in a changing world, are ich gcp guidelines covering...
TRANSCRIPT
In a changing world, are ICH GCP guidelines covering new challenges?
Olga Martínez-Casares Head of Clinical Research Strategy, Early Phases and Patient Advocacy
Munich, 13 October 2016
Harmonize: the key word-ICH birth
• 1960s -1970s Rapid increase in laws,
regulations and guidelines for reporting and
evaluating the data and expansion of industry,
seeking new markets
• Divergence in technical requirements from
country to country. Duplication of time-
consuming and expensive test procedures, in
order to market new products, internationally.
• The urgent need to rationalise and harmonise
regulation: rising costs of health care, escalation
of the cost of R&D. Public expectation of
minimum of delay for new treatments.
• Pioneered by the European Community (EC),
in the 1980s.
• The birth of ICH took place at a meeting in April
1990, hosted by EFPIA in Brussels
From the need to regulate to the need to rationalize and harmonize
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ICH Mission
• Harmonisation for pharmaceutical product registration through the development of ICH
Tripartite Guidelines.
• Benefits to both regulatory authorities and the pharmaceutical industry with beneficial
impact for the protection of public health:
– preventing duplication of clinical trials in humans
– minimising the use of animal testing
– streamlining the regulatory assessment process for new drug applications;
– reducing the development times and resources for drug development.
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The Evolution of ICH
• Development of Tripartite ICH
Guidelines.
• New millennium: to expand
communication and dissemination of
information with non-ICH regions and
implementation of ICH Guidelines in ICH's
own regions.
• Collaboration with Standards Development
Organizations, e.g. the development of
electronic standards.
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Succes for two decades- Collaboration and commitment to implementation
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First decade Second decade
Third decade
• Extending the benefits of harmonisation
beyond the ICH regions.
• Globalization: to achieve greater
harmonisation worldwide to ensure that
safe, effective, and high quality medicines
are developed and registered in the most
resource-efficient manner.
Why changes were needed?
“To keep pace with the scale and complexity of clinical trials and to ensure appropriate
use of technology we should modernise our approach to GCP to enable
implementation of innovative approaches to clinical trial design, management,
oversight, conduct, documentation, and reporting that will better ensure human subject
protection and data quality. “*
“ICH E6 has been misinterpreted and implemented in ways that impede innovation,
emphasising less important aspects of trials (e.g., focusing on the completeness and
accuracy of every piece of data) at the expense of critical aspects (e.g., carefully
managing risks to the integrity of key outcome data).”*
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Perceived problem
ESP/INS/2005/16 *Source: ICH Concept Paper
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2_Concept_Paper_July_2014.pdf
Globalization Technological capabilities Study Complexity
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Scope of the Changes & process to follow
Geographical Impact is GLOBAL in practice
• ICH Countries: USA, EU, Japan, Switzerland, Canada
Process for change
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Addendum for ICH E6 GCP
Step One
Final concept paper & Bussines plan
Approved by SC on 5 June 2014
Step Two
Draft Addendum 11 June 2015
Industry Consultation and review of indutry feedback
Jul 2015 - May 2016
Step Three
Expert Draft Guideline June 2016
Step Four
Final guideline November 2016
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Process
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Step Five
Implementation FDA 2017; Japan TBC; EU TBC
What solution(s) is the ICH Addendum Proposing?
Harmonization - based on position papers from regulators FDA, EMA,
MHLW/PMDA, Transcelerate & ICH Q9 (Quality Risk Management) on quality
management and risk based approaches
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Quality Risk
Management
Quality By Design
Risk Based Monitoring
Technological Tools
Monitoring Plan
Root Cause Analysis
Risk identification
Critical process
Risk Evaluation
Risk Control
Risk Communication
Risk Review
Risk Reporting
Investigator Responsibilities
Section 4.2. Adequate Resorces
Supervision of individual or party to whom investigator delegates study tasks
Ensure qualification of individuals or any party to perform study tasks
Implement procedures to ensure integrity of tasks performed and data
generated
Section 4.9. Records and Reports
Source documents and trial records for each
trial subject:
“Attributable, legible, contemporaneous,
original, accurate and complete”
Changes should be traceable
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Sponsor-Quality Management
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New section 5.0.
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Implement a system to manage quality
throughout the study (design-archiving-clinical
study report)
Focus on essential trial activities
Methods used to assure and control quality
proportionate to trial risks
Avoid unnecessary complexity procedures
and data collection
QMS should use Risk based approach
- Critical process & data identification-Protocol
development
- Risk identification, Evaluation, Control,
Communication, Review, Reporting
Sponsor
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Section 5.4.:Contract Research Organizations
Ensure oversight of activities conducted on its
behalf
Document approval of suncontracted trial
related duties and functions
Section 5.5.: Trial Management, Data Handling
and Record Keeping
Electronic trial data handling. SOP should
cover system use, validation, data collection,
system security, back up… contingency plan
and decomisioning. Training should be provided
to users
Sponsor - Monitoring
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Section 5.18.3.: Extent and Nature of Monitoring
Develop systematic, prioritized, risk based approach to monitoring
Flexibility in the extent and nature of monitoring, permits varied approached to improve
effectiveness and efficiency
Includes risk based, centralized and on-site approaches
Monitoring Strategy documented with the rational in the monitoring plan
Section 5.18.6.: Monitoring report
Documentation of all monitoring activities & results to demonstrate compliance with the
monitoring plan
Section 5.18.7.: Monitoring plan
Development of a monitoring plan tailored to the human subject protection and the data
integrity risks of the trial including
• Copies used to replace original
document should fulfill
requirements for certified copies
• Sponsor should ensure that investigator
has control and access to CRF data
reported to sponsor
• Sponsor & Investigator should
maintain record of location of the
essential documents
• Investigator/institution should control
documents and record generated by
them before, during and after the trial
• Storage system should provide
document identification, search and
retrieval
Essential Documents/(e)TMF
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Thank you