Marketing, Manufacturing, Packaging & Labeling, Advertising
All about marketing, manufacturing, packaging & labeling, advertising in Belgium. Prepared in association with ALTIUS, a leading law firm in Belgium, this is an extract from The Pharma Legal Handbook: Belgium, available to purchase here for USD 99.
1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?
First of all, the medicines must be the subject of clinical trials. These clinical trials must be submitted to the FAMHP and an ethics committee for review and approval (see also Preclinical and Clinical Trial Requirements).
If these clinical trials have been successful, the applicant can submit an application for a MA. Obtaining a MA is a sine qua non condition for the marketing of the medicines on the Belgian market. Such application can be submitted applying one of the following procedures:
i. Centralised Procedure:
Medicines can be authorised by means of a single application procedure at the European Medicines Agency (‘EMA’). It is important to note that some products, such as biological medicines, must be centrally authorised.
The application is assessed by the EMA’s Committee for Medicinal Products for Human Use (‘CHMP’) during a period of maximum 210 days. The CMHP’s scientific opinion is sent to the European Commission for a final decision.
Once granted, the centralised MA is granted with a European authorisation number that is valid in all EU states, Iceland, Liechtenstein and Norway.
ii. Decentralised Procedure and Mutual Recognition Procedure:
The decentralised procedure (‘DCP’) aims to obtain a MA simultaneously in several Member States for a not yet authorised medicine. The applicant can choose the Member States where obtaining a MA is envisaged. Each Member State chosen by the applicant is called a “Concerned Member State” (‘CMS’) and, among those Member States, the applicant has to choose one state that will be responsible for the evaluation of the application and that is called “Reference Member State” (‘RMS’).
The mutual recognition procedure (‘MRP’) enables an applicant to have a MA already obtained in one Member State (=RMS) recognised in one or more other Member States (=CMS).
Following approval, the applicant receives national MAs with national authorisation numbers for each of the Member States involved in the proceeding.
It is mandatory to use one of these two procedures if a MA application has already been submitted in another Member State. These procedures allow also obtaining authorisation for generic medicines of medicines that have already been authorised under the centralised procedure.
iii. National Procedure:
In Belgium, the request for a national MA must be submitted with the FAMHP. The Commission for Medicines for Human Use decides on the benefit/risk balance of a medicine on the basis of three criteria: the efficacy, safety and quality of the medicine. After an assessment, the applicant receives the decision from the Minister or the FAMHP. If positive, the applicant receives a national MA that is only valid on Belgian territory.
2. What is the authorization process for the marketing of generic versions of these products?
Please refer to Regulatory, Pricing and Reimbursement Overview, Question 6: “How does the authorisation process differ between brand-name products and generic products?”.
3. What are the typical fees for marketing approval?
Please refer to Regulatory, Pricing and Reimbursement Overview, Question 4: “What are the approximate fees for each authorisation?”.
4. What is the period of authorization and the renewal process?
Please refer to Regulatory, Pricing and Reimbursement Overview, Question 5: “For how long are marketing authorisations/registrations valid? How are mare marketing authorisations/registrations renewed?”.
5. What are the requirements, if any, for post-approval pharmacovigilance?
The bodies within the administrative authorities responsible for assessing and monitoring the safety of human medicines are the Belgian Pharmacovigilance Centre for medicines for human use (‘BPC’) established at the FAMHP, and the Pharmacovigilance Risk Assessment Committee (PRAC) at the EMA.
The MA holder must also set up a pharmacovigilance system (sensu lato), consisting of (i) a pharmacovigilance system that is company specific and (ii) a risk management system that is product specific. The MA holders should keep detailed reports of all possible side effects that have occurred in or outside the European Union, and report to the relevant authorities serious adverse reactions within a maximum period of fifteen days. Additionally, they should also at regular intervals submit actualised periodical reports regarding the safety to the competent authorities.
The MA holder must also appoint a pharmacovigilance manager, called the qualified person responsible for pharmacovigilance (‘QPPV’), who is responsible for the above actions. If the QPPV is not physically present in Belgium, a local contact person should be appointed as well.
Following the evaluation of the pharmacovigilance data, the FAMHP may decide to suspend, withdraw or amend the MA. It must then communicate this decision to the EMA, the other Member States and the MA holder.
6. Are foreign marketing authorizations recognized?
Foreign marketing authorisations can only be recognised provided that they are rendered by a Member state of the European Union and not by a third country. In such case, the so-called mutual-recognition procedure should still be followed (see also Question 1 above).
7. Are parallel imports of medicines or devices allowed?
Yes, parallel import or parallel distribution of medicines is allowed within the European Economic Area.
When it concerns centrally authorized medicines (i.e. one authorisation for the entire EU), reference is not made to ‘parallel import’, but to ‘parallel distribution’. In such case, a notification of the EMA of the intended parallel distribution is required.
In case of nationally granted MAs, parallel import is allowed, provided that the following conditions are met:
- A MA has been granted in the Member State of origin (part of the EU or of the European Economic Area) for the medicine to be imported;
- A MA has been granted in the Member State of import for the reference medicine;
- The imported and the reference medicine should at least:
o have the same qualitative and quantitative composition in active ingredients;
o have the same therapeutic indications;
o be therapeutically equivalent;
o have the same pharmaceutical form;
- No further differences may exist between the imported and reference medicinal product that could be therapeutically relevant and/or could pose a danger to public health.
The applicant for a parallel import authorisation is required to compile a file and submit it to the FAMHP in order to obtain this authorisation and the setting of the maximum price.
Finally, parallel distribution and import should respect intellectual property rights, such as trade mark rights, and should in this regard comply with the principles that have in this regard been set by the Court of Justice of the European Union.
As for medical devices, once a device has been CE-marked, it can be marketed anywhere in the EU, as long as the general requirements for medical devices are complied with.
8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?
Belgian law prohibits the requesting, offering, accepting, or providing of “gifts, monetary advantages or benefits in kind” to wholesalers, persons qualified to prescribe, deliver or administer medicines or medical devices and institutions where prescribing, delivering or administering medicines or medical devices take place.
The above prohibition does not apply to:
- gifts or benefits of limited value that concern medical, dental or veterinarian practices (such as EUR 50 per gift and up to a maximum of EUR 125 per year),
- invitations and payment of costs for participation in scientific events, including the hospitality of healthcare professionals if certain conditions are met; and
- the reasonable compensation of legitimate services of a scientific nature (compensation for clinical trials, research papers, symposiums, etc.).
9. How is the manufacturing of medicines and devices regulated and by which agencies?
The manufacturing of medicines in Belgium is subject to a manufacturing authorisation. The application for this authorisation must be submitted to FAMHP.
Once this authorisation has been granted, the holder of the authorisation is required to comply with a number of obligations, such as compliance with Good Manufacturing Practices issued by the EMA and the appointment of a recognized qualified person (‘QP’) who can provide services to only one pharmaceutical company and who is responsible for batch release to verify and ensure the quality of the medicines (incl good manufacturing practices when manufactured in Belgium). Compliance with these practices is then monitored by a team of inspectors from the FAMHP’s Inspection Directorate General.
To be put on the Belgian market, all medical devices must bear a CE marking. The procedure depends on the class of the medical device:
- The manufacturer of Class I medical devices may affix the CE marking himself under his own responsibility. However, he is required to notify himself to the FAMHP, which is responsible for controlling the manufacturing processes.
- For Class II (a) medical devices up to Class III medical devices, the CE marking must be authorised by a notified body. A notified body is a private organisation accredited and designated by the FAMHP and then notified to the European Commission. If this body decides to give its authorisation, it shall issue the manufacturer with a certificate of conformity valid for a maximum of five years. This body is responsible for controlling the manufacturing process of those medical devices.
10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the US Food & Drug Administration (US FDA) and/or the European Medicines Agency (EMA)?
Yes, the local manufacturing practices are in accordance with the Good Manufacturing Practices issued by the EMA.
11. What is the inspection regime for manufacturing facilities?
The inspection regime is carried out by FAMHP for the manufacturing of medicines and Class I medical devices. By contrast, the inspection regime is carried out by a notified body in the case of Class II (a) medical devices up to Class III medical devices (see also Question 9 above).
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
Statutory agents or permanent employees of FAMHP (or, in some cases, judicial officers) shall carry out the inspections. Nevertheless, those inspections may be conducted at the request of other agencies, including the FDA/EMA.
13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?
Apart from the fact that these acts can only be carried out by an entity that has a wholesale license, the storage, packaging and handling of medicines and medical devices shall also comply with:
- The Guidelines of 7 March 2013 on Good Distribution Practice of medicinal products for human use (2013/C 343/01);
- The principles and guidelines on good distribution practices included in Annex V of the Royal Decree of 14 December 2006.
14. What information must be included in medicine and device labeling?
The labeling of a medicine shall be drawn up in accordance with the SmPC and shall contain the following information:
1) For the identification of the medicine:
- the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults. The common name shall be included where the product contains only one active substance and if its name is an invented name;
- the pharmaco-therapeutic group or type of activity in terms easily comprehensible for the patient;
2) The therapeutic indications;
3) A list of information which is necessary before the medicinal product is taken:
- appropriate precautions for use;
- forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product;
- special warnings;
4) The necessary and usual instructions for proper use, and in particular :
- the dosage;
- the method and, if necessary, route of administration;
- the frequency of administration, specifying if necessary the appropriate time at which the medicinal product may or must be administered;
- and, as appropriate, depending on the nature of the product:
- the duration of treatment, where it should be limited;
- the action to be taken in case of an overdose (such as symptoms, emergency procedures);
- what to do when one or more doses have not been taken;
- indication, if necessary, of the risk of withdrawal effects;
- a specific recommendation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product;
5) a description of the adverse reactions which may occur under normal use of the medicinal product and, if necessary, the action to be taken in such a case;
6) a reference to the expiry date indicated on the label, with:
- a warning against using the product after that date;
- where appropriate, special storage precautions;
- if necessary, a warning concerning certain visible signs of deterioration;
- the full qualitative composition (in active substances and excipients) and the quantitative composition in active substances, using common names, for each presentation of the medicinal product;
- for each presentation of the product, the pharmaceutical form and content in weight, volume or units of dosage;
- the name and address of the marketing authorisation holder and, where applicable, the name of his appointed representatives in the Member States;
- the name and address of the manufacturer;
7) where the medicinal product is authorised in accordance with Articles 28 to 39 under different names in the Member States concerned, a list of the names authorised in each Member State;
8) the date on which the package leaflet was last revised.
The information on the labeling of a medical device depends on the type of medical device, but shall least contain at least the following information:
- the name or trade name and address of the manufacturer. For devices imported into the Community, in view of their distribution in the Community, the label, or the outer packaging, or instructions for use, shall contain in addition the name and address of the authorised representative where the manufacturer does not have a registered place of business in the Community;
- the details strictly necessary to identify the device and the contents of the packaging especially for the users;
- where appropriate, the word ‘STERILE’;
- where appropriate, the batch code, preceded by the word ‘LOT’, or the serial number;
- where appropriate, an indication of the date by which the device should be used, in safety, expressed as the year and month;
- where appropriate, an indication that the device is for single use. A manufacturer’s indication of single use must be consistent across the Community;
- if the device is custom-made, the words ‘custom-made device’;
- if the device is intended for clinical investigations, the words ‘exclusively for clinical investigations’;
- any special storage and/or handling conditions;
- any special operating instructions;
- any warnings and/or precautions to take;
- year of manufacture for active devices other than those covered by (e). This indication may be included in the batch or serial number;
- where applicable, method of sterilization;
- in the case of a device within the meaning of Article 1(4a), an indication that the device contains a human blood derivative.
In Belgium, it is mandatory that this information be made available in the three national languages: German, French and Dutch.
15. What additional information may be included in labeling and packaging?
All the information necessary to use the medicine or medical device safely provided that it complies with the criteria set out in Question 16 (below) may be included in labeling and packaging. The specific characteristics of certain medicines or medical devices may therefore be included.
16. What items may not be included in labeling and packaging?
The packaging may not include any element, logo, sign or pictogram that:
- Is contrary to the summary of product characteristics as approved by the FAMHP;
- Is contrary to the Guideline on readability;
- Is false;
- Is confusing;
- Is contrary to rules of decency;
- Is promotional;
- Does not contribute to health information.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
Advertising is always prohibited for unauthorised, banned or suspended medicines. Advertising is further prohibited to the general public for medicines that can be obtained only with a medical prescription and for narcotics and psychotropics. Medicines that may be advertised to the general public are medicines that, according to their composition and purpose, are intended and designed for use without the intervention of a medical practitioner for diagnostic purposes or for the prescription or monitoring of treatment, with the advice of the pharmacist, if necessary.
When permitted, the advertising has to comply with the general rules surrounding all advertising and aimed at protecting consumers, as well as the specific rules such as:
- It shall comply with the particular listed in the summary of product characteristics;
- It shall encourage the rational use of the medicine, by presenting it objectively, without exaggerating its properties and without being misleading;
- It shall be accurate, up-to-date, verifiable;
- It shall not contain any element that:
- gives the impression that a medical consultation or surgical operation is unnecessary, in particular by offering a diagnosis or by suggesting treatment by mail;
- suggests that the effects of taking the medicine are guaranteed, are unaccompanied by adverse reactions or are better than, or equivalent to, those of another treatment or medicine;
- suggests that the health of the subject can be enhanced by taking the medicine, or that the health of the subject could be affected by not taking the medicine (except for vaccination campaigns and information campaigns about vaccines);
- is directed exclusively or principally at children;
o refers to a recommendation by scientists, health professionals or persons who are neither of the foregoing but who, because of their celebrity, could encourage the consumption of medicines;
- suggests that the medicine is a foodstuff, cosmetic or other consumer product;
- suggests that the safety or efficacy of the medicine is due to the fact that it is natural;
- by a description or detailed representation of a case history, could lead to erroneous self-diagnosis;
- refers, in improper, alarming or misleading terms, to claims of recovery;
- uses, in improper, alarming or misleading terms, pictorial representations of changes in the human body caused by disease or injury, or of the action of a medicine on the human body or parts thereof;
- would use images, drawings, photographs or representations liable to infringe on the very essential informational character and the restraint which must characterise the advertising of medicines or which, on the part of the persons to whom they are addressed, would use grounds other than those rationally persuading them to use a medicine for the purpose of the treatment or prevention of a disorder or a disease, in the course of making a medical diagnosis, or for the purpose of restoring, correcting or modifying organic functions;
- It shall bear the words “this is a drug, not for prolonged use without medical advice”;
Advertising is for medical devices is not allowed for devices not bearing the CE marking. Advertising to the public for implantable medical devices and for the acts of performing them is also prohibited. This prohibition may be extended to other medical devices depending on the risk they pose to public health. However, advertising to the public for other medical devices is permitted.
It should also be noted that the rules are different when advertising is addressed to health care professionals.
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
Medicines can only be sold and delivered to the public by pharmacists in a pharmacy open to the public or by hospital pharmacists. Medical devices can be sold not only by pharmacists, but also by any distributor or even by the device manufacturer.
The delivery of medicines in the pharmacy remains the basic principle. However, an exemption is provided for pharmacies open to the public and authorised in Belgium to sell via the Internet, under very strict conditions, authorised and non-prescription medicines and certain medical devices (see Question 19 below). The ordered product is then delivered via post, brokers or deliverers.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by internet, social media, and other channels?
When a pharmacist wishes to sell medicines via the Internet, he must notify the FAMHP and the Order of Pharmacists, via the appropriate form, within one month of the publication of his website.
The pharmacist’s website must comply with a number of conditions. First, it must be designed to promote the rational use of medicines and medical devices, in particular by presenting them in an objective and non-misleading manner and without exaggerating their properties. The website must also contain a certain amount of mandatory information, which is listed in Article 29 of the Royal Decree of 21 January 2009 on instructions for pharmacists. For example, the pharmacist is required to indicate on his website the information contained in the notice of the medicine or medical device offered for sale.
There are no specific legal rules on advertising on the Internet. Therefore, it is subject to the general rules applicable to the advertising of medicines and medical devices (see Question 17 above). However, advertising for medicines by electronic mail is expressly prohibited.
20. May medicines and devices be advertised or sold directly to consumers?
Regarding advertising, please refer to Question 17: “What are the restrictions and requirements for the marketing and advertising of medicines and devices?”.
Regarding sale, please refer to Question 18: “Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?”.
21. How is compliance monitored?
The advertising of medicines distributed to the general public are subject to control prior to their distribution:
- Advertising broadcast on radio or television requires a prior visa to be granted by the Minister of Public Health, on the advice of the Medicines Advertising Control Commission.
- All types of advertising other than radiophonic or televisual advertising must be notified to the FAMHP at least 30 days before broadcast.
In addition, the MA holder must collaborate with an information officer approved by the Minister. This officer is responsible for checking in advance whether the holder’s advertising practices are in compliance with the regulations relating to the advertisements for medicines. This compliance is regularly verified by the FAMHP.
22. What are the potential penalties for noncompliance?
In such case, the Minister may suspend or withdraw the approval of the information officer or withdraw the visa. If the Minister or the FAMHP consider it necessary to protect the public interest, they may order the cessation or prohibit an advertising campaign for a medicine.
The sanctions mentioned in Regulatory, Pricing and Reimbursement Overview, Question 9 may also apply.