CHAPTER 2:
International Harmonization via ICH, WHO, and Other Global Initiatives
Regulatory Affairs Professionals Society 19
his chapter focuses on the current international environments
for the regulation of medicinal products, including a com-
prehensive overview of the critical roles of the International
Council for Harmonisation of Technical Requirements for Pharma-
ceuticals for Human Use (ICH) and the World Health Organization
(WHO), which is the sole United Nations (UN) agency leading the
initiatives and collaborations for the global health ecosystem. The
chapter also discusses international organizations focused on harmo-
nization and continuous improvements for efficiencies in the global
regulatory processes.
International Council for
Harmonisation
Established in 1990, the purpose of ICH is “to make recommen-
dations toward achieving greater harmonization in the interpreta-
tion and application of technical guidance and requirements for
pharmaceutical product registration.”1
Regulatory harmonization offers many benefits to global reg-
ulatory authorities and the pharmaceutical industry in terms of
protecting public health. The key benefits of this harmonization
effort include preventing the duplication of clinical trials in humans
and minimizing the use of animal testing without compromising
safety and effectiveness streamlining the regulatory assessment
process for marketing applications and reducing the development
times and resources for drug development.2
The founding members of ICH were regulatory and
pharmaceutical industry representatives from developed nations,
including the US, EU, and Japan.3 Membership has expanded to
other countries and organizations holding observer status (see
Table 2-1).4
ICH prioritizes transparency regarding its harmonization
work as one way to build and maintain public trust. The ICH As-
sembly and Management Committee works to ensure that the
ICH process remains transparent and has recognized that all
stakeholders should have current information on the important
decisions and real-time progress of ICH guideline development.
ICH harmonization activities fall into four categories: formal
ICH procedures, Q&A procedures, revision procedures, and
maintenance procedures. For each activity, a concept paper and/or
a business plan may be required (see Figure 2-1).5
The formal ICH procedure consists of five steps. It is followed
for the harmonization of all new ICH topics. An expert working
group (EWG) is established, which works on the following steps
and procedures for implementation.
Step 1: Consensus Building
• The EWG prepares a consensus draft of the technical docu-
ment based on the objectives in the concept paper.
Step 2a: Confirmation of Consensus on the
Technical Document
• This step is approached when the assembly agrees, per the
EWG report, that there is sufficient scientific consensus for
the technical document to proceed to the next stage of regu-
latory consultation.
Step 2b: Adoption of the Draft Guideline
• Based on the technical document, regulatory members will
take the necessary actions to develop the draft guideline.
• Regulatory members endorse the draft guideline.
Step 3: Regulatory Consultation and Discussion
• Stage I – applies to the regional regulatory consultation stage
• Stage II – applies to the discussion of regional consultation
comments after obtaining all comments from the consulta-
tion process and
• Stage III – the finalization of the step 3 expert draft guide-
line. The step 3 expert draft guideline with regulatory EWG
signatures is submitted to the regulatory members of the as-
sembly to request adoption.
Step 4: Adoption of an ICH Harmonised Guideline
• The assembly agrees that there is sufficient consensus on the
draft guideline. The ICH regulatory members adopt the step
4 final document as an ICH harmonised guideline.
Step 5: Implementation
• Implementation is carried out according to the same national/
regional procedures that apply to other regional regulatory
guidelines and requirements in the ICH regions.6
T
International Harmonization via ICH,
WHO, and Other Global Initiatives
Linda McBride, RPh, RAC-US
CHAPTER 2
International Harmonization via ICH, WHO, and Other Global Initiatives
Regulatory Affairs Professionals Society 19
his chapter focuses on the current international environments
for the regulation of medicinal products, including a com-
prehensive overview of the critical roles of the International
Council for Harmonisation of Technical Requirements for Pharma-
ceuticals for Human Use (ICH) and the World Health Organization
(WHO), which is the sole United Nations (UN) agency leading the
initiatives and collaborations for the global health ecosystem. The
chapter also discusses international organizations focused on harmo-
nization and continuous improvements for efficiencies in the global
regulatory processes.
International Council for
Harmonisation
Established in 1990, the purpose of ICH is “to make recommen-
dations toward achieving greater harmonization in the interpreta-
tion and application of technical guidance and requirements for
pharmaceutical product registration.”1
Regulatory harmonization offers many benefits to global reg-
ulatory authorities and the pharmaceutical industry in terms of
protecting public health. The key benefits of this harmonization
effort include preventing the duplication of clinical trials in humans
and minimizing the use of animal testing without compromising
safety and effectiveness streamlining the regulatory assessment
process for marketing applications and reducing the development
times and resources for drug development.2
The founding members of ICH were regulatory and
pharmaceutical industry representatives from developed nations,
including the US, EU, and Japan.3 Membership has expanded to
other countries and organizations holding observer status (see
Table 2-1).4
ICH prioritizes transparency regarding its harmonization
work as one way to build and maintain public trust. The ICH As-
sembly and Management Committee works to ensure that the
ICH process remains transparent and has recognized that all
stakeholders should have current information on the important
decisions and real-time progress of ICH guideline development.
ICH harmonization activities fall into four categories: formal
ICH procedures, Q&A procedures, revision procedures, and
maintenance procedures. For each activity, a concept paper and/or
a business plan may be required (see Figure 2-1).5
The formal ICH procedure consists of five steps. It is followed
for the harmonization of all new ICH topics. An expert working
group (EWG) is established, which works on the following steps
and procedures for implementation.
Step 1: Consensus Building
• The EWG prepares a consensus draft of the technical docu-
ment based on the objectives in the concept paper.
Step 2a: Confirmation of Consensus on the
Technical Document
• This step is approached when the assembly agrees, per the
EWG report, that there is sufficient scientific consensus for
the technical document to proceed to the next stage of regu-
latory consultation.
Step 2b: Adoption of the Draft Guideline
• Based on the technical document, regulatory members will
take the necessary actions to develop the draft guideline.
• Regulatory members endorse the draft guideline.
Step 3: Regulatory Consultation and Discussion
• Stage I – applies to the regional regulatory consultation stage
• Stage II – applies to the discussion of regional consultation
comments after obtaining all comments from the consulta-
tion process and
• Stage III – the finalization of the step 3 expert draft guide-
line. The step 3 expert draft guideline with regulatory EWG
signatures is submitted to the regulatory members of the as-
sembly to request adoption.
Step 4: Adoption of an ICH Harmonised Guideline
• The assembly agrees that there is sufficient consensus on the
draft guideline. The ICH regulatory members adopt the step
4 final document as an ICH harmonised guideline.
Step 5: Implementation
• Implementation is carried out according to the same national/
regional procedures that apply to other regional regulatory
guidelines and requirements in the ICH regions.6
T
International Harmonization via ICH,
WHO, and Other Global Initiatives
Linda McBride, RPh, RAC-US
CHAPTER 2