Concept Paper

for the Establishment of an

ICH Risk Management: Application to Quality Requirements and Practices

Expert Working Group (EWG)


Proposed by the Informal GMP Risk Management Discussion Group


I.       Type of Harmonisation Action Proposed

Risk Management is a process consisting of well defined steps which when taken in sequence, support better decision making by contributing to a greater insight into risks and their impacts.  It includes elements such as risk identification, assessment, mitigation, elimination and communication. 


A tripartite, harmonised guideline is necessary to define how principles of risk management can be more effectively applied and consistently integrated into decisions, both by regulators and industry, regarding the quality of pharmaceuticals across the product lifecycle, including GMP compliance.  This guideline will include a framework of risk management for pharmaceutical quality, which will contribute to more consistent, science-based, decision-making and support the establishment and revision of quality related practices, guidelines, requirements and standards.


II.     Statement of the Perceived Problem

There is no internationally harmonised comprehensive guideline for applying risk management principles to the quality of pharmaceuticals.  Therefore, there are inconsistent uses of risk management in determining appropriate quality requirements and industry practices around the world.  Although all industry and regulator parties are using risk management concepts, there is no common understanding of terms, principles and application. 


The absence of a harmonised risk management approach has the following impacts on the patient, regulator and/or industry:


·       Product may not be available to patients, when needed

·       May increase the potential for the release of unacceptable product to the market

·       New product introductions to the marketplace may be delayed

·       Delays may occur during implementation of changes and improvements to processes

·       Safe and effective drugs may be discarded or recalled from the market

·       Manufacturers may be reluctant to implement new technologies or continuous improvements to the products or processes

·       Scarce resources may not be optimally allocated

·       Lack of appropriate data to evaluate risk most effectively


III.   Issues to be Resolved

The following issues need to be resolved:

·       Terminology including a definition of quality, risk, risk management, etc.

·       Principles for how risk management should be effectively applied and consistently integrated into decisions regarding product quality and impact on the patient

·       How to operationalise the integration of risk management into the decision making process

·       Identifying circumstances when applying risk management principles is not feasible or appropriate

·       Defining what principles of risk management apply to the industry, to the regulators, and to both, throughout the product lifecycle

·       How, what and when information is exchanged between and within industry and regulators, in a global context

·       How to ensure synergy with the Pharmaceutical Development EWG and the resulting guidelines

·       Defining roles and responsibilities of regulators and industry, including communication responsibilities

·       How risk can be incorporated into resource allocation decisions


IV.  Background to the Proposal

At the ICH meeting in Brussels in July 2003, a consensus vision statement was developed by all parties and observers involved.


“Develop a harmonized pharmaceutical quality system applicable across the life cycle of the product emphasizing an integrated approach to risk management and science.”


The integration of risk management in to the pharmaceutical quality system is an important component of this vision.   Therefore, the Risk Management Guideline must be synergistic with the Pharmaceutical Development Guideline and should be a source document for future ICH quality topics.


In constructing the risk management guideline, the EWG should consider programs that have been developed in other industries and regulatory bodies such as the aerospace, medical devices, foods, health and safety.  In addition to this, the EWG for risk management should discuss current examples being used in the pharmaceutical industry and its regulatory bodies.


      Benefits of the harmonized risk management guideline to all ICH parties and observers:


·       Enhanced patient confidence in decision making on pharmaceutical quality

·       Promotes more effective use of regulatory agency and industry resources

·       Establishes a systematic, well-informed and thorough method of decision making which leads to greater transparency and predictability

·       Increased knowledge of exposure to risk

·       Fosters quality by design, continuous improvement and new technology introduction, which generally leads to enhanced product quality


 V.  Type of Expert Working Group

The Expert Working Group (EWG) should be extended beyond the six primary parties and be composed of experts in the risk management, Quality, Regulatory and Manufacturing fields.  They will be charged with developing the guideline. 


To keep the size of the EWG manageable, it is suggested that the core group comprise two members from each of the ICH parties and one representative from each observer (including IGPA, WSMI, WHO, and Canada).  In addition, the EWG will ensure appropriate linkages with the Pharmaceutical Development EWG and other external expert groups. 


Initiation of this work by the EWG should begin as soon as possible.



Adoption of topic by ICH Steering committee – Osaka                         November 11, 2003

First EWG – Venue to be determined in Europe March/April 2004

Second EWG – Washington                                                               June 2004

Adoption of Step 2 Document  Tokyo                                               November 2004