FDA - Clinical Trial Guidelines Consultation PDF

Clinical Trial Regulation
Guidelines
Maria Lourdes C. Santiago, MSc, MM, CESO II
Deputy Director General
Food and Drug Administration
7 August 2018
Outline
▪Brief Overview of Clinical Trial in the Philippines
▪Current Guidelines and Recommendations
▪ Proposed Revision Regulating the Conduct of Clinical
Trials
▪Objectives
▪Scope
▪General Guidelines
CLINICAL TRIAL/STUDY
Any investigation in human subjects intended to discover or verify the
clinical, pharmacological and/or other pharmacodynamic effects of an
investigational product(s), and/or to identify any adverse reactions to an
investigational product(s), and/or to study absorption, distribution,
metabolism, and excretion of an investigational product(s) with the object
of ascertaining its safety and/or efficacy. The terms clinical trial and
clinical study are synonymous.
ICH GCP E6 R2 Definition

SPONSOR
An individual, company, institution, or organization which
takes responsibility for the initiation, management, and/or
financing of a clinical trial.
CONTRACT RESEARCH ORGANIZATION (CRO)
A person or an organization (commercial, academic, or other)

contracted by the sponsor to perform one or more of a
sponsor's trial-related duties and functions.
Clinical Trial Guidelines Title
1. FDA Circular 2012-007 Recognition of Ethical Review Board/Committee (ERB/ERC) for
Purposes of the Conduct of Clinical Trials on Investigational Medicinal
Products in the Philippines for Other Purposes
2. FDA Circular 2013-003 Post Market Surveillance and Periodic Safety Update Report
3.FDA Circular No. 2013-004 Post Market Surveillance (PMS) of Authorized Drug Products
4. FDA Circular No. 2013-018 Adoption of the International Conference on Harmonization (ICH)
Safety and Efficacy Guidelines
5. FDA Circular No. 2014-009 Filing and Submission of Applications for the Approval of Clinical
Trial Protocol, Compassionate Special Permit (CSP), Import Permit for
Investigational Drug Products, Pharmacovigilance, Adverse
Events/Adverse Reaction Reports, and Other Related Documents
6. Administrative Order No. 2014- Rules and Regulations on the Licensing of Establishments Engaged in
0034 the Manufacture, Conduct of Clinical Trial, Distribution, Importation,
Exportation, and Retailing of Drug Products, and Issuance of Other
Related Authorizations
Clinical Trial Regulation
FDA Circular 2012-007
Published on June 7, 2012
➢First comprehensive guideline for the conduct of Clinical Trials on Investigational
Medical Products in the Philippines
➢Recognition of PHREB-Accredited IRBs to serve as Ethical and Technical Reviewers
for CT Applications
➢Mandatory inclusion of CT in Philippine CT Registry
➢Issuance of Import Permit
➢Inspection of clinical trial by FDA
➢Safety reporting
➢Imposition of Sanctions
Overview of Regulatory Procedure
Licensing of CROs and Conduct of Clinical Trial
Sponsors Study
Applicant
Applicant Start
Start
FDA receives
Applications 7 to 15 days
Incomplete
e-portal
30 days Complete
FDA Evaluation FDA Assigns
Accredited
Regulatory Reviewer
ERB 60 days
and Issue Regulatory
-Technical
Issuance of Review Permit
and Ethical
LTO Part B Part A & C Review
FDA Reviewer
Post-Licensing
7 to 15 days
Inspection Approval/Denial
CDRR Director
CT Licensed Establishments
Type
Sponsor 24
Contract Research
27
Organization (CRO)
Data as of 31 July 2018,

Valid and with Pending Renewal
Clinical Trial Applications
Phase 2012 2013 2014 2015 2016 2017 Total
Phase 1 1 7 3 4 2 0 17
Phase 1/2 0 3 0 1 0 2 6
Phase 2 9 3 9 12 6 9 48
Phase 2/3 2 3 0 1 2 1
9
Phase 3 60 74 69 36 42 33 314
Phase 3/4 0 0 1 0 0 2 3
Phase 4 9 9 7 4 4 2 35
Gaps in Implementation
Moving forward
2012-2017 (5 Years) 2018
FDA Review of CT Policies,
FDA Circular 2012-007 Systems and Procedures
Concerns and weaknesses Creation of Clinical Trial
were expressed after Regulatory Roadmap for
implementation… the Philippines
Improve CT regulatory
framework and guidelines
FDA REVIEW OF CLINICAL TRIAL REGULATIONS
March 2018 FDA Internal Review of CT Policies, Systems

and Procedures
May 2018 Initial Consultation with Stakeholders (CROs,
Sponsors, IRBs)
FDA Clinical Trial Regulatory Management Plan

FDA REVIEW OF CLINICAL TRIAL REGULATIONS
8 Elements:
❑ Legal Basis ❑ Assessment Procedures
❑ Guidelines ❑ Human and Other Resources
❑ Ethical Oversight ❑ Records and Outputs
❑Organization and Structure ❑ Availability of Information
The WHO data collection tool for the control of clinical trials
Clinical Trial Regulation: Implementation gaps
1 Legal Basis Already mandated by Law

RA 3720-Food Drug and Cosmetics Act and its amendments
RA 9711- Food and Drug Administration Act of 2009
2 Guidelines Revision of the Current Guidelines (FDA Circular 2012-007) to

cover:
• Scope of Regulation
• Registration of Investigational New Drugs
• Pharmacovigilance system to manage the collection, verification, presentation
and evaluation of all reported Adverse Events/Reactions (including SUSARs)
• Inspection Guidelines for the Inspectorate
• Phase I to Phase IV approval
Ethical Oversight There is a need for an established

3 system to provide oversight to Ethical
Reviewers
Organization and Technical and Scientific Review Process is
structure not fully in line with what is promoted by
4 World Health Organization
Scientific and Technical experts should
be within FDA
Assessment GCP Inspection is not conducted

5 Procedures Unpredictability of the release of Import
Permits
Human and Other The FDA is currently understaffed and there
6 Resources is a lack of expertise internally to review
protocols
7 Records and Outputs Paper based transfer of information is

inefficient
No single database for all applications
Availability of Not all studies are posted 30 days after

8 Information approval
There is no monitoring/audit mechanism
Coordination with PCHRD is needed
THE CLINICAL TRIAL REGULATORY
MANAGEMENT PLAN
Clinical Trial Regulatory Management Plan
Phase I: Phase II:
Training for Regulatory Reviewers
1. Revised Policies on Clinical Trial
Implementation
2. Guidance Document for Stakeholders
3. Review Tools Phase III:
Regulatory Impact Assessment
4. Training Module for Scientific and
Technical Reviewers
CALENDAR (PHASE 1)
Activities or Workplan Expected Output M1 M2 M3 M4 M5 M6 M7

Aug 2018 Sep 2018 Oct 2018 Nov 2018 Dec 2018 Jan 2018 Feb 2018
Initial Policy Review Revised Policies
Consultative Meetings Dissemination of revised
Analysis and Revision of Policies policies
Policy Dissemination
Creation of Review Tools
Creation of Guidance Document Guidance Document for
for Stakeholders Stakeholders
Training Module for
Creation Training Module for Reviewers and
Reviewers and Inspectors Inspectors
PROPOSED ADMINISTRATIVE ORDER ON
THE CONDUCT OF CLINICAL TRIALS FOR
PHARMACEUTICAL PRODUCTS AND
BIOLOGICS
OBJECTIVES (Draft)
This Administrative Order aims to achieve the following objectives:
1. Ensure the full protection of rights and safety of human subjects and the integrity
of clinical trial data through the adoption and implementation of international
standards on Good Clinical Practice (GCP) and maintenance of a Clinical Trial
Database;
2. Streamline the process and requirements for the approval of Phase I to Phase III
clinical trial protocols;
3. Provide standards and requirements for the regulation and importation of
Investigational New Drugs;
4. Creation of Regulatory Review Board and Scientific Advisory Committee as
recommending bodies to the FDA in the review of Clinical Trial Protocols;
OBJECTIVES (Draft)
This Administrative Order aims to achieve the following objectives:
5. Establishment of Clinical Research Section (CRS) to act as Secretariat to the
Scientific, Technical and Ethical Review of Clinical Trials;
6. Establishment of Pharmacovigilance system to manage the collection,
verification, presentation and evaluation of all reported Adverse
Events/Reactions; and
7. Strengthen the monitoring of compliance of all organizations, institutions
and entities to GCP and other related FDA regulations through regulatory
inspections
SCOPE (Draft)
This Administrative Order (AO) shall apply to Sponsors, Contract
Research Organizations (CROs), Investigators, and Ethical Review
Committees (ERCs) in the approval, conduct, monitoring and
inspection of clinical trials, in all phases, for product registration or
marketing purposes.
This will not cover products with issued Marketing Authorization.
Also, locally manufactured Herbal Drug Products are excluded
from this AO.
GENERAL GUIDELINES (Draft)
1. Only Study Sponsor and/or CROs, as defined by ICH-GCP, including
those government-owned institutions, with FDA license, can conduct
Clinical Trials in the Philippines.
2. All establishments involved in the conduct of Clinical Trials shall be under
the supervision of a qualified person(s) as required by pertinent rules
and regulations.
3. All Clinical Trials on investigational new drug for human use, from Phase
I to Phase III, including amendment/s thereto, are required to undergo
mandatory approval from FDA.
PHASE IV
Phase IV begins after drug approval. Therapeutic use studies go beyond the
prior demonstration of the drug’s safety, efficacy and dose definition.
Studies in Phase IV are all studies (other than routine surveillance) performed after
drug approval and related to the approved indication.
They are studies that were not considered necessary for approval but are often
important for optimising the drug's use.
They may be of any type but should have valid scientific objectives.
Commonly conducted studies include additional drug-drug interaction, dose-response
or safety studies and studies designed to support use under the approved indication,
e.g. mortality/morbidity studies, epidemiological studies.
ICH E8: General Considerations for Clinical Trials

4. Evaluation of the clinical trial protocol, including scientific, technical and
ethical review, shall be conducted by FDA Regulatory Reviewers and
Scientific Advisory Committee (SAC). The composition of FDA Regulatory
Reviewers and SAC, as well as the method of evaluating application shall
be identified by the FDA.
5. A clinical trial can only commence once the FDA has issued the
approval.
6. Imported Investigational Drug to be used in the conduct of clinical trials
shall be issued an “Import Permit.” The responsibility of ensuring the
quality of products used in the conduct of clinical trials shall rest upon
the Sponsor/s and CRO/s involved in the conduct of the studies.
7. All Serious Adverse Events (SAE) of products used in the
conduct of CT shall be reported to the FDA.
8. All Clinical Trials shall be uploaded in the registry which
shall be made available to the public for transparency. The
registry for Clinical Trials conducted in the country shall be
monitored by the FDA.
9. FDA shall have the authority to enter any establishment for inspection
of compliance and/or verification of submitted documents in relation
to any application.
10. Only FDA will give the final decision to approve or deny an
application. Likewise, FDA shall give sanctions, as appropriate, to any
violation which undermines the rights and safety of human subjects.
11. Disapproved application(s) may be appealed to for reconsideration.

Now we would like to hear your
thoughts…
Please email:
[email protected]
[email protected]
FOR FEEDBACK AND COMMENTS

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Clinical Trial Regulation

ICH GCP E6 R2 Definition

A person or an organization (commercial, academic, or other)

Data as of 31 July 2018,

March 2018 FDA Internal Review of CT Policies, Systems

FDA Clinical Trial Regulatory Management Plan

1 Legal Basis Already mandated by Law

2 Guidelines Revision of the Current Guidelines (FDA Circular 2012-007) to

Ethical Oversight There is a need for an established

Assessment GCP Inspection is not conducted

7 Records and Outputs Paper based transfer of information is

Availability of Not all studies are posted 30 days after

Activities or Workplan Expected Output M1 M2 M3 M4 M5 M6 M7

ICH E8: General Considerations for Clinical Trials

11. Disapproved application(s) may be appealed to for reconsideration.

FOR FEEDBACK AND COMMENTS

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