Case 5
1. How does a drug come into the market?
Stages of drug development
1. Pre-clinical studies: test tubes, laboratory, animal testing
2. Clinical studies: Phase I + II + III clinical trials
Phase 1: small group of health volunteers. To evaluate safety and determine a safe dosage.
Phase 2: larger group of volunteers and patients, up to 200.
Phase 3: confirm findings by research on a large patient population with randomized control (new
drug vs usual care = gold standard). In this phase, also the efficacy, safety and side-effects are
observed.
3. Marketing authorization (EMA or DFA) and reimbursement
4. Pharmacovigilance (geneesmiddelenbewaking)
As showed in the figure; you start with a pre-clinical research. After this you do clinical studies in
phase I, II and III. This can take upon 10 years. The last two or three years are used for administrative
procedures which consist: market authorization and reimbursement. Of course, administrative
procedure will only take place AFTER APPROVAL.
Market authorization
Licensing and regulatory approval are important parts within the pharmaceutical market. Important
parties who play a big role in licensing and regulatory approvals are:
- EMA: European Medicine Agency They operate on EU-level and observe three criteria: efficacy,
safety and quality and analyze the benefit-risk ration.
- FDA: The U.S. Food and Drug Administration.
-CHMP: EMA’s Committee for Medicinal Products for Human Use: assess applications submitted by
medicine developers and recommends whether or not a medicine should be granted marketing
authorization
,- After market authorization, reimbursement criteria and pricing decisions are made.
OR:
4. Pharmacovigilance: (=product surveillance) testing long term safety in real-life patients and
monitor side-effects when the drug is on the market
Reimbursement criteria and pricing decisions = commercial success of the drug
- Always at national level. In the Netherlands this means these decisions are made by the Dutch
Healthcare Authority. There can be difference within countries.
- They work with the following criteria: efficacy, safety and pharmaceutical quality, based on
effectiveness, cost-effectiveness (!), budgetary impact, severity of disease and quality of evidence.
- On the base of relative effectiveness, added therapeutic value (ATV) and cost-effectiveness. ATV can
be defined as the positive patient-relevant endpoints and relevant levels of effectiveness, safety and
efficacy; the expected benefits of a new treatment.
, - A good example in the Netherlands is ZiN: National Healthcare Institute. They appraises three
criteria for reimbursement in basic healthcare package: 1)therapeutic value, 2) budget impact and 3)
cost-effectiveness
From laboratory to patient: the journey of a centrally authorised medicine.
Additional: from laboratory to patient
Step 1. Initial research: The initial research on medicines is usually done by pharmaceutical and
biotechnology companies. Doctors and academics also perform research, and may get together to
research either new medicines or new uses of old medicines.
Step 2. Scientific advice: Scientific advice is about advising medicine developers on the most
appropriate way to generate robust evidence on a medicine’s benefits and risks.
- EMA provides scientific advice to support the timely and sound development of high-quality,
effective and safe medicines, for the benefit of patients
Step 3. Evaluation of medicines: lots of initial assessments and list of questions evaluate the
medicine. Last around a year.
- A few months before the assessment starts, EMA provides guidance to medicine developers
to ensure that their applications for marketing authorisation comply with legal and
regulatory requirements to avoid unnecessary delays.
Step 4. Commission decision: European Commission takes final, binding decision whether medicine
can be market in EU.
- EMA is a scientific body with the expertise required to assess the benefits and risks of
medicines. However, under EU law it has no authority to actually permit marketing in the
different EU countries. The role of EMA is to make a recommendation to the European
Commission which then takes a final legally binding decision on whether the medicine can be
marketed in the EU.
Step 5. Discussion at nation level on access and pricing: when EU gives green light, the medicine can
be marketed throughout EU.
- Once a medicine has received an EU-wide marketing authorisation, decisions about pricing
and reimbursement take place at national and regional level. As those choices must be made
in the context of the national health system of each country, EMA has no role in decisions on
pricing and reimbursement. However, the Agency collaborates with national bodies, such as
HTA bodies, to facilitate these processes
Step 6. What happens once a medicine is marketed: after a medicine is market, EU member states
constantly monitor its safety and take action when new information indicates the medicine is now
longer safe/not that effective as thought.
- The safety monitoring of medicines involves a number of routine activities ranging from:
assessing the way risks associated with a medicine will be managed and monitored once it is
authorised; continuously monitoring suspected side effects reported by patients and
healthcare professionals identified in new clinical studies or reported in scientific
publications; regularly assessing reports submitted by the company holding the marketing
authorisation on the benefit-risk balance of a medicine in real life; and assessing the design
1. How does a drug come into the market?
Stages of drug development
1. Pre-clinical studies: test tubes, laboratory, animal testing
2. Clinical studies: Phase I + II + III clinical trials
Phase 1: small group of health volunteers. To evaluate safety and determine a safe dosage.
Phase 2: larger group of volunteers and patients, up to 200.
Phase 3: confirm findings by research on a large patient population with randomized control (new
drug vs usual care = gold standard). In this phase, also the efficacy, safety and side-effects are
observed.
3. Marketing authorization (EMA or DFA) and reimbursement
4. Pharmacovigilance (geneesmiddelenbewaking)
As showed in the figure; you start with a pre-clinical research. After this you do clinical studies in
phase I, II and III. This can take upon 10 years. The last two or three years are used for administrative
procedures which consist: market authorization and reimbursement. Of course, administrative
procedure will only take place AFTER APPROVAL.
Market authorization
Licensing and regulatory approval are important parts within the pharmaceutical market. Important
parties who play a big role in licensing and regulatory approvals are:
- EMA: European Medicine Agency They operate on EU-level and observe three criteria: efficacy,
safety and quality and analyze the benefit-risk ration.
- FDA: The U.S. Food and Drug Administration.
-CHMP: EMA’s Committee for Medicinal Products for Human Use: assess applications submitted by
medicine developers and recommends whether or not a medicine should be granted marketing
authorization
,- After market authorization, reimbursement criteria and pricing decisions are made.
OR:
4. Pharmacovigilance: (=product surveillance) testing long term safety in real-life patients and
monitor side-effects when the drug is on the market
Reimbursement criteria and pricing decisions = commercial success of the drug
- Always at national level. In the Netherlands this means these decisions are made by the Dutch
Healthcare Authority. There can be difference within countries.
- They work with the following criteria: efficacy, safety and pharmaceutical quality, based on
effectiveness, cost-effectiveness (!), budgetary impact, severity of disease and quality of evidence.
- On the base of relative effectiveness, added therapeutic value (ATV) and cost-effectiveness. ATV can
be defined as the positive patient-relevant endpoints and relevant levels of effectiveness, safety and
efficacy; the expected benefits of a new treatment.
, - A good example in the Netherlands is ZiN: National Healthcare Institute. They appraises three
criteria for reimbursement in basic healthcare package: 1)therapeutic value, 2) budget impact and 3)
cost-effectiveness
From laboratory to patient: the journey of a centrally authorised medicine.
Additional: from laboratory to patient
Step 1. Initial research: The initial research on medicines is usually done by pharmaceutical and
biotechnology companies. Doctors and academics also perform research, and may get together to
research either new medicines or new uses of old medicines.
Step 2. Scientific advice: Scientific advice is about advising medicine developers on the most
appropriate way to generate robust evidence on a medicine’s benefits and risks.
- EMA provides scientific advice to support the timely and sound development of high-quality,
effective and safe medicines, for the benefit of patients
Step 3. Evaluation of medicines: lots of initial assessments and list of questions evaluate the
medicine. Last around a year.
- A few months before the assessment starts, EMA provides guidance to medicine developers
to ensure that their applications for marketing authorisation comply with legal and
regulatory requirements to avoid unnecessary delays.
Step 4. Commission decision: European Commission takes final, binding decision whether medicine
can be market in EU.
- EMA is a scientific body with the expertise required to assess the benefits and risks of
medicines. However, under EU law it has no authority to actually permit marketing in the
different EU countries. The role of EMA is to make a recommendation to the European
Commission which then takes a final legally binding decision on whether the medicine can be
marketed in the EU.
Step 5. Discussion at nation level on access and pricing: when EU gives green light, the medicine can
be marketed throughout EU.
- Once a medicine has received an EU-wide marketing authorisation, decisions about pricing
and reimbursement take place at national and regional level. As those choices must be made
in the context of the national health system of each country, EMA has no role in decisions on
pricing and reimbursement. However, the Agency collaborates with national bodies, such as
HTA bodies, to facilitate these processes
Step 6. What happens once a medicine is marketed: after a medicine is market, EU member states
constantly monitor its safety and take action when new information indicates the medicine is now
longer safe/not that effective as thought.
- The safety monitoring of medicines involves a number of routine activities ranging from:
assessing the way risks associated with a medicine will be managed and monitored once it is
authorised; continuously monitoring suspected side effects reported by patients and
healthcare professionals identified in new clinical studies or reported in scientific
publications; regularly assessing reports submitted by the company holding the marketing
authorisation on the benefit-risk balance of a medicine in real life; and assessing the design
