Dr Neil McAuslane

1

Strategies for Global Clinical Development
Clinical Trial Approvals

• Dr Neil McAuslane
• Professor Stuart Walker
• CMR International
• Institute for Regulatory Science

2
Strategies for Global Clinical Development
Clinical Trial Approvals

1. Global Drug Development in the Asia-Pacific
Region. 2. Approaches to Review of Clinical
Trials 3. Summary Conclusions
3
Pharma is investing 70 more on RD whilst NME
output has decreased by 30 compared to 10 years
ago
Global sales
Global RD expenditure
Development times
Global NME output
The development time data point for 2006
includes data from 2005 and 2006 only
Source CMR International IMS Health
CMR International /2007 Pharmaceutical RD
Factbook
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There has been a significant growth in patient
recruitment in non-core countries
Percentage of patients
Data are shown for Phase II (including Phase Ip)
and Phase III studies where patient enrolment was
completed in the year specified and the patient
number is available. n percentage of patients
in each group. (n) the number of studies in the
year for a consistent cohort of 18 companies that
supplied data each year between 1997-2005.
Reference CMR International R and D Fact book
2007
Core countries include USA, Canada, UK, France,
Spain, Germany, Italy and Japan
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Institute for Regulatory Science Survey
Asias contribution to the global Development of
New Medicines An Industry Perspective - 2006
Comparison of Emerging Markets Approval Process
for NDA and Clinical Trial Approval- 2007
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Institute for Regulatory Science Survey Asias
contribution to the global Development of New
Medicines An Industry Perspective

• Conducted August 2006 with the objective of
  looking at
• Companies current development strategies
• Submission and development Strategies
• Timing of Submissions Strategies
• Current clinical and regulatory environment in
  Asia Pacific Region
• Business drivers for undertaking clinical
  development
• Regulatory environment for clinical development
• Future perspectives
• 16/31 member companies responded
• 9 out of the top 12 companies (RD budget gt1.8bn
  USD)
• 13 of the 16 develop new medicines for global
  marketing
• For the purpose of the survey, Asia refers to
• India, Pakistan, China, Taiwan, South Korea,
  Japan and the 10 ASEAN countries

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Based on your current Strategy (2006), indicate
the approximate timing from first submission to
the following Regulatory Authorities
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Median time in roll out to Emerging Market (EM)
countries for New Active Substance (NASs)
approved 2004-2006

Company StrategyCountry RequirementsModel of
Review
Please note, data are included for one approval
in 2007 in each of the following countries South
Africa, China, Indonesia, Malaysia and Taiwan. n
in bar median number of days (n1,n2) number
of NASs, number of companies NASs included in
this analysis include those with 1st Worldwide
submission, 1st Worldwide approval, Application
submission and application approval dates only.
median value of -4 for orange bar (median gap
between 1st market approval and EM submission)
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What is your current and future company strategy
for clinical development?
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What is your current and future company strategy
for clinical development?
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Places in Asia (in addition to Japan) where
Companies are currently undertaking clinical
trials
N16
Unaudited data
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Business Drivers for integrating clinical
development in Asia as part of a global
development strategy
Patient availability\enrolment
High Quality Clinical Trial Centres
Cost Efficiency

• Other Factors
• Early access to markets
• Commercial potential in markets
• To meet bridging requirements
• Accommodate local requirements

Unaudited data
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Patients recruited by country/region as an
estimated proportion of global number of Patients

(n)the number of companies able to provide data
for both 2006 and an estimate for 2012
Unaudited data
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Strategies for Global Clinical Development
Clinical Trial Approvals
1. Global Drug Development in the Asia-Pacific
Region. 2. Approaches to Review of Clinical
Trials 3. Summary Conclusions

15
Emerging Markets Programme Data Collection
Clinical Trial Data
From Companies
From Agencies
Drug application type Review status Therapeutic
area Assessment routes CPP characteristics Questio
ns asked
Numbers of submissions approvals Average
approval times Target times View on Ethics
Committees Supporting data requirements Success
factors Barriers and hurdles
Types of ApprovalEthical Committee Approval
models Supporting data requirements Target and
actual times Number of applications
Participating authorities - Argentina, Brazil,
Mexico, Egypt, Saudi Arabia, South Africa, India,
Indonesia, Malaysia, Singapore, South Korea and
Taiwan
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Prior to submission
Ethics Board Clearance
Authority data
In parallel with submission
Agencies Malaysia Singapore South Korea Taiwan

Agencies India Indonesia

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Options for Initiating Clinical Trials

• Register of Clinical Trials
• Specific authorisation is not required
• Details of the trial are provided to the agency
• The Agency has the right to object and terminate
  trials
• Clinical Trial Authorisation
• The sponsor must apply for a Clinical Trial
  Authorisation before carrying out trials in the
  country
• The Agency must grant the authorisation before
  trials can commence
• Application data is submitted and assessed before
  the authorisation is granted
• Notification Scheme/Exemption from a full CT
  Authorisation
• Certain trials are exempt from the need for a
  full application and data assessment
• Specified information (e.g., Investigators
  Brochure) and Ethics Committee approval is
  required
• Objections can be raised within a fixed time
  period and a full CT application may then be
  needed

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Assessment (by each authority)
Agency Data
Information obtained from the public domain
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Key Comparisons Questions to sponsors

• Most agencies batch the questions at the end of
  the assessment
• Target times for response to questions vary
  widely across agencies
• Argentina 60 days
• Brazil 30 days extendable
• Mexico 5-20 days
• China Within 4 months
• Malaysia No limit
• India NA
• Singapore 2 weeks 2 months depending on the
  complexity of the question
• South Korea 30 days
• Taiwan 2 months but can extend by 1 month

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Target times for Clinical Trial Application (NAS)
Agency Data
Category A trials approved by a recognised
agency Category B all other
Information obtained from the public domain
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Strategies for Global Clinical Development
Clinical Trial Approvals

1. Global Drug Development in the Asia-Pacific
Region. 2. Approaches to Review of Clinical
Trials 3. Summary Conclusions
22
Clinical Trial Application Process Summary of
main points

• The process is similar across agencies although
  differences occur
• Scientific assessment is carried out by internal
  staff
• Use of scientific committees during the review
  process
• Target timeline of the agency approval process
• Time to respond to questions also differs widely
• The key issue seems to be
• Ethics approval in relation to the CT application
  approval process
• Long timelines at some agencies for Clinical
  Trial Approval
• Guidance requirements and procedures

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Global Drug Development Asias Role and
Contribution
Workshop - Tokyo October 2006 Regulators
(Australia, Canada, EU, Japan, S Korea,
Singapore, Taiwan and USA) and Industry
Recommendations On Clinical Trials.
Support the movement of clinical programmes to
Asia Pacific. This brings major benefits in
investment, improved clinical infrastructure and
patient welfare and regulatory agencies should
balance their public health obligations with a
willingness to cooperate.
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Global Drug Development Asias Role and
Contribution
Workshop - Tokyo October 2006 Regulators
(Australia, Canada, EU, Japan, S Korea,
Singapore, Taiwan and USA) and Industry
Recommendations On Clinical Trials.
Harmonisation of CTA requirements as a priority
In order to share assessment reports and
approvals for clinical trial applications there
needs to be agreement on a standard format for
CTAs, the requirements for supporting data and on
a common review template. Ideally there should be
similar timings for review so that global and/or
multi-country clinical trials can be synchronised.
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Global Drug Development Asias Role and
Contribution
Workshop - Tokyo October 2006 Regulators
(Australia, Canada, EU, Japan, S Korea,
Singapore, Taiwan and USA) and Industry
Recommendations On Clinical Trials.
Streamlining the procedure for obtaining clinical
trial approvals by agreeing a process whereby,
once the basic data for a clinical trial
application (CTA) has been reviewed and approved
by one major agency the authorisation should be
recognised by other participating countries..
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Strategies for Global Clinical Development
Clinical Trial Approvals

• Dr Neil McAuslane
• Professor Stuart Walker
• CMR International
• Institute for Regulatory Science