Marketing, Manufacturing, Packaging & Labeling, Advertising
An intro to the legal situation for marketing, manufacturing, packaging & labeling, and advertising in Luxembourg. Prepared in association with Wildgen, a leading global law firm, this is an extract from The Pharma Legal Handbook: Luxembourg, 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?
Please refer to question 3 in Chapter 1.
2. What is the authorization process for the marketing of generic versions of these products?
Please refer to question 6 in Chapter1.
3. What are the typical fees for marketing approval?
Please refer to question 4 in Chapter 1.
4. What is the period of authorization and the renewal process?
Please refer to question 5 in Chapter 1.
5. What are the requirements, if any, for post-approval pharmacovigilance?
According to Chapter 5-1 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, a pharmacovigilance system has to be implemented and consists of the monitoring of unexpected side effects of medicinal products on humans or animals:
– on one part, by the Ministry of the Health: useful information are collected, that includes the risks of the medicinal products to the health of the patients or public health as well as undesirable effects on humans;
– on the other part, by the marketing authorization holder. The main requirements are the followings:
- the marketing authorization holder should carry out a scientific evaluation of all relevant information, in order to consider options for preventing or minimizing risks and, if necessary, for taking appropriate measures;
- the marketing authorization holder should carry out a periodic audit of his pharmacovigilance system. It records the main results of this audit in writing in the permanent file of the pharmacovigilance system and, based on these results, takes the necessary steps to develop and implement an appropriate action plan to solve the problems identified. Once the corrective measures fully implemented, the records may be deleted.
More detailed requirements related to the pharmacovigilance are available in articles 45-3 to 45-9 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended.
6. Are foreign marketing authorizations recognized?
In principle, foreign marketing authorization are not recognized in Luxembourg and all medicinal products for human use should be authorized by the Ministry of Health in order to marketed.
European Union law has however introduced some specific procedure:
- Under the centralized procedure laid down in Regulation (EC) No 726/2004, a marketing authorization is granted by the European Commission which is valid for all the members of the EU;
- Under the decentralized procedure introduced by Directive 2004/27/EC and implemented in Luxembourg law with article 5-1 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, it is possible to submit an application simultaneously to several Member States that will be commonly assessed. One of the Member States will take the lead in evaluating the application as a “reference Member State”;
- Under the mutual recognition procedure laid down in Directive 2001/83/EC and implemented in Luxembourg law with article 5-1 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, marketing authorizations from one EU Member State may be recognized in another EU Member State through a common assessment procedure.
7. Are parallel imports of medicines or devices allowed?
Yes, parallel imports of medicinal products or devices are allowed in accordance with the principle of free movement of goods within EU countries.
According to the guideline as provided for in European Commission Communication on parallel imports of proprietary medicinal products for which marketing authorizations have already been granted, parallel imports of medicinal products within EU countries should fulfill the following requirements:
- the imported product has been granted a marketing authorization in the Member State of exportation;
- the imported product is sufficiently similar to a product that has already received marketing authorization in the Member State of destination even if there are differences relating to the excipients.
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?
According to article 25 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended:
- as part of the promotion of medicinal products to persons authorized to prescribe or to deliver them, it is prohibited to grant, offer or promise to such persons a bonus, monetary benefit or benefit in kind unless they are of negligible value and are related to the practice of medicine or pharmacy;
- however, the hospitality offered, directly or indirectly, at events of an exclusively professional and scientific nature is not prohibited. This hospitality must always be strictly limited to the main scientific purpose of the meeting and it should not be extended to people other than health professionals.
9. How is the manufacturing of medicines and devices regulated and by which agencies?
i. Manufacturing of Medicinal Products
Pursuant to the law of 4 August 1975 relating to manufacturing and import of medicinal products as amended, the manufacturing of medicinal products is regulated through prior manufacturing authorization by the Ministry of Health. To deliver a manufacturing and import authorization, the Pharmacy and Medication Department carries out inspections to verify the compliance with Good Manufacturing Practices (“GMP”).
ii. Manufacturing of Medical Devices
No prior authorization is required for the manufacturing of the medical devices.
However, the manufacturer should fulfill the requirements of the Grand-Ducal regulations related to medical devices, among which there are requirements related to conception and production of the device.
The Pharmacy and Medication Department / Ministry of Health is the competent authority for the surveillance of medical devices, among other duties.
10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?
Yes, local manufacturing requirements are compatible with the European Medicines Agency.
11. What is the inspection regime for manufacturing facilities?
The Pharmacy and Medication Department / Ministry of Health has authority over the manufacturing of medicinal products. Several pharmacist inspectors are designated by the Pharmacy and Medication Department to ensure that manufacturing facilities are in compliance with the laws and regulations.
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
According to article 7-1 of the Grand-Ducal Regulation of 19 November 2004 relating to the manufacturing, the distribution and the brokerage of medicinal products, as amended, the Pharmacy and Medication Department is responsible for the inspection of manufacturing facilities located in Luxembourg which means that, as a principle, inspection by foreign inspectors or third party inspectors is not allowed within the Luxembourg territory.
The Regulation (EC) No 726/2004 laying down a centralized Community procedures for the authorization and supervision of medicinal products for human use, foresees in its article 8 that the Committee for Medicinal Products for Human Use, part of the European Medicines Agency, may require an applicant for a marketing authorization based in Luxembourg to undergo a specific inspection of the manufacturing site. This inspection will be however carried out by the Luxembourg Pharmacy and Medication Department accompanied by a rapporteur or an expert appointed by said Committee.
13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?
i. Medicinal Products
The conditions of storage of a medicinal product shall be mentioned on the leaflet and shall be complied with (temperature, humidity, …).
ii. Medical Devices
According to Annex I of the Grand-Ducal Regulation of 11 August 1996 concerning medical devices as amended, as general principle, medical devices shall be packaged in such a way that the characteristics and performances shall not be altered in the storage conditions and transport conditions as foreseen by the manufacturer (temperature, humidity, …)
14. What information must be included in medicine and device labeling?
i. Medicinal Products
According to articles 10, 11 and 12 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, the main requirements related to the packaging of medicinal products are the following:
– the outer packaging or, in the absence of an outer packaging, the immediate packaging of any medicinal product shall bear certain information as provided for in article 10 as for instance:
- the name of the medicinal product followed by its dosage and pharmaceutical form and, where appropriate, the indication of the recipient (infants, children or adults); when the medicinal product contains up to three active substances, the international nonproprietary name (INN) or, if it does not exist, the common name;…
- the qualitative and quantitative composition of active ingredients per dosage unit or, depending on the form of administration, for a given volume or weight, using the common names;
- the pharmaceutical form and the content by weight, by volume or in units per use;
– when the immediate packaging is contained in an outer packaging compliant with the requirements of the above mentioned article 10, the immediate packaging , which is in a form of blister, must bear certain information as provided for in article 11, as for instance. the name of the medicinal product, the name of the marketing authorization holder, the expiration date, the manufacturer’s batch number,…;
– the information on the outer packaging or the immediate packaging must be written in an easily legible and in a clear comprehensible way. In addition, this information has to be written in at least one of the official languages (French, German, Luxemburgish).
ii. Medical Devices
According to Annex I of the Grand-Ducal Regulation of 11 August 1996 concerning medical devices as amended, the compulsory information on device labeling includes the following (without being exhaustive):
- the contact details of the manufacturer, and for devices imported into EU and to be distributed inside EU, the labeling, the outer packaging or the instructions for use should contain, in addition, the name and the address of the representative when the manufacturer is not established in EU;
- the indications strictly necessary to identify the device and the contents of the packaging in particular for users;
- special conditions of storage and/or handling;
- special instructions for use;
- warnings and/or precautions to take.
In addition, the device of the manufacturer should also put a “CE” mention on the labelling in accordance with the requirements of the conformity of “CE” mention as provided in Annex XII of the above-mentioned regulation.
15. What additional information may be included in labeling and packaging?
i. Medicinal Products
According to article 10 of Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, the following additional information may be included in medicinal products labeling and packaging:
- the outer packaging may include signs or pictograms to clarify some of the mandatory information, and
- other information compatible with the summary of medicinal product characteristics, useful for health education, excluding any items that may be promotional in nature.
ii. Medical Devices
To our knowledge, there is no relevant regulation about additional information that may be included in labeling and packaging, except for specific medicinal devices regulated by specific laws/provisions…
16. What items may not be included in labeling and packaging?
General provisions related to advertising shall apply (prohibition of advertising regarding medicinal products which can only be issued on a medical prescription, …) as well as common rules regarding misleading information.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
i. Medicinal Products
According to article 19 of the law of 11 April 1983 on the regulation of the marketing authorization and advertising of medicinal products as amended, states, as general rule, that any advertising to the general public is prohibited except:
- with a prior authorization granted by Ministry of Health; or
- where it is limited to general advertising, only mentioning the name and the composition of the medicinal product, the name and address of the manufacturer.
A prior tax has to be paid.
More detailed restrictions and requirements for the advertising of medicinal products to the general public and to the healthcare professionals are foreseen in the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended.
ii. Medical Devices:
General rules apply and it is forbidden to advertise medical devices which are not compliant with the applicable laws and regulations.
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
i. The Sale and Delivery of Medicinal Products
According to articles 3 of the law of 25 November 1975 concerning the deliverance of medicinal products to the public as amended, medicinal products can only be dispensed to the public in pharmacies, except in cases where they can also be delivered by the pharmacist, under specific conditions, to patients accommodated in the following establishments:
– centers, homes and services for the elderly;
– geriatric or accommodation centers of services for authorized people according to the law of 8 September 1998 regulating relations between the State and organisations working in the domain of social, family and therapeutic as amended.
Pursuant to the law of 4 August 1975 relating to manufacturing and import of medicinal products as amended, OTC medicinal products can be sold on the internet, through a dedicated website created and managed by a pharmacist having made a prior notification to the Ministry of Health, and send from the pharmacy.
ii. The Sale and Delivery of Medical Devices:
Pursuant to article 2-1 of the law of 16 January 1990 on medical devices as amended, which constitutes the main regulation for medical devices, medical devices can be delivered by pharmacists or other authorized persons in accordance with the Luxembourgish legislation in force.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?
There is no specific regulation about electronic marketing and advertising of medicinal products, so the general regulation framework as provided for in the law of 11 April 1983 on the regulation of the marketing authorization and advertising of medicinal products as amended would apply.
20. May medicines and devices be advertised or sold directly to consumers?
According to article 19 of the Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended, medicinal products except the following categories can be advertised directly to consumers:
- which can only be issued on a medical prescription,
- which contain psychotropic substances or narcotics,
- which are reimbursable by social insurance.
21. How is compliance monitored?
According to articles 28 and 29 of Grand-Ducal regulation of 15 December 1992 relating to the marketing of medicinal products as amended:
- compliance with advertising regulation is monitored and evaluated by the Pharmacy and Medication Department / Ministry of Health;
- the person responsible for marketing authorization should establish within his company a scientific service responsible for the information relating to the medicinal products he introduces on the market, and
– keep at the disposal of the authorities or bodies responsible for the control of pharmaceutical advertising or communicate them a copy of any advertisement issued by his company, accompanied by a notice indicating the recipients, the way of diffusion and date of first diffusion;
– ensure that the pharmaceutical advertising made by his company complies with the legal requirements that apply;
– verify that the medical representatives employed by his company are adequately trained and respect their legal obligations;
– provide the authorities or bodies responsible for the control of pharmaceutical advertising with the information and assistance required;
– ensure that decisions taken by the authorities or bodies responsible for the control of pharmaceutical advertising are immediately and completely respected.
22. What are the potential penalties for noncompliance?
According to article 20 of the law of 11 April 1983 on the regulation of the marketing authorization and advertising of medicinal product as amended, the potential penalties for non-compliance are the following:
- 8 days to 6 months of imprisonment and/or
- a fine of 251 to 10,000 euros.