and the United States. It was
developed by the European Medicines Agency (EMA, Europe), the Food and Drug Administra on (FDA, U.S.)
and the Ministry of Health, Labour and Welfare (Japan).

TYPES OF DMFs (FDA)

Type I

- Manufacturing Site, Facili es, Opera ng Procedures, and Personnel (no longer applicable)

Type II

-Drug Substance, Drug Substance Intermediate, and Material Used in Their Prepara on, or Drug Product

Type III

-Packaging Material

Type IV

-Excipient, Colorant, Flavor, Essence, or Material used in Their Prepara on

Type V

-FDA Accepted Reference Informa on

Status of DMF database as per US FDA

“A” = Ac ve. This means that the DMF is not closed and it’s s ll accep ng
“C” = Complete
“I” = Inac ve. This suggests the Holder or FDA has closed the DMF submission
“P” = Pending
“N” = Not an assigned number

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4/1/2018 Overview on DMF/CEP - Need of Regulatory Submission

DMF Formats

Different countries follow different DMF formats and submissions. For instance, the United States Food and
Drug Administra on asks for two copies of each Type DMF in the CTD format, but not in CTD module form.
One con nuous document in the CTD format is mandatory. In US there are no different sec ons as an
“Applicant’s Part” or “Restricted Part” followed unlike European DMF format.

It’s suggested to submit drug master file in Electronic format as submission of the data in a mixed format of
paper and electronic may delay its review.

All electronic submissions must have a pre-assigned number. However, this pre-assigned number is not
required when data is converted to paper to electronic format from paper. A 6-digit assigned number is used
e.g. 2345 must be submi ed as 002345. “0000” is used as sequence number for first submission in electronic
format.

While paper format can be converted into electronic format, the electronic format however cannot be
converted back to paper format. Therefore, every consecu ve submission should be processed in electronic
format once the DMF applica on form has made an electronic submission.

Benefits of DMF services

Ensures confiden ality of proprietary informa on

Gives you an edge over your compe tors
Several applicants can refer the informa on
Adds value to the product and company on the whole
Considered more reliable in terms of quality and regulatory stand by manufacturing companies
Builds confidence within the customers
Improves sales anywhere in the world
Penetrates high entry barrier US market

What is CEP?

CEP is Cer ficate of Suitability to the monographs of the European Pharmacopoeia or Cer fica on of
suitability of European Pharmacopoeia monographs. It is also informally referred to as Cer ficate of Suitability
(COS)

This cer ficate, which is issued by Cer fica on of Substances Division of European Directorate for the Quality
of Medicines (EDQM), was established in 1994. It is issued only when the manufacturer of any drug product
provides proof regarding the quality of the product which is then suitably guarded by the significant
monographs of the European Pharmacopoeia.

Benefits of the CEP

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4/1/2018 Overview on DMF/CEP - Need of Regulatory Submission

Ensures confiden ality of the submi ed data

Facilitates consolidated evalua on by the EDQM
Offers recogni on by all Member States of the European Pharmacopoeia Conven on across 36
countries na ons
Smooth dealing of applica ons for marke ng authoriza on (MAA) for medicinal products across those
na ons
Simplifies the approval process of a medicinal product as compared to the ac ve substance master file
(ASMF) or European drug master file (EDMF)

Who needs CEP?

Manufacturers or suppliers who are willing to avail for a marke ng authoriza on for

Ac ve products or excipients (natural/synthe c substance formulated side by side the ac ve

ingredient of a medica on) to regulate the purity of the chemicals used and microbiological quality of
their products
Substances whose TSE risk has been reduced down as per the general monograph
Herbal items used in the manufacturing of pharmaceu cal products are to be evaluated according to
the suitability of the monograph

(The data is shared as described in Resolu on AP CSP 1 and Direc ves 2001/83/EC, 2001/82/EC)

Submission of drug master file by the manufacturers to the authority creates the quality impact on the
consumers and hence it can increase the trust of the manufacturer in the market pertaining to organisa on
& quality of product.

CATEGOR Pharmaceu cal (/blog/category/pharmaceu cal)

Y: Regulatory Affairs (/blog/category/regulatory-affairs)

Regulatory Consul ng (/blog/category/regulatory-consul ng)

Publishing & Submissions (/blog/category/publishing-and-submissions)

Health Authority Updates (/blog/health-authority-updates)

BLOG ANDA (/blog-tags/anda) API (/blog-tags/api) CMC (/blog-tags/cmc)

TAGS: DMF (/blog-tags/dmf) Drug Master File (/blog-tags/drug-master-file)

EMA (/blog-tags/ema) FDA (/blog-tags/fda) IND (/blog-tags/ind)

NDA (/blog-tags/nda)

Regulatory Submission (/blog-tags/regulatory-submission)

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