REGULATION CONCERNING MARKET AUTHORIZATION
1. Regulatory authorities for registration (MA/VHB)
1.1 Factors influencing availability of medicinal products in the EU/Belgium
The availability of medicinal products in Belgium/EU depends on both regulatory authorities
and non-regulatory factors.
Regulatory authorities Non-regulatory factors
• EMA • Scientific publications / study results
• National agencies, e.g. FAGG in Belgium • Patient associations / advocacy groups
• Flemish/regional government • Public opinion, e.g. crowdfunding cases
• Ministry (BE: FOD) of Social ACairs – RIZIV • Politicians
• Ministry of Public Health • Institutes and their opinions, e.g. KCE, NICE
• Ministry of Budget • Regulatory authorities outside the EU, e.g. FDA
• Ministry of Economic ACairs • Marketing
• Other authorities • Authority-based / consensus guidelines
In some countries, regulation also occurs at a regional level. In Belgium, for example, Flanders
has responsibilities related to:
• welfare: assistance to persons and welfare
• healthcare policy: preventive and curative health policy
So, availability and access to medicines are influenced not only by EU and national authorities,
but sometimes also by regional healthcare responsibilities.
1.2 Impact of regulations on marketing authorization
In the EU, a new marketing authorization (MA) is based on a positive benefit/risk ratio.
MA is not static and can be adjusted:
• extension of MA → based on more eLicacy/safety data
• restriction of MA → based on less favorable benefit/risk, often through
pharmacovigilance
→ Therefore, MA can evolve after approval when new evidence becomes available.
1.3 Public trial registration, data sharing and reporting
Clinical trials must be included in public databases, making registered trial information publicly
accessible.
Examples of public trial databases/registers:
• ClinicalTrials.gov → FDA-related register, but also includes many European trials
• WHO ICTRP → international clinical trial registry platform
• Eudra-CT / clinicaltrialsregister.eu → European trial register with increased public
accessibility
Since 1 January 2014, the joint EFPIA–PhRMA Principles for Responsible Clinical Trial Data
Sharing became eLective.
1
, • EFPIA = European Federation of Pharmaceutical Industries and Associations
• PhRMA = Pharmaceutical Research and Manufacturers of America
Under these principles, researchers can submit proposals to access clinical trial data for new
medicines approved in the US and EU after 1 January 2014.
This access can include:
• patient-level data, protocols, and clinical study reports
The aim is to make existing clinical trial data useful for further research and to benefit the
scientific community and patients, while still protecting:
• patient privacy, the integrity of national regulators, and incentives for companies to keep
investing in biomedical research
Access to clinical trial results, including patient-level data, is debated because transparency
advocates push for more open access.
• EMA position: privacy protection must guide data sharing → patient privacy must be
protected with robust and proportionate safeguards, in line with data-protection
legislation.
• Industry concern: data sharing could disclose trade secrets or proprietary information
to competitors → competitors could “free ride” on innovators’ investments → this may
reduce incentives for future biomedical research.
For EUDRA-CT studies (= EU-registered clinical trials), trial results must be reported after the
study ends.
• If the study is discontinued: within 1 year, a CSR (Clinical Study Report) with a summary
of results should be submitted to the EC (Ethics Committee).
• If the study is completed: within 1 year, the results should be published in the EUCTR
(European Clinical Trial Database).
• The EUCTR report can be used as the CSR for EC research.
• A scientific publication alone is not suTicient, because scientific journals are not
considered publicly available to the general public in this regulatory context.
1.4 Challenges & regulations in EU clinical research
Complex regulations: investigators face strict EU regulations including:
• GDPR (General Data Protection Regulation): applied starting 25 May 2018
o strengthens personal data protection and creates a single legal framework
across the digital single market
o impact of privacy protection on research is much larger in the EU than in the US
o specifically restricts research involving data, FGS (full genome sequencing), and
HBM (human biological material) samples
• Clinical Trials Regulation: replaced the Clinical Trials Directive on 31 January 2022
o applies directly and identically to all EU member states without local translation,
legally forcing a single, harmonized process across the entire EU.
• MDR (Medical Device Regulation): entered into application on 26 May 2021
o enforces strict compliance guidelines across the entire medical device supply
chain
2
, • IVDR (In Vitro Diagnostics): entered into application 26 May 2022
o impacts manufacturers, authorized representatives, importers, distributors, and
quality management professionals
• Future legislations: European Health Data Space legislation and the EU AI Act
This rigid, complex and strict legal environment makes procedures highly time-consuming,
raising concerns about slowed innovation within the EU. Additionally, complex rules are rarely
translated for lay participants, creating an administrative burden for them. Therefore, balancing
health data protection and participant’s rights with scientific advancement remains diLicult.
2. The process of market authorization: role of national agencies in the EU/EMA
2.1 Challenges & regulations in EU clinical research
The EMA (European Medicines Agency) started in 1995 and introduced two new European
procedures for medicine registration/MA:
• Centralized procedure → one EU-level application, evaluation and authorization
o A company submits one MAA (marketing authorization application) with all required
quality, non-clinical and clinical data.
o The application is evaluated at EU level through the EMA/CHMP, using experts from
national agencies.
o If the medicine has a positive benefit–risk balance, the European Commission grants
the marketing authorization.
o This authorization is valid throughout the EU, so the company does not need
separate approval in each member state.
o → one EU-level application, evaluation and authorization
• MRP/DCP procedures → involve several EU member states, coordinated by a reference
member state
o MRP (Mutual Recognition Procedure): a national MA already exists and other
countries recognize it.
o DCP (Decentralized Procedure): no national MA exists yet; several countries assess
the medicine together.
2.2 From laboratory to patient: centralized authorization pathway
For a centrally authorized medicine, the journey from laboratory to patient includes:
initial research → scientific advice → evaluation of medicines → commission decision →
discussion at national level on access and pricing → post-marketing follow-up.
Drug development required several critical bridging/extrapolation steps, meaning that data
from one setting must be translated to another:
• animals → humans: preclinical data must be
extrapolated to humans
• physicochemical properties → biological properties
eLects: product characteristics must be linked to
biological activity
3
1. Regulatory authorities for registration (MA/VHB)
1.1 Factors influencing availability of medicinal products in the EU/Belgium
The availability of medicinal products in Belgium/EU depends on both regulatory authorities
and non-regulatory factors.
Regulatory authorities Non-regulatory factors
• EMA • Scientific publications / study results
• National agencies, e.g. FAGG in Belgium • Patient associations / advocacy groups
• Flemish/regional government • Public opinion, e.g. crowdfunding cases
• Ministry (BE: FOD) of Social ACairs – RIZIV • Politicians
• Ministry of Public Health • Institutes and their opinions, e.g. KCE, NICE
• Ministry of Budget • Regulatory authorities outside the EU, e.g. FDA
• Ministry of Economic ACairs • Marketing
• Other authorities • Authority-based / consensus guidelines
In some countries, regulation also occurs at a regional level. In Belgium, for example, Flanders
has responsibilities related to:
• welfare: assistance to persons and welfare
• healthcare policy: preventive and curative health policy
So, availability and access to medicines are influenced not only by EU and national authorities,
but sometimes also by regional healthcare responsibilities.
1.2 Impact of regulations on marketing authorization
In the EU, a new marketing authorization (MA) is based on a positive benefit/risk ratio.
MA is not static and can be adjusted:
• extension of MA → based on more eLicacy/safety data
• restriction of MA → based on less favorable benefit/risk, often through
pharmacovigilance
→ Therefore, MA can evolve after approval when new evidence becomes available.
1.3 Public trial registration, data sharing and reporting
Clinical trials must be included in public databases, making registered trial information publicly
accessible.
Examples of public trial databases/registers:
• ClinicalTrials.gov → FDA-related register, but also includes many European trials
• WHO ICTRP → international clinical trial registry platform
• Eudra-CT / clinicaltrialsregister.eu → European trial register with increased public
accessibility
Since 1 January 2014, the joint EFPIA–PhRMA Principles for Responsible Clinical Trial Data
Sharing became eLective.
1
, • EFPIA = European Federation of Pharmaceutical Industries and Associations
• PhRMA = Pharmaceutical Research and Manufacturers of America
Under these principles, researchers can submit proposals to access clinical trial data for new
medicines approved in the US and EU after 1 January 2014.
This access can include:
• patient-level data, protocols, and clinical study reports
The aim is to make existing clinical trial data useful for further research and to benefit the
scientific community and patients, while still protecting:
• patient privacy, the integrity of national regulators, and incentives for companies to keep
investing in biomedical research
Access to clinical trial results, including patient-level data, is debated because transparency
advocates push for more open access.
• EMA position: privacy protection must guide data sharing → patient privacy must be
protected with robust and proportionate safeguards, in line with data-protection
legislation.
• Industry concern: data sharing could disclose trade secrets or proprietary information
to competitors → competitors could “free ride” on innovators’ investments → this may
reduce incentives for future biomedical research.
For EUDRA-CT studies (= EU-registered clinical trials), trial results must be reported after the
study ends.
• If the study is discontinued: within 1 year, a CSR (Clinical Study Report) with a summary
of results should be submitted to the EC (Ethics Committee).
• If the study is completed: within 1 year, the results should be published in the EUCTR
(European Clinical Trial Database).
• The EUCTR report can be used as the CSR for EC research.
• A scientific publication alone is not suTicient, because scientific journals are not
considered publicly available to the general public in this regulatory context.
1.4 Challenges & regulations in EU clinical research
Complex regulations: investigators face strict EU regulations including:
• GDPR (General Data Protection Regulation): applied starting 25 May 2018
o strengthens personal data protection and creates a single legal framework
across the digital single market
o impact of privacy protection on research is much larger in the EU than in the US
o specifically restricts research involving data, FGS (full genome sequencing), and
HBM (human biological material) samples
• Clinical Trials Regulation: replaced the Clinical Trials Directive on 31 January 2022
o applies directly and identically to all EU member states without local translation,
legally forcing a single, harmonized process across the entire EU.
• MDR (Medical Device Regulation): entered into application on 26 May 2021
o enforces strict compliance guidelines across the entire medical device supply
chain
2
, • IVDR (In Vitro Diagnostics): entered into application 26 May 2022
o impacts manufacturers, authorized representatives, importers, distributors, and
quality management professionals
• Future legislations: European Health Data Space legislation and the EU AI Act
This rigid, complex and strict legal environment makes procedures highly time-consuming,
raising concerns about slowed innovation within the EU. Additionally, complex rules are rarely
translated for lay participants, creating an administrative burden for them. Therefore, balancing
health data protection and participant’s rights with scientific advancement remains diLicult.
2. The process of market authorization: role of national agencies in the EU/EMA
2.1 Challenges & regulations in EU clinical research
The EMA (European Medicines Agency) started in 1995 and introduced two new European
procedures for medicine registration/MA:
• Centralized procedure → one EU-level application, evaluation and authorization
o A company submits one MAA (marketing authorization application) with all required
quality, non-clinical and clinical data.
o The application is evaluated at EU level through the EMA/CHMP, using experts from
national agencies.
o If the medicine has a positive benefit–risk balance, the European Commission grants
the marketing authorization.
o This authorization is valid throughout the EU, so the company does not need
separate approval in each member state.
o → one EU-level application, evaluation and authorization
• MRP/DCP procedures → involve several EU member states, coordinated by a reference
member state
o MRP (Mutual Recognition Procedure): a national MA already exists and other
countries recognize it.
o DCP (Decentralized Procedure): no national MA exists yet; several countries assess
the medicine together.
2.2 From laboratory to patient: centralized authorization pathway
For a centrally authorized medicine, the journey from laboratory to patient includes:
initial research → scientific advice → evaluation of medicines → commission decision →
discussion at national level on access and pricing → post-marketing follow-up.
Drug development required several critical bridging/extrapolation steps, meaning that data
from one setting must be translated to another:
• animals → humans: preclinical data must be
extrapolated to humans
• physicochemical properties → biological properties
eLects: product characteristics must be linked to
biological activity
3
