Latin America as an opportunity for

Clinical Research

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

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

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.

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.

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

Compared Recruitment

Region Recruited

subjects/site/month

2006

Recruited

Subjects/site/month

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

Recruitment Potential

Region Number of

Studies

Analyzed

#of

recruited

subjects

% of

recruited

patients

Patients per

million

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

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).

Why Latin America?

Quality

OUTSTANDING ENVIRONMENT FOR

PERFORMING QUALITY CLINICAL RESEARCH

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.

Why Latin America?

Costs

NON-EXPENSIVE OPERATIVE COSTS

FOR CLINICAL RESEARCH SERVICES

Why Latin America?

RESEARCH REQUIREMENTS AND

NEEDS ARE EASILY MET

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.

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.

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.

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.

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

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

Drug

Brochure

FDA

IND

Req?

Steps

Involved

GCP-MOH

Inspections

Witness

Required

Country

Level

LAR

Argentina Y N S/CRO,

IRB/IEC,

ANMAT (3)

Y Y(1) Y

Brazil Y (t) Y S/CRO,

IRB/CONEP/

ANVISA (2)

Y N Y

Chile Y N S/CRO, IRB,

JIRB, ISP (3)Y N Y

Regulatory Overview

Opportunities Challenges

CTA REVIEW

PROCESS

•CONEP and ANVISA reviews are now

parallel process.

•ANMAT back to adhering with 5330/97.

•GICONA is a new electronic CTA

submission system in CHILE.

•Importation process in all countries may

delay FPFV planned date

INSPECTIONS

BY MOH

•ANMAT consolidates Inspections

program and plans for sponsor/CRO

overview, ISP ongoing since 2008

ANVISA starting.

ETHICS/ ICF •ANMAT incorporates GCP compliance

requirement for all Institutional IRBs

reviewing research

•Questions about rational for placebo

use and trial design by ANMAT/CONEP.

•ANVISA requires treatment availability

after study at no cost.

OTHER New national GCP related Regulations

planned for the next year.

•ANVISA Data to be exported needs to

have an open site with originating CA

and intention to commercialize locally.

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.

Argentina, Brazil and Chile

Argentina

PHARMACEUTICAL PROTOCOLS ASSESSED

AND APPROVED BETWEEN 1994 – 2006

(Argentina)

8095

105116

134122

161 158144

119

158150

223

0

50

100

150

200

250

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

2004 2005 2006

1894 TRIALS (until Dec.31st 2006)

SPONSORS PROFILE - Argentina

(1994 - 2006)

1083

198

104

286

0

200

400

600

800

1000

1200

INTERNAT.PHARMAC.COMP. NATIONAL PHARMAC.COMP.

INDEPENDENT RESEARCHERS CRO/SMO

Source: ANMAT

Clinical Trials According to Research

Phase- Argentina- (1994-2006)

55%

20%

5% 3%17%

PHASE I PHASE II PHASE III PHASE IV BIOAVAIL.

1894 TRIALSSource: ANMAT

Regulatory Flowchart

Argentina

Document

Translation

and Review Investigator

ANMATRegulatory Agency

IRBInstitutional Review

BoardIEC

Independent Ethics

Committee(If IRB not GCP compliant)

Study

Start

Ministry

of Justice (PHI)

DNPDP

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)

Chile

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.

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

Clinical Research Investment

in Chile

Regulatory Flowchart Chile

Document Translation

and Review Investigator

ISP- Regulatory Agency

IRB Institutional Review Board

IEC Independent (Jurisdiction) Ethics Committee

Study

Start

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

Brazil

Protocol Issues Identified by

CONEP

Source: CONEP 2000-2005

Regulatory Flowchart Brazil

Document Translation

and Review 4-6 W

Investigator

ANVISARegulatory Agency CEP

Local Ethics Committee

CONEP National Ethics Committee

Product Importation

Study

Start

Submission of LEC

approval to ANVISA

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

Contact us

Echeverría 3989

Apt. 2 “B”- Buenos Aires City

C1430BTL

ARGENTINA

1172 South Dixie Hwy

Suite# 442 - Coral Gables

FL33146

USA

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

Blanchard & Asociados

Echeverría 3989 – 2 B

Buenos Aires

C1430BTL

ARGENTINA

Blanchard & Associates1172 South Dixie Hwy

Suite# 442

Coral Gables

FL33146

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

Find out more, contact us!