The document discusses the acceptance and regulatory framework surrounding foreign clinical trials (FCT) by the FDA, highlighting the increasing globalization of drug development and the significant percentage of trials conducted outside the U.S. It outlines the conditions under which the FDA accepts foreign trial data, emphasizing compliance with good clinical practices and the necessity for inspection validation. Additionally, it addresses the challenges of managing inspections and data volume and proposes strategic approaches to improve oversight and compliance.

1. Acceptance of Foreign
Clinical Trials
FDA Guidance for industry -
Presented by
Dipak Kendre
[M. Pharm 1st Year Regulatory Affairs]
Under Guidance of
Dr. P.P. Nerkar Sir
[HOD- Department of Regulatory Affairs]
13/03/2023 1
R.C. Patel Institute of Pharmaceutical Education and research

2. 13/03/2023
Contents
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 Challenges
 Strategies for addressing the challenges
 References
 Foreign clinical Trials
 Distribution of studies
 Acceptance of FCT Data
 Good clinical practice

3.  FCT refer to Studies Conducted outside the USA to support
marketing applications submitted to the FDA
13/03/2023
 Prior to the 1975, it was uncommon for a Sponsor to
submit FCTs data.
In 1975 provisions that permit the submission of FCTs data
not conducted under an IND were codified in 21CFR312.120.
Since then, medical product discovery & development have
become increasingly globalized.
Foreign Clinical Trials (FCTs)
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Foreign Clinical Trials (FCTs)
In the past three decades, drug development, production &
distribution moved from a national and regionally‐ centred
activity to a global one.
The number of sites of FCT contributing data to support
U.S. Marketing applications for drug approval is increasing.
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Distribution of studies
51%
32%
6%
12%
Non US only
US only
Both US and
non US
Not
specified
Location Percentage of
total registered
study
Non US 51%
US 32%
Both US and Non
Us
6%
Not Specified 12%
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Data gathered from studies registered on https://clinicaltrials.gov/

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OIG Report
 Over half of all clinical trial sites are
outside the U.S
 % of non -U.S. clinical investigators
conducting trials has doubled over the
last decade
 87 % of all subjects in recent biologics
trials were enrolled outside the U.S.
According to the Office of inspector general’s [OIG] Report :
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OIG Report
 78 % of all subjects were enrolled outside the U.S
7
519656
345282
0
100000
200000
300000
400000
500000
600000
Non US US
Number of enrolled subjects

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What Drives company to conduct
clinical trial outside the USA
 Reduced cost or economic drivers (clinical care/
Operational/ training)
 Motivated subjects & investigators
 Availability of large no of volunteers
 Faster recruitment rates/ short timeline
Availability of CROs focused on global trials
Less regulatory red tape
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Foreign Clinical Trials Conducted Under IND.
When a study is conducted under an IND but is located
outside of the United States, the study still must comport
with all relevant FDA regulations as if it were being conducted
within the United States. A Sponsor is not required to
conduct an FCT under an IND in order to use it as support for
an NDA or IND.
Acceptance of FCT Data
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Foreign Clinical Trials Not Conducted Under an IND
Acceptance of Foreign Clinical Data: FDA Accepts Foreign
Clinical data from studies not conducted under an IND if the
following conditions are met:
1. Study was conducted in accordance with Good Clinical
Practice (GCP).
2. FDA is able to validate the data from the study through an
onsite inspection.
Acceptance of FCT Data
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GCP is a standard for the design, conduct, performance, monitoring
, auditing, recording, analysis and reporting of clinical trials in a way
that provides assurance that are credible and accurate and that the
rights safety of trial subjects are protected.
Sponsor need to submit supporting information to FDA to ensure
research conformed to GCP
Good Clinical Practices
What is GCP ?
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1. CI’s qualifications.
2. Description of the research facilities.
3. Summary of the protocol & results of the study
4. Description & details of the product/drug used.
5. Information showing that the study is adequate & well controlled.
6. Name & address of the IEC, a summary of the IEC’s decision.
7. A description: – how IC was obtained – what incentives, if any,
were provided to subjects in the study – how the sponsor(s)
monitored the study – how CIs were trained to comply with GCP.
Good Clinical Practice
Supporting Information
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1. May be requested
2. Explanation of why compliance unnecessary or cannot be
achieved.
 Description of alternative submission or course of action
that satisfies the purpose of the requirement
 Other information justifying waiver
 FDA may grant waiver if it finds that doing so would be in
interest of public health.
Waivers from GCP Principles
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1. If study submitted in support of marketing application – for 2
years after an agency decision on that application
2. If the study is submitted in support of an IND but not a
marketing application – for 2 years after submission to the IND
Good Clinical Practice
Record Retention
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 Help to ensure the protection of rights, safety and welfare of
research participants.
 Help to ensure data that are submitted in marketing applications
are fit for the purpose
• For regulatory decision making (Approval)
• As the evidence base for clinical use of the drug (Label)
 Allow evaluation of compliance with FDA regulations.
Inspection
Validation of data Onsite Inspections
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 Importance of the
study
Inspection
Factors to consider when to inspect -
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History of the
clinical investigator
Data
Contribution

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Consequences of non-compliance
Warning Letter
Disqualification
Rejection of data
IND clinical holds
Termination of IND
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Challenges
Increase in Breadth of Inspections.
FDA inspects 0.7 % of all foreign clinical sites, compared to 1.9%
of all domestic clinical sites.
Increasing volume of data
Increasing data from other regions submitted in support of
marketing submissions submitted to FDA.
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Strategies for addressing the challenges
Leveraging Knowledge/ Resources:
 Utilize finite resources strategically and efficiently and leverage
inspection – EMA-FDA Collaboration GCP Inspection Initiative
 Develop a joint GCP program – Plan, coordinate, schedule, and
conduct collaborative GCP inspections
 Establish joint procedures – Share information related to drug
applications – FDA International Offices:
 Provide a platform for inspection of foreign facilities.
 Offices collect & leverage local & regional knowledge.
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Strategies for addressing the challenges
Building Quality:
Build quality during the planning stages: – incorporate quality
management approach into clinical studies & their oversight to
prevent the errors, and monitor for those and focus less on the
less important matters.
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Strategies for addressing the challenges
Utilize Data Standards:
Encouraging sponsors to utilize data standards to improve
analysis and site selection for inspection.
Risk-Based Monitoring and Inspection – Using innovative
strategies & tools to identify sites for clinical inspection(ex.
GCP risk-based site selection tool for clinical inspection).
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Strategies for addressing the challenges
Science-Based Standards:
 Working to converge regulatory standards (to share a
common foundation of science-based goals for product safety,
quality, and efficacy).
 Strengthening the regulatory capacity of governments to
manage, assess, and regulate drug development ( such as
providing information, tools, training & exchange programs).
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References
1. https://clinicaltrials.gov/
2. https://www.fda.gov/regulatory-information/search-fda-
guidance-documents
3. https://www.fda.gov/inspections-compliance-enforcement-
and-criminal-investigations/inspection-classification-database
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