Download Global Regulatory Affairs_Latin America - IPD

Global New Drug Development –
Opportunities for Brazil
Jurij Petrin, M.D.
ENIFarMed
9 Sep 2014
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Agenda
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Global New Drug Development - Background
Where is Brazil?
Preclinical and Clinical Aspects
Opportunities
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Pharmaceutical Business Environment Innovative Products
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Globalization
Speed-to-market
Increased competition
Advances in science
New therapeutic classes
Need for strong intellectual property protection
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Global Regulatory Environment –
Innovative Products
• Different tiers of regulatory agency sophistication
• Need for sequential approvals
• Harmonized regulations vs local regulatory independence &
authority
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Local acceptance of foreign data
Climatic zones
Ethnic differences
International Conference on Harmonization (ICH)
Regional initiatives (EU, Andean Pact, ASEAN, Mercosul….)
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Companies Face Global Dilemmas
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Concentrate on major markets first?
If yes, for how long?
Utilize research capabilities of the international markets?
If yes, should they launch the product in these markets and when?
Available in-house expertise and resources
If not – can we outsource? What?
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Decision to Go Global
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What kind of a molecule?
Disease target: unmet medical need? Life saving or recreational?
Investment, timing, resource needs
IP protection issues
Business interest
Competitive environment
Risk of early generic competition
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Global Regulatory Development of
Innovative Products
• Main scientific development of new drugs done in major countries
around the world, with less experienced countries providing clinical
sites
• Normally, new drug submissions are done sequentially - US, Europe,
smaller markets - usually in this order
• Main reason – only selected regulatory agencies willing/able to review
a dossier before other countries!
• When approved in major markets, follow with submissions in smaller
markets
• In global environment, this is becoming unacceptable
• Ultimate goal - to be able to develop and launch a new product
worldwide as simultaneously as possible in key markets
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Regulatory Development Experience
GROUP A
GROUP B
GROUP C
Australia
Argentina
Canada
Brazil
Remainder of Asia Pacific
Bangladesh, Brunei, Cambodia, Hong Kong, Indonesia,
Laos, Macao, Myanmar, Pakistan, Philippines, Sri Lanka,
Taiwan, Vietnam
Middle East
Japan
Africa (except S. Africa)
New Zealand
China
United States
Malaysia
Mexico
Russian Federation
Singapore
European Union
South Africa
South Korea
Thailand
Central America and Remainder of South America:
Bolivia, Chile, Colombia,
Costa Rica, Ecuador,
El Salvador, Guatemala, Honduras, Nicaragua, Panama,
Paraguay, Peru, Uruguay, Venezuela
Caribbean (except PR)
India
Armenia, Azerbaijan, Georgia, Kazahkstan, Kyrgistan,
Tajikstan, Uzbekistan
Belarus, Moldova, Ukraine
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Goal?
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Regulatory Development Experience
GROUP A
GROUP B
GROUP C
Australia
Argentina
Remainder of Asia Pacific
Bangladesh, Brunei, Cambodia, Hong Kong, Indonesia,
Laos, Macao, Myanmar, Pakistan, Philippines, Sri Lanka,
Taiwan, Vietnam
Middle East
Brazil
Canada
Japan
New Zealand
United States
European Union
Africa (except S. Africa)
China
Malaysia
Mexico
Russian Federation
Singapore
South Africa
South Korea
Thailand
Central America and Remainder of South America:
Bolivia, Chile, Colombia,
Costa Rica, Ecuador,
El Salvador, Guatemala, Honduras, Nicaragua, Panama,
Paraguay, Peru, Uruguay, Venezuela
Caribbean (except PR)
India
Armenia, Azerbaijan, Georgia, Kazahkstan, Kyrgistan,
Tajikstan, Uzbekistan
Belarus, Moldova, Ukraine
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Is this possible?
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Current Status with New Drug Development
in Brazil
• Strong and well developed generic industry
• Sporadic local development of improved or novel products, often
based on rich biodiversity sources of Brazil
• Many development activities performed abroad (preclinical, clinical)
• No organized new chemical/biotechnology discovery efforts ongoing
(for example, high-throughput screening methodology)
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Current Status with New Drug Development
in Brazil
• GMP, GLP, GCP standards not closely followed in Brazil
• Regulatory environment not very supportive of new drug
development
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Appropriate regulations do not exist
No formal regulatory or scientific advice meetings available
Data reviews primarily bureaucratic
Extremely long and non-transparent review timelines
• US – 30 days (IND)
• EU – 60 days (CTA)
• Brazil – several months (improvements being discussed)
– Data developed under such circumstances would not be acceptable in
most developed countries
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Benefits of Local Innovative, R&D Driven
Pharmaceutical Industry
• Advancement of local science and expertise: better connection of
academia and industry
• Faster availability of new drugs to treat unmet medical needs in
Brazil and elsewhere
• Decreased dependence on imported innovative drugs
• Growth of the domestic pharmaceutical sector
• Transition to export oriented industry
• Very positive results for the Brazilian economy
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Can a Consensus on How to Get There Be
Reached?
• Education and training of all stakeholders:
– Regulators
– Local industry personnel
– Academia
– Medical practice personnel (doctors, nurses…)
– Patients/public
• Establish a regulatory environment that will be supportive of new
drug discovery and development
• Financial incentives: research grants, tax benefits, intellectual
property protection
• Help local researchers and industry, and attract foreign investment
• Consider concentration of R&D activities
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Singapore Biopolis
• Biopolis is an international research and development center for
biomedical sciences located in Singapore
• Almost 40 corporations with research and manufacturing activities
• Within a decade, Biopolis has established a reputation as a worldclass biomedical research hub and put Singapore on the scientific
world map
• The biomedical sciences industry has also generated economic
wealth for Singapore, created well paid jobs and improved human
health and quality of life
• Since 2000, biomedical science manufacturing output has increased
by nearly five-fold from $6 billion in 2000 to $29.4 billion in 2012
NOTE: Singapore population-5.3 million (2012)
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How To Improve the Regulatory Environment for
New Drug Development in Brazil?
Consider an Investigational New Drug (IND)
approach
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IND
• Data necessary to establish that the product will not expose human
subjects to unreasonable risks in early studies:
– Animal pharmacology and toxicology studies
– Manufacturing (CMC) information
– Clinical protocols and investigator information
• IND is a “living document” – initial submission is supplemented with
new data as research continues
• Rapid regulatory review of new data (30-60 days max)
• Allow scientific and procedural questions to be discussed at
formal meetings or via Email/teleconferences
• Result: Brazilian regulators actively involved with the
development
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Main Components of IND
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Administrative Part (country specific)
Table of Contents
General Investigational Plan
Investigator’s Brochure
Clinical Protocols (s)
CMC Information
Pharmacology and Toxicology
Previous Human Experience (if any)
Additional Information
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New Drug Development Cascade
Target Discovery (identification, validation)
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Lead Discovery (High Throughput Screening)
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Medicinal Chemistry (library development, structure based design)
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Cellular & Molecular Pharmacology (in vitro, mechanism of action)
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Preclinical Development (PK/PD, toxicology)
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Drug Candidate
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New Drug Development Cascade
Target Discovery (identification, validation)
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Lead Discovery (High Throughput Screening)
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Medicinal Chemistry (library development, structure based design)
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Cellular & Molecular Pharmacology (in vitro, mechanism of action)
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Preclinical Development (PK/PD, toxicology)
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Drug Candidate
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New Drug Development Cascade
Target Discovery (identification, validation)
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Lead Discovery (High Throughput Screening)
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Medicinal Chemistry (library development, structure based design)
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Cellular & Molecular Pharmacology (in vitro, mechanism of action)
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Preclinical Development (PK/PD, toxicology)
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Drug Candidate
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New Drug Development Cascade
Target Discovery (identification, validation)
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Lead Discovery (High Throughput Screening)
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Medicinal Chemistry (library development, structure based design)
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Cellular & Molecular Pharmacology (in vitro, mechanism of action)
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Preclinical Development (PK/PD, toxicology)
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Drug Candidate
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Early Development
• Preclinical development needs to identify the most promising drug
candidate to take into the clinical phase
• Modern global preclinical development needs to:
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Follow ICH guidelines
Good Laboratory Practice (GLP) standards
Be of highest quality
Best possible speed (not to waste resources if the drug candidate has
problems)
– Acceptable cost
• Overseeing regulatory agency must enable and assist good quality
preclinical development
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Preclinical Drug Development
• Purpose of preclinical development is to:
– Define potential toxicities in humans and the likely target organs
– Provide data from which the potential dose range in humans can be
calculated
– Provide basic information regarding the potential ADME of the drug
– Reduce potential for harm to subjects
• Consider establishing Centers of Excellence – research, education,
training.
Good example: CIEnP in Florianopolis!
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Clinical Drug Development
• Protection of clinical trial subjects
• Scientific approach in design and analysis
• Strict adherence to GCP
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Classification of Clinical Studies According
to Objective
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Human Pharmacology (Phase I)
Therapeutic Exploratory (Phase II)
Therapeutic Confirmatory (Phase III)
Therapeutic Use (Phase IV)
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Possible Goals for Brazil in Clinical Trial
Development
• Participation in multicenter multinational trials of new products
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Offer existing and further improve local expertise
Experience with new drugs
Earlier access of Brazilian patients to new therapies
Financial benefits
• Improve quality of local clinical trials
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Marketing Application Submissions
• Consider changes to improve Brazil’s standing in global drug
development:
– Closer harmonization of local guidelines with ICH guidelines
– Implementation of Good Review Practices
– Faster regulatory reviews and decisions
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Principles of Good Review Practices
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Quality (expertise, training)
Efficiency (keeping targeted timelines)
Clarity (accurate review + effective communication)
Transparency (applicants’ awareness of each review step)
Consistency (across departments, drug types, therapeutic areas)
Results:
• More scientific and less bureaucratic procedures
• Efficient and transparent regulatory processes
• Faster availability of needed drugs in Brazil
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Summary
• Brazil can and should play a bigger role in global drug development
• This is true for both preclinical as well as clinical phases
• Mandatory prerequisites are:
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High quality of scientific and procedural work at all levels
Compliance with ICH
Strict GLP-GMP-GCP control
Transparent local guidelines
Adherence to Good Review Practices performed in line with globally
competitive timelines
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