Belgium Regulatory Agency for New Drug Submissions 2014

1. BELGIUM
Prepared by
ZUBER BOBAT
2014
Research Director: Professor Peivand Pirouzi

2. About FAMHP
• Federal Agency for Medicines and Health Products, FAMHP (former
Directorate-General for Medicinal Products of the FPS Public Health)
Created: 01.01.2007
Minister responsible: Maggie De Block, Minister of Social Affairs and
Public Health
Chief Executive Officer: Xavier De Cuyper Public service institution with a
legal personality, classified under category A Competent authority for the
quality, safety and efficacy of medicines and health products
• Fields of competency: research and development (R&D), registration and
marketing authorization, production and distribution (inspection and
control activities), vigilance, proper use of medicines and health products
• Personnel: 390 employees on 01.01.2012 most with scientific
qualifications (doctors, pharmacists, veterinarians)
• Slogan : “Your medicines and health products are our concern.”

3. Who are we ?
Federal Agency For Medicines and Health Products
• The FAMHP(Federal Agency For Medicines and
Health Products) is the competent authority
responsible for the quality, safety and efficacy
of medicines and health products. We work
together with health professionals and other
competent authorities at the national and
international level to ensure the population
the optimal use of the medicines and health
products they need.

4. Our role
• In the interest of public health the FAMHP
ensures the quality, safety and efficacy of
medicines and health products in clinical
development and on the market.

5. Our mission in its legal context
• The FAMHP ensures, from development to use, the
quality, safety and efficacy of medicines for human and
veterinary use (including homeopathic medicines,
herbal medicines, pharmacy made and officinal
preparations) and also medical devices and
accessories, and raw materials for the preparation and
production of medicines.
From collection to use, the FAMHP ensures the quality,
safety and efficacy of all the operations involving with
blood, cells and tissues.
• The law of 20.07.2006 concerning the establishment
and functioning FAMHP

6. Our fields of competency or activities.
• In terms of research and development (R&D) the FAMHP evaluates, approves,
follows and controls the requests for clinical trials for medicines and health
products. We also give scientific advice.
• In terms of registration or marketing authorization of medicines, the FAMHP is in
charge of evaluating new requests for registration or marketing authorization of a
medicine or of requests to change existing registrations or marketing
authorizations.
• In terms of vigilance the FAMHP supervises the adverse effects due to the use of
medicines or health products by collecting information. Information is gathered
and evaluated and, if necessary, measures are taken.
• In terms of production and distribution the FAMHP grants authorizations and
checks that medicines and health products are conform current regulations
concerning manufacture, distribution, delivery, imports and exports. It also
controls pharmacists’ activities and combats illegal practices.
• In terms of proper use the FAMHP sees to it that patients have relevant
information so that medicines and health products are used rationally and safely. It
also controls advertising for medicines and health products.

7. European GMPS
• European Union GMP Guide Volume 4 – EUDRALEX
• Commission Directive 2003/94/EC , of 8 October 2003, laying down the
principles and guidelines of good manufacturing practice in respect of
medicinal products for human use and investigational medicinal products
for human use.
http://ec.europa.eu/health/documents/eudralex/vol-
4/index_en.htm

8. Our new organisation chart (PDF, 4.3 MB)
• From February 1th 2009 our activities are divided into three
Directorates-General (DG), also called pillars: DG PRE, DG POST and
DG INSPECTION.
• DG PRE authorisation (PDF, 22.36 Kb) or all the activities prior to the
first marketing authorisation for a medicine or health product.
• DG POST authorisation (PDF, 23.09 Kb)or all the activities after the
first marketing authorisation for a medicine or a health product.
• DG INSPECTION (PDF, 13.23 Kb)or all inspection and control
activities.
•
Organisation chart of the Chief Executive Officer departments (PDF,
16.86 Kb)
• Organisation chart of the support departments (PDF, 13.27 Kb)

10. Committees established within the FAMHP
Three committees provide direct advice to the Chief Executive Officer about how
the famhp is functioning and how it can achieve its objectives.
Transparancy Committee provides advice on management issues.
Representatives of the sectors contributing to the Agency’s income are
represented in the Transparency Committee, as well as an inspector
of finance, the Chief Executive Officer of famhp and a representative of the
Minister for Public Health.
Consultative Committee provides the FAMHP with advice on all matters relating
to present or future policy. Representatives of patients and consumers and from
all sectors involved in products falling under the Agency’s competency are
involved in the Consultative Committee, as well as representatives from the
relevant federal public services.
Scientific Committee provides advice regarding matters for which the Agency is
competent.
This Committee is a body of scientific expertise and coordinator for various
commissions active within the FAMHP.

11. Advice commissions established within the FAMHP
Various commissions have been established within the FAMHP.
These include the following commissions (link to the page "Commissions"):
- Commission for medicines for human use
- Commission for homeopathic medicines for human and veterinary use
- Commission for herbal medicinal products for human use
- Commission for medicines for veterinary use
- Evaluation Commission for Medical Devices
- Joint Commission - Chamber for products for human use
- Joint Commission - Chamber for products intended for animal
In order to ensure transparency and in compliance with legal requirements,
the FAMHP publishes information relating to these commissions set up within
the Agency. This is information about the mission, the composition, the house
rules, and the agenda of meetings of each committee listed above.
This information shall be supplemented regularly by the public agendas and
minutes of the meetings and by the declaration of interests of its members.

12. Medicines for human use
Scientific-technical advice

13. Introduction
• The DG PRE-Authorisation of the Federal Agency for Medicines and
Healthcare Products (FAMHP) in Belgium offers applicants the
possibility to request national scientific and/or technical (eg.
regulatory) advice (STA) related to the research and development
aspects of human or veterinary drug products in view of potential
clinical trial applications (CTA’s), marketing authorization
applications (MAA’s), introduction of variations to marketed drug
products or line extensions. The FAMHP’s main objective in
providing STA to applicants at a national level is to promote and
facilitate as much as possible the development of new drug
products from a regulatory perspective in order to enhance the
availability of innovative drug products to patients, especially in
therapeutics areas where an unmet medical need exists.

14. For this purpose the scientific-technical advice unit of the DG
PRE-Authorisation offers a centralized and transparent service
within the agency which should ensure the processing of national
STA requests in a timely fashion while assuring full confidentiality
and potential conflict of interest of the involved experts. The
FAMHP also aims to provide a consistent follow-up of previous
national and European advices (eg. through its interface with the
SAWP and SAWP-V at the EMA) in order to assure the quality and
consistency of the national STA’s issued by the FAMHP.

15. The Royal Decree of July 16th 2012 implements the modification of the
definitions, procedures and fees that are applicable to requests for national
scientific-technical (eg. regulatory) advice (STA) which are being treated by the
unit for STA within the Directorate-General (DG) PRE-Authorisation of the
FAMHP.
The RD of July 16th 2012 modifying the Royal Decree of March 31st 2009 in
execution of Article 6sexies of the Belgian Medicines law of March 25th 1964,
was published in the “Moniteur Belge” on October 8th 2012 and entered into
force on October 18th 2012.
Any general or specific questions that applicants may have related to the
national scientific and/or technical (regulatory) advice service of the FAMHP
can be sent to the following mailbox: sta@fagg-afmps.be
However applicants are kindly being requested to consult the “Detailed
guidance for National Scientific-Technical Advice (STA) requests (PDF, 142.4
Kb)” before sending questions to the mailbox mentioned above.

16. Procedures for the introduction and the follow-up of a
scientific-technical advice application
1.Submission
Any official request for national STA falling within the legal scope of
a Type I, II or III STA request should be submitted to the Directorate-
General PRE-authorisation of the FAMHP. These requests should be
sent electronically to our central mailbox: sta@fagg-afmps.be
Alternatively, eg. in case large electronic files above 5 MB would be
submitted, electronic STA requests can also be sent on CD-rom or
USB key.
In addition, applicants are asked to send at least two hard copies of
the national STA request by post to the following address:
Federal Agency for Medicines and Health Products
Directorate-General PRE-authorisation (desk 8D222)
Victor Hortaplein 40/40
B-1060 Brussels
BELGIUM
To the attention of Ms. Greet Musch

17. Each STA request must contain sufficient supportive documentation and
a completed electronic application form in order to ensure an effective
and efficient handling of the advice requests throughout the procedure
and to allow the FAMHP to provide a pointed advice of sufficient quality.
Detailed information regarding the supportive documentation to be
included in a STA request can be found in annex below:
« National Scientific-Technical Advice (STA) : dossier content and format
– Guidance for applicants (PDF, 56.34 Kb) »
Applicants can download the electronic application form (access format)
mentioned below and should (1) include the completed electronic
document in the STA request that will be submitted electronically and
(2) include a paper copy in the STA dossiers that should be sent by post
to the FAMHP.
Electronic application form (ZIP, 670.25 Kb)
Important remark for completing the application form :
Temporarily, Type I STA requests can still be indicated in the electronic
application form as “Ad Hoc” STA requests whereas Type II and Type III
STA requests can be indicated in the electronic application form as “Full”
STA requests. The electronic application form will be adapted soon in
function of the new definitions for national STA requests which entered
into force on October 18th 2012.

18. 2. Fee payment
Each submitted STA request must be accompanied by
payment of the appropriate fee:
Each type I STA request requires payment of 1007,72 €
Each type II STA request requires payment of 6046,35 €
Each type III STA request requires payment of 8061,80 €
The fees are applicable to both initial or follow-up STA
requests.
Payment must be made on the following bank account nr.
of the FAMHP: 679-0021942-20.
Contact details of the bank :
Poste financière
Chaussée d'Anvers 59
B-1100, Bruxelles (Belgium)
IBAN : BE28 6790 0219 4220
BIC : PCHQBEBB

19. Applicants should clearly mention on the bank statement the type of STA
request that is being submitted to the FAMHP and if the STA request
concerns an initial or follow-up STA request; followed by the name of the
applicant. The topic of the STA request (eg. product name) should also be
clearly mentioned.
For each initial or follow-up STA requests a separate payment should be
made.
For payments from abroad the transfer fees should be paid by the payer.
Applicants are also requested to include a proof of payment (eg. a bank
statement) to the STA request since this is verified during the validation of
the STA request.
In case that an inappropriate fee was paid by the applicant which does not
correspond to the correct fee (eg. when submitting the STA request under
the wrong procedure), the applicant will be contacted during validation of
the STA request in order to make the appropriate payment.
In case the applicant should ask for a withdrawal of his STA request after
payment of the fee (as part of the formal submission to the FAMHP), the fee
will not be refunded by the FAMHP.
When a formally submitted STA request is declared invalid by the FAMHP at
the end of the validation phase of the procedure, the fee will be refunded to
the applicant.

20. 3. Procedure
All submitted STA requests are subjected to a validation step in order to verify
compliance with the dossier requirements outlined in paragraph 1.
Type I STA requests will be addressed by the FAMHP in writing, within 30 calendar days
after validation.
Type II and Type III STA requests will be addressed by the FAMHP in a face-to-face
meeting or through a teleconference meeting with the applicant within 70 calendar
days after validation. On exceptional basis Type II, III STA requests can be addressed in
writing on special request of the applicant if justified. Applicants are requested to draft
up the meeting minutes and send them back to the FAMHP within 14 calendar days
after the meeting. The FAMHP will send back the validated meeting minutes to the
applicant within 14 calendar days after receiving the draft minutes.
Further detailed information regarding the definition of a Type I, II or III STA
request, legal scope, procedures, timelines, etc. can be found in annex below:
«Detailed guidance for National Scientific-Technical Advice (STA) requests» (PDF, 142.4
Kb)
After the final STA advice has been given, the applicant will receive a feedback
questionnaire which can be filled in on a voluntary basis and which can be sent back to
the FAMHP.
The questionnaire is intended to obtain the applicant’s opinion on the quality aspects of
the received national STA service:
«FAMHP questionnaire on national scientific technical advice (STA)». (DOC, 156 Kb)

21. 1Law
Law of 25 March 1964 concerning the medicinal products (french version)
2. Royal Decree
Royal Decree of 31 March 2009 in execution of Article 6sexies of the Belgian Medicines law of 25-03-1964
Royal Decree of July 16th 2012 modifying the Royal Decree of March 31st 2009 in execution of Article
6sexies of the Belgian Medicines law of March 25th 1964
3. Guidance document
Detailed guidance for National Scientific-Technical Advice (STA) requests (PDF, 142.4 Kb)
FAMHP advice for CTA and MAA versus STA - Discussion paper 5.0 (PDF, 66.67 Kb)
Overview of procedures for submitting an application for clinical trials with GMO-medicinal products for human
and veterinary use in Belgium (PDF, 247.05 Kb) (22/04/2014)
Regulation and guidance documents

22. Clinical trials
Submitting an application
Each clinical trial protocol is identified at European level with a unique number. This
number has to be asked by the requesting company in the EudraCT database before
submission of any demand. The European application form, which is part of the dossier,
has also to be completed in the EudraCT database.
A clinical trial can only start after receiving a favorable opinion from the Ethics
Committee ( recognized Ethics committees (PDF, 7.65 Kb) ) and if the relevant authority
(FAMHP: R&D) has not indicated any major insufficiency within the legal timeframe
provided for in the law dated 7th May 2004 related to experiments on human people.
An application for the FAMHP, is a full electronic file and a cover letter (seecircular letter
575 (PDF, 1.1 MB) and Detailled guidance CT1 ).
The application must be sent to:
Federal Agency for Medicines and Health Products
Research and development division
Eurostation II
8th floor
Victor Horta Place 40/40
1060 BRUSSELS

23. Each submitted file must be accompanied by payment of a fee. Each complete file
requires payment of € 3672.23 and each modification requires payment of € 604.63.
Payment must be made on the following account : 679-0001514-59
A circular letter is published each year with the exact amounts and specificities.
Contact details of the bank :
Poste financière
Chaussée d'Anvers 59
B-1100, Bruxelles (Belgium)
SWIFT code: PCHQBEBB
IBAN code: BE84 6790 0015 1459
For each file and / or modification a separate payment should be made.
The validation phase only begins when the R&D division has received the file and the
proof of payment from the bank.
The maximum time taken by FAMHP to give an opinion is 15 days for monocentric
phase I clinical trials and 28 days for all other clinical trials with a possible clock-stop of
maximum one month.
For formulating a CTA you will find all the details in the following document : "
Detailed guidance for the request for authorisation of a CT on a medicinal product for
human use : "CT Application (PDF, 878.07 Kb)". For Belgium only one copy of each
document is required.

24. If any stage in the manufacture, storage or distribution of an
Investigational Medicinal Product (IMP) takes place in Belgium
this IMP has to be declared to the DG Inspection of the FAHMP.
For this please consult circular letter 581 (PDF, 1.11 MB).
For the submission of applications for clinical trials with GMO
medicinal products please follow the guidance
document: Overview of procedures for submitting an
application for clinical trials with GMO-medicinal products for
human and veterinary use in Belgium (PDF, 247.05 Kb)

25. Special requirements:
In view of the particular nature of the production method, it
is possible to grant a "conditional approval" for the annual
update of flue vaccines that have already been authorized.
This means that such a trial can be approved even if some
data about the quality (in particular certificates of analysis)
are missing. But that is only valid if these data are submitted
to AFMPS one week before the start of the clinical trial and if
the evaluation is positive.

26. Development safety Update Reports - DSUR
In accordance with article 28, § 2 of the Law of 7
May 2004 concerning experiments on the human
person, once a year, during the entire duration of
the experiment, the sponsor should provide the
Minister and the Ethics Committee in Belgium and
those of the Member States on whose territory the
trial is conducted in the case of multicenter trials a
list of all suspected serious adverse events that have
occurred during that period as well as a report on
the safety of the participants.
Additional information is available in circular 593
(PDF, 115.28 Kb).

27. Legal texts
The European directive 2001/20 has been incorporated in national law by the law dated
7th May 2004 (French version) published in the Belgian Monitor of 18th May 2004. The
new legal framework has been in force since 1st May 2004.
The law of 7 May 2004 has been modified several times (see below)
Note: the laws, royal decrees and circulars are (except for a few) not translated in
English. Therefore we refer to the links on the French and the Dutch version of the
website.
Laws
Law dated 7th May 2004 (French version) related to experiments on human people.
Modified by the following laws :
Programme law dated 27/12/04 (French version) modifying the law dated 7/05/04
(French version)
Programme law dated 27/12/05 (French version)
Health law dated 13th December 2006 (French version)
Programme law dated 13th December 2006 (French version)
Programme law dated 27th April 2007 (French version)
Law dated 24th July 2008 related to various dispositions (French version)
Law dated 19th December 2008 related to various health dispositions (French version)

28. The Ethics Committees
A clinical trial can only start after receiving a favorable opinion from Ethics Committee (recognized
Ethics Committees (PDF, 7.65 Kb)) and if relevant authority (FAMHP : R&D) has not indicated any
major insufficiency within the legal timeframe.
Legal texts
The European directive 2001/20 has been incorporated in national law by the law dated 7th May 2004
(French version) published in the Belgian Monitor of 18th May 2004. The new legal framework has
been in force since 1st May 2004.
The law of 7 May 2004 has been modified several times (see below)
Note: the laws, royal decrees and circulars are (except for a few) not translated in English. Therefore
we refer to the links on the French and the Dutch version of the website.
Laws
Law dated 7th May 2004 (French version) related to experiments on human people.
Modified by the following laws :
Programme law dated 27/12/04 (French version) modifying the law dated 7/05/04 (French version)
Programme law dated 27/12/05 (French version)
Health law dated 13th December 2006 (French version)
Programme law dated 13th December 2006 (French version)
Programme law dated 27th April 2007 (French version)
Law dated 24th July 2008 related to various dispositions (French version)
Law dated 19th December 2008 related to various health dispositions (French version)

29. EudraLex - Volume 10 Clinical trials guidelines
GENERAL INFORMATION
The application dossier for the commencement of a clinical trial, to be
submitted to the competent authorities of the Member States and the
Ethics Committees, consists of administrative information and the
necessary demonstration of quality, safety and efficacy of the
investigation medicinal product. For applications submitted in
accordance with Article 8 and Article 9 of Directive 2001/20/EC,
applicants should clearly indicate under which conditions the application
is made (competent authority or Ethics Committee). Each volume of the
dossier should be sequentially paginated throughout, in Arabic numerals,
legible and suitably bound. Each volume should be clearly identified.
Particular care should be given to proper and consistent cross-
referencing throughout the dossier. If spectra or photographic material
are supplied in the dossier, legible copies and photographs should be
supplied in each copy submitted. Full copies of all bibliographical
references should be provided, translated if necessary

30. compassionate use - medical need
The new Royal Decree of 25 April 2014 (RD in French version ) amending the
Royal Decree of 14 December 2006 on medicinal products for human and
veterinary use (RD in french version ) was published in the Belgian Official
Journal on 12 June 2014 and comes into effect on 1 July 2014.
All compassionate use programs and medical need programs submitted from that
date must follow the procedure described in that text.
Each submitted file must be accompanied by payment of a fee. Each complete file
(cfr. article 106, § 6 and article 108, § 6 of the aforementioned Royal Decree of
14th December 2006) requires payment of € 4.508,28 and each modification
requires payment of € 4.508,28. Payment must be made on the following account :
679-0001514-59
Contact details of the bank :
Poste financière
Chaussée d'Anvers 59
B-1100, Bruxelles (Belgique)
SWIFT code : PCHQBEBB
IBAN code : BE84 6790 0015 1459

31. Marketing Authorization procedures - MA

32. Marketing Authorisation procedures - MA
Common Technical Document
An application for marketing authorisation for a medicine for human use must be submitted in
CTD format. This is described in Appendix 1 of the Royal Decree dated 14/12/2006 relating to
medicines for human and veterinary use and in the appendix of the European
directive 2001/83/EChttp://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm
The CTD format includes 5 sections that are identical for all member states of the European
Union. The exact structure of the format is described in part 2B of the Eudralex collection,
published by the European Commission
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol2_en.htm
In that volume you will find references to the European and international guidelines concerning
the scientific contents of a file and also a Question & Answer document concerning the practical
use of this format in the European Union.
Sections 2 to 5 are identical for the European Union, the United States and Japan. You will find
more detailed information on the website of the ICH international discussion forum (International
Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human use) : http://www.ich.org

33. e-Submission
The document called 'Guidance for Industry on Providing Regulatory Information in
Electronic format : Non-eCTD electronic Submissions (NeeS)' was published on the
EMEA website on 22/02/2008:http://esubmission.ema.europa.eu/new.htm .
The national guideline has been adapted.
Moreover In the context of the EU's Better Regulation policy, the "eSubmission
guidelines" concerning the electronic submission of dossiers for variation of marketing
authorisation for medicines for human use has been updated.
The «eSubmission guideline v.2.12 (PDF, 371.72 Kb)» applies to any electronic dossier
introduced from 1st July 2013.
Automatic mails
Document "Automatic mails (DOC, 320.5 Kb)".
Full compliance (Zero tolerance)
Since 01/02/07 each electronic file submitted to FAMHP (Federal Agency for Medicines
and Heath Products) for medicines for human use undergoes two technical checks:
- Compliance towards the CTD tree structure
- Compliance towards folder and file naming
Both technical checks are based on the “notice to applicants” requirements for module 1
(DOC, 1.02 MB), and the ICH requirements for modules 2 à 5 (PDF, 1.03 MB).

34. The score that a file must achieve for all technical checks in order to
be accepted by FAMHP is determined by a «road map (DOC, 20
Kb)» (up-dated May 2008). This road map should always be consulted
before submitting a file so that you have the latest information about
the minimum scores.
By means of checker v.4.0 (to be used from 1.9.2013) (ZIP, 30.47
MB) the two technical checks can be made before submitting the file
in case of a national procedure or a DCP/MRP for which Belgium is
CMS. (Please uninstall all versions of the checker before installing
checker 4.0 Sept 2013 version)
Checker change requests (DOC, 264 Kb)
Checker change requests Part II (DOC, 228 Kb)
Checker change requests Part III (DOC, 231.5 Kb)
Checker change requests part IV (PDF, 282.03 Kb)
Checker change requests part V (PDF, 44.32 Kb)
Checker change requests part VI (PDF, 23.27 Kb)
Checker change requests part VII (PDF, 30.25 Kb)
updated CTD structure (ZIP, 2.38 MB)

35. When a DCP/MRP NeeS dossier for which Belgium is RMS is to be submitted, this
always has to be contain a valid Extedo or Lorenz NeeS report (for example:Nees
Report (ZIP, 265.79 Kb)).
In case of an eCTD dossier, a valid eCTD report as to be supplied (always in context
of the other sequences) with the actual versions of the Lorenz or Extedo tools.
On 27th March 2007 FAMHP gave an Information session (PPT, 6.34 MB) about full
compliance. During this session, the CTD structure (ZIP, 1.25 MB) et le " Best
verification report (DOC, 2.17 MB)" ont été expliqués. This "Best verification report"
(DOC, 2.17 MB) shows errors made in the CTD structure and in the names of the
files and documents.
Since 17/09/2007 the full compliance principle (zero tolerance) has been applied.
That means that files submitted to AFMPS, where one or two scores from the road
map are not reached, are rejected.
The Best Verification Report is sent as an appendix to the automatic mail created by
the system with the comment “Refused”.
In this case the file must be resubmitted to AFMPS. If the minimum scores are
achieved the Best Verification Report is sent with the comment “Accepted”.

36. Language
Information about the language to be used when submitting a file is shown in chapter 7 of
the Notice to Applicants.
In practice:
- National procedure : French or Dutch, according to the location of the (future) license
holder
- European procedures : English
The SPC (Summary of Product Characteristics), instructions and packaging should be
submitted in French or Dutch, according to the location of the (future) license holder
Samples
Supplying samples is not necessary when submitting the file but the applicant must be able
to supply them if requested by FAMHP (Federal Agency for Medicines and Health Products).
Fees
The fees for marketing authorisation for medicines are mentioned in article 25 of the law
dated 3rd July 1969 relating to registration of medicines.
• Summary of fees (PDF, 29.16 Kb)
(PDF, 14.15 Kb)Le form for fees (DOC, 27.5 Kb)must be completed.
Fees should be paid into the following account number: 679-0021942-20
At the following bank:
Poste financière
Chaussée d'Anvers, 59
B-1100 Bruxelles

37. Parallel import
A medicine sold in Belgium and in another member state of the European Union can be imported
by a company from that member state as long as a certain number of legal requirements are met.
That explains why a medicine with the same name can be distributed by several companies.
Such parallel imports are in line with the European principle of free circulation of goods and are
applicable in all the member states.
The European legislation does not stipulate that the composition of the imported medicine must be
100% identical to the medicine that is acting as the reference point.
But the qualitative and quantitative composition in terms of active substance must be the same
and the imported medicine must have the same therapeutic effect as the reference medicine.
Imported medicines are controlled by the Medicines Commission so that the quality, efficacy,
harmlessness and supervision of the medicines are guaranteed.
To obtain authorisation to import in parallel a certain number of conditions have to be met as
described in article 3, § 2 from the Royal Decree of 19th April 2001 (French version) which relates
to parallel imports of medicines for human use and to parallel distribution of medicines for human
and veterinary use.
The conditions that must be met for authorisation of parallel importation to be valid are described
in articles 6 and 7 of the Royal Decree of 19th April 2001 (French version) .
The company applying for authorisation to import in parallel has to make a file and submit it to
the FAMHP (Federal Agency for Medicines and Health Products), place Victor Horta 40, box 40, B-
1060 Brussels, for the attention of Mrs. Christine PUTTEMAN.

38. The type of request must be specified :
•New authorisation
•Modification
•Renewal
The file should contain the following items (see article 4 of the Royal Decree dated 19th April 2001 (French version) ) :
•An accompanying letter
•1 form : "authorisation for parallel import (DOC, 280.5 Kb) (in French)“
•A copy of the leaflet of the reference medicine
•A copy of the leaflet of the imported medicine
•A draft patient leaflet: this draft should be the last version of the reference medicine leaflet that must be accompanied, on the first page,
by the appropriate form (DOC, 40.5 Kb) that, upon approval, will be an integral part of the leaflet. It will thus be available in the packaging
of each medicine imported in parallel (see press release dated 16/08/2012).
•A declaration of conformity (DOC, 21.5 Kb) (in French) indicating that the leaflet of the imported medicine is identical to the leaflet with
the reference medicine. This is subject to the importer making changes concerning his identity, the identity of the manufacturer and / or
other differences that are mentioned in the statement
• A sample of the reference medicine
•A sample of the medicine to be imported in its original packaging
•A sample or a mock up of the medicine as it is intended to be marketed in Belgium
•A statement indicating that the original state of the medicine has not been modified directly or indirectly
•A contract between the parallel importer and the person responsible for the repackaging
•A GMP certificate if the person responsible for the packaging is not based in Belgium

39. Any application for parallel import authorisation is subject to payment of a fee, in
accordance with Article 13 of the Royal Decree of 19 April 2001.
Section 1 1°: Application for parallel import
New application for parallel import in accordance with article 4 or article 7 § 2 and
§ 3 :
1951,20 €/licence
Section 1 2°: Renewal
Renewal of licence for parallel import in accordance with Article 7 § 1 : 975,61 €
/licence
Section 2: Application for modification
Application for modification of licence for parallel import, except for modifications
in accordance with Article 7 sections 2 and 3 : 650,40 euro/ licence
Parallel imports are based on European legislation (+ jurisprudence), but not on
any specifically medical rules : just article 28-30 of the EU Treaty on the ‘free
circulation of goods’.
Communication (PDF, 105.22 Kb) of the European Commission concerning parallel
imports.

40. Important information concerning the names
Several parallel import authorizations were recently issued for medicines
whose name in the country of origin differs significantly from the Belgian
name.
However it is the same medicine, imported from another Member State,
whose secondary packaging (outside) and leaflet mention two names, but
whose primary packaging (blister pack) mentions only the name of the
Member State of origin.
The list (PDF, 10.45 Kb) of the relevant medicines mentions the Belgian name
and the corresponding name in the Member State of origin stated on the
blister pack.
The purpose of this list (PDF, 10.45 Kb) is to educate pharmacists who deliver
these medicines and to allow them to properly advise their patients in order to
avoid any doubt about the quality, safety and effectiveness of those medicines.
The obligation to put a label with the Belgian name on the blister pack is
currently required for new authorizations for medicines with a different name
in the country of origin. This label must be adhered so that it does not impede
the removal of the tablets from the packaging.
Parallel importers were also asked to put such a label on the medicines
included in the list above.
The label of the blister pack is now a part of the application of a parallel import
authorisation. Since publication of the listed no new medicine has been issued
without such approval

41. Links :
http://eur-lex.europa.eu/fr/index.htm
http://curia.europa.eu/
Contact:
Mrs. Christine PUTTEMAN
Federal Agency for Medicines and Health Products
place Victor Horta 40, box 40
B-1060 Brussels
Phone: 00 32 2 524 80 99
e-mail: christine.putteman@fagg-afmps.be

42. Pharmacovigilance

43. Data collection, evaluation and measures
Pharmacovigilance data collection
The BCPH (Belgian Centre for Pharmacovigilance for medicines for
Human use) receives both individual reports and compilations of data
concerning the adverse effects of medicines. This requires the
collaboration of healthcare professionals, marketing authorization holders
and research centers conducting clinical studies with medicines.
- Healthcare professionals (doctors, pharmacists, dentists) can inform
the BCPH via the “yellow card” about any suspicion they have concerning
adverse effects of medicines they come across in daily practice.

44. It is nevertheless particularly important to report in the following situations:
• Serious adverse effects: adverse effects that have led to hospitalization or prolongation of the
hospitalization, that have been life-threatening, or that have caused death, permanent or
significant disability or inability to work, or congenital disorder or malformation.
• Unexpected adverse effects: adverse effects of which the nature, the seriousness and/or the
evolution do not correspond with what is mentioned in the Summary of Product Characteristics
(SPC).
• Suspected adverse effects: adverse effects that are known but of which the frequency, the
seriousness or the result is abnormal.
• Adverse effects occurring in the following particular situations:
1. Vulnerable populations (e.g. children, pregnant or breastfeeding women, elderly, patients
with hepatic of renal failure).
2. Administration of vaccines.
3. Switch from one specialty to another during treatment, regardless if it concerns the switch
between “original” medicines, from a “generic” to an “original” medicine, from an
“original” to a “generic” medicine or between “generic” medicines.
4. “Inappropriate” or “off-label” use of a medicine.
It is also important to report adverse effects with the so-called “Black triangle drugs”. These include
the medicines that contain a new active substance and the new biological medicines. They are
indicated by the symbol ▼ in the “Répertoire Commenté des Medicaments”. The ▼ symbol appears
for the first 3 years after the marketing of the medicine.

45. It is important that these ▼ medicines are followed closely as soon as they are
marketed. Indeed, at the time that a medicine is authorized, the knowledge about its
adverse effects is still limited. The clinical studies conducted for marketing
authorization are mainly intended to show the efficacy of the medicine and have
limitations in detecting adverse effects:
• The number of patients included in the studies is usually too low to detect rare
adverse effects;
• The duration of the studies is not long enough to detect adverse effects that
appear later on;
• The studies usually do not include patients that present a high risk of adverse
effects (e.g. pediatric or elderly patients, patients with important comorbidity or
polymedication, patients with kidney and liver failure).
The BCPH requests the healthcare professionals to report any suspicions they may
have of adverse effects – serious and non serious – with these ▼ medicines, even
when there is some doubt about the causality.

46. The list of these ▼ medicines (PDF, 121.39 Kb) (in French) is updated monthly.
Healthcare professionals are encouraged to report all adverse effects they consider as being medically
significant, even if they do not meet the above mentioned criteria.
The causality between the suspected medicine and the adverse effect should not necessarily be established to
report.
The electronic version of the yellow card for the online reporting of adverse effects is accessible
via www.fichejaune.be (in French). Click here (PDF, 197.21 Kb) for more information (in French).
The paper version (PDF, 57.31 Kb) of the yellow card can be printed and sent by post to the BCPH. The “paper
yellow card” is also available in the “Répertoire Commenté des Médicaments” and three times a year via the
Folia Pharmacotherapeutica. In case you wish to receive a paper reporting form, you can request this at any
time via the email address: adversedrugreactions@fagg-afmps.be
The paper version can be sent by post to the address mentioned at the back of the yellow card (postage paid
by the recipient):
Federal Agency for Medicines and Health Products (FAMHP)
Belgian Centre for Pharmacovigilance for medicines for Human use (BCPH)
Eurostation II
Place Victor Horta 40/40
B-1060 Brussels

47. - Patients experiencing an adverse effect after taking a medicine are recommended
to contact their doctor, pharmacist or dentist who will fill in the reporting form.
- The marketing authorization holders (MAH) who are informed about a serious
adverse effect, either by healthcare professionals, or by investigators for clinical
trials, or by scientific publications, must report this to the BCPH within 15 days of
the receipt of the information. In this context a serious adverse effect is defined as
an adverse effect that:
• causes hospitalization or prolongation of the hospitalization;
• is life-threatening;
• causes death;
• leads to permanent or significant disability or inability to work;
• causes a congenital disorder or malformation.
Marketing authorization holders must also regularly write and submit to the
BCPH Periodic Safety Update Reports or "PSUR's" - see circular 476 (PDF, 177.36 Kb)
(PDF, 177.36 Kb) (in French) + Guidelines (PDF, 30.08 Kb) (PDF, 20.11 Kb) + Template
for the e-submission of PSURs/ARSs (DOC, 38.5 Kb) + e-submission guidelines (PDF,
185.35 Kb) (PDF, 185.35 Kb) andcircular 530 (PDF, 91.53 Kb) (PDF, 91.53 Kb).

48. At regular intervals, they need to communicate an overview and an evaluation of all
reactions, serious and non serious, that occurred both inside and outside the
European Union. After 5 years they must provide a global overview in the context of a
marketing authorization renewal dossier.
- Since 2004 promoters of clinical trials are also required to submit all SUSARs
(“Suspected Unexpected Serious Adverse Reactions”) that occurred during their
clinical trial, both for medicines with and without marketing authorization. The
former are the responsibility of the BCPH. In order to evaluate the safety of the
medicines used in clinical trials, the promoter must each year write a safety report
about the serious adverse events that happened during a clinical trial and submit it
to the BCPH = ASR (Annual Safety Report) – see circular 476 (PDF, 177.36
Kb) (in French) + Guidelines (PDF, 30.08 Kb) +Template for the e-submission of
PSURs/ARSs (DOC, 38.5 Kb) + e-submission guidelines (PDF, 185.35 Kb) .
The BCPH can, if it considers this necessary, ask for a “specific safety report” in which
the marketing authorization holder has to evaluate a specific safety problem
concerning a medicine.

49. Evaluation of the data
The evaluation of the available pharmacovigilance data consists of two parts.
The BCPH evaluates the individual reports of adverse effects (spontaneous reports
and SUSARs) but also evaluates the summary reports:
• periodic safety reports concerning a medicine;
• annual safety reports concerning a clinical trial (in case of medicines disposing
already of a marketing authorization);
• specific safety reports.
For these tasks, the BCPH is assisted by a team of internal and external experts.
The individual reports are evaluated at regular intervals by a specific working
group. The evaluation reports about periodic safety reports and the marketing
authorization renewal dossiers are submitted to a second specific working group.
In case of medicines for which the responsibility for the evaluation is at national
level, it is the Commission for Medicines for Human Use that gives the final advice
about whether or not the measures suggested by the two working groups can be
implemented.
Based on the conclusions of these evaluations on national and European level, the
BCPH takes the necessary measures.

50. Taking measures
If required, after the evaluation of a dossier, the BCPH can take the necessary measures, by:
• Asking the marketing authorization holder to modify the information in the « undesirable
effects », « special warnings and precautions for use », « contraindications » sections of the SPC
(Summary of Product Characteristics) and the leaflet for the patient;
•Limiting the indications of a medicine and, in some rare cases, suspending or withdrawing the
marketing authorization of a medicine following the decision of the Ministry of Public Health;
• In urgent cases informing healthcare professionals about a specific pharmacovigilance problem
by means of a press release or a circular.
The authorization holder can also be requested to send a “Direct Healthcare Professionals
Communication” to the concerned healthcare professionals to inform them about the
pharmacovigilance problem.
Furthermore, the BCPH collaborates actively with the Belgian Centre for Pharmacotherapeutic
Information (in French) which publishes each month a “Communication from the
Pharmacovigilance Centre” for healthcare professionals. This describes discussions about
adverse effects reported to the BCPH or new data from the specialized literature.

51. Active pharmacovigilance
Active pharmacovigilance" project - December 2010
The goal of the project
At the beginning of 2008 the Belgian Centre for Pharmacovigilance for medicines
for Human use (BCPH) of the Federal Agency for Medicines and Health Products
(FAMHP) launched the “Active Pharmacovigilance” project. This project is at
present one of the four centers of excellence identified by FAMHP: the center of
excellence "Proactive Vigilance".
The goal of the “Active Pharmacovigilance” project is to improve the knowledge of the
safety profile of medicines thanks to:
• An increase in the number of reports of adverse effects of medicines, directly
transmitted to the BCPH by the healthcare professionals.
• An improvement of the quality of these reports.

52. Recruitment phase
The first stage of the project was to obtain the collaboration of a group of about200
healthcare professionals (general practitioners, specialists, pharmacists and hospital
pharmacists - including clinical pharmacists).
At the end of April 2008 the number of participants in the project had already largely
exceeded the target. At present, 335 healthcare professionals are involved in the project.
Repartition by category of healthcare professionals and linguistic role:
Number of participants DU FR Total
GPs 50 39 89
Specialists 36 46 82
Pharmacists 44 34 78
Hospital pharmacists 39 47 86
Total 169 166 335
Percentage of participants DU FR Total
GPs 14,9% 11,6% 26,6%
Specialists 10,7% 13,7% 24,5%
Pharmacists 13,1% 10,1% 23,3%
Hospital pharmacists 11,6% 14,0% 25,7%
Total 50,4% 49,6%

53. Reporting in the context of the project
The project participants are invited to report systematically to the BCPH:
• Serious adverse effects: adverse effects that have lead to hospitalization or
prolongation of the hospitalization, that have been life-threatening, or that have caused
death, permanent or significant disability or inability to work, or congenital disorder or
malformation.
• Unexpected adverse effects: adverse effects of which the nature, the seriousness
and/or the evolution do not correspond with what is mentioned in the Summary of
Product Characteristics (SPC).
• Suspected adverse effects: adverse effects that are known but of which the frequency,
the seriousness or the result is abnormal.
• Adverse effects occurring in the following particular situations:
-Vulnerable populations (e.g. children, pregnant or breastfeeding women, elderly,
patients with hepatic of renal failure).
-Administration of vaccines.
-Switch from one specialty to another during treatment, regardless if it concerns the
switch between “original” medicines, from a “generic” to an “original” medicine, from
an “original” to a “generic” medicine or between “generic” medicines.
-“Inappropriate” or “off-label” use of a medicine.
It is also important to report adverse effects with the so-called “Black triangle drugs”. These
include the medicines that contain a new active substance and the new biological
medicines. They are indicated by the symbol ▼ in the”Répertoire Commenté des
Medicaments”. The ▼ symbol appears for the first 3 years after the marketing of the
medicine.

54. The actions
To announce the project, increase the number and improve the quality of reports, several actions were undertaken
and are still planned:
• A communication announcing the project was published in the Folia Pharmacotherapeutica of January 2008.
• A leaflet (PDF, 1.15 MB) (French version) about the project was distributed with the Folia Pharmacotherapeutica
of April 2008.
• A call for participation was published on the website of the FAMHP, CBIP, several professional associations and
the Medical Pharmaceutical committees.
• A letter was sent at the end of February 2008 to doctors and pharmacists who had reported one or more
adverse effects in the past years.
• A more detailed and individualized feedback is sent to the reporter in response to each report (it includes a
summary of the evaluation by the BCPH working group and the used documentation).
• An electronic newsletter "VIG-NEWS" is sent to the project participants and is, since May 2010, available on the
FAMHP’s website. The VIG-NEWS includes recent pharmacovigilance news from different sources (ao FAMHP,
BCPH, FDA, EMA, literature);
• Articles about pharmacovigilance are regularly published in specialized journals.
• Awareness sessions for pharmacovigilance have been and will continue to be organized for universities,
hospitals and various medical and pharmaceutical associations.
• A new, more user-friendly "paper yellow card (PDF, 57.31 Kb)", has been distributed via the Folia
Pharmacotherapeutica since March 2009 and via the “Répertoire Commenté des Médicaments” of the Belgian
Centre for Pharmacotherapeutic Information.
• The online reporting tool has been made available for the project participants in September 2010 in the context
of a testing phase. Since December 2010 the "online" reporting tool is available to all healthcare professionals in
Belgium.
French training sessions (PDF, 414.77 Kb) concerning active pharmacovigilance are being organized on Thursday
28/04, 09/06 and 16/06/2011.

55. Results: yellow cards received by the BCPH
Number of reports
The number of reports received by the BCPH through the "yellow cards" has almost
doubled since the start of the project in 2008. This positive evolution continued in 2009:
•In 2006: 360 yellow cards
•In 2007: 320 yellow cards
•In 2008: 616 yellow cards
•In 2009: 716 yellow cards
Quality of the reports
The actions in the context of the "Active Pharmacovigilance" project seem to have a
positive effect on the quality of the reports.
Overall, the reports are more complete than in the past and thanks to the new paper
yellow card some important elements (such as dechallenge-rechallenge , the description
of the adverse effect, the comorbidity and the comedication) are better documented.
Greater involvement of the part of hospitals has also been observed.
The reports are better documented and allow a more qualitative evaluation.

56. Inspections
Introduction
The coming into effect on 1st November 2 of the new European pharmaceutical legislation has
profoundly changed the approach to pharmacovigilance (PHV).
If the single market in pharmaceuticals and the maintaining of a high level of protection of public
health remain the two main objectives, the new legislation benefits especially patients by giving them
faster access to new medicinal products.
To prevent this from happening to the detriment of safe use for the patient, these new provisions
have been accompanied by increased market surveillance and strengthening of procedures for
monitoring and pharmacovigilance.
Today, pharmacovigilance is assimilated to risk management and can be described as the sum of
techniques for the evaluation of the risk of occurrence of adverse effects with medicines after being
marketed.
The objectives of pharmacovigilance are:
• Early detection of unknown or insufficiently documented adverse effects and interactions.
• Detection of an increase of the frequency of a known adverse effect.
• Identification of risk factors and mechanisms that are at the basis of the occurrence of adverse
effects.
• Continuous reevaluation of the risk-benefit balance of medicines.
• Distribution of information about adverse effects and interactions so that they occur less
frequently and in order to have less therapeutic errors.
At the Federal Agency for Medicines and Health Products (FAMHP), this desire to move from passive
pharmacovigilance to active pharmacovigilance, has resulted in the implementation of various
projects and in programming of PHV inspections.

57. Conclusion
The "Active Pharmacovigilance" project has been successful amongst the healthcare
professionals: 335 doctors and pharmacists are involved, the number of reports of
adverse effects received by the BCPH has increased and the quality of the reports has
improved. The project seems to meet a real need.
The BCPH hopes that thanks to this project, pharmacovigilance will be better integrated
into day-to-day clinical practice.
The healthcare professionals alert to the occurrence of adverse effects in his patients will
allow, by early recognition of a drug etiology, to limit the adverse effects of medicines.
If the healthcare professionals have the reflex to report adverse effects to the BCPH, they
contribute to public health through their contribution to:
• More complete pharmacovigilance databases;
• Faster signal detection;
• A better evaluation of the benefit-risk balance;
• Improved knowledge of the safety profile of medicines.
For this reason, the FAMHP encourages healthcare professionals to participate in its
"Active Pharmacovigilance" project.

58. Planning pharmacovigilance inspections
PHV inspections began in Belgium during the second quarter of 2008 according to a schedule
developed within the Vigilance and Production-Distribution departments.
This schedule includes
• Inspections to be carried out by Belgium under the inspection program designed by the
European EMEA for medicinal products (human and veterinary) authorized via the centralized
procedure;
• National routine inspections with a priority given to inspections of MA holders of medicinal
products for human use;
• and targeted national inspections [initiated following the notification of incidents reported by
the evaluators and / or by case managers of the Belgian Centre for Pharmacovigilance for
Medicinal Products for Human Use (CBPH), requested by other departments following
complaints or by the competent authorities of other Member States, ...]. Unlike routine
inspections, targeted inspections may not be advertised to MA holder.
The choice of firms subject to routine inspections is based on risk factors identified by the Vigilance
Department and areas of excellence of FAMHP.
The choice of firms subject to targeted inspections is based on a signal brought to the attention of
inspectors.
Objective of pharmacovigilance inspections
The goal of PHV inspections is to ensure that MA holders have a qualified person in PHV and a
pharmacovigilance system in accordance with the current legislation, and to appreciate the
effectiveness of department(s) and / or system(s) involved in the tasks of pharmacovigilance.

59. Ranking of deficiencies in PHV
Deficiencies in pharmacovigilance are classified into three categories.
Critical Deficiencies
Gaps in the PHV system, practices and processes that
- Cause significant effects that run counter to the rights, safety or welfare of patients, or
- Cause a serious risk to public health, or
- Indicate a serious violation of the law.
Major Deficiencies
Gaps in the PHV system, practices and processes that
- Could cause significant effects that run counter to the rights, safety or welfare of patients,
or
- Could cause significant risk to public health or
- Indicate a major divergence from the law.
Minor deficiencies
Gaps in the PHV system, practices and processes that should not cause non-compliance of
rights or harmful effect on the safety or the well-being of patients.
Given the individual nature of each inspection, critical, major or minor deficiencies will be
evaluated on a case by case basis depending on the negative impact they generate (or are
likely to generate) on human or animal public health.
Gaps, not considered as major in isolation, can become a major deficiency when combined.

60. Possible actions of FAMHP for non-compliance of the PHV system
In case of non-compliance with legal obligations concerning PHV, FAMHP currently
considers various actions:
• education and recommendations to the MA holder to improve its system of
pharmacovigilance, its practices or processes and introduction of an action plan;
• formal warning reminding the legal obligations of PHV;
• administrative fines;
• urgent actions (suspension or cancellation of registration of the QPPV on the list,
amendments to the SPC, withdrawal, suspension of the MA, recall ....).
These actions will be taken in the order listed above, FAMHP wishing to keep the radical
measures for "serious" non-compliance or for non-compliance with previous
commitments.
Pharmacovigilance inspections in the European context
PHV inspectors of FAMHP maintain regular contacts with national authorities of other
Member States and with the Committee for Medicinal Products for Human Use (CHMP)
and the Committee for Medicinal Products for Veterinary Use (CVMP).
They are part of the PHV Inspectors Working Group, which meets four times a year and is
responsible for harmonizing PHV inspection procedures in the Community and drafting
the guidelines.
They participate in the EU Inspector's Training Courses.
They participate and carry out inspections of PHV at the request of the EMEA.

61. Pharmacovigilance inspections in the European context
PHV inspectors of FAMHP maintain regular contacts with national authorities of other Member States and
with the Committee for Medicinal Products for Human Use (CHMP) and the Committee for Medicinal
Products for Veterinary Use (CVMP).
They are part of the PHV Inspectors Working Group, which meets four times a year and is responsible for
harmonizing PHV inspection procedures in the Community and drafting the guidelines.
They participate in the EU Inspector's Training Courses.
They participate and carry out inspections of PHV at the request of the EMEA.
Person responsible for pharmacovigilance (QPPV) and local contact person
•The role and responsibilities of the person responsible for pharmacovigilance are detailed in GVP Module I
.
•The requirements for the local contact person are detailed in article 66 §2 in the royal decree of 14th
December 2006 concerning medicines for human use.
Administrative formalities in connection with the person responsible for pharmacovigilance
•The holder of a marketing authorisation (MA) must be assisted permanently and continuously by a qualified
person responsible for pharmacovigilance who resides in the EEA (European Economic Area)
•The holder of a marketing authorisation (MA) must also be assisted by a local contact person.
Circular 600 (PDF, 660.55 Kb) (and annex I (PDF, 164.2 Kb) andannex II (PDF, 131.54 Kb)) gives more
information regarding the obligation for the MAH to notify the local contact person and current information
regarding pharmacovigilance to the FAMHP.
More explanation regarding the requirements for the local contact person and related legislation are
described in a Q&A (PDF, 38.52 Kb) (version October 2013).

62. Production

63. Good Manufacturing Practice
Please refer to Slide No. 7

64. Qualified person
The conditions for being approved as a qualified person are described in article 84 of the
Royal Decree dated 14th December 2006 (French version) (part 1 -part 2 ).
If you meet these conditions and wish to receive approval as a qualified person please
send the following documents to :
FAMHP (Federal Agency for Medicines and Health Products)
Place Victor Horta, 40 ( box 40)
1060 Brussels
for the attention of Mr Nicolas CULQUIN:
•A copy of your diploma(s). All diplomas obtained abroad must already be recognised by
the appropriate authority
•A certificate of the training programe signed by the qualified person at the company
where you did your training
•A copy of your identity card
•form 65 (DOC, 297.5 Kb) correctly completed
The approval can only be granted when all the conditions mentioned in the Royal Decree
dated 14th December 2006 (French version) (part 1 - part 2 ) are met and when all the
required documents are in our possession.

65. Distribution & delivery

66. Good Distribution Practice
Revised guidelines regarding Good Distribution Practice : workgroup FAMHP/FAQ
On the 7th of march 2013, the revised guidelines regarding the Good Distribution Practices have been
published in the Official Journal of the European Union.
These guidelines will enter into force on the 8th of September 2013. They are applicable to wholesale
distribution authorization holders of medicinal products (according to article 12ter of the law of 25th 25th of
march 1964 on medicinal products) as well as to manufacture authorization holders (according to article 12bis
of the law of the 25th of march 1964 on medicinal products) involved in distribution activities (storage
included).
These revised guidelines are more precise and explicit than the previous version. Some new requirements
have also been set.
In order to answer any questions and to clarify any interpretation that may arise with these revised guidelines,
a specific workgroup has been set up at the FAMHP. Please address your questions to industry@fagg-
afmps.be with “NEW GDP” in the subject line. Questions should be submitted in one of the national languages
ne should, where applicable, mention the reference to the concerned guideline (e.g. : 3.2 : §2 )
Questions have to be submitted before the 31st of august 2013. The answers will be published by early
October 2013. The FAQ will be further updated following subsequent questions.

67. Sunset clause
According to article 6 §1 section 3 of the law of 25th March 1964 (French version) about medicinal
products, marketing authorization or registration of a medicinal product expires if the medicinal product
has not effectively been marketed within three years of receiving approval. This is the so-called « sunset
clause ». This is also valid for a medicinal product that is (has been) sold but will not be marketed for 3
consecutive years.
The term « marketing » includes being freely available to other commercial operators than the
authorization holder, such as distributors and pharmacists.
Not covered by this clause are medicines that have received authorization for parallel import.
The provision of the sunset clause to medicinal products for which marketing authorization has been
granted by the European Commission (centralized procedure) is the responsibility of the European
Commission.
The conditions of the sunset clause apply to marketing authorisation in the « global » sense, i.e. for
different doses, pharmaceutical forms, methods of administration and different presentations of the
same medicine. This implies that, once one of the presentations of the same medicine has been
marketed, the 3-year period no longer counts for the other presentations of the same medicine and the
marketing authorisation of all the presentations is upheld.
In order to apply this clause correctly, the FAMHP set the date to be considered as a starting point for
the “period of 3 years of unavailability on the market” in the following cases:

68. 1. MA or registration not followed by effective marketing
1.1. MA or registration approved for the first time before 1 April 2007.
Date of commencement of the "period of 3 years of unavailability on the market" = 1 April 2007.
All marketing authorization holders or registration holders have been invited to advise FAMHP if
their medicinal product(s) was (were) marketed on the Belgian market or not as of 1 April 2007
(see Circular 481 (French version) (PDF, 97.05 Kb)). In April 2010 the marketing authorization of
medicinal products that have not been marketed will be revoked.
1.2. MA or registration approved for the first time since 1 April 2007.
Date of commencement of the "period of 3 years of unavailability on the market" = first date of
approval of marketing authorization or registration.
2. The medicinal product has been marketed but no longer available on the market for three
consecutive years.
2.1. Medicinal product unavailable on the market on 1 April 2007.
Date of commencement of the "period of 3 years of unavailability on the market" = 1 April 2007
(see 1.1.)
2.2 Medicinal product no more available on the market after 1 April 2007.
Date of commencement of the "period of 3 years of unavailability on the market" = date of
notification to stop marketing.
In exceptional circumstances and for reasons of public health, a derogation from the provisions of
the sunset clause may be granted by the Minister or his delegate.
The document “application of measures relating to the sunset clause in Belgium for medicinal
products authorized at the national level (French version) (PDF, 265.01 Kb)” reminds the reader
of the basic rules of the sunset clause and provides all information about derogation.

69. Important reminder
In accordance with article 6 §1 sexies of the law on
medicinal products, the holder of a marketing
authorization for any medicinal product has to advise the
date when it will be marketed. This is also required if
marketing is temporarily or permanently stopped and
should be advised at the latest 2 months before
marketing is stopped.
Holders of marketing authorization for medicines are
requested to advise FAMHP about changes in marketing:
see the procedure on page "Marketing/ Unavailability"

70. Wholesalers-Distributors
List of wholesalers-distributors. (PDF, 75.87 Kb)
In order to be complete this list includes not only the
wholesalers-distributors authorised to distribute
medicines for human use (their authorisation number in
the table is followed by the letter H) but also those
authorized to distribute medicines for veterinary use
(their authorization number is followed by the letter V) or
those to distribute medical devices for veterinary use
(their authorization number is followed by letters MD).

71. Pharmacy for the public
A pharmacy open to the general public can only exist if has been authorized to open or move by
the Minister responsible for public health.
It must be managed by a registered pharmacist, who can be assisted or replaced by one or
more other pharmacists. They can use assistants to work with them.
It is subject to complex regulations, which in particular cover :
•The different conditions for keeping and delivering medicines for human or veterinary use;
•The working of magistral and officinal preparations;
•Keeping registers and relevant documentation
•narcotic and psychothropic drugs .
All pharmacists are held responsible for the quality and conformity of the medicines delivered
but he (she) must also take the necessary measures, within the limits of his ability, to ensure
that the medicines are correctly used : detecting interaction between different medicines taken
by the same patient, giving advice about dosages, the possibility of adverse effects, etc.
Controlling that these rules are respected is the responsibility of pharmacist inspectors (PDF,
18.31 Kb) , who can sanction pharmacists for any infringement.
Website of a pharmacy

72. Hospital pharmacy
Each hospital that comes under the law on hospitals that was coordinated on 7 August 1987 must
have a hospital pharmacy or a medicinal product depot. The hospital pharmacy or the medicinal
product depot is under the responsibility of a registered pharmacist, who may be assisted or
replaced by one ore more pharmacists. They are allowed to be assisted, under their responsibility,
by pharmacy assistants. The registered pharmacist of a hospital pharmacy is subject to all legal and
regulatory requirements that apply to the management of a pharmacy that is open to the public.
These requirements are concerning:
• Storage, reception and delivery of medical devices;
• Conservation of medicinal products and raw materials
• Implementation and monitoring of a medicinal product delivery system inside the hospital,
compliant with the regulations;
• Achieving sterile and non-sterile magistral and officinal preparations
• Supervision of the sterilization of reusable medical devices;
• Holding of records and documentation about performed acts.
All pharmacists are responsible for quality and conformity of medicinal products and medical
devices that they deliver. He must, within the limits of his powers, take the necessary measures to
ensure the proper use of those medicinal products and medical devices: detection of interactions
between different medicinal products taken by the same patient, advice on dosage, possible side
effects etc…
The enforcement of this regulation is given to pharmacist inspectors (PDF, 5.75 Kb), who can punish
pharmacists who are in violation.