Regulatory procedures for drugs in Belgium Société Belge de Pédiatrie Belgische Vereniging voor Kindergeneeskunde 19/03/2005 Anne Matrie HUBERT
Regulatory procedures for drugs in Belgium
Société Belge de PédiatrieBelgische Vereniging voor Kindergeneeskunde
19/03/2005Anne Matrie HUBERT
Overview of procedures in BelgiumOverview of procedures in Belgium
1. Registration
2. Price
3. Reimbursement
Sales possible (without reimbursement) Full launch
M. Public Health
(or EU Commission)
M. Economy
M. Social affairs
Regulatory procedures in BelgiumRegulatory procedures in Belgium
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
Product registrationProduct registration
• Development of a new drug
• Content of a registration dossier
• Procedures
• Development of a new drug
• Content of a registration dossier
• Procedures
Product developmentProduct development
?Synthesis/production of new molecules or proteins?Screening? Tests in animals: toxicology & pharmacology?Development of a pharmaceutical formulation
(pilot scale & full production scale)
? Tests in humans:? phase I studies: pharmacodynamic and pharmacokinetic studies (volunteers)? phase II and phase III studies to define safety and efficacy profile in patients populations
?Synthesis/production of new molecules or proteins?Screening? Tests in animals: toxicology & pharmacology?Development of a pharmaceutical formulation
(pilot scale & full production scale)
? Tests in humans:? phase I studies: pharmacodynamic and pharmacokinetic studies (volunteers)? phase II and phase III studies to define safety and efficacy profile in patients populations
Mean duration of developmentMean duration of development
3.25.1 5.9 6.1
2.5
4.42.4
2.1
2.8 1.8
6.35.5
14.2 Years14.2 Years
11.6 Years
8.1 Years
1960's 1970's 1980's 1990's
Approval Phase
Clinical Phase
Preclinical Phase
Source: DiMasi et al., “New Drug Development in U.S. 1963-1999.” Clinical Pharmacology &Therapeutics 2001. May, 69(s).
±12 years of development ; cost ? 800 mio USD
Content of a new product registration dossier
Content of a new product registration dossier
Should ensure quality, safety, efficacy
? Chemical and pharmaceutical data?defines the product quality
? Pharmacological and toxicological data (non-clinical data):?defines the product pharmacological properties?defines the product safety & toxicology in animals
? Clinical data (data in humans)?defines the product actions in humans:
pharmacokinetics, efficacy and safety.
Should ensure quality, safety, efficacy
? Chemical and pharmaceutical data?defines the product quality
? Pharmacological and toxicological data (non-clinical data):?defines the product pharmacological properties?defines the product safety & toxicology in animals
? Clinical data (data in humans)?defines the product actions in humans:
pharmacokinetics, efficacy and safety.
Content of a product registration dossier
Content of a product registration dossier
Admin. info
Quality
overall summary
Non clinical
overall summary
Clinical
overall summary
Quality body of data
Module 1
Module 2
Module 3 Module 4 Module 5
Non clinical study reports
Clinical study reports
Procedures for drug registrationProcedures for drug registration
3 possibilities:
1. National procedure 2. European procedure by mutual recognition3. European centralised procedure
3 possibilities:
1. National procedure 2. European procedure by mutual recognition3. European centralised procedure
National procedureNational procedure
Product registration delivered by the Belgian authorities, on the basis of an evaluation by national authorities
? the only existing procedure for products registered before 1976
? still the procedure used for most products registered before 1998
? very strong limitations since 1998: can only be used for local products (products not intended to be marketed in more than one member state)
? exception: new extension for an already existing product approved by national procedure (e.g. new pharmaceutical form).
Product registration delivered by the Belgian authorities, on the basis of an evaluation by national authorities
? the only existing procedure for products registered before 1976
? still the procedure used for most products registered before 1998
? very strong limitations since 1998: can only be used for local products (products not intended to be marketed in more than one member state)
? exception: new extension for an already existing product approved by national procedure (e.g. new pharmaceutical form).
European procedure by mutual recognition
European procedure by mutual recognition
The assessment of the first member state is ‘recognised’ by the other EU member states.
? The first member state to approve a new product acts as the ‘reference member state’.
? The reference member state justifies its basis for approval by issuing an assessment report which is sent to all other concerned member states
?Other member states have 60 days to object the decision of approval (only on the basis of serious public health issues)
The assessment of the first member state is ‘recognised’ by the other EU member states.
? The first member state to approve a new product acts as the ‘reference member state’.
? The reference member state justifies its basis for approval by issuing an assessment report which is sent to all other concerned member states
?Other member states have 60 days to object the decision of approval (only on the basis of serious public health issues)
European centralised procedureEuropean centralised procedure
Central evaluation made for Europe and coordinated by the European Medicines Agency (EMA) based in London
?An application is submitted to the EMEA? The EMEA appoints a rapporteur and a co-rapporteur who
should coordinate the assessment of the dossier.? The scientific European Committee for Human Medicinal
Products gives an advice? To be confirmed by the European commission? The product licence is delivered by the European
Commission: one licence for the whole of Europe.
Central evaluation made for Europe and coordinated by the European Medicines Agency (EMA) based in London
?An application is submitted to the EMEA? The EMEA appoints a rapporteur and a co-rapporteur who
should coordinate the assessment of the dossier.? The scientific European Committee for Human Medicinal
Products gives an advice? To be confirmed by the European commission? The product licence is delivered by the European
Commission: one licence for the whole of Europe.
Regulatory procedures in BelgiumRegulatory procedures in Belgium
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
Price dossierPrice dossier
• Details on the product (dose, pack size, indications, etc.)
• Prices of equivalent products in Belgium• Prices of same product in other European countries• Country of origin• Details on price requested with:
– Purchase price– Costs for import, quality assurance, transport– Distribution costs: medical information, salaries,
others– Profit margin– Wholesaler, pharmacist and public prices
• Details on the product (dose, pack size, indications, etc.)
• Prices of equivalent products in Belgium• Prices of same product in other European countries• Country of origin• Details on price requested with:
– Purchase price– Costs for import, quality assurance, transport– Distribution costs: medical information, salaries,
others– Profit margin– Wholesaler, pharmacist and public prices
Procedure for reimbursable products
Procedure for reimbursable products
New product or price increaseNew product or price increase
Price application
Pricing committeeC.P.S.P./P.F.S.
Concertation committee
Decision minister
Notification
90 days
Regulatory procedures in BelgiumRegulatory procedures in Belgium
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
1. Drug registration? Ministry of public health
2. Pricing? Ministry of economic affairs
3. Reimbursement by the sick funds? Ministry of social affairs (INAMI/RIZIV)
Reimbursement procedureReimbursement procedure
sec
0 10 20 30
expertssec
M. Economic Aff.
40 60 8050 70 90 100 120 140 160 180110 130 150 170 190 200
CRM/CTG
CRM/CTG
M.SocialAff.
fin
bud
StateCouncil
Publication
Applicant Applicant
6 months for the decision, 2-3 months for publication
• Milestones: day 60 report, provisional motivated decision (d 120), definitive decision (d 150) and minister’s decision (d 180)• 2 opportunities to comment: after day 60 report and after day 120
CRM/CTG
experts
Composition of reimbursement committee (CRM/CTG)
Composition of reimbursement committee (CRM/CTG)
Experts (universities)
Sick funds
Physicians
Pharmacists
External expertsInternal experts (5) +
Bureau CRM/CTG (1+2)
CRMdecides (2/3)
77
88
4433
+ 2 industry rep.consult. voice
Admission criteriaAdmission criteria
?Reimbursement allowed only for products under prescription
? Products must present a social interest and meet certain criteria:– Therapeutic value (see next slide)– Price and basis of reimbursement requested– Interest in the medical practice in function of
therapeutic and social needs (N/A generics)– Budget impact– Ratio between cost for the sick funds and
therapeutical value ? P/E dossier! (N/A generics)
?Reimbursement allowed only for products under prescription
? Products must present a social interest and meet certain criteria:– Therapeutic value (see next slide)– Price and basis of reimbursement requested– Interest in the medical practice in function of
therapeutic and social needs (N/A generics)– Budget impact– Ratio between cost for the sick funds and
therapeutical value ? P/E dossier! (N/A generics)
Admission criteriaAdmission criteria
? Therapeutic value:– Added value when therapeutic value is
higher than that of a standard treatment.– 3 classes of products:
• Class 1: added value demonstrated compared to existing alternatives ?higher price possible
• Class 2: no demonstrated added value but no generic of copy product ? no higher price
• Class 3: generics and copy products ?lower price
? Therapeutic value:– Added value when therapeutic value is
higher than that of a standard treatment.– 3 classes of products:
• Class 1: added value demonstrated compared to existing alternatives ?higher price possible
• Class 2: no demonstrated added value but no generic of copy product ? no higher price
• Class 3: generics and copy products ?lower price
Content of a reimbursement dossier
Content of a reimbursement dossier
?Details on the product (dose, pack size, indications, etc.)
?Copies of product registration documents?Copy of price application?Reimbursement proposal (with price, conditions,
category, etc)? Justification of the proposal with scientific
motivations, clinical, epidemiological, pharmaco-economic studies, published (or not-published)
?Details on the product (dose, pack size, indications, etc.)
?Copies of product registration documents?Copy of price application?Reimbursement proposal (with price, conditions,
category, etc)? Justification of the proposal with scientific
motivations, clinical, epidemiological, pharmaco-economic studies, published (or not-published)
ConclusionConclusion
• Product development is an expensive, risky and lengthy process
• Registration application review and approval process lasts in average about 16-18 months
• Price & reimbursement applications takes about 8-9 months to complete (when successful!)
• Product development is an expensive, risky and lengthy process
• Registration application review and approval process lasts in average about 16-18 months
• Price & reimbursement applications takes about 8-9 months to complete (when successful!)