guidance for providing regulatory information in electronic format

REPUBLIC OF CYPRUSMINISTRY OF HEALTH

PHARMACEUTICAL SERVICES1475 LEFKOSIA

Our ref.: 5.21.02.1, 5.13.02 11 November 2009Tel.: +357 22 407 112Fax: +357 22 407 149

GUIDANCE FOR PROVIDING REGULATORY INFORMATION IN ELECTRONIC FORMAT SUBMISSIONS

Note: This guidance is in accordance to EMEA respective guidance.

CONTENTSA. IntroductionB. Types of electronic submissions (NeeS and eCTD)C. Procedures

a. Type of procedures/submissionsb. Format of submissionsc. Paper-electronic requirementsd. Disk formatse. File formatsf. Packaging/Labelling and Security of submissionsg. Electronic signaturesh. Virus check

D. Validation of electronic submissionsE. How and where to submit an electronic application

a. New MAsb. Variationsc. Renewalsd. DMFe. Written responses

F. Summary of some important requirements

A. INTRODUCTION

The Pharmaceutical Services, Ministry of Health will be accepting electronic submissions within the National Procedure, the Mutual Recognition Procedure and the Decentralised Procedure. This is applicable to all submissions concerning applications for approval of marketing authorisation and all post-authorisation submissions for human medicinal products. Hence, submissions will be accepted electronically in eCTD or NeeS. An eCTD or Non-eCTD (NeeS) is

______________________________________________________________________Pharmaceutical Services, Ministry of Health, 1475 Lefkosia (Nicosia)

Tel.:+357 22 407 107, Fax: +357 22 407 149, Webpage: http://www.moh.gov.cy/phs1

http://www.moh.gov.cy/phs

the format of electronic submission of registration files without accompanying papers. Additionally the Pharmaceutical Services will consider the possibility of accepting only electronic submission in the near future.

However, the Cover Letter and the Application Form has to be submitted in paper with handwritten (original) -blue ink- signatures. The criteria for accepting electronic submissions as originals in all procedures, are included in the current ICH and EU specifications (http://estri.ich.org/) and the EU eCTD or NeeS (http://esubmission.emea.europa.eu/new.htm) harmonised guidance is followed.

The purposes of establishing the electronic scheme include: Abolition of paper Reduction of physical archiving space Reduction of administrative burden Facilitation of the review process:

Enhanced screen legibility Enhanced printability Ease of navigation Provision of search capabilities Simplification of the assessment procedure.

The switch from paper-only to electronic can be made during any phase of the life cycle of a medicinal product. Once the switch to electronic is made it is highly recommended to submit further correspondence on the particular medicinal product in electronic format.

B. TYPES OF ELECTRONIC SUBMISSION

Nees (Non-e-CTD Electronic Submissions)NeeS is formatted as a simple set of electronic files and folders organized into module folders in accordance with the paper CTD guidance. The structure of folders, their names as well as the names of the files contained in the CD/DVD have to be adapted to the standard ICH eCTD Specification V 3.2 and the file format should generally be PDF 1.4. Please refer to the EMEA website (http://esubmission.emea.europa.eu/new.htm) for:

“Guidance for Industry on Providing Regulatory Information in Electronic Format: Non-eCTD electronic Submissions (NeeS)” for human medicinal products.

If the non-eCTD submission being handled is not an initial submission, but belongs to a set of submissions that have thus far been submitted in eCTD format, the submission should be rejected and an eCTD format submission should be requested from the applicant. Non-eCTD




http://esubmission.emea.europa.eu/new.htm





http://estri.ich.org/

http://estri.ich.org/

submissions cannot be accepted within an eCTD lifecycle. The NeeS in question should then NOT be loaded into the review system.eCTDeCTD is an electronic version of the Common Technical Document (CTD). The structure, folder and file names corresponds to those of the CTD. As a submission format, however, it contains additional technical components which enable the lifecycle of individual files in the application, and the lifecycle of the product itself, to be managed.

An eCTD has the following components: Folder structure, Contents (files) and XML backbone. The XML backbone is recognisable as ‘index.xml’ at the root level of the submission folder of an eCTD and provides two useful functions:

1. It provides a hyperlinked table of contents of the entire submission when viewed in a web browser with a suitable style sheet

2. It provides descriptive information (‘metadata’) on the files that make up the actual contents of the eCTD.

Please refer to the ICH website for the ICH Specifications (Module 2-5) and to the Notice to Applicants website for the EU Module 1 specifications. For MRP and DCP applications in eCTD format, please also refer to the CMDh website for the “CMDh Best Practice guide on the use of eCTD in the MRP/DCP (html://www.hma.eu/225.html) . The folder structure for module 1 can be downloaded from the European Commission website (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_2007-03/eum1-v1.2.1.zip).

C. PROCEDURES

a. Type of procedures/submissionsRegulatory information can be submitted in electronic format for every type of procedure/submission, ranging from initial applications (national, mutual, decentralised), to Variations, Renewals (national, mutual recognition), DMF, responses, supplementary information, Follow-Up Measures (FUMs), Periodic Safety Update Reports (PSURs), Notifications .Guidance on placement of documents within the eCTD structure for particular submission types can be found in:

-The EU-CTD Notice to Applicants http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm

-The CTD question and answer document published by the Notice to Applicants http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/

ctd_qa_05_2006.pdf-The ICH CTD Q&A

http://www.ich.org/LOB/media/MEDIA1189.pdf




http://www.ich.org/LOB/media/MEDIA1189.pdf

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_qa_05_2006.pdf

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_qa_05_2006.pdf

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_2007-03/eum1-v1.2.1.zip



http://www.hma.eu/225.html

http://www.hma.eu/225.html

http://estri.ich.org/eCTD/eCTD_Empty_Folder_Template_v3_02.zip

-The EMEA post-authorisation guidance http://www.emea.europa.eu/htms/human/postguidance/index.htm

b. Format of SubmissionsRegulatory information must be structured in accordance with the Common Technical Document (CTD) see http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm the breakdown of the electronic submission should be in conformity with the ICH Granularity Document: http://www.ich.org/MediaServer.jser?@_ID=554&@_MODE=GLB. For NeeS applications it is highly recommended that the eCTD structure is used so that all sections of the CTD are in the right order. The breakdown of the electronic submission should be in conformity with the ICH Granularity Document and eCTD file naming conventions should be followed.

c. Paper - Electronic requirements

Procedures In Paper Electronic FormatCTD CTD

MRP 1 originally signed cover letter, 1 originally signed application form and 1 copy of the form.

1 set CD Rom(s) orDVD (s)

DCP 1 originally signed cover letter, 1 originally signed application form and 1 copy of the form.

1 set CD Rom(s) or DVD (s)

National 1 originally signed cover letter, 1 originally signed application form and 1 copy of the form.


Variations 1 originally signed cover letter, 1 originally signed variation application form and 1 copy of the form.


Supplement 1originally signed 1 set CD Rom(s) or




http://www.ich.org/MediaServer.jser?@_ID=554&@_MODE=GLB

http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm

http://www.emea.europa.eu/htms/human/postguidance/index.htm

documents cover letter DVD (s)Renewals (national/MRP)

1 originally signed cover letter, 1 originally signed renewal application form and 1 copy of the form.


PSURs 1 originally signed cover letter


The Pharmaceutical Services, Ministry of Health have a strong preference for the submission of electronic regulatory information and sees clear benefits for both regulators and industry.

d. Disk Formats:The following disk formats are acceptable:

CD-ROM, CD-R, CD-RW, DVD-R, DVD-RWThe Pharmaceutical Services will not accept hardware (laptops, zip drives, etc) from applicants in connection with the submission of information in electronic format, bootable CD/DVDs or floppy disks.

Applicants should provide the electronic information on the smallest number of media units possible, taking into consideration the size of the submission. As mentioned above both CD-ROM and DVD are considered acceptable. If more than one CD-ROM or DVD is needed avoid spanning of the content of a Part or a Module of the dossier over two CD-ROMs or DVDs. Applicants are encouraged to include a Module of the dossier within one media unit. If in the case of large modules, where a split over multiple CDs is inevitable necessary, subfolders should not be split between CDs, even if this requires a CD to be sent not full to capacity.

e. File formatsThe regulatory information on an e-CTD (CD-DVD) should be structured in accordance with the Common Technical Document. Pharmaceutical Services accepts file formats in compliance with the ICH eCTD specification document v3.2 http://estri.ich.org/eCTD/eCTD_Specification_v3_2.pdf and the EU Module 1 v1.1 specification document http://ec.europa.eu/pharmaceuticals/eudralex/homev2.htm. All files submitted on disk should be in Adobe Acrobat PDF format and the structure of the e-CTD should be an XML language. As far as possible all data should originate from electronic files rather than from scanned data making it possible for assessors to easily navigate and manipulate the document.

To facilitate this process the following points should be noted when creating PDF documents: PDF documents should not be file protected as this prevents the printing and

manipulation of the document.




http://ec.europa.eu/pharmaceuticals/eudralex/homev2.htm

http://estri.ich.org/eCTD/eCTD_Specification_v3_2.pdf

Fonts that are not supported by Microsoft Word should not be used on PDF documents.

All PDF documents should be appropriately bookmarked to ensure that assessors can jump directly to the sections of interest. Only the simplest of PDF documents (simple respond letter) should be submitted without bookmarks. All documents larger than 50 pages should be bookmarked to section headings (will happen automatically if headed documents are converted for MS Word). Short documents should be considered for bookmarking if they are particularly complex and/or require frequent cross referencing within the document.

Supporting data and references should comply with the Vancouver convention where appropriate (http://www.icmje.org).

In accordance with EU Module 1 specifications Word and RTF file format (.rtf) can be acceptable but always in addition to the PDF files made of the same documents.

PDF files should be saved as “optimized” to reduce the size. Overviews (CTD module 2) must always be generated from electronic source files.

Submissions in PDF should be readable with Acrobat Reader version 5.0 or higher. For graphics, if PDF is not possible then JPEG, PNG, SVG, GIF, MPEG format could be used.

If scanning is unavoidable, readability and file sizes need to be balanced. The following is recommended: resolution 300 dpi (photographs up to 600 dpi), avoid grayscale or color where possible, use only lossless compression techniques.

Fonts should be chosen of a type, color and size that allow easy reading of documents on screen (1024x768 points) and after printing; examples of strongly recommended font-types are:

Times New Roman, 12-point, black Arial, 10-point, black (colored fonts are discouraged).

Try to avoid the use of color. If colors other than black are used, legibility after printing should be tested before submission.

All fonts used in a document (except Times New Roman, Arial and Courier) should be embedded, including all the characters for the font; in other words, limit the number of fonts used in document and avoid customised fonts

Print area for pages should fit on an A4 sheet of paper; margins should allow binding in multi-ring binders without affecting readability.

Landscape-oriented tables should automatically appear in landscape on screen.Additional details on PDF can be found in the ICH eCTD Specification Document, Appendix 7, to http://www.emea.europa.eu/htms/human/qrd/docs/43183607en.pdf and related documents.

Please refer to http://www.emea.europa.eu/pdfs/human/regaffair/59688107en.pdf regarding the acceptable file formats.Please be also informed that the product information text (SPC, Labeling, PIL) must be included as a word format or RTF in addition to the PDF, for ease of review – note that Word files should be sent in a separate folder and should not be included in the eCTD backbone. Provision of Word files as opposed to RTF is preferred.




http://www.emea.europa.eu/pdfs/human/regaffair/59688107en.pdf

http://www.emea.europa.eu/htms/human/qrd/docs/43183607en.pdf

http://www.icmje.org/

f. Packaging / Labelling and Security (Physical, Data) of the submissionThe physical security of the submission during transmission is responsibility of the applicant. The sets of electronic information should be submitted at the same time as the paper documentation (cover letter and application form where applicable). The electronic media should be packed adequately to prevent damage to the media or to their content. One-time security settings or password protection of electronic submissions is acceptable for security purposes during transportation/transmission from the applicant to the Pharmaceutical Services. This protection is only accepted when one password is used to protect the complete submission. It is not allowed to protect the submission on file level. Once received within the Pharmaceutical Services, these settings should be removable; additionally security and submission integrity is the sole responsibility of the Pharmaceutical Services. Please be reminded to always label the actual disk not the case-providing that the two can become separated.

g. Electronic Signatures:Currently, the use of digital signatures for electronic submissions within the EU is not fully supported and digital signatures should therefore not be used. The authenticity of certain documents (covering letters, Application forms) should be guaranteed by paper copies with a handwritten signature. Until the proper system is in place for the use, tracking and maintenance of electronic signatures, the signed cover letter and an originally signed application form should be submitted both electronically and in paper.

h. Virus-Check:The applicant is responsible for checking the submission for viruses and for informing the Pharmaceutical Services of the type of software used for this purpose. Checking should be performed with at least one, but preferably more, up to date virus checkers.After receipt at the Pharmaceutical Services, a similar, multiple program, internal virus check will be performed. A positive check can constitute sufficient grounds for refusal of the eCTD.

D. VALIDATION OF ELECTRONIC SUBMISSIONS

Technical validation and regulatory validation must be clearly separated. The following items will be checked during technical validation:

Required paper copies. Adequate cover letter (as mentioned below). virus check at the Pharmaceutical Services Compliance with general requirements (PDF, XML). compliance with the EU Module 1 Specification compliance with specific details of pure PDF submissions with special attention to

bookmarks




security settings or password protection any other serious defect, incident, etc. associated with the initial processing of the

electronic submission

If during the further administrative handling of the electronic submission or during the actual review (and regulatory validation) process serious defects are found and those defects are reproducible on the original copy of the electronic submission as received from the applicant, the application will be deferred back to the applicant. Examples of such defects could be a substantial number of non-functioning hyperlinks, hyperlinks to non-existing documents, etc. As a consequence, this might lead to a serious delay in the review process.

Cover Letter (in accordance with CMDh Guidance and the Chapter 7 of the Notice To Applicants).Information to be included in the cover letter which will be provided in a hard copy along with the CD/DVD of the electronic submission:

Name of the applicant and address/date of the submission Name of the medicinal product Name of the active substance(s) and the ATC code. The allocated MRP/DCP procedure number (if applicable). Legal basis of the application. Use of European reference medicinal product (when appropriate). Indicate if the strength(s) and/or the pharmaceutical form(s) and/or the indication(s) of

the reference medicinal product differ between RMS/CMS (when appropriate-usually in MRP-DCP).

Confirmation of identical dossiers in the RMS and CMS concerned (if applicable). Information whether multiple/duplicate applications are submitted, also in cases where

the duplicates are not submitted simultaneously. When submitted later, a reference to the first application should be given (if applicable-usually in MRP-DCP procedures).

A clear description of the enclosures Proof of fees payment Number of media units per application (full set) and number of copies Index (content) of each media unit Statement that the submission is checked with an up-to-date and state-of-the-art virus-

checker (name and version of the anti-virus program should be mentioned) The submission sequence number An annex document with the history of the sequences (Sequence Tracking Table). Statement that the content of the electronic information is identical to the content of

the parts that are submitted in paper. Statement that the content of the electronic information is identical to the content of

the dossier submitted through the portal of the Pharmaceutical Services.






http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/procedural_guidance/Application_for_MA/Cover_letter_NA_MRP-DCP_2008_04_Rev2.pdf

Additionally to the above cover letter, it could be very useful if an annex to the Cover letter is provided in form of an eCTD “Reviewer’s Guide” that may contain the following sections if applicable, in addition to those specified above:

Particularities relating to presentation and delivery of the eCTD (hard media) Information on file sizes by module Legacy documents and scanned pages details File formats (if any particularities to report) Files referenced at multiple locations within the backbone. Documents with relevance to more than one CTD module Hyperlink appearance and strategy Bookmarks Particularities of module organization Distribution list Documents available on request

Applicants are encouraged to include the below mentioned information on the label of the CD/DVD (e-CTD):

1. The applicant´s name2. The product´s (invented) name(s)3. The International Nonproprietary4. Name (INN) of the product5. The full application number (if known)6. The sequence number(s) of the eCTD submissions contained on the CD/DVD7. The submission date (YYYYMMDD)8. The submission type of each eCTD submission(s) contained on the CD/DVD (e.g. Initial

Application, Variation Type II), as per the eCTD envelope information.9. A description of each submission type of each eCTD submission(s) contained on the

CD/DVD.

The cover letter should include as a minimum, the information specified in the CMDh Guidance document which also includes a template that can be used. Please see Chapter 7 of the Notice to Applicants for details on the provision of signed paper documents.

E. HOW AND WHERE TO SUBMIT AN APPLICATION






http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/procedural_guidance/Application_for_MA/Cover_letter_NA_MRP-DCP_2008_04_Rev2.pdf

a. New Authorisation Applications (National, MRP and Decentralised Procedure)All documents should be submitted in PDF format with one PDF file for each document, including:

Marketing authorisation application form. Supporting data files - named correctly- (please refer to the current EU M1 specification

v1.3) with release date -May 2008- at (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm) with one PDF file for each CTD document.

The Product information text (SPC, Labeling, Package Leaflet) should be submitted as a word format in a separate CD/DVD along with the PDF file.

Applicants should be familiar with the definition of the Common Technical Document (CTD) as defined in Volume 2B of Notice to Applicants (June 2006 and May 2008) (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_06-2006.pdf and http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_200805/ctd_05-2008.pdf ). To support efficient processing of submissions it’s required that the relevant section of the CTD is prefixed to the file name of all submitted PDF files. Example: In Module 2.3 of the CTD (Quality Overall Summary), section 2.3.P.1 describes the Description & Composition of the Drug Product. The single PDF document supporting this section should be named M2-3-P-1 Description and Composition of Drug Product or m2-3-p-drug-product (in order to be consistent with ICH M4). For further examples regarding the names of the PDF files (that can be used in the e-CTD) in accordance with CTD please refer to http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm

The disk itself should be either formatted into the full CTD directory and sub-directory structure or submitted as a flat file with no directory structure. However, in either case, it is essential that the individual document filenames comply with the convention outlined above. Only one MA application should be submitted per disk. National MA applications should be separated from MRP and DCP applications. Additionally please refer to http://hma.eu/uploads/media/BPG_eCTD_in_MRP_DCP_Rev0.pdf (version April 2008) for further information regarding the use of the electronic common technical document (eCTD) in the mutual recognition and decentralised procedures.

b. Variation ApplicationsAll documents should be submitted in PDF format with one PDF file for each document, including:

Adobe PDF Variation application form New or replacement data files – named correctly with one PDF file for each CTD

document.




http://hma.eu/uploads/media/BPG_eCTD_in_MRP_DCP_Rev0.pdf


http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_200805/ctd_05-2008.pdf

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_200805/ctd_05-2008.pdf

http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_06-2006.pdf


Variations to the SmPC should be accompanied by the appropriate section(s) of the SmPC submitted as individual along with the entire SmPC.

All documents should be submitted and named according to the CTD format (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm).

A mixture of variation types should not be included in a single disk. Type IA, IB and II variations should be submitted in separate disks. Mutual Recognition variations should be kept separate from National variations. If application forms and supporting data files are common to multiple applications, they should be replicated in each of the relevant disks so that each disk constitutes a ‘stand alone’ application.

All variation applications affecting the SmPC should be accompanied by the appropriate section(s) of the SmPC submitted as individual along with the entire SmPC.Bear in mind that paper copies of the application form (2 copies) and cover letter with handwritten (original) -blue ink- signature must be provided along with the CD/DVD.

c. Renewal of marketing authorisationsAll documents should be submitted in PDF format with one PDF file for each document named as below:

• Application form (e.g. as m1-2-form).• Covering letter.• Post-authorisation submissions since last authorisation/renewal list.• Follow-up measures/specific obligations.• Certificate of compliance with good manufacturing practice (GMP).• Summary of product characteristics (SmPC).• Product label (individual disk must be submitted).• Product leaflet.• Quality overview (Quality Expert Statement).• Clinical overview (Clinical expert statement).• Post-marketing experience (PSURs). The PSUR should be named as M-5-3-6-reports-

of-postmarketing-experience regardless of whether it is part of a renewal package, a new license PSUR or a three-yearly PSUR. For the latter to cases the covering letter should state the nature of the submission.

All documents should be submitted and named according to CTD format (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm).

d. Active Substance (Drug) Master File (ASMF)The submitted documentation should be broken down into individual CTD sections. The applicant’s part, restricted part and quality overall summary should be submitted as a number






of individual PDF documents as defined in the relevant sub-sections of the CTD. On the CD the Restricted Part and Applicant’s part should be put into labeled folders.

For new applications the following documents should be included:• Covering letter (should state the current version of the DMF’s, the active substance, the

name and the address of the Drug Master File Holder and the Manufacturing site. If the number of the DMF is known this must be clearly indicated).

• Applicants part (comprising relevant individual CTD documents e.g. m3-2-s-1-2-structure).

• Restricted part (comprising relevant individual CTD documents e.g. m3-2-s-2-3-control-of-materials).

• Quality overall summary (comprising relevant individual CTD documents e.g. m2-3-p-drug-product).

• Letter of access (should clearly indicate the pharmaceutical products and the procedure numbers-if applicable and the Name of the Marketing Authorisation Holder and any other relevant information).

Note that the applicant’s part, restricted part and quality overall summary should be submitted as a number of individual PDF documents as defined in the relevant sub-sections of the CTD. All documents should be submitted and named according to the CTD format.For updates to ASMFs, the documents above should be resubmitted in their updated form and an additional document with a table summarising the changes should be included.

e. Written ResponsesThe organisation of the subsequent electronic submission of information based on a list of questions from the Pharmaceutical Services should follow the same basics as the original, first submission. In this case the high level folder structure of the each electronic submission irrespective of the combination dossier format and file format would be mydrug/0001 (the last sequence submitted increased with increment 1). It should be noted that for any combination no empty folders should be submitted.

Where you should be sending electronic submissions

The electronic submission should be sent to the following address:

Registrar Drug CouncilPharmaceutical ServicesMinistry of Health1475 Nicosia




CYPRUS

Any questions arising before or after the submission of the electronic information can be directed to the following email address under reference of “electronic submission”:

[email protected]

F. SUMMARY OF SOME IMPORTANT REQUIREMENTS

Full electronic submission of regulatory information is possible, with the exemption of a handwritten (original) -blue ink- signature copy of the cover letter and Application Form and the restriction of compliance with this guidance document.

The Pharmaceutical Services has a strong preference for electronic submissions and a continuous electronic-only (‘once-electronic-always-electronic’) approach during the life cycle of a medicinal product.

The switch from paper-only to electronic can be made during any phase of the life cycle of a medicinal product. Once the switch to electronic is made it is recommend to submit further correspondence in electronic format. When an application is filed in ICH eCTD format the Pharmaceutical Services has of course a preference for a continuous eCTD approach.

In the case of eCTD format, it is recognised by the Pharmaceutical Services that there are phases in the procedures where submission in eCTD format might be difficult due to time constraints, e.g. during of the finalization of centralised or decentralized procedure. In those cases the Pharmaceutical Services will accept non eCTD submissions (i.e. without the xml files and/or util folder) during the procedure. After finalisation of the procedure it is the responsibility of the company to provide the Pharmaceutical Services with the relevant eCTD submission to update the life cycle of the medicinal product.

Acceptable file-formats are PDF for narratives, XML for structured information and in addition to PDF, JPEG, PNG, SVG, MPEG and GIF for graphics.

Word files are acceptable as long as a PDF copy of those files is also available in the submission.

The PDF files generated from an electronic source document are highly preferred over PDF files produced from scanned paper.

Overviews (CTD Module 2) must always be generated from electronic source files. Acceptable electronic submissions should be readable on Pharmaceutical Services

hardware; no company hardware will be accepted. Submissions in PDF should be readable with Acrobat Reader version 5.0 or higher. Information submitted in electronic format should be completely identical to the

information on paper in terms of content.




Only one-time security settings or password protection are acceptable for increased security during transport/transmission; after receipt at the Pharmaceutical Services these security settings or password protection should be removable. This protection is only accepted when one password is used to protect the complete submission. It is not allowed to protect the submission on file level.

CD-ROM or DVD should be used for exchange of regulatory information.

Pharmaceutical ServicesNicosia2 Nov 09


