Transcript FDA

Overview of the Role of the
Regulatory Agencies and of
Regulations in Product
Development for Pharma
Remit of EMA/FDA
Objectives/Agenda
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The role of regulation
History of regulation
Control points
Control of clinical trials
NDA/MAA submission
Comparison of pharma and device
controls
Objectives/Agenda, contd
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Review of FDA and EMEA
ICH
Post marketing surveillance
Health technology and comparative
efficacy
Role of Regulation
• Consumer protection (consumer = a
patient)
• Controls the placing on the market (a
European Term)
• Post marketing surveillance
Extended Controls
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Manufacturing
Clinical trials
Life cycle management
Post marketing surveillance
Advertising
History of Regulation
• Pharmacopoeias (quality standards) London
Pharmacopoeia 1618 B.P. 1853
• 1906 FDA
• 1914 Health Select Committee
• 1950’s therapeutic substances
• 1960’s thalidomide tragedy – the real trigger
for the modern regulatory environment
History of Regulation, contd
• 1965 first EU Directive 65/65
• 1968 UK Medicines Act
• 1995 EMEA established; Centralised
procedure
• 1995 EU Device regulations introduced
• 1998-2001 Extended to medical
diagnostics
Clinical Trial Controls
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Phases I to IV,
Clinical Trials Applications (Europe)
Marketing Authorisation (Europe)
Investigational New Drugs Program
(US)
• New Drug Applications (US)
Application Dossier
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Pharma NDA/MAA
Full dossier covers:
safety
efficacy
quality
Determination of Risk/Benefit
Output:
authorisation/licence
SmPC/labelling
conditional approval
The FDA Route
• The results of the testing program are
codified in an FDA-approved public
document that is called the product label,
package insert or Full Prescribing
Information.
• The prescribing information is widely
available on the web, from the FDA drug
manufacturers, and frequently inserted
into drug packages.
The FDA Route
• The main purpose of a drug label is to
provide healthcare providers with
adequate information and directions for
the safe use of the drug.
The FDA Route
• The documentation required in an NDA is
supposed to tell the drug’s whole story,
including what happened during the
clinical tests, what the ingredients of the
drug formulation are, the results of the
animal studies, how the drug behaves in
the body, and how it is manufactured,
processed and packaged.
The FDA Route
• Once approval of an NDA is obtained, the
new drug can be legally marketed starting
that day in the U.S.
• Of original NDAs submitted in 2009, 94 out
of 131 (72%) were in eCTD format.
The European Route
• Before any medicines can be used in the
Europe they have to be licensed. Drugs
are licensed for use in the Europe with a
European licence through the European
medicines Agency
The European Route
• The EMEA co-ordinate drug licence
applications within the European Union
(EU). There are 6 committees within the
EMEA. Each committee looks at a
particular area.
• There is a Committee for Proprietary
Medicinal Products (CHMP) who are
responsible for medicines for human use
The European Route
• There are different systems within the
EMEA that pharmaceutical companies can
use to license drugs.
• The first is called the ‘centralised system’.
Any drugs for AIDS, cancer, neurodegenerative conditions, diabetes or
orphan drugs have to be licensed this way.
The European Route
• The committee that reviews drugs for
human use (the CHMP) assess the
application, and then recommend whether
a drug should have ‘marketing
authorisation’ (a licence) or not.
The European Route
• The other ways that pharmaceutical
companies apply for a license is either the
‘decentralised system’ or the mutual
recognition system. They will use these
systems for medicines that don't fit into the
categories within centralised system.
The European Route
• With the decentralised system the company
applies to several member states at the same
time. One member state assesses the
application (this is the MHRA in the UK).
• If they recommend that the drug be licensed, the
other member states then either agree or object.
If everyone agrees, the drug is given marketing
approval. If someone objects, the CPMP will
step in and decide.
• They then advise the EU Commission whether
to license the drug or not.
The European Route
• Once a drug has EU marketing
authorisation, it is ‘licensed’, ‘registered’ or
‘approved’. All these terms mean the same
thing. This means the company can
market the drug in any EU country - but
they don’t have to. For one reason or
another, they may choose to market the
drug in some countries but not others.
The European Route
• When a drug has marketing authorisation,
it is not available straight away. The
company first have to apply to market their
product in each individual country. In the
UK, they will apply to the MHRA. When
this last small step is done, the product is
‘launched’, and doctors can prescribe it.
EMA? MHRA?
• These bodies follow the usual European
Structure.
• The European Marketing Agency is the
European Body
• Each state ahs a competent authority – in
the U.K. this is the Medicines and
Healthcare Regulatory Products
Regulatory Authority (MHRA)
Line Extensions
• Life cycle management
• Abridged/abbreviated files
-new indications, new dosage forms
-variations
• Generic applications
• OTC products
Post Marketing Surveillance
• Spontaneous reporting systems
– Yellow card reports
– Vigilance reporting
– User reporting
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Structured data bases
– Data mining/signal detection
Post- Marketing
• Risk management plans (Europe)
• REMS (FDA)
FDA
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Structure
Commission
Advisory panels
Fees
Independence
EU
• National agencies – MHRA, AFSSAPS,
MPA
• EMA role
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Centralised procedure, CHMP
Decentralised procedure
Mutual Recognition Procedure
CMD(h)
• EU Commission grants the MAA
International Harmonisation
• ICH (International Conference on
Harmonisation)
• GHTF (Global Harmonisation Task
Force) Devices
• ICDRA (International Conference Drug
Regulatory Authorities)
• ISO and EN, BSI standards
• Pharmacopeias (EP, VSP, BP, JP)
Health Technology
Assessment (HTA)
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NICE
Requirements for comparative efficacy
Quality of life data
Role of the payers
HTA Development
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Comparative effectiveness
Cost effectiveness
Value based pricing
Pricing for risk
Japanese Regulatory
Authorities
Roles and Responsibilities
• Ministry of Health, Labour & Welfare
(MHLW)
– makes all final decisions based on
recommendations of PMDA
• The PMDA (Pharmaceuticals and Medical
Devices Agency) was established in April
2004
• Incorporated Administrative Agency of the
MHLW
PMDA
• Integrated Regulatory Agency
• Pharmaceutical Affairs Law
• GMP inspections collaboration with the
prefecture administrations
Senior
Councillor
PMDA
Structure
Office of General Affairs
Office of Planning &
Co-ordination
Office of Relief Funds
Office of Review
Administration
Office of New Drug 1
Office of New Drug II
Chief Executive
Director, Centre for
Product Evaluation
Executive Director
Associate
Centre Directors
Office of New Drug III
Office of Biologics
Office of OTCs / Generic
Evaluation
Office of Medical Devices
Office of Conformity
Auditor
Chief Safety Officer
Office of Safety Division
Office of Compliance
Standards
Office of R&D Promotion
Priority
Review
Director
Rest of the World
• Primary evaluation countries/regions:
FDA, EMA, PMDA, Australian,
Canada, Switzerland
• Countries requiring local studies a
evaluation:
China, South Korea, India, Taiwan
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Conclusion
• In this lecture we have looked at the way
the FDA and the EU regulate market
access
• They are different but broadly achieve the
same end
• We have briefly looked at other
approaches