Explanatory Notes on the Enforcement of the Ordinance on

Transcription

Notes on the Enforcement of the AMG-EV, Version 5.0, of 1 Juli 2007
Explanatory Notes on the Enforcement
of the Ordinance on the Submission of Documents
within Licensing and Renewal Procedures for Medicinal Products
(AMG-Submission Ordinance,
AMG-Einreichungsverordnung,
AMG-EV)
of 21 December 2000
- Version 5.0 of 1 July 2007Contents
Explanatory Notes on the Enforcement of the Ordinance on the Submission of Documents within
Licensing and Renewal Procedures for Medicinal Products (AMG-Submission Ordinance, AMGEinreichungsverordnung, AMG-EV) of 21 December 2000 - Version 5.0 of 1 July 2007- .............. 1
1
General remarks ........................................................................................................................ 4
2
E-mail address for the electronic submission ............................................................................ 4
3
Information................................................................................................................................. 4
4
3.1
Hotline contact for electronic submissions in accordance with AMG-EV as well as
explanatory notes on the on-line procedure “electronic notification of variation“ .............. 4
3.2
Contact person for procedural and scientific questions..................................................... 5
3.3
Contact person eCTD........................................................................................................ 5
Modalities of electronic submission ........................................................................................... 5
4.1
General.............................................................................................................................. 5
4.2
Documents to be submitted............................................................................................... 6
Table 1 – CTD-Module according to NTA Vol 2 B ..................................................................... 6
5
4.3
Supplementsl and additions .............................................................................................. 8
4.4
New applications for marketing authorisation in accordance with Section 21ff. AMG /
Request for ENR ............................................................................................................... 8
Technical specifications concerning e-mails.............................................................................. 9
5.1
E-mail subject.................................................................................................................... 9
5.2
E-mail content ................................................................................................................... 9
5.3
E-mail attachments and file formats .................................................................................. 9
5.3.1
Problems with the MS-TNEF format in Outlook ............................................................ 9
5.3.2
Zip containers.............................................................................................................. 10
5.3.3
Files with documents to be submitted ......................................................................... 10
5.3.4
Files with metadata ..................................................................................................... 11
Table 2 – Construction of attribut.txt for procedure types ........................................................ 11
5.3.5
Search for ENR / PNR................................................................................................. 12
5.3.6
Encryption of the container.......................................................................................... 12
Version 5.0 of 1 July 2007
Page 1 / 38
5.3.7
Encryption software..................................................................................................... 12
5.3.8
Encryption with the BfArM key .................................................................................... 12
5.3.9
Downloading of the BfArM key, encryption of the zip container .................................. 12
5.4
5.4.1
File name convention ...................................................................................................... 19
Elements of file names for electronic submission to BfArM ........................................ 20
Table 3 – Types of Document, set file names ......................................................................... 21
5.4.2
File name convention in accordance with ICH eCTD Specification ............................ 25
5.4.3
Checklist to monitor whether all conditions have been fulfilled ................................... 26
Table 4 – Checklist Item .......................................................................................................... 26
6
Verification and confirmation of e-mails................................................................................... 27
6.1
Confirmation of receipt and confirmation as to the coherence of the
formal/technical properties .............................................................................................. 27
6.2
Confirmation as to the intellectual verification of content ................................................ 28
6.3
Possible error messages regarding electronic verification of coherence of
formal/technical characteristics ....................................................................................... 29
Table 5 – Error message ......................................................................................................... 29
6.4
Possible error messages regarding intellectual verification of submitted e-mails ........... 32
Table 6 – Error message ......................................................................................................... 32
6.5
System response............................................................................................................. 32
6.6
What to do in the case of false-positive system responses............................................. 32
6.6.1
Submission under a wrong ENR ................................................................................. 32
6.6.2
Submission of partly wrong data ................................................................................. 33
7
Important information concerning permission of exclusive submission of paper documents
in accordance with Section 3 AMG-EV.................................................................................... 34
8
List of changes......................................................................................................................... 35
Table of figures:
1.
Fig 1 Dialogue for download of BfArM public key .................................................................... 13
2.
Fig 2 Download subdirectory ................................................................................................... 13
3.
Fig 3 Import of key into key manager / „Schlüsselverwaltung“ ................................................ 14
4.
Fig 4 Selection and iImport of BfArM public key ...................................................................... 14
5.
Fig 5 „Schlüsselimport“/”key import” dialogue ......................................................................... 15
6.
Fig 6 Status message „Schlüsselimport“ ................................................................................. 15
7.
Fig 7 Display of imported key .................................................................................................. 15
8.
Fig 8 Fingerprint – degree of trust ........................................................................................... 16
9.
Fig 9 Fingerprint check ............................................................................................................ 16
10. Fig 10 Ownertrust .................................................................................................................... 17
11. Fig 11 Encryption of zip container ........................................................................................... 17
Page 2 / 38
12. Fig 12 Selection of BfArM key ................................................................................................. 18
13. Fig 13 Email with attached zip container ................................................................................. 18
14. Figure 14 Cancellation of a false-positive system response.................................................... 33
Page 3 / 38
1
General remarks
The AMG-Submission Ordinance (AMG-Einreichungsverordnung, called AMG-EV in the following)
regulates the electronic submission of documents for applications for authorisation, variation or
renewals in Module 1 and Module 2 of the Common Technical Documents (CTD,
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_06-2006.pdf). Within this
purview, the AMG-EV as well as these Explanatory Notes override earlier regulations on the
submission of documents. Divergent requirements in previous notifications are replaced by these
Explanatory Notes. Aside from this, unless otherwise specified by the AMG-EV, the currently
existing regulations on the submission of documents apply. This means, e.g., that if documents
can or must be submitted on paper according to Sections 3 and 4 of the AMG-EV, the existing
requirements for such submissions must still be observed.
These Explanatory Notes override the previous explanatory notes of version 4.09 dated 01 August.
2
E-mail address for the electronic submission
zulassung@amg-zulassung.de
Attention:
For test purposes, documents can be sent to the following address: testeinreichung@amgzulassung.de
Electronic submissions to the test address exclusively serve for testing for possibly existing formal
errors and are not further processed by BfArM.
In no case do positive test messages replace the actual submission.
3
Information
3.1 Hotline contact for electronic submissions in accordance with
AMG-EV as well as explanatory notes on the on-line procedure
“electronic notification of variation“
Request for advice as to problems with electronic submission in accordance with AMG-EV should
be addressed to the hotline account amg-ev.hotline@bfarm.de.
Contact person: Ms. Dudszus-Hentschel
The hotline can be contacted by phone:
01888 307-3700 / -4319 or 0228 207-3700 / -4319
Attention:
For enquiries about submitted documents refer to the ’serial number of the day’ (Tagesnummer) of
the BfArM response mail. This number is found in the e-mail subject line (Betreffzeile) of the
positive or negative response message. For further details see 6.5 System response.
Questions about the application for a PNR or ENR or other frequently asked general and technical
questions including system response are answered under FAQ on BfArM homepage.
Page 4 / 38
Questions about the use or functionality of compression tools are principally not answered by
BfArM.
Information about the on-line procedure ”electronic notification of variation“:
Submissions via the procedure “electronic notification of variation” need not be additionally made
to the a.m. e-mail address.
However, the AMG-EV conventions, especially for the file format (rtf for SPC and PIL/Fach- and
Gebrauchsinformation), remain valid unchanged.
You will find further information on "Electronic notification of variation" on the BfArM homepage
www.bfarm.de or PharmNet homepage: http://www.pharmnet-bund.de/dynamic/en/index.html
3.2 Contact person for procedural and scientific questions
Procedural and scientific questions concerning ongoing procedures are answered by the
responsible project management. Please contact the e-mail address amg-ev.hotline@bfarm.de.
3.3 Contact person eCTD
The AMG-EV for electronic submission does not interfere with the eCTD submission procedure.
Web addresses of eCTD specifications are:
http://www.ich.org/cache/compo/276-254-1.html
http://www.emea.eu.int/
eCTD contact persons are
General questions:
Dr. Menges, phone: 01888-307-3458 oder 0228/207-3458,
e-mail: menges@bfarm.de
Technical questions:
Mr. Kunz, phone: 01888-307-5948 or 0228/207-5948,
e-mail: kunz@bfarm.de
4
Modalities of electronic submission
4.1 General
Electronic submission of documents is to be made to the e-mail address < zulassung@amgzulassung.de >. At the same time the written version (paper) is to be sent to the regular mailing
addresses – depending on which procedure is used.
For electronic submission of documents in accordance with Section 1 sub-section 2 of the AMGEV only the web-technology e-mail is to be used. Thus, transfer of data via disk or CD is
impossible. For more information please refer to the reasoning of the Federal Council of Germany
(Bundesrat) on the AMG-EV of 10 November 2000 (BR-Drs/resolution 745/2000).
The same applies to supplements, insofar as they are included in Section 2 sub-section 1 of the
AMG-EV.
Page 5 / 38
4.2 Documents to be submitted
All documents listed in Section 2 sub-section 1 AMG-EV are to be submitted electronically, i.e.
drafts for
•
Labelling in accordance with Section 10 AMG
•
Patient information in accordance with Section 11 AMG
•
Expert information ("Fachinformation") in accordance with Section 11a AMG
•
Expert Reports in accordance with Section 24 sub-section 1 numbers 1-3 AMG.
In accordance with Commission Directive 2003/63/EC of 26 June 2003 and the "Hinweise zum
Einreichen von Zulassungsanträgen im CTD-Format beim Bundesinstitut für Arzneimittel und
Medizinprodukte" (Instructions on Submitting Applications for Marketing Authorisation in CTD
Format to the Federal Institute for Drugs and Medical Devices) of 2 July 2003, use of the CTD
format is mandatory as of 1 November 2003 (apart from the exceptions permitted in the a.m.
instructions). Therefore, as of 1 November 2003 the term "Expert Report in accordance with
Section 24 sub-section 1 numbers 1-3 AMG" is considered to mean the corresponding documents
according to the Notice to Applicants, Vol 2 B, edition July 2003 as presented in the following
comparison:
Table 1 – CTD-Module according to NTA Vol 2 B
NTA
IC
IC1 rsp.
Section 24 (1)
no. 1 AMG
IC1
NTA Vol 2 B, edition 1998
Expert Reports
Expert Report on the chemical,
pharmaceutical and biological documentation
EU CTD (NTA Vol 2 B, edition 2005)
CTD
Product profile
2.2
IC1
Critical Assessment
IC1*
IC1
IC1
IC 2 rsp.
Section 24 (1)
no. 2 AMG
IC2
IC2
Signature, Information on the expert*
Appendix 1: Tabular Formats
Appendix 2: Written Summary
Expert Report on the toxico-pharmacological
documentation
Introduction
Quality Overall Summary
Quality Expert Statement
Information about the experts*
-
IC2*
IC2
Signature, Information on the expert*
IC2
(Pharmacology)
IC3 rsp.
Section 24 (1)
no. 3 AMG
IC3
Expert Report on the clinical documentation
Product profile
IC3
Critical Assessment
Product profile
Critical Assessment
Introduction
Nonclinical Overview
Nonclinical Expert Statement
Nonclinical Summary
Pharmacology Tabulated Summary
Pharmacokinetics Tabulated Summary
Toxicology Tabulated Summary
Nonclinical Summary
Pharmacology Written Summary
Pharmacokinetics Written Summary
Introduction
Clinical Overview
Clinical Expert Statement
2.3
1.4*
-
2.2
2.4
1.4*
2.6
2.6.3
2.6.5
2.6.7
2.6
2.6.2
2.6.4
2.2
2.5
Page 6 / 38
NTA
IC3*
IC3
IC3
NTA Vol 2 B, edition 1998
Signature, Information on the expert1 *
EU CTD (NTA Vol 2 B, edition 2005)
Synopsis of individual studies
Clinical Summary
CTD
1.4*
2.7.5
2.7
1
Notice to Applicants Vol. 2A, 2B and 2 C is found on the EUDRALEX website:
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev2.htm
Notice to Applicants, Vol. 2B - Common Technical Document (CTD), June 2006, on:
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ctd_06-2006.pdf
Notice to Applicants, Vol. 2B – Electronic Common Technical Document (eCTD), December
2006, on:
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/update_2007-03/eum1-v1.2.1.zip
The complete list of types of document to be submitted (cf. Point 5.4.1 Elements of file names)
applies to all applications for marketing authorisation, renewals of marketing authorisation in
accordance with Section 31 and/or 105 AMG, and variations in accordance with Section 29 AMG.
In order to accelerate all mutual recognition and decentralised procedures (RMS and CMS
procedures) it is recommended to submit all informative texts during the procedure in coordination
with the responsible project management. On completion of a procedure, the final version of the
product information texts are to be submitted in accordance with the regulations of the AMG-EV
and these Explanatory Notes.
Registration procedures in accordance with Section 38 AMG and centralised European Procedures
are not subject to the purview of Section 1 AMG-EV.
Electronic submission for registration and/ or re-registration of homeopathic medicines 2 are not
prescribed by law, however, in the interest of accelerating the procedure it is urgently
recommended.
The documentation according to Sections 10, 11, 11a as well as the Expert Reports according to
Section 24 AMG must be submitted electronically as separate files (i.e. no summary of drafts of
labelling and wording in accordance with Sections 10, 11 and 11a in one file). Furthermore, all links
to other files in the respective file must be removed prior to saving.
Any type of document must only be saved in one single file. Aside from this, splitting the types of
documents (cf. Point 5.4.1 Elements of file names) into individual files in the style of the eCTD is
only permissible in the following exceptions.
Exception:
In the case of Modules 2.3, 2.6 and 2.7 a splitting as in the eCTD is possible. When doing this, the
type of document is always to be provided with a 3-digit sequential number (cf. 5.4.1 Elements of
file names). This sequential number is also to be assigned if only one file is submitted.
*
Until introduction of the electronic signature, these documents must be submitted on paper. However,
in addition, they can also be submitted electronically (e.g. as a .pdf file).
2
Homeopathic medicines without specified indications are covered by the procedural type of
registration or post-marketing registration.
Page 7 / 38
Example: qos-001.rtf
For a transitional period, submission of the documents CTD 2.2, 2.3, 2.4, 2.5, 2.6 and 2.7, instead
of the Expert Report in accordance with Section 24 AMG, is considered to be sufficient to fulfil the
AMG-EV.
For each application (= processing number of the medicinal product = ENR hier ergänzen, s. folg.
Hinweis ) a separate e-mail is to be sent to BfArM.
Attention:
If, for one ENR, one and the same type of document occurs repeatedly within an e-mail, this e-mail
is rejected; exception cf. 5.4 File name convention.
4.3 Supplementsl and additions
After 1 January 2001, electronic submission is required also for supplements or additional
documents concerning drafts for
•
Labelling (Section 10 AMG)
•
Patient information leaflet (Section 11 AMG)
•
Expert information ("Fachinformation") (Section 11a AMG)
•
Expert Reports (Section 24 AMG sub-section 1, numbers 1-3,
corresponding to Section 2 subsection 1 AMG-EV).
This also applies to applications filed prior to 1 January 2001.
Attention:
With supplements take care that the dates stated in attribut.txt are identical with the date of
application in the paper version, otherwise the reference might get lost.
4.4 New applications for marketing authorisation in accordance with
Section 21ff. AMG / Request for ENR
If the pharmaceutical company intends a new authorisation procedure, the BfArM is first to be
informed of this in writing under the mailing address:
Bundesinstitut für Arzneimittel und Medizinprodukte
Z14.1.01 – Antragseingang / Fachregistratur
Kurt-Georg-Kiesinger-Allee 3
53175 Bonn,
preferably via telefax no.:+49 (0)228/207-3681, stating the name of the medicinal product and the
pharmaceutical form. As a response to this informal letter, the applicant will receive a processing
number (ENR) reserved for this procedure.
In the case that the pharmaceutical company, as the applicant, has commissioned a consultant to
apply for the ENR on the applicant’s behalf, the PNR of the pharmaceutical company (applicant)
must always be stated. Enclose a power of attorney unless already available at BfArM.
Once received, the processing number should always be stated throughout the documents for
application as well as in the dossier (e.g. in the corresponding field of the application forms).
Page 8 / 38
Attention:
Please do not reserve processing numbers as so-called "variables". The application should be
submitted within four weeks after reservation of a processing number.
As before, only actual submission of the application is relevant for the date of receipt of the
application and not the advance assignment of the processing number.
5
Technical specifications concerning e-mails
More than one electronic submissions for one and the same ENR are possible. Since the system
allocates ’serial number of the day’, previous submissions do not get overwritten.
The files to be sent with the submitted document should be compressed with the help of a
compression program (e.g. zip or tar-formats) (cf. 5.3.1 Zip container).
Attention:
The following examples use zip containers, but they also apply to tar containers.
5.1 E-mail subject
Only the 7-digit processing number (ENR) which is intended for the submission is to be stated in
the subject line of the e-mail. The validation program checks whether the subject line exclusively
states the processing number (ENR), if not, the e-mail is rejected. The e-mail is likewise rejected if
the subject line is empty. The sender is not informed of this fact as the e-mail is considered spam
mail.
5.2 E-mail content
The text (“content”) of the e-mail is optional and is not evaluated by BfArM but is returned as an
attachment to the confirmation of receipt. Therefore, the text can be used for in-company
purposes.
5.3 E-mail attachments and file formats
Every e-mail contains a zip container attachment with the files of the documents to be submitted
including the attribut.txt with its metadata. If necessary, the zip container can be encrypted (cf.
5.3.4. Checklist).
5.3.1
Problems with the MS-TNEF format in Outlook
The use of MS outlook (MS-TNEF format) may cause problems because MS-TNEF chabges the
file name: it packs the zip container in a winmail.dat thus blocking the electronic submission; the
sender will wait in vain for a system response. For this reason, deactivate MS-TNEF in Outlook.
Deactivation of MS-TNEF-formats:
Select ”e-mail format“ in the index card/in der Registerkarte „E-Mail-Format“ auswählen
Change to “text only“ in format selection/Formateinstellung auf „Nur Text“ ändern
Save the changes and re-write the e-mail.
Page 9 / 38
5.3.2
Zip containers
Exactly one zip container shall be provided with every e-mail. The name of the zip container shall
be as follows: <7-digit ENR>. zip
Example: 1999023.zip
Websites for information about data compression
http://www.tu-chemnitz.de/ods/waldenburg/linux/packen/zusammenfassung.htm
http://www.linux-forum.biz/tutorial_tar.php
www.zdnet.de (Freeware-Download-Portal)
http://www.pcmagazin.de/datatip/common/dtt/file.php?areaid=56&orderby=lastModified&dsp_start=0&fileid=772
&modus=suche&such=winzip&DTT_filter=
5.3.3
Files with documents to be submitted
Currently, the only file format readable by the BfArM with a justifiable effort in accordance with
Section 1 sub-section 2 AMG-EV is the Rich Text Format (*.rtf) (cf. BR-Drs./resolution 745/00,
p. 5).
Use of the .pdf format (*.pdf) is permissible for complete documents if the text contained therein is
additionally submitted separately as an .rtf file with identical name (cf. 5.4 File name convention).
Furthermore, it is allowed to submit Module 2.3 “Quality Overall Summary” (also for Quality Expert
Statement) exclusively as a .pdf file.
However, the .pdf files must not contain any restricted or scanned documents.
Modules 1.4.1 - 1.4.3
ixq = Information about the Expert - Quality Expert;
ixn = Information about the Expert -Non-Clinical Expert;
ixc = Information about the Expert -Clinical Expert)
are currently not part of the electronic submission. In any case they are to be submitted in paper
and can additionally be submitted as .pdf files.
Due to the possibility of transmitting macro viruses, files in MS Word format are excluded from
processing.
Furthermore, the use of text fields in the actual text is not permitted for safety reasons (with the
exception of headers and footers).
Attention:
The files must be saved with MS Word as .rtf files. It is not sufficient to change the file extension to
".rtf".
Page 10 / 38
5.3.4
Files with metadata
Each zip container (attached to each submission mail) includes a file with metadata (attribut.txt), as
already stated in 5.3 E-mail attachments and file formats. The file format is text (.txt), the standard
file name is: attribut.txt
The file contains the following describing attributes:
Table 2 – Construction of attribut.txt for procedure types
authorisation:
renewal:
post-approval:
zulassung
verlaengerung
nachzulassung
Variation:
aenderung
Note: a. m. types of procedure apply likewise
to the authorisation of homeopathic
medicines with specified indication/s.
Content of attribut.txt for the authorisation
procedure for homeopathic medicines
without specified indication/s:
Registration
Post-registration
registrierung
nachregistrierung
pnr = pharmaceutical manufacturer number
enr = entry number
verf = type of procedure
edat = dd.mm.yyyy (date of submission
identical with the date of cover letter of
paper version submission)
pnr = pharmaceutical manufacturer number
enr = entry number
verf = variation
aend = dd.mm.yyyy (date of submission
identical with the date of cover letter of
paper version submission)
Example attribut.txt:
Example attribut.txt:
pnr = 0000000
enr = 1999023
verf = authorisation
edat = 24.12.2006
pnr = 0000000
enr = 1999023
verf = variation
aend = 24.12.2006
Attention:
As in the above examples the following notation is preferred:
lower case letters for the field names,
blanks before and after the equals signs,
lower case letters for the value list
date format (dd.mm.yyyy).
pnr (number for pharmaceutical company) always 7-digit, if necessary, leading zeros.
enr (processing number) always 7-digit.
Page 11 / 38
5.3.5
Search for ENR / PNR
ENR and PNR can be searched for at www.dimdi.de in AMIS Public Section (chargeable part of
the DIMDI database offer).
5.3.6
Encryption of the container
Optionally, the zip container can be encrypted.
The encryption software will automatically add to the file name of the container „.pgp“ or „.gpg“,
depending on the software used, so the file name is
either
<7-digit ENR>. zip.pgp
or
<7-digit ENR>. zip.gpg
Only entire zip or tar containers should be encrypted. Individual files of a zip container shall not be
encrypted.
5.3.7
Encryption software
Exclusively the PGP (Pretty Good Privacy) program or a product compatible with OpenPGP are to
be used for encryption. Other encryption methods cannot be processed or used without an
unjustifiable effort. The free program GnuPG and information on its use can be found on the
internet under www.winpt.org or www.gnupg.de. The product is called, e.g., Windows Privacy Tray
(WinPT Tray … released).
Depending on the version of the program, German is not used continuously. Example: Windows
Privacy Tray, Version 07.96rc1 (2003-04-26).
The following is a description of the necessary steps for downloading the encryption software:
1. Download of "gnupp-1.1-de-installer.exe" to a specified directory (e.g. C:\Programs\GnuPP)
and installation of the program.
2. The programme ”Windows Privacy Tray” is started from the start menu
(Start -> Programs -> GnuPP -> Windows Privacy Tray);
it is then constantly available in the taskbar.
5.3.8
Encryption with the BfArM key
You will find the respective valid public key of the BfArM in the file:
http://www.bfarm.de/cln_042/nn_424576/DE/Arzneimittel/amgEv/umsetzung/umsetzungnode.html__nnn=true .
You can download the key (file BfArM-OpenPGP-AS-Key.asc) for encryption in the course of
submissions in accordance with the AMG-EV and save as BfArM-OpenPGP-AS-Key-asc.txt in
your computer.
The public key is replaced by a new one every six months on 2 January and 1 July.
This serves to increase the safety of both parties.
Use of an expired key generates an error message.
5.3.9
Downloading of the BfArM key, encryption of the zip container
The following is a description (Figures 1 to 11) of the necessary steps for downloading the public
BfArM key and encrypting the zip container (Fig. 13 shows an e-mail prepared for an electronic
submission plus attachment with encrypted zip container):
Page 12 / 38
1.
Fig 1 Dialogue for download of BfArM public key
2.
Fig 2 Download subdirectory
The file with the key is stored in your system in a download subdirectory you create yourself.
Page 13 / 38
3.
Fig 3 Import of key into key manager / „Schlüsselverwaltung“
The BfArM public key is integrated via the menu option "Schlüsselverwaltung"/“key manager” of
the Windows Privacy Tray. Click on "Import" in the "Schlüssel"/”key” menu.
4.
Fig 4 Selection and iImport of BfArM public key
The downloaded BfArM key file is selected and then imported.
Page 14 / 38
5.
Fig 5 „Schlüsselimport“/”key import” dialogue
Click on "Öffnen" to open the "Schlüsselimport" dialogue. Click on "Import" to receive status
message as in Fig. 6.
6.
Fig 6 Status message „Schlüsselimport“
7.
Fig 7 Display of imported key
Click on "OK" as in Fig. 6 to display the imported key in ”Schlüsselverwaltung“/”key manager”. If
the key is not displayed immediately close the ”Schlüsselverwaltung“/”key manager” and reopen.
Page 15 / 38
8.
Fig 8 Fingerprint – degree of trust
In the "Schlüssel" menu option "Eigenschaften" you can check the fingerprint and adjust the
degree of trust.
9.
Fig 9 Fingerprint check
For verification of key identity compare the fingerprint of the imported key with the published
fingerprint.
Page 16 / 38
10.
Fig 10 Ownertrust
11.
Fig 11 Encryption of zip container
Open the file to be encrypted. Open “Datei”/file in the “Dateimanager”/file manager and click on
“Verschlüsseln“ to encrypt the .zip-file.
Page 17 / 38
12.
Fig 12 Selection of BfArM key
Select the BfArM key in the "Datei verschlüsseln"/encrypt file dialogue.
The status in the file manager states that the file has been encrypted. This is also apparent from
the automatically added extension ".gpg". The file with the double extension "~.zip.gpg" is the
encrypted zip file to be sent to the BfArM.
13.
Fig 13 Email with attached zip container
Now the mail is ready for electronic submission and can be sent. The encrypted zip container, e.g.
1234567.zip.gpg, is attached.
Page 18 / 38
5.4 File name convention
In accordance with the AMG-EV, the applicant must name the files in a zip container of an
electronic submission pursuant to a harmonised file name convention:
The minimum designation for the BfArM (cf. 5.4.1 Elements of file name, Table 3 - type of
document, file name requirements) shall precede any company term.
Attention:
The following types of document have been newly adopted:
palen for patient information leaflets in English (while document type pal has ceased to exist)
palde for patient information leaflets in German (while document type pal has ceased to exist)
phvsis for parmacovigilance system and qualified person
riskmp for risk management action plan.
Type of document (possibly with a respective sequential number which is added after a hyphen)
and company term are separated by a hyphen. The hyphen after type of document is only
necessary if a company term is added. Further hyphens can be included within this designation.
The file name convention of the ICH eCTD Specification V 3.0 of 8 October 2002 shall be observed
(cf. 5.4.2 file name convention).
As a rule, only one file of one type of document may be sent per mail.
For several types of document, submission of multiple files per type is permitted. In this case the
files are to be named with the corresponding type of document and a sequential 3-digit number.
The numbering is an inherent part of the file name and must also be assigned if only a single file is
submitted. Thus, the following file name would result, e.g., for "labelling (inner pack)":
labip-001.rtf
labip-002.rtf
etc
It is permitted and even encouraged that the files be submitted, possibly with the text corrections
automatically made by MS Word highlighted. However, the identification of such files in the name
of the file is not required. Further versions of this file (e.g. without the markings (clean version))
shall not be submitted.
If a document contains diagrams or pictures, handling can be simplified as follows:
a) in the .rtf format, diagrams and pictures are omitted
b) in addition to the .rtf file, a .pdf file shall be submitted with the same file name which contains
the complete text including diagrams and pictures.
Example: labip-001.rtf and labip-001.pdf
Page 19 / 38
Attention:
The pdf file must not contain any restrictions. The submission is also rejected if only the pdf file is
submitted without the corresponding rtf file.
The sole exception is the type of document “Quality Overall Summary”, which can be submitted
either as .rtf file or as pdf file (cf. 5.4.1, Table 3 under qos-001).
The types of document ixq, ixn and ixc are to be submitted in paper and can additionally be
submitted as .pdf files.
Hyperlinks are not permissible.
5.4.1
Elements of file names for electronic submission to BfArM
Only those types of document stated in the list below shall be submitted electronically. The
required file names are arranged in column 1 (left). See also our example zip container
1999023.zip published on our homepage.
Example:
palde.rtf
qos-001.rtf
In accordance with the file name convention (cf. 5.4.2.), you can make optional name extensions
by hyphens.
Example:
qos-001-optional-extension.rtf
It is recommended that the file name be structured:
<document-><enr>-<procedure>-<yyyy-mm-dd>
(yyyy-mm-dd is identical with the date of application in paper)
Example:
palen-1999023-verl-2005-09-29.rtf
Please remember that in additional submissions of pdf-documents, rtf file name and pdf file name
are identical.
Example:
palen-1999023-verl-2005-09-29.rtf
palen-1999023-verl-2005-09-29.pdf
For files with diagrams and pictures:
<Type of document according to the list below>[-<optional>].extension.
Attention:
The brackets are not part of the file name. They specify the part that can be inserted
optionally. Of course, the limitations stated in Point 5.4.2 with regard to use of upper and
lower case and characters are also to be observed for this part.
Example:
labbl-1999023-verl-2005-09-29.rtf
Observe the notes following Table 3.
Page 20 / 38
Table 3 – Types of Document, set file names
Type of
German Term /
Document
designation in
(always first
accordance with
component of
file name)
English Term (NTA,
Vol 2 B)
spcde
§ 11a AMG:
Fachinformation
Summary of Product
(CTD 1.3.1)
Characteristics (Part IB) Summary of Product
Characteristics
.rtf (always)
.pdf (if
applicable,
additionally)
spcen
Summary of Product
characteristics (the
English version to be
harmonised)
Summary of Product
Characteristics
.rtf (always)
.pdf (if
applicable,
additionally)
spcpal
Section 11a paragraph
4 AMG
Kombinierte Fach- und
Gebrauchsinformation
labbl
Section 10 AMG:
Beschriftung der
Durchdruckfolie (for
tablets)
Labelling (Blister)
(CTD 1.3.1)
Labelling Blister
.rtf (always)
.pdf (if
applicable,
additionally)
labip-001
(cf. notes at
end of Table)
Section 10 AMG:
Beschriftung des
Packungsinhalts
(z.B.Tablettenröhrchen,Tropffläschchen)
Labelling (inner pack)
(CTD 1.3.1)
Labelling inner pack
.rtf (always)
.pdf (if
applicable,
additionally)
labop-001
(see notes at
end of Table)
Section 10 AMG:
Beschriftung der
Packungsumhüllungen
(z.B. Faltschachteln)
Labelling (outer pack)
(CTD 1.3.1)
Labelling outer pack
.rtf (always)
.pdf (if
applicable,
additionally)
labpal-001
(see notes at
end of Table)
Section 10 AMG:
package leaflet
(z.B. Etikettaufkleber
auf
Mineralwasserflaschen)
palde
Section 11 AMG:
German product
information,
(Beipackzettel,
Patienteninformation)
Package Leaflet
(CTD 1.3.1)
Package Leaflet
.rtf (always)
.pdf
(if applicable,
additionally)
palen
Section 11 AMG:
English product
information,
(Beipackzettel,
Patienteninformation)
Package Leaflet
(CTD 1.3.1)
Package Leaflet
.rtf (always)
.pdf (if
applicable,
additionally)
ixq-001
(see notes at
end of table)
Lebenslauf /
Veröffentlichungen des
Sachverständigen zum
analytischen Gutachten
(EU Module 1;
1.4.1)
Information
about the Expert
Quality Expert
in paper
(always)
.pdf (if
applicable,
additionally)
Term according to
NTA (CTD, NTA, Vol 2
B)
(CTD 1.3.1)
Summary of Product
Characteristics
Permissible
File Formats
.rtf (always)
.pdf (if
applicable,
additionally)
.rtf (always)
.pdf (if
applicable,
additionally)
Page 21 / 38
Type of
German Term /
Document
designation in
(always first
accordance with
component of
file name)
English Term (NTA,
Vol 2 B)
Term according to
B)
Permissible
File Formats
ixn-001
(see notes at
end of table)
Lebenslauf /
Pharmakologischtoxikologischen
Gutachten
(EU Module 1;
1.4.2)
Information about the
Expert
- Non-Clinical Expert
in paper
(always)
.pdf (if
applicable,
additionally)
ixc-001
(see notes at
end of table)
Lebenslauf /
klinischen Gutachten
(EU Module 1;
1.4.3)
Information about the
Expert
- Clinical Expert
in paper
(always)
.pdf (if
applicable,
additionally)
era
Umweltrisikobewertung
(CTD 1.6)
Environmental Risk
Assessment
(CTD Annex)
.rtf (always)
.pdf (if
applicable,
additionally)
phvsys
Section 22 2.
Pharmacovigilance
paragraph 6 AMG
system and qualified
PharmakovigilanzPerson
system und qualifizierte
Person
(EU Module 1;1.8.1)
PharmacovigilanceSystem
optional:
.rtf
.pdf
riskmp
Maßnahmenplan zur
Risikoüberwachung
Risk Management Plan (EU Module 1;
1.8.2)
Risk-ManagementSystem
optional:
.rtf
.pdf
intro
Produktprofil
Product Profile
(CTD 2.2)
Introduction
.rtf (always)
.pdf (if
applicable,
additionally)
qos-001
(see notes at
end of Table)
Analytisches
Sachverständigengutachten
Quality Expert Report
(I.C.1)
(CTD 2.3)
Quality Overall
Summary and
Quality Expert
Statement
optional:
.rtf
.pdf
qts
Anhang 1:
Tabellarische
Aufstellung zum
Appendix 1:
Tabular Formats
Safety Update Report
Licensing Status
.rtf (always)
.pdf (if
applicable,
additionally)
qws
Anhang 2:
Appendix 2:
Schriftliche
Written Summary
Zusammenfassung des
Sachverständigengutachtens
Safety Update Report
Sales Volume
.rtf (always)
.pdf (if
applicable,
additionally)
qoses
Erklärung des Sachver- Expert Statements
ständigen gemäß
BfArM-
Environmental Risk
Assessment
(IIIR / II H)
.rtf (always)
.pdf (if
applicable,
Page 22 / 38
Type of
German Term /
Document
designation in
(always first
accordance with
component of
file name)
Bekanntmachung vom
27.11.2000 (Punkt 7)
English Term (NTA,
Vol 2 B)
nco
Section 24 sub-section
1 Nr. 1 AMG
Pharmakologischtoxikologisches
Preclinical Expert
Report
(I.C.2)
(CTD 2.4)
Nonclinical Overview
.rtf (always)
.pdf (if
applicable,
additionally)
co
1 Nr. 3 AMG
Klinisches Sachverständigengutachten
Clinical Expert Report
(I.C.3)
(CTD 2.5)
Clinical Overview and
Clinical Expert
Statement
.rtf (always)
.pdf (if
applicable,
additionally)
ncs
Zusamenfassung des
Pharmakologisch-toxikologischen Sachverständigengutachtens
(CTD 2.6)
.rtf (always)
.pdf (if
Nonclinical Summary,
possibly separated into: applicable,
additionally)
ncsi
Einführung
(CTD 2.6.1)
Nonclinical Summary
Introduction
.rtf (always)
.pdf (if
applicable,
additionally)
plws
Zusammenfassung
Written Summary
des pharmakologischen (I.C.2)
Gutachtens
(CTD 2.6.2)
Pharmacology Written
Summary
.rtf (always)
.pdf (if
applicable,
additionally)
plts
Tabellarische
Aufstellung zum
pharmakologischen
Gutachen
(CTD 2.6.3)
Pharmacology
Tabulated Summary
.rtf (always)
.pdf (if
applicable,
additionally)
pkws
Zusammenfassung des Written Summary
pharmakokinetischen
(I.C.2)
Gutachtens
(CTD 2.6.4)
Pharmacokinetics
Written Summary
.rtf (always)
.pdf (if
applicable,
additionally)
pkts
Tabellarische
Aufstellung zum
pharmakokinetischen
Gutachten
(CTD 2.6.5)
Pharmacokinetics
Tabulated Summary
.rtf (always)
.pdf (if
applicable,
additionally)
tows
Zusammenfassung
des toxikologischen
Gutachtens
(CTD 2.6.6)
Toxycology Written
Summary
.rtf (always)
.pdf (if
applicable,
additionally)
tots
Tabellarische
Aufstellung zum
toxikologischen
(CTD 2.6.7)
Toxicology Tabulated
Summary
.rtf (always)
.pdf (if
applicable,
additionally)
Term according to
B)
Permissible
File Formats
additionally)
Tabular Formats
(I.C.2)
Written Summary
(I.C.2)
Tabular Formats
(I.C.2)
Page 23 / 38
Type of
German Term /
Document
designation in
(always first
accordance with
component of
file name)
English Term (NTA,
Vol 2 B)
Term according to
B)
Permissible
File Formats
cs
Klinische
Zusammenfassungen
(CTD 2.7)
.rtf (always)
.pdf (if
Clinical Summary,
possibly separated into: applicable,
additionally)
sbpm
Bekanntgabe der bioWritten Summary
pharmazeutisch-analyti- (I.C.3)
schen Methoden
(CTD 2.7.1)
Summary of
Biopharmaceutics and
Associated Analytical
Methods
.rtf (always)
.pdf (if
applicable,
additionally)
scps
Bekanntgabe der
klinischpharmakologischen
Studien
(CTD2.7.2)
Summary of Clinical
Pharmacology Studies
.rtf (always)
.pdf (if
applicable,
additionally)
sce
Erklärung zur klinischen Written Summary
Wirksamkeit
(I.C.3)
(CTD 2.7.3)
Summary of Clinical
Efficacy
.rtf (always)
.pdf (if
applicable,
additionally)
scs
Erklärung zur klinischen Written Summary
Sicherheit/Unbedenklic (I.C.3)
hkeit
(CTD 2.7.4)
Summary of Clinical
Safety
.rtf (always)
.pdf (if
applicable,
additionally)
syis
1 Nr. 3 AMG
Inhaltsangabe/Gegenüberstellung zum klinischen Sachverständigengutachten
(CTD 2.7.6)
Synopsis of Individual
Studies
.rtf (always)
.pdf (if
applicable,
additionally)
Written Summary
(I.C.3)
Tabular Formats
(I.C.3)
Notes:
The set file names (column 1 left) for types of document characterised by sequential 3-digit
numbers (e. g. qos-001) are inherent parts of the file names. The sequential number must also be
assigned if only one sinlge file is submitted electronically:
For submission of different drafts of labelling in accordance with Section 10 AMG regarding various
package sizes, beginning with the smallest size
For diverse information on the expert in an e-mail structured according to the order of the EU
Modules:
EU Module 1.4 "Information about the Expert" is divided into two documents
•
illustration of the scientific and occupational development of the expert
- declaration by the expert concerning the delivered Expert Report.
•
Both documents must be signed by hand. Therefore, they currently need not be part of the
electronic submission; however, they can be submitted electronically (e.g. also as a .pdf
file) and must be submitted on paper in any case.
Page 24 / 38
The analytical Expert Report shall be submitted preferably in a single file in .rtf format or in .pdf
format. However, since some companies already use a structure in accordance with the eCTD, the
individual submodule can alternatively be numbered serially beginning at 001.
5.4.2
File name convention in accordance with ICH eCTD Specification
File extension:
All files must have only one file extension (i.e. only 1 dot!), e.g.
nnnnn.pdf nnnnn.rtf
Name:
The file name must have no more than 64 characters. Only lower case letters are allowed – this
also applies to the extension. The following characters are admissible:
•
- letters from "a" to "z" [U+0061 to U+007A]
•
- numbers "0“ to "9" [U+0030 to U+0039]
•
- special characters "-" [HYPHEN, U+002D]
The notation "U" refers to Unicode.
Note: incorrect file names without extension are e.g.:
part a
(' '; blank is not permissible)
myfile.xml
('.'; dot is not permissible)
hello:pdf
(':'; colon is not permissible)
part_a
('_': underscore is not permissible)
änd
('ä' or 'ö' or 'ü' umlauts are not permissible).
Page 25 / 38
5.4.3
Checklist to monitor whether all conditions have been fulfilled
Table 4 – Checklist Item
Item
Entry
Example
Create .txt file with metadata
with the standard name
"attribut.txt" (cf. Point 5.3.3 File
with metadata)
pnr =
number for
pharmaceutical
company
enr = processing number
verf = value list:
aenderung
nachzulassung
registrierung
nachregistrierung
verlaengerung
zulassung
Type of date
either
edat = date of submission
dd.mm.yyyy
or
aend = date of variation
(only in case of
notifications of
variation)
dd.mm.yyyy
pnr = 7654321
enr = 1234567
verf = zulassung
edat = 12.12.2002
File name convention for text
files
(cf. 5.4.1 Elements of file names
5.4.1 File name convention)
64 characters
no special characters
only lower case letters
term for type of document
comes first separated from
company file name by a hyphen
.rtf is the only file format
permissible
spcde-optional-20030303-dkl.rtf
Treatment of documents that
contain diagrams and pictures:
create .rtf file with text and enter
wildcards [<Type of DocumentENR-pdf>] for the pictures.
Additionally submit complete
document as .pdf file (must not
contain any restrictions). Except
for the extension, both files
must be given the same file
name
5.4.1 Elements of file names
5.4.2 File name convention…
hyphen
company file name
.rtf (for the text file)
hyphen
company file name
.pdf (for the complete document
(text with diagrams and
pictures)
spcde-optional.rtf
spcde-blabla.pdf
Page 26 / 38
Item
Entry
Example
Expert Report
File name (cf. Point 5.4.1
Elements of file names)
Expert Reports must likewise
be renamed in accordance with
the file name convention. The
analytical Expert Report (qos =
Quality Overall Summary) can
alternatively be submitted as an
.rtf file or as a .pdf file
qos001-optional.rtf
Compress files: make
containers (cf. 5.3.1 Zip
container)
Put the file "attribut.txt" and the
files with the documentation to
be submitted into a container by
way of a compression program
(.zip format or .tar format). The
container receives the ENR as
file name.
Example: 1999023.zip
Encryption of containers (cf.
5.3.5)
Encryption of containers is
optional
Example: 1999023.zip.pgp
Sending of e-mail attachments
(cf. Point 5.3)
The container is attached to the
e-mail
Example:1999023.zip
or
1999023.zip.pgp
E-mail subject (cf. Point 5.1)
Processing number (ENR)
Example: 1999023
E-mail content (cf. Point 5.2)
optional
The following files have been
submitted for procedure xyz,
application date ??.??.200x
6
Verification and confirmation of e-mails
The submitter receives several confirmations by e-mail, depending on the status of the verification.
All response mails contain unique numbers in the subject-line (e.g. positive response 1 (P20060317_000039) for ENR 1999023). This number is to be quoted in case of queries.
6.1 Confirmation of receipt and confirmation as to the coherence of the
formal/technical properties
After receipt of the e-mail at the DIMDI's server designated for submissions in accordance with the
AMG-EV, it is verified according to the following purely formal criteria:
•
Does the e-mail contain the required attachments (zip container) with the required
extensions?
•
Are file names in accordance with the file name convention?
•
Is the name of the zip container in accordance with the name convention?
•
Are the characteristics of the "attribut.txt" file as required?
•
Does the e-mail subject line exclusively contain the 7-digit processing number (ENR)
•
Has the zip container been encrypted exclusively with the mandatory encryption?
•
Are the files in the zip container unencrypted?
Page 27 / 38
•
Was the BfArM key used to encrypt the file container?
•
Was the required compression program (.zip or .tar) used?
If no mistakes are found, the submitter receives a confirmation of receipt in the subject line
"Positivmeldung <sequential number>"; however, this merely refers to the formal accuracy of the email. There are no further positive notices.
Incorrect e-mails are rejected promptly with a confirmation of receipt in the subject line:
"Negativmeldung <sequential number>".
E-mails with no or faulty subject lines are discarded as spam without notification of the sender.
6.2 Confirmation as to the intellectual verification of content
Further formal mistakes can only be determined intellectually, e.g.
•
Processing number and content do not correspond.
•
The file cannot be opened.
•
The file cannot be read.
•
The file is not in the correct format.
The submitter is informed of these mistakes via e-mail.
The intellectual verification of the submission content can result in different confirmations (notice of
marketing authorisation etc.). Should further mistakes be observed during the course of this, they
will be communicated via individual correspondence.
Should one of the formal/technical errors be recognised in the course of processing, further
validation is discontinued and a mail with the corresponding error message (cf. 6.3 Possible error
messages) is returned to the sender's address. We kindly ask that such error messages be first
analysed by the sender before BfArM is contacted with possible queries.
If a submission is correct as to formal/technical aspects, receipt is confirmed in an e-mail (subject
line: "Positivmeldung").
Page 28 / 38
6.3 Possible error messages regarding electronic verification of
coherence of formal/technical characteristics
Note:
This list of errors is dynamic and will be updated on an ongoing basis as new errors emerge.
Table 5 – Error message
Error Message
Possible Cause
Proposed Solution
Die Maildatei ist fehlerhaft.
The structure of the mail is incorrect and it
can therefore not be processed.
Check type, version, or
settings of own mail client.
Der Mailanhang konnte nicht
entschlüsselt werden.
The structure of the encrypted file is
presumably defective.
Check type, version, or
settings of own encryption
software.
Die Mail enthält mehr als
eine GPG/PGP-Datei. Es
darf nur eine verschlüsselte
Datei im Mailanhang
vorhanden sein.
Only one encrypted container per mail is
permitted.
Send a separate mail per
container.
Fehler beim Entpacken der
Zip-Datei. Die Zip-Datei ist
wahrscheinlich beschädigt.
The archiving format employed (*.zip) is
faulty (the check sum is incorrect, data is
incomplete, etc.)
Check the archiving program
employed and settings.
Create a new mail with
archive file and send.
Die Anzahl oder der Typ der
Mailanhänge entspricht nicht
den formalen Vorgaben.
Only the container and its separate
signature may be attached.
archive and signature file and
send.
Fehler beim Extrahieren der
tar-Datei. Die tar-Datei ist
wahrscheinlich beschädigt.
The archiving format employed (*.tar) is
faulty (the check sum is incorrect, data is
incomplete, etc.)
Check the archiving program
employed and settings.
Der Mailanhang enhält nicht
zulässige Dateitypen. Die
Datei <DATEI> entspricht
nicht den formalen
Vorgaben.
Only files with the extensions .rtf, .pdf, and
the "attribut.txt" file are permissible.
Correct types of file and
create new container.
Der Name der Datei
<DATEI> enthält nicht
zulässige Zeichen.
Permissible characters are: lower case
letters [a-z], numbers [0-9], and hyphens.
The container shall be
named "<ENR>.zip" or
"<ENR.tar".
Die Mail enthält keine
Attributdatei im Anhang.
The "attribut" file is necessary for validation
and processing of the submission
Cf. Explanatory notes in
5.4.3 File with metadata
Die Mail enthält mehr als
eine Attributdatei im
Anhang.
Only one "attribut.txt" is permitted.
Delete redundant files and
create new container.
Die Angaben in der
Attributdatei sind nicht
vollständig.
Syntax error in the file "attribut.txt".
5.4.3 File with metadata
Das Format der ENR
<ENR> in der Attributdatei
ist nicht korrekt. Die ENR
muss immer siebenstellig
Syntax error in the file "attribut.txt". The
ENR must always consist of 7 digits.
5.4.3 File with metadata The
correct ENR can be found in
"AMIS Public Section".
Page 29 / 38
Error Message
angegeben werden.
Possible Cause
Proposed Solution
Das Format der PNR
<PNR> in der Attributdatei
ist nicht korrekt.
PNR must always consist of 7 digits.
Your correct PNR can be
found in "AMIS Public
Section".
Das Format des Feldes
EDAT in der Attributdatei ist
nicht korrekt.
format is "dd.mm.yyyy".
Check spelling, observe date
format, cf. Point 5.4.3 File
with metadata
Der Name einer Datei
(<DATEI>) im Mailanhang
entspricht nicht den
formalen Vorgaben.
Permissible characters are: lower case
letters [a-z], numbers [0-9], and hyphens.
5.4.1 Elements of file names
… and 5.4.2 File name
convention
Der Mailanhang enthält nicht
zulässige Dokumenttypen.
Die Datei ERRVAO>
enspricht nicht den formalen
Vorgaben
The file name convention was disregarded.
Cf. with the list of types of
document in 5.4.1 Elements
of file names, and change
accordingly.
Der Mailanhang enthält nicht
zulässige Dokumenttype.
Die Datei <ERRVA>
entspricht nicht den
formalen Vorgaben
The file name convention of the palde
and/or palen type of document was
disregarded.
‘pal’ has been replaced by ‘palde’ for the
German language and by ‘palen’ for the
English language patient information leaflet
Compare with the list of
types of document 5.4.1
Elements of file names and
change accordingly
Die ENR (<ENR>) in der
Attributdatei ist unbekannt.
The ENR is possibly incorrect.
Your correct ENR can be
Section".
Es sind mehrere
Dateiarchive (zip oder tar)
im Mailanhang vorhanden.
Exactly one archive file must be attached
Es ist kein Dateiarchiv (zip
oder tar) im Mailanhang
vorhanden.
Exactly one archive file must be attached
Die ENR (<ENR>) aus MailBetreff, Containernamen
und Attributdatei stimmen
nicht überein.
Only the 7-digit ENR is to be stated in the
subject line.
Cf. Explanatory notes in 5.2
E-mail subject
Die ENR im Betreff-Feld der
Mail ist unbekannt.
Section".
Der Name der Archivdatei in
der Mail ist nicht korrekt.
The name must read <ENR>.zip or
<ENR>.tar. Cf. Explanatory notes in
5.3.2 Zip container
Give archive file correct
name, create a new mail with
Die ENR (<ENR>) im
Namen der Archivdatei der
Mail ist unbekannt.
Section".
Die Bezeichnung des
Verfahrens (<VERF>) in der
Datei "attribut.txt" ist nicht
korrekt.
Syntax error in the file "attribut.txt".
Check spelling, observe date
format, cf. also 5.4.3 File with
metadata
Page 30 / 38
Error Message
Possible Cause
Proposed Solution
Der Datencontainer im
Mailanhang enhält
verschlüsselte Dateien.
Files in a container must not be encrypted.
Make new container with
unencrypted files. Send mail
again.
Das Format des Feldes
"AEND" (<ERRVARO>) in
der Attributdatei ist nicht
korrekt
Typing error
Date = dd.mm.yyyy
cf. 5.4.3 File with metadata
Die Datei <ERRVARO>
enthält nicht das
angegebene Dateiformat
The extension of a doc-file was changed to
.rtf
.doc files must be saved as
.rtf files.
Der Datencontainer im
Mailanhang enthält
Unterverzeichnisse
Result of copying.
Delete subdirectories.
Das Einreichungsdatum ist
ungültig
Typing error, invalid date such as
30.2.2004.
Date = dd.mm.yyyy
Das Änderungsdatum ist
ungültig
Typing error, invalid date such as
30.2.2004.
Date = dd.mm.yyyy
Die PNR (<ERRVARO>) in
der Attributdatei ist
unbekannt
Typing error.
7-digit number
Section".
Mehrere Dokumente eines
Dokumenttyps
(<DOCTYPE<) sind nicht
zulässig
Several files were created for one type of
document.
Exception cf. 5.4 File name
convention
Otherwise merge all files to a
type of document.
Das Änderungsdatum ist in
der Attributdatei nicht
vorhanden
The declaration verf = aenderung lacks the
respective date.
Date = dd.mm.yyyy
cf. 5.3.3. File with metadata
Die Angabe eines
Einreichungsdatums in der
Attributdatei im Verfahren
"aenderung" ist nicht
zulässig
Typing error.
State the date of the variation
in the "attribut" file
Das Einreichungsdatum ist
in der Attributdatei nicht
vorhanden
Die Angabe eines
Änderungsdatums in der
Attributdatei im Verfahren
"<ERRVARO>" ist nicht
zulässig
State the date of submission
in the "attribut" file
The following is not stated under
"procedure": verf = aenderung.
Check which procedure is
meant
Im Dokumentnamen
"<ERRVARO>" fehlt ein
Bindestrich nach dem
Dokumenttyp.
cf. 5.4.2 File name
convention
Das Format der ENR im
Betreff-Feld der Mail ist nicht
korrekt. Die ENR muss
immer siebenstellig
angegeben werden
Send the mail again with the
corrected subject line.
Page 31 / 38
6.4 Possible error messages regarding intellectual verification of
submitted e-mails
Attention:
This list of errors is dynamic and will be updated on an ongoing basis as new errors emerge.
The following error messages are intellectually marked in the document management system
docuBridge and are generated within the program:
Table 6 – Error message
Error Message
Possible Cause
Proposed Solution
Datei enthält fehlerhafte
Daten
For instance, submitted texts for medicinal
product and processing number (ENR) do
not match.
Check allocation of ENR and
file
Datei kann nicht gelesen
werden
Incorrect character set, wrong format, even
though extension is permissible.
Check character set and
format
Datei kann nicht geöffnet
werden
Wrong format, even though extension is
permissible.
Check format
Falsches Dateiformat
Format is neither .rtf nor .pdf; the extension
is permissible but is not suitable for the
format.
For details cf. 5.4.2 File
name convention
6.5 System response
You will receive an automatic system response (positive or negative response), at the earliest, half
an hour after your electronic submission was sent.
Should you not receive a system response within one day, contact the hotline per email <amgev.hotline@bfarm.de>.
If you have problems with your electronic submission, if you do not receive a system response or a
negative response and if you do not understand what the error is, please do not make further
attempts of submission; instead, contact the hotline immediately via e-mail: amgev.hotline@bfarm.de. In such cases you are advised to provide the original submission e-mail to
the hotline for analysis of the problem.
6.6 What to do in the case of false-positive system responses
6.6.1
Submission under a wrong ENR
If an electronic submission was made under a wrong ENR by mistake, contact the hotline amgev.hotline@bfarm.de for cancellation (cf. Example in Fig. 14). Then repeat the electronic
submission under the correct ENR.
Page 32 / 38
14.
Figure 14 Cancellation of a false-positive system response
6.6.2
Submission of partly wrong data
No cancellation is made if some of the data in the zip container are wrong (among correct ones). In
this case inform the hotline amg-ev.hotline@bfarm.de only about the false-positive system
response (e. g. positive response 1 (P-20060317_00003) for ENR 1999023) and the invalid files
contained in it. Then send another electronic submission with the correct data.
In both cases the hotline will inform those in charge.
Page 33 / 38
7
Important information concerning permission of exclusive
submission of paper documents in accordance with Section 3
AMG-EV
We advise you that applications for exceptional permissions in accordance with Section 3 number
1 AMGEV can only be made related to the procedure, i.e. with reference to the individual medicinal
product.
As a rule, an exception can only be granted without further inquiry, if the reasoning of the
application shows comprehensibly and conclusively that the applicant fulfils all prerequisites of an
"undue hardship". Global statements without further explanation necessarily lead to procedural
delays and/or to rejection of the application. In this context please also observe the following:
If an undue financial burden is claimed, more details are necessary especially as to the expected
costs of compilation and electronic submission of the required documents as well as a comparison
of these costs with the presumed turnover from the medicinal product concerned.
In the case of technical reasons these are to be explained in detail and justified. Where applicable,
it should be stated why electronic submission of the documents is impossible also if the help of
others is enlisted.
Exceptional permissions in accordance with Section 3 number 1 AMG-EV are generally only
granted temporarily. This means that the documents must be supplemented electronically in the
procedure after termination of the exemption. In order to ensure that an adequate time limit is fixed,
applicants are requested to declare, upon submitting the application, when the obstacles asserted
will presumably be removed.
Page 34 / 38
8
List of changes
Date
Version
Chapter/Paragraph Reason for change
16 May
06
4.09
The Explanatory Notes have been revised resulting in changed numbers for headings.
Links to websites have been added. We have no influence, though, on possible
changes of web addresses.
16 May
06
4.09
1. General remarks
Category “remarks“ deleted.
16 May
06
4.09
2. E-mail addresses
Revised.
25 May
07
16 May
06
4.09
6. Information
Shifted forward to become Chapter 3. Information plus subchapters
3.1
Contact for electronic submissions/AMG-EV-Hotline/ online variation procedures
3.2
Contact for procedural and scientific questions
3.3
Contact eCTD
16 May
06
4.09
3 Modalities /
Procedures for
electronic
submission
Current number: 4. Modalities / Procedures……
16 May
06
4.09
3.2 Documents to
be submitted
Current number: 4.2 Documents to be submitted
Reference to the Notice to Applicants was updated (October
2005).
16 May
06
4.09
3.4 New
applications for
marketing
authorisation in
accordance with
Section 21 ff AMG
Current number:
4.4. New applications for marketing authorisation in accordance
with Section 21 ff AMG.
Additions to PNR for pharmaceutical company (applicant) and
commissioned consultant for the procedure (application for ENR,
electronic submissions).
16 May
06
4.09
4. Technical
specifications
concerning e-mails
Current number 5. Technical specifications concerning e-mails.
16 May
06
4.09
Punkte
4.1 E-mail subject
4.2 E-mail content
4.3 E-mail
attachments and file
formats
Current numbers:
5.1 E-mail subject
5.2 E-mail content
5.3 E-mail attachments and file formats
16 May
06
4.09
16 May
06
4.09
Addition of new sub-item:
5.3.0 Problems with the MS-TNEF format in Outlook
4.3.1 – 4.3.7
Current numbers:
5.3.1 – 5.3.8
Partly revised, especially for:
date format edat or aend (cf. attribut.txt).
Choice of type of procedure „registrierung“ (authorisation of
homeopathic medicines without specification of indication) for
Page 35 / 38
Date
Version
authorisations from abroad.
16 May
06
4.09
16 May
06
4.09
4.3.7 Downloading
of the BfArM key
Current number:
5.3.8 Downloading of the BfArM key
Fig. 12. E-mail with encrypted zip container updated.
16 May
06
4.09
4.4. File name
convention
4.4.1
4.4.2
4.4.3
Current numbers:
5.4. File nameconvention
5.4.1 Elements of file name for the electronic…
5.4.2 File name convention in accordance with ICH eCTD
specification
5.4.3 Checklist to monitor whether all conditions
In 5.4.1 Elements of the file names …
Information on additional new types of document
palen for English language patient information
palde for German language patient information (cancellation of
pal document type)
phvsis for parmacovigilance system and qualified person
riskmp for risk management plan.
Corresponding supplementation of Table 3.
16 May
06
4.09
4.4.1 Elements of
New examples of file names
file names for the
Revision of the entire table structure and supplements,
electronic…to BfArM especially:
Column „Deutsche Bezeichnung“
Column „Bezeichnung gemäß NTA …“ for
CTD 2.3 „ … sowie Quality Expert Statement“
CTD 2.5 „ … sowie Clinical Expert Statement“
16 May
06
4.09
4.4.1 Elements of
file names for the
electronic…to
BfArM, Table, type
of document,
footnote
Former footnote under table in 4.4.1 has become text in 5.4.1
Element of file names ……., stating that file name in document
type …-001* must be strictly adhered to.
Omission of footnote **“If the dossier was submitted in the
course of an MR procedure prior to July 2003, it is possible to
submit under these types of document in the old EU format until
the end of 2004.“
16 May
06
4.09
5. Verification and
confirmation of emails
5.1
5.2
Current numbers:
6. Verification and confirmation of e-mails
Insertion of new sub-items: 6.1 – 6.6
6.1 Confirmation of receipt and confirmation as to the coherence
of the formal/technical properties.
6.2 Confirmation as to the intellectual verification …
6.3 Possible error messages regarding electronic….
6.4 Possible error messages regarding intellectual …
6.5 System response
6.6 What to do in the case of false-positive system responses
01 August 4.08
04
4.3.2
4.4
5. • listing
The types of document ixq, ixn and ixc are to be submitted in
paper and can additionally be submitted as .pdf file.
01 August 4.08
4.4.1
New column in the list of types of document with the permissible
Addition of a new sub-item:
5.3.4 Search for ENR- / PNR
Page 36 / 38
Date
04
Version
file formats for each type of document
15 March
2004
4.07
3.2
4th paragraph from
the bottom
Based on many comments it has been registered that the type
of document "qos" (Quality Overall Summary) is already
separated into individual documents in accordance with eCTD
by numerous companies. Therefore, multiple submission of this
type of document is possible now by appending a 3-digit
sequential number. The reference to .rtf-file was deleted from
this paragraph as Module 2.3 (qos = Quality Overall Summary)
can now alternatively be submitted as a .pdf file.
15 March
2004
4.07
3.2
3rd paragraph from
the bottom
Deleted as the transmission of electronic signatures is
technically not yet possible.
15 March
2004
4.07
3.2
last paragraph
Information on sending duplicates has been clarified due to
inquiries.
15 March
2004
4.07
4.1
Receipt of an e-mail is not confirmed if either the subject line is
empty or contains something other than the 7-digit ENR alone. It
is assumed to be a spam mail which is immediately discarded.
15 March
2004
4.07
4.3.1.1 new last
paragraph
Assessment of the most frequently occurring errors showed that
apparently merely by renaming the extension (e.g., from .doc to
.rtf) would-be .rtf files are created. However, this is not the case:
they still are .doc files that can be opened, but they are not
encouraged due to the danger of macroviruses or such. The
desired format is only achieved by saving a file as an .rtf file.
15 March
2004
4.07
4.3.2
1st paragraph
Module 2.3 (qos = Quality Overall Summary) can now
alternatively be submitted as an .rtf file or as a .pdf file as this
document is frequently only available to industry in .pdf format.
However, the .pdf file must neither contain restrictions nor
scanned documents.
15 March
2004
4.07
4.3.3
The file "attribut.txt" shall preferably be filled with lower case
letters, however, the validation program also permits upper and
lower case. Furthermore, with consideration to submissions from
abroad, the German umlauts were broken down ("aenderung"
instead of "Änderung"). In this case the validation program is
tolerant and allows both spellings. Furthermore, it is planned
that – after translation of these notes into English – the English
terms for the procedures are also permitted.
15 March
2004
4.07
4.4
2nd paragraph from
the top
Use of the hyphen within the file name was construed
differently. Therefore, it was made clear that the hyphen is a
fixed component of the name of the type of document, if this
type of document can be submitted in multiple by adding a
sequential number. If the type of document is extended by a
company term, the hyphen serves as separation. Within the
company term, as many further hyphens as desired can be
used. Examples for possible alternatives:
spcde.rtf
spcde-internal.rtf
spcde-internal-term-blabla.rtf
qos-001.rtf
qos-001-internal.rtf
qos-001-internal-term-blabla.rtf
Page 37 / 38
Date
Version
15 March
2004
4.07
4.4
4th paragraph from
the top
Some types of document can now be submitted repeatedly with
a sequential numbering following a hyphen. The numbering is a
fixed component of the name of the type of document and must
also be assigned if only one file is submitted (cf. above,
comment on Item 3.2, 4th paragraph from the bottom).
15 March
2004
4.07
4.4
6th paragraph from
the top
Based on several inquiries, the handling of files with diagrams
and pictures has been facilitated. Now, text files without
diagrams and pictures can be submitted in .rtf format and at the
same time the complete file with text and pictures can be
submitted additionally in .pdf format.
An exception to this rule is the type of document "qos" (Quality
Overall Summary), which can either be submitted as an .rtf file
or as a .pdf file.
15 March
2004
4.07
4.4.1
new 1st paragraph
Again and again it is attempted to submit "other" documents
(e.g. cover letters); therefore, it is again expressly pointed out
that only the documents stated in the types of document list are
to be submitted electronically.
15 March
2004
4.07
4.4.1
after the 2nd
paragraph
Adaptation of description and examples to the altered
conventions for submission of documents that contain diagrams
and pictures (cf. above, comment on 4.4, 6th paragraph from
the top).
15 March
2004
4.07
4.4.1 list of types of
documents
In the case of the type of document "labbl" (Labelling (Blister))
there is no longer the possibility of multiple submission with
sequential numbers.
In the case of the type of document "qos" (Quality Overall
Summary), multiple submission is possible now (cf. above,
comment on Item 3.2, 4th paragraph from the bottom).
15 March
2004
4.07
4.4.1 footnote
It is pointed out that the numbering of a type of document is a
fixed component that must always be included.
In point c) it is pointed out that the type of document qos
(Quality Overall Summary) can either be submitted as an .rtf file
or as a .pdf file.
15 March
2004
4.07
4.4.3
Checklist adapted according to the a.m. changes
15 March
2004
4.07
5.
new paragraph
after the 6th
paragraph
The absence of a confirmation of receipt within an appropriate
period of time indicates that the subject line of the e-mail was
missing or not in accordance with the conventions. Such e-mails
are discarded as spam and are not answered.
15 March
2004
4.07
5.1
List of error
messages
Updated.
Page 38 / 38

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