The Belgian healthcare system is characterised by a compulsory health insurance system covering 99.9% of the population, which is funded from health insurance contributions and general taxation (79%), from out-of-pocket costs (18%) and from other, external sources (3%), such as a contribution of premiums paid for complementary health insurance, a yearly (licence) fee chargeable to pharmaceutical companies and a levy on the turnover of pharmaceutical companies on the Belgian market [1].
The Federal Agency for Medicines and Health Products (Agence Federerale des Medicaments et des Produits de Sante, FAMHP), formerly the Directorate-General for Medicinal Products of the FPS Public Health, created in January 2007, is the official authority for licensing medicines and health products in Belgium [2].
The role of the agency is to ensure the quality, safety and efficacy of medicines and health products in clinical development and on the market. It is also responsible for granting the first national marketing application for a medicinal product according to the mutual recognition procedure, the decentralised procedure and the national procedure described in the Royal Decree of 12 December 2006 [3, 4].
Delivery of licences for marketing
No drug can be commercialised in Belgium without registration or authorisation for marketing. This licence is granted either:
- by the Minister of Health, following advice from the Medicines Commission within the FAMHP (for all national procedures, procedures of mutual recognition or decentralised procedures).
- by the European Community, if necessary after advice from the Committee for Medicinal Products for Human Use (CHMP) or the Committee for Medicinal Products for Veterinary Use (CVMP) within the EMA (for all centralised procedures).
Quality, safety and effectiveness of generic drugs
The experts appointed in the different authorities evaluate the quality, safety and efficacy of the drug based on scientific data submitted by the applicant. During this evaluation, they rely on scientific standards at the European level.
Authorisation for the marketing of a drug is only granted to products whose quality, safety and effectiveness is unequivocally demonstrated.
All medicines licensed for marketing, whether original or generic, must meet same scientific standards, with regard to quality, safety and effectiveness.
Arguments concerning the safety and efficacy of a drug may be submitted in different ways to the competent authority. For a generic medicine this usually happens in the following ways:
Submission of a generic file
If an active ingredient has been authorised for at least 10 years in a Member State of the EU and the patent has expired, it can be marketed as a generic medicine (G: letter used by the Belgian social security (rijksinstituut voor ziekte-en invaliditeitsverzekering, RIZIV) in the reimbursement system). The applicant may refer to the results of the studies carried out with the original product (the reference product), provided that both are ‘essentially equivalent’. This is a shortened file.
Essentially similar products must have the same qualitative and quantitative composition in active ingredient(s), the same pharmaceutical form and bioequivalence with a reference product was demonstrated by appropriate comparative bioavailability studies.
Appearance, colour and/or taste of both drugs may vary as the composition of the non-active ingredients or excipients may differ. Moreover, the full range, e.g. pharmaceutical forms or dosages of the reference product as a generic drug is not always available. The opposite is also correct: there are generic drugs for which the reference medicine of the same dosage or form is not available [5].
Submission of a bibliographic file
Another possibility to prove the safety and efficacy is to refer to published scientific literature. This must reflect the fact that the medicine can be accepted to have comparable pharmacological, toxicological and clinical aspects.
This opportunity may only be used if the active component has been in medicinal use for at least 10 years in the EU (‘well established use’) and also recognised as effective and safe. Such files are sometimes called ‘bibliographic records’ and, as such, the drugs approved are termed ‘copies’ (C: used by the Belgian social security (RIZIV) in the reimbursement system) [5].
References
1. Österreichisches Bundesinstitut für Gesundheitswesen (ÖBIG). Surveying, Assessing and Analysing the Pharmaceutical Sector in the 25 EU Member States. July 2006.
2. Federal Agency for Medicines and Health Products (FAMHP) [homepage on the Internet]. Brussels, Belgium, FAMHP c2008 [cited 2011 May 13]. Available from: www.fagg-afmps.be/en/contact
3. Federal Agency for Medicines and Health Products (FAMHP), The FAMHP moves up a gear: Annual Report 2009, June 2010. Available from: www.fagg-afmps.be/en/binaries/Annual%20Report%202009_tcm292-103495.pdf
4. Koninklijk besluit betreffende geneesmiddelen voor menselijk en diergeneeskundig gebruik (Royal Decree regarding medicines for human and animal use) [Dutch] 14 December 2006. Available from: www.fagg-afmps.be/nl/binaries/AR-KB-2006-12-14_tcm290-27173.pdf
5. Federal Agency for Medicines and Health Products (FAMHP), Originele en generische geneesmiddelen [Dutch] [monograph on the Internet]. Brussels, Belgium, FAMHP c2008 [cited 2011 May 13]. Available from: www.fagg-afmps.be/nl/items-HOME/originele_generische_geneesmiddelen/
Useful information sources
EMA, Committee for Proprietary Medicinal Products (CPMP), Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1) 24 July 2008 [monograph on the Internet] London, UK, EMA [cited 2011 May 13]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003011.pdf
EMA, Committee for Medicinal Products for Human Use (CHMP), EMEA Procedural Advice for Users of the Centralised Procedure for Generic/Hybrid Applications (EMEA/CHMP/ 225411/2006) 2 July 2008 [monograph on the Internet] London, UK, EMA [cited 2011 May 13]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004018.pdf
EMA, Committee for Proprietary Medicinal Products (CPMP), Note for guidance on modified release oral and trans-dermal dosage forms: Section II (pharmacokinetic and clinical evaluation) (CPMP/EWP/280/96) 1999 [monograph on the Internet] London, UK, EMA [cited 2011 May 13]. Available from: www.ema.europa.eu/pdfs/human/ewp/028096en.pdf
EMA, Committee for Proprietary Medicinal Products (CPMP), Note for guidance on the clinical requirements for locally applied, locally acting products containing known constituents (CPMP/EWP/239/95) 1995 [monograph on the Internet] London, UK, EMA [cited 2011 May 13]. Available from: www.ema.europa.eu/pdfs/human/ewp/023995en.pdf
