Note – for information on the compilation of eCTD dossiers please follow this link

Documents to be submitted with an application for the APIMF procedure

Submission of an application for the APIMF procedure involves preparation and submission of:

• the covering letter (in Word or text-selectable PDF (portable document) format)
• the APIMF procedure application form (in both Word and PDF format)
• a completed Letter of Access (in PDF format)
• the APIMF correctly formatted (see Documentation requirements for submission of an APIMF).

Responses to requests from the WHO Prequalification Team: medicines for information should include:

• an electronic version of the covering letter (in Word or text-selectable PDF format)
• the applicant’s responses to the questions raised (in Word or text- selectable PDF format)
• if requested, an electronic version(s) of any APIMF subsections that have been updated (see Documentation requirements for submission of  an APIMF below).

APIMFs and revised subsections submitted as amendments should be submitted in electronic format only. Paper copies should not be submitted unless these have been requested by the WHO Prequalification Team: medicines.

How to organize the APIMF

All APIMFs should follow the format for module M4Q-R1 of the common technical document (CTD) format of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (commonly known as ICH). This includes following the M4Q-R1 headings and sub-headings.

The APIMF should be divided into two parts (one each for the open part (OP) and the restricted part (RP) of the APIMF). It can be submitted as two documents. Each document should include a table of contents with headings listed in accordance with the 3.2.S.1 to 3.2.S.7 section levels of M4Q-R1. Alternatively, NeeS (non-eCTD electronic Submission) requirements) can be followed. I.e. each of the two parts of the APIMF can be divided into multiple sub-sections (i.e. documents). NeesS guidance includes information specific to the submission of information within the European Union but it provides excellent technical guidance on electronic document formats.

Documents should be paginated throughout. Page numbers may be set at 1 at the start of each section or subsection.

The use of PDF bookmarks or hyperlinks is encouraged. Ideally, bookmarks will be inserted to at least the 3.2.S.X.X level. In very detailed sections, use of additional bookmarks is suggested.

Officially certified translations should be provided for any documents that are not in English.

Submitted documents should enable an assessor to navigate between sections easily and to copy critical information. Inclusion of summaries, conclusions, and most importantly analysis and discussion of raw data, will facilitate assessment of the API information provided.

Since further questions may arise, APIMF holders should not submit a revised version of their APIMF when they submit responses to these, unless specifically requested to do so and/or any issues have been resolved.

Version numbering

Each of the two documents should be assigned a unique document version number. This number should appear on the document cover page, together with the name of the API and the APIMF holder’s name, indicate whether it refers to the open or RP of the APIMF, and give the date of issue. For example:

Drugs Inc/Artemether/OP/01/Feb-2013.

If a replacement subsection of an APIMF is issued by the applicant, it is referred to as an amendment and should be assigned an amendment version number. The amendment version number should include reference to the “parent” OP document. For example:

Drugs Inc/Artemether/OP/01/Feb-2013/Amend 01 – April-2013.

A change to the open-part version number, from OP/01 to OP/02 for example, would indicate the availability of a complete and revised version of the OP document. This new version (AP/02) would be assumed to incorporate all the accepted amendments made to the earlier version (AP/01), including all applicable CTD headings.

Example of the life cycle of an APIMF
The table below presents an example of the life cycle of an APIMF. Three amendments to the OP were received, following submission of the original APIMF. Each time an amendment was received, the amendment number and date were added to APIMF version number. Finally, a year after submission of the APIMF, a revised version of the OP was submitted, consolidating the previous amendments. Since no changes were made to details in the RP, submission of a revised RP was not necessary.

Electronic requirements

No single electronic file should exceed 50 MB in size.

File or folder names should not exceed 64 characters in length.

Path lengths should not exceed 180 characters, including the file name, and extension. Abbreviated file or folder names can be used.

The use of special characters in folder or file names should to be avoided in order to prevent software conflicts. These special characters include:

• angle brackets (<>)
• ampersand (&)
• asterisk (*)
• backslash (\)
• braces ({})
• colon (:)
• forward slash (/)
• number sign (#)
• percent (%)
• plus sign (+)
• pipe (|)
• question mark (?)
• quotation mark (")
• tilde (~).

An application for the APIMF procedure and subsequent responses to questions raised by WHO assessors should be sent either:

1. On CD or DVD to:

World Health Organization
WHO Prequalification Team: medicines
MHP/RPQ/PQT Room M613
20, Avenue Appia
1211 Geneva 27
Switzerland

Please include a paper cover letter with the CD/DVD submission to facilitate processing.

or

2. Via a secure link to an online document repository.  The link should be sent in an email  to the following email address: APIassessment@who.int.  The Subject line of the emails should clearly indicate the application and the specific medicine procedure referred too. The date of receipt will be the date the file is successfully downloaded.

WHO prequalification guidance

Application form

Application for active pharmaceutical ingredient master file (APIMF) procedure (11 October 2022)

Template

Model letter of access: active pharmaceutical ingredient master file (APIMF) (14 February 2016)

Link

Harmonised technical guidance for non-eCTD electronic submissions (NeeS) (October 2013)