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