ICH Guidelines

Regulatory bodies and research-based

Industry
Region Regulatory Body Research Based Industry
•
• -

Japan MHLW - Ministry of JPMA - Japan

Health, Labour and Pharmaceutical
Welfare Manufacturers
Association
Europe EU European Union EFPIA - European
Federation of
Pharmaceutical
Industries and
Associations
USA FDA - Food and Drug PhRMA - Pharmaceutical
Administration Research and
Manufacturers of
America
 PROCESS OF HARMONISATION
• Formal ICH procedure
• Question and answer procedure
• Revision procedure
• Maintenance procedure.
PROCESS OF HARMONISATION
 Step 1: Consensus building(Agreement)

• The process of unanimity starts when the Steering

Committee acquires a Concept Paper as a new topic. Step
1 is started when the EWG begin the preparation of a
unanimity draft of the technical document, depending on
the objectives set out in the Concept Paper.
• Work is conducted via e-mail, telephonic conferences and
web conferences. If supported by the Steering committee,
the EWG will also meet face to face at the 2 years SC
meetings. Meanwhile reports on the progress of the draft
technical document are made to the SC on a regular
interval
Step 2a: Confirmation of six-party unanimity
on the technical document
• Step 2a is reached when the Steering Committee
accepts based on the report of the EWG, that there
is enough scientific consensuses on the technical
issues for the Technical Document to proceed to the
next stage of regulatory consultation.
• The unanimity text approved by the Steering
Committee is signed-off by the Steering Committee
as the Step 2a Final Technical Document.
Step 2b: Espousal of the draft Guideline:

• Based on the technical document, the three

ICH regulatory members will take the actions
they deem essential to develop the “draft
Guideline”. The unanimity text approved by
the three regulatory ICH members is signed-
off by the three regulatory ICH members as
Step 2b Draft
 Step 3: Regulatory consultation and
Discussion:
• Stage I: Regional regulatory consultation
• Stage II: Discussion of regional consultation
comments:
• Stage III: Finalisation of Step 3 Experts Draft
Guideline
 Step 4: Acceptance of an ICH Harmonised
Tripartite Guideline:
• Step 4 is completed when the Steering Committee
accepts, on the basis of the report from the
Regulatory Chair and the regulatory Rapporteur
of the EWG, that there is sufficient unanimity on
the draft guideline. Step 4 is reached when the
Step 4 Final Document is signed-off by the SC
signatories for the regulatory members of ICH as
an ICH Harmonised Tripartite Guideline at Step 4
of the ICH procedure.
 Step 5: Implementation:
• After completing Step 4, the harmonised
tripartite Guideline moves immediately to
the final step of the process that is the
regulatory execution or Step 5. Step 5 is
accomplished according to the same
national/regional procedures that apply to
other regional regulatory requirements, in
the, USA, Japan and the European Union.
Objective

1. More efficient use of human, animal and

material resources.
2. Elimination of unnecessary and unreasonable
delay in the global development and
availability of new medicines while
maintaining safeguards on quality, safety and
efficacy.
3. Regulatory obligations to protect public health .
Q- Series Guidelines
Q1A - Q1F Stability
Q2(R1)- Validation of analytical procedure
Q3A - Q3D Impurities
Q4A - Q4B Pharmacopoeias
Q5A - Q5E Quality of Biotechnological Products
Q6A- Q6B Specifications
Q7 Good Manufacturing Practice
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
Q11 Development and Manufacture of Drug Substances
Q12 Lifecycle Management
 Q1A - Q1F Stability

Q1A(R2) Stability Testing of New Drug Substances and

Products Q1A
Q1B Stability Testing : Photostability Testing of New
Drug Substances and Products
Q1C Stability Testing for New Dosage Forms
Q1D Bracketing and Matrixing Designs for Stability
Testing of New Drug Substances and Products
Q1E Evaluation of Stability Data
Q1F Stability Data Package for Registration Applications
in Climatic Zones III and IV
Q2(R1)- Validation of analytical procedure

Text & methodology for analytical method

validation for stability study.
 Q3A - Q3D Impurities
Q3A(R2) Impurities in New Drug Substances
Q3B(R2) Impurities in New Drug Products
Q3C(R6) Impurities: Guideline for Residual Solvents
Q3C(R7) Impurities: Guideline for Residual Solvents
Q3D Guideline for Elemental Impurities
Q3D(R1) Revision of Q3D Cadmium Inhalation PDE
Q3D(R2) Revision of Q3D for cutaneous and
transdermal products
Q3D training Implementation of Guideline for
Elemental Impurities
 Q4A - Q4B Pharmacopoeias

Q4A Pharmacopoeial Harmonization

Q4B Evaluation and Recommendation of Pharmacopoeial Texts for
Use in the ICH Regions
Q4B Annex 1R1 Residue on Ignition/Sulphated Ash General
Chapter
Q4B Annex 2R1 Test for Extractable Volume of Parenteral
Preparations General Chapter
Q4B Annex 3R1 Test for Particulate Contamination: Sub-Visible
Particles General Chapter
Q4B Annex 4AR1 Microbiological Examination of Non-Sterile
Products: Microbial Enumeration Tests General Chapter
Q4B Annex 4BR1 Microbiological Examination of Non-Sterile
Products: Tests for Specified Micro-Organisms General Chapter
Q4B Annex 4CR1 Microbiological Examination of Non-Sterile Products:
Acceptance Criteria for Pharmaceutical Preparations and Substances for
Pharmaceutical Use General Chapter
Q4B Annex 5R1 Disintegration Test General Chapter
Q4B Annex 6 Uniformity of Dosage Units General Chapter
Q4B Annex 7R2 Dissolution Test General Chapter
Q4B Annex 8R1 Sterility Test General Chapter
Q4B Annex 9R1 Tablet Friability General Chapter
Q4B Annex 10R1 Polyacrylamide Gel Electrophoresis General Chapter
Q4B Annex 11 Capillary Electrophoresis General Chapter
Q4B Annex 12 Analytical Sieving General Chapter
Q4B Annex 13 Bulk Density and Tapped Density of Powders General
Chapter
Q4B Annex 14 Bacterial Endotoxins Test General Chapter
Q4B FAQs Frequently Asked Questions
Q5A - Q5E Quality of Biotechnological Products
Q5A(R1) Viral Safety Evaluation of Biotechnology
Products Derived from Cell Lines of Human or Animal
Origin Q5A
Q5B Analysis of the Expression Construct in Cells Used for
Production of r-DNA Derived Protein Products
Q5C Stability Testing of Biotechnological/Biological
Products
Q5D Derivation and Characterization of Cell Substrates
Used for Production of Biotechnological/Biological
Products
Q5E Comparability of Biotechnological/Biological
Products Subject to Changes in their Manufacturing
Process
 Q6A- Q6B Specifications

Q6A Specifications : Test Procedures and

Acceptance Criteria for New Drug Substances and
New Drug Products: Chemical Substances

Q6B Specifications : Test Procedures and

Acceptance Criteria for
Biotechnological/Biological Products
 Q7 Good Manufacturing Practice

Q7 Good Manufacturing Practice Guide for Active

Pharmaceutical Ingredients Q7A

Q7 Q& As Questions and Answers: Good

Manufacturing Practice Guide for Active
Pharmaceutical Ingredients
 Q8 Pharmaceutical Development

Q8(R2) Pharmaceutical Development

Q8/9/10 Q&R4 Q8/Q9/Q10 - Implementation

 Q9 Quality Risk Management

Q9 Quality Risk Management

Q8/9/10 Q&AsR4 Q8/Q9/Q10 - Implementation
 Q10 Pharmaceutical Quality System

Q10 Pharmaceutical Quality System

Q8/9/10 Q&AsR4 Q8/Q9/Q10 – Implementation.

Q11 Development and Manufacture of Drug
Substances

Q11 Development and Manufacture of Drug

Substances (Chemical Entities and
Biotechnological/Biological Entities)

Q11 Q&As Questions & Answers: Selection and

Justification of Starting Materials for the
Manufacture of Drug Substances
 Q12 Lifecycle Management

Q12 Technical and Regulatory Considerations for

Pharmaceutical Product Lifecycle Management.
Safety Guidelines:
S1A - S1C Carcinogenicity Studies
S2 Genotoxicity Studies
S3A - S3B Toxicokinetics and Pharmacokinetics
S4 Toxicity Testing
S5 Reproductive Toxicology
S6 Biotechnological Products
S7A - S7B Pharmacology Studies
S8 Immunotoxicology Studies
S9 Nonclinical Evaluation for Anticancer Pharmaceuticals
S10 Photosafety Evaluation
S11 Nonclinical Pediatric Safety
Efficacy Guidelines
E1 Clinical Safety for Drugs used in Long-
Term Treatment
E2A - E2F Pharmacovigilence
E3 Clinical Study Reports
E4 Dose-Response Studies
E5 Ethnic Factors
E6 Good Clinical Practice
E7 Clinical Trials in Geriatric Population
E8 General Considerations for ClinicalzTrials
E9 Statistical Principles for Clinical Trials
E10 Choice of Control Group in Clinical Trials
E11 - E11A Clinical Trials in Pediatric
Population
E12 Clinical Evaluation by Therapeutic
Category
E14 Clinical Evaluation of QT
E15 Definitions in Pharmacogenetics /
Pharmacogenomics
E16 Qualification of Genomic Biomarkers
E17 Multi-Regional Clinical Trials
E18 Genomic Sampling
E19 Safety Data Collection