The mission of the International Conference on Harmonization (ICH) is to make recommendations towards achieving greater harmonization
in the interpretation and application of technical guidelines and requirements for pharmaceutical product registration. The
organization, launched in 1990, brings together the drug regulatory authorities and the pharmaceutical industry associations
of Europe, Japan, and the United States.
Regulatory harmonization offers many direct benefits to both regulatory authorities and the pharmaceutical industry with beneficial
impact for the protection of public health. Key benefits include: streamlining the regulatory assessment process for new drug
applications, and reducing the development times and resources for drug development.
Harmonization is achieved through the development of ICH Tripartite Guidelines, which are developed through a process of scientific
consensus among regulators and industry. Key to the success of this process, however, is the commitment of the ICH regulators,
including FDA, EMA, and Japan's Ministry of Health, Labor & Welfare, to implement the final guidelines.
The new ICH paradigm
In 2003, the quality experts in ICH developed a new vision: "Develop a harmonized pharmaceutical quality system applicable
across the lifecycle of the product emphasizing an integrated approach to quality risk management and science" (1). This goal
led to the creation of the following Quality guidelines: ICH Q8 Pharmaceutical Development; ICH Q9 Quality Risk Management; ICH Q10 Pharmaceutical Quality System, and the pending ICH Q11 Development and Manufacturing of Drug Substance (see cover story in this issue for details).
These guidelines represented methodologies addressing the challenges of the pharmaceutical industry with regard to emerging
techniques based on the rapid growth of technology and new opportunities in drug development and manufacturing. These guidelines
introduced in detail a new quality vision for industry, one focused on science- and risk-based concepts and approaches, and
one that emphasized an adequate quality system. In addition, ICH Q9 was the first harmonized document applicable to processes
performed by both industry and regulators.
Following these developments, the ICH Quality Implementation Working group (Q–IWG) worked out a way to facilitate harmonized
implementation of this new paradigm. The Q8, Q9, and Q10 guidelines, although independent, are interlinked. As a consequence,
implementation support was needed and provided.
The ICH Steering Committee endorsed the establishment of the Q–IWG to ensure the globally consistent implementation of ICH
Q8, Q9, and Q10, and to make sure that maximum benefit is achieved from the interaction between these guidelines (1). In parallel,
Q–IWG supported the development of ICH Q11 to guarantee a harmonized approach. As its first deliverable, Q–IWG developed a
Question-and-Answer document (Q&A) about the guidelines as well as enhanced training (2).
The Q&A document answers key questions raised at several conferences and workshops. For example, clarification of process
validation and continuous process verification are included, as are answers related to questions about quality by design (QbD),
including design space, real-time release testing (RTRT), and control strategy. The series of answers about the pharmaceutical
quality system focus on inspection practices, knowledge management, and software solutions (2).
Defining how the ICH Quality guidelines work together throughout the product lifecycle was a key goal of the Q–IWG training
and workshop series, held from 2009 to 2011, in Tallinn; Washington, DC; Ottawa; and Seoul, with participation from the ICH
Global Cooperation Group and the Asia–Pacific Economic Community. A case study was developed for the training workshops to
explain how a product developed using a science- and risk-based approach might be challenged during regulatory assessment.
Postapproval manufacturing implementation, quality system considerations, and potential thoughts during inspections were included
in the case-study discussion.
In addition, key messages on design space, control strategy, pharmaceutical quality systems, and quality risk management were
discussed through interactive sessions among participants and Q–IWG members. Slides of the presentations are available in
English and Japanese (3). During these training workshops, participants brought up many additional questions not addressed
in the Q&A document, which triggered the need for further clarifications.