2. Latin America
21 countries, Area: 21 069 501 km2
Population: 569 million people
Heterogeneous population
Two major official Languages: Spanish and
Portuguese
Average Life expectancy 75 years
Population Concentrated in Major Urban Areas
such as Mexico City, Sao Paulo or Buenos Aires
Estimated population Growth 12.5% by 2015
Economic growth rate: 5.3% (2006) = per capita
Increase 3.8%
GDP: 3,3 Trillion exchange Rate
Source: wikipaedia.com, www.paho.org and www.unep.net
3. Latin America as a Pharma
Market
7 Major Players: Argentina, Brazil, Chile,
Colombia, Mexico, Peru and Venezuela
3 Top Markets: Argentina, Brazil and Mexico.
50 billion (2008) projected to 80 billion (2013)
Different growth between countries:
•Government cost containment policies
•Economic Stability a concern
Generics Drug Industry encouraged
Health Care reforms for more people to access
Medication
Source: Julianne Lewis. International Regulatory Affairs. John Hopkins University
4. Growth Rate of Clinical
Research in Latin America
Latin America Clinical Trial authorizations. Overview and Update. Regulatory Focus.
June 2009. Denis Hurley, Mirta Lipezker and Daniel Mazzolenis.
5. Southern Cone
The 3 major countries in Latin America,
with a total population of 300 million people are:
Brazil (192.09 million),
Argentina (40.48 million),
Chile (16.99 million).
The region's ethnicity make up makes
patient enrollment for any clinical study simpler.
6. Why Latin America?
Recruitment
1. Large, ethnically diverse population.
2. Availability of treatment-naive patients in all therapeutic areas.
3. Complementary to Northern hemisphere sites for indications with
seasonal variations (such as respiratory diseases).
4. Strong patient-doctor relationship.
5. Good compliance & retention rates (minimal dropout rates).
6. Niche for emerging and neglected diseases.
7. Many significant metropolitan areas with population concentration
in big cities:
Sao Paulo 19.88m in Brazil
Buenos Aires 13.35m in Argentina
Santiago 7.2m in Chile
(www.worldpharmaceuticals.net/editorials/013_march08/013_latin.pdf; http://www.ghf06.org/reports/35)
OUTSTANDING ENVIRONMENT FOR
EXCELLENT RECRUITMENT PERFORMANCE
7. Compared Recruitment
Region Recruited Recruited
subjects/site/month Subjects/site/month
2006 2008
Latin America 2.2 2.3
Spain 1.6 2.2
France 1.4 2.2
USA 0.8 2.1
UK 1.0 2.1
Canada 1.2 1.2
Source: Leem- Leem Recherche. Place de la France dans la Recherche Clinique Internationale Enquete 2008. Paris 10 Octobre 2008
8. Recruitment Potential
Region Number of #of % of Patients per
Studies recruited recruited million
Analyzed subjects patients citizens
Latin America 161 23 341 7.5% 46
USA 181 40 433 12.9% 133.1
Australasia 185 9 653 3.1% 140.8
UK 173 16 873 5.4% 276.9
Canada 191 14 695 4.7% 442
Source: Leem- Leem Recherche. Place de la France dans la Recherche Clinique Internationale Enquete 2008. Paris 10 Octobre 2008
9. Why Latin America?
Quality
Quality proven regional vendors for support services: couriers,
warehouses, local central labs, investigator meeting locations.
ACRP Certification and Post Graduate, University Level, Clinical
Research Masters available locally for Physicians, Study Coordinators
and CRAs since 2007.
Highly Controlled regulatory environment, aligned and experienced
with ICH-GCP guidelines compliance (e.g. in Argentina since 1996).
OUTSTANDING ENVIRONMENT FOR
PERFORMING QUALITY CLINICAL RESEARCH
10. Why Latin America?
Costs
Reasonable costs for research monitoring and regulatory services
without compromising quality.
Decreased travel to and from sites (densely populated cities)
Multiple academic, public and private hospitals in small areas.
Lower budgets due to currency exchange and over availability of
PI’s, keeps cost down. Average cost is 25% less than US Trials.
Salaries and Professional fees for Researchers and Medical
procedures involved in research highly competitive compared to
those of USA/Canada/Europe.
NON-EXPENSIVE OPERATIVE COSTS
FOR CLINICAL RESEARCH SERVICES
11. Why Latin America?
Similar time Zone as the USA/ Europe (5 hour difference or less)
Adequate communication & IT technology at most sites
Presence of major pharmaceutical companies.
Just two Languages spoken across the region: Spanish and
Portuguese.
RESEARCH REQUIREMENTS AND
NEEDS ARE EASILY MET
12. Why Argentina, Brazil and
Chile?
Fast accrual of patients.
Small competition for patients, when
comparing to European countries and USA.
High prevalence of certain diseases.
Climate, racial and social diversity.
Independent Ethics Committees which meet
the norms of the ICH and GCP Guidelines.
Specific legislation for Clinical Research
continuously reviewed.
13. Clinical Trials in Latin America
- Environmental factors-
Disparities in economic resources and access to health.
Most Health Research funded by industry.
Significant treatment naïve patient Population
Poor access to newly available (expensive) treatments
and frequent enforcement for experimental treatment
and procedures (control or study drug) to be provided at
no cost.
14. Clinical Trials in Latin America
-Areas we are still working on-
Ethical Review Committees: following up, independence,
transparency, competency, ethical training for members.
Research dedicated infrastructure.
Legal instruments at local or district level must synergize
to stimulate research and improve quality and control.
Informed consent process strategies and tools;
compliance with international + local regulations.
Lengthy approvals due to government regulations.
15. Regulatory Agencies in
Latin America
Country Agency Website
Argentina www.anmat.gov.ar
Chile www.ispch.cl
Colombia www.invima.gov.co/Invima/index.jsp
Costa Rica www.ministeriodesalud.go.cr
Bolivia www.sns.gov.bo
Brazil www.anvisa.gov.br
Ecuador www.msp.gov.ec
Guatemala www.mspas.gob.gt
Mexico www.salud.gob.mx
Paraguay www.mspbs.gov.py
Uruguay www.msp.gub.uy/index_1.html
16. Regulatory Aspects in
Southern Cone
ICH Good Clinical Practices have been adopted by Argentina, Chile ,Mexico,
and Brazil. PAHO - Network for Drug Regulatory Harmonization and part of
ICH Global Cooperation (Americas GCP guideline Issued).
Highly Controlled regulatory environment, aligned and experienced with ICH-
GCP guidelines compliance (e.g. in Argentina since 1996).
Universal coverage to care overcomes ethical issues.
Country Investigator FDA Steps GCP-MOH Witness Country
Drug IND Involved Inspections Required Level
Brochure Req? LAR
Argentina Y N S/CRO, Y Y(1) Y
IRB/IEC,
ANMAT (3)
Brazil Y (t) Y S/CRO, Y N Y
IRB/CONEP/
ANVISA (2)
Chile Y N S/CRO, IRB, Y N Y
JIRB, ISP (3)
17. Regulatory Overview
Opportunities Challenges
CTA REVIEW •CONEP and ANVISA reviews are now •Importation process in all countries may
PROCESS parallel process. delay FPFV planned date
•ANMAT back to adhering with 5330/97.
•GICONA is a new electronic CTA
submission system in CHILE.
INSPECTIONS •ANMAT consolidates Inspections
BY MOH program and plans for sponsor/CRO
overview, ISP ongoing since 2008
ANVISA starting.
ETHICS/ ICF •ANMAT incorporates GCP compliance •Questions about rational for placebo
requirement for all Institutional IRBs use and trial design by ANMAT/CONEP.
reviewing research •ANVISA requires treatment availability
after study at no cost.
OTHER New national GCP related Regulations •ANVISA Data to be exported needs to
planned for the next year. have an open site with originating CA
and intention to commercialize locally.
18. Our tips for your strategy
Early planning a must: review processes and
steps involved.
Selecting a CRO based in the region a plus:
Regulatory affairs professionals native to the country,
and familiar with culture, laws and regulations and
standards.
Be aware of local requirements on regulatory setup
critical documentation .
Plan ahead, pick sites smartly and fit them into
your strategy.
23. Clinical Trials According to Research
Phase- Argentina- (1994-2006)
5% 3%
17%
20%
55%
PHASE I PHASE II PHASE III PHASE IV BIOAVAIL.
Source: ANMAT 1894 TRIALS
24. Regulatory Flowchart
Argentina
Document
Translation
and Review Investigator
IRB
Institutional Review
IEC Board
Independent Ethics
Committee
(If IRB not GCP compliant)
Ministry ANMAT
of Justice Regulatory Agency
(PHI)
DNPDP
Study
Start
25. Argentina- Regulatory Process
Day 0 We receive Protocol, Brochure and ICF from Sponsor. Translation ordered.
Day 5 Collection of signature and Protocol Agreement Page to Investigator. Start
Contract Review Process by sites.
Day 10 ICF Translation Finalized (Review of ICF to local requirements, start of Back
translation)
Day 15 Review ICF for local Requirements and further Back translation Finished
submission for sponsor approval
Day 20 Translation of Protocol and Brochure Finalized, sponsor approved ICF:
Submission to IEC and IRB
Day 40 Final Approval from IEC/ IRB. Submission of Final ICF to MINJUS.
Notification to Ministry of Health City of Bs As.
Day 47 Submission to ANMAT.
Day 157 Approval by ANMAT. (supposing no questions asked in the middle, otherwise
clock will stop)
27. Chile
World Class regulatory environment including internationally
recognized ethical committee guidelines.
Financial Incentives by government Agency (CORFO)
designed to attract clinical research.
Over 1274 reliable, competitive and highly skilled
researchers.
28. Chile
1274 Clinical Trial Investigators
Main clinical trials carried out in Chile: Infectious Diseases,
Oncology, Bronchiopulmonary and Cardiology
120 Clinical Trials approved in 2007
Patients readily recruited from both public and private health
systems
31. Chile - Regulatory Process
Day 0 We receive Protocol, Brochure and ICF from Sponsor. Translation ordered.
Day 5 Collection of signature and Protocol Agreement Page to Investigator. Start
Contract Review Process by sites.
Day 10 ICF Translation Finalized (Review of ICF to local requirements, start of Back
translation)
Day 15 Review ICF for local Requirements and further Back translation Finished
submission for sponsor approval
Day 20 Translation of Protocol and Brochure Finalized, sponsor approved ICF:
Submission to Independent IRB and Jurisdictional EC
Day 80 Final Approval from IEC/IRB. Submission of Notification to ISP.
Day 90 ISP does not Object Study
34. Regulatory Flowchart Brazil
Document Translation
and Review 4-6 W
Investigator
ANVISA
Regulatory Agency Submission of LEC CEP
approval to ANVISA Local Ethics Committee
Product Importation CONEP
National Ethics Committee
Study
Start
35. Regulatory Timelines
in Brazil
Day 0 Receipt of Protocol, Brochure and ICF from Sponsor. Translations ordered
Day 5 Collection of signature and Protocol Agreement Page to Investigator. Start
Contract Review Process by sites.
Day 10 ICF Translation Finalized (Review of ICF to local requirements, start of Back
translation)
Day 15 Review ICF for local Requirements for Back translation Finished submission
for sponsor approval
Day 20 Translation of Protocol and Brochure Finalized, sponsor approved ICF:
Submission to IEC and IRB.
Day 70 Submission to ANVISA/ CONEP – The EC submits it to CONEP. Ok, if EC
don´t ask for some clarifications. If it is applicable, depending on the queries,
we should answer within 5 days or less.
Day 240 Final Approval from ANVISA/ CONEP
36. Contact us
Echeverría 3989 1172 South Dixie Hwy
Apt. 2 “B”- Buenos Aires City Suite# 442 - Coral Gables
C1430BTL FL33146
USA
ARGENTINA
TEL: +54 11 4553 2682/4554 9346
FAX: +54 11 4554 8933
Anne Blanchard, CCRA, Managing Partner
anne@blanchardyasociados.com.ar
anne74@ciudad.com.ar
www.blanchardyasociados.com.ar
37. Find out more, contact us!
Blanchard & Asociados Blanchard & Associates
Echeverría 3989 – 2 B 1172 South Dixie Hwy
Buenos Aires Suite# 442
Coral Gables
C1430BTL FL33146
ARGENTINA USA
TEL: +54 11 4553 2682/ 4554-9346
FAX: +54 11 4554 8933
Anne Blanchard, CCRA, CEO
anne@blanchardyasociados.com.ar
anne74@ciudad.com.ar
www.blanchardyasociados.com.ar
