Latin American Clinical Trial
Authorizations: Overview and
2008 – 2009 Update
Dennis Hurley, DrSc – VP of Latin America, Kendle LatAm
Alcione Braga, RPh, MBA – General Director, Kendle Brazil
Mariagabriela Alterio, MSc – Regional Director of PM, Kendle LatAm
Jacqueline Zeuner, MSc – General Director, Kendle Peru
When we have completed this presentation, you will be
1. Quantify growth of Clinical Trials activity in Emerging
Markets and explain principal drivers for growth.
2. Identify recent changes in CT Authorization regulations
and their effect on approval timelines and information
requirements: BR and MX.
What are the Trends in Emerging Markets?
FDA-Regulated Investigators 1996 vs. 2006 and 2004 vs. 2007
2006 % of Total Annualized 10 Annualized 3 yr
yr GR GR
N-America 14,555 63.2 % 1.8 % -5.2%
W-Europe 3,923 17.0 % 7.5 % -6.1%
CEE 1,793 7.8 % 41.4 % 15.9%
L-America 1,095 4.8 % 27.3 % 12.1%
Asia – Pac 1,054 4.6 % 25.6 % 10.2%
ROW (ME/Afr) 617 2.7 % 11.0 % 3.9%
Sources: Tufts Center for the Study of Drug Development / ACT Sept. 2007
CenterWatch Monthly, August 2008
What are the Trends in Emerging Markets? (Continued)
• Growing % of patients are from Emerging Markets
Region % of total patients enrolled in trials in 2007
• Not surprising when you consider that 90% of the World’s
population live in Emerging Markets.
* USA, Canada, W.Europe
** Methodology: based on FDA 1572 investigators in regions and assumption of 3 times
as many patients per site in Emerging Markets vs. Traditional Markets.
What are the Trends in Emerging Markets? (Continued)
Will growth continue?
Yes, because in Emerging Markets:
1. Quality is good: Recent FDA inspections show that OAIs less frequent ex-
From 2006 – 2009 (September):
- USA: 41 OAIs/753 inspections = 5.4% OAIs.
- Ex-USA: 1 OAI/247 inspections = 0.4% OAIs.
2. Saturation of sites is less:
Region Trial Site/1 million inhabitants
Based on FDA
W. Europe 11
Form 1572 data
CEE 8 (2007)
3. So, on the average Emerging Market sites produce more patients per site
per month than Traditional Market sites.
Sources: Clinical Investigators Inspection List, FDA. (Consulted on 23/September/2009)
CenterWatch, August 2008 (Investigator Participation by FDA Form 1572)
What are the Trends in the LatAm Region?
Main Reasons for Increase:
1. Sponsor and CA trust on quality delivered: gained and
maintained over many years.
2. Greater enrolment per site (3 to 5 times vs. traditional
regions) speeds CT completion and so saves Time to
3. LatAm cost at ~75% to 80% USA cost.
4. Same time zones and close to USA. E.g: a Phase 2A trial
site can be contacted frequently and visited easily by
clinical scientist from USA staff of sponsor company.
Latin America: Sequential Review Process
Country Approximate Timing (weeks)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
IEC/Local EC/MoH ANMAT
Local-Central EC/MoH ANVISA +
CONEP Approval (parallel process to MoH ANVISA)
Local & Central EC/MoH ISP
Local EC/MoH INVIMA
Local EC/MoH SS
Local EC/MoH INS
EC/IRB Approval: Minimum Maximum
MoH Approval: Minimum Maximum
US & European Review Process: Rate Limiting Steps
• So in Latin America the review process is sequential: first EC
and then MoH.
– In the USA, each trial requires IND submission to the FDA and
in parallel an IRB approval. The rate limiting step is mainly the
IRB submissions and approval process.
– In EU, there is a parallel review process, and so submissions to
EC’s and Competent Authority (MoH) can be performed
simultaneously (i.e: in parallel.)
Regulatory Flowchart Brazil
Total Set Up & Sponsor Time to documents translation into
Approval Portuguese after all required documents
or CRO arrival from sponsor and dossier preparation
Process: 7.5 – before submission: 3 – 5 weeks
MoH Local Ethics Time to IRB/EC
(ANVISA) MoH submission Committee approval: 5 – 8 weeks
after getting the
approval: 1 week
Time to MoH approval: National Ethics
18 – 23 weeks Committee
Time to CONEP approval:
Time to import:
18 – 23 weeks
3 – 4 weeks Study
Brazil: Recent Updates on Clinical Trial Authorization (CTA)
1. Resolution 39 went into effect on 5 July 2008.
2. Made the national EC (CONEP) and CA (ANVISA) reviews for
approval a truly parallel process as in EU:
- Potential savings of 6-8 weeks for first site (Coordinator Site) to
3. Granted competent authority (ANVISA) ability to approve all
study sites in one submission and review cycle.
- Saving 4-6 week for subsequent sites to reach SIV.
4. Importance: As Resolution 39 comes into full effect, it will
reduce approval time in BR from average of 10 to
approximately 8.5 months (Assuming no questions from
CONEP or ANVISA).
Regulatory Flowchart Mexico
Translation of docs.
from sites 2 – 3 weeks
E.C., Hospital, study Commercial
staff Protocol Submission to Invoice content is
4 – 6 weeks MOH reviewed with
MOH (COFEPRIS) Approval
9 – 12 weeks
Total Set Up & Approval
Process: 3.75– 5.25 months
* If the study needs
medical equipment, the Customs release
timeline will increase to 1 – 2 days
4.25 – 6 Months
MX Drug Storage Depot
Mexico: Recent Updates on Clinical Trial Authorization (CTA)
1. Custom Code 4.3 reestablished for Clinical Trial drugs & lab kits
import and clinical sample export on 31/July/2008 specifically for
- Reduction of 2 to 3 weeks in time required to import drugs and lab
- Savings of Regulatory Import hours expended (10 to 15% of total.)
- Reduction of 2 to 3 weeks in time required to export biological
samples including tissue samples.
- Importance: Mexico total time from final Protocol to SIVs is reduced
from 3.5 - 4.5 months to 3 - 4 months. I.e: as fast as quickest EU
countries total process.
3. In June, 2009, regulations for review times was increased.
COFEPRIS now has up to 3 calendar month to review protocols
(an increase of ~2 months).
Suggestions for Your Next Steps
1. Continue to work together with your country’s:
- Regulatory Authorities
- Local and National Ethics Committees
- Pharmaceutical and CRO Chambers of Commerce
- Patients Organizations
- Medical Organizations
2. To make the Clinical Trial Authorization process faster
and more in adherence to the PAHO’s “Document of the
“The patients are waiting .”
(Theresa Musser, Past President of DIA)
– email: email@example.com