ICH guideline.pdf

Key importance of ICH guideline, a brief summary on the international guidelines for new drug development.
Specifically for regulatory affairs student of MPharm

1. ICH –INTERNATIONAL COUNCIL
FOR HARMONIZATION & IT’S
GUIDELINES
By: Zeel Shah
Masters of Regulatory Affairs
Semester: 1

2. Contents
History
Objective
Amendments
Members
Four Pillars
Website

3. FOUNDATION OF ICH:
Pioneered by the EC, Europe, in the 1980s for development of a single
market for pharmaceuticals.
At the WHO Conference of Drug Regulatory Authorities (ICDRA), in
Paris, in 1989, that specific plans for action began.
Authorities approached International Federation of Pharmaceutical
Manufacturers and Associations (IFPMA) to discuss a joint regulatory-
industry initiative on international harmonization.
The birth of ICH took place at a meeting in April 1990, hosted by EFPIA
in Brussels.
Regulatory agencies and industry associations of Europe, Japan and
the US met.
Work also included discussion on MedDRA(Medical Dictionary for
Regulatory Activities) and the CTD (Common Technical Document).

4. To achieve greater harmonization worldwide to ensure that
safe, effective, and high quality medicines are developed and
registered in the most resource-efficient manner.
To maintain a forum for a constructive dialogue on scientific
issues between regulatory authorities and the pharmaceutical
industry.
To contribute to the protection of public health in the interest
of patients from an international perspective.
To monitor and update harmonized technical requirements
leading to a greater mutual acceptance of research and
development data.
To encourage the adequate implementation and integration
of common standards.

5. •Increasing international outreach.
•Changing ICH’s governance
structure.
•Disseminating more information
on ICH processes to a wider
number of stakeholders.
•Establishing ICH as a legal entity
to provide for a more stable
operating structure.
Reforms
of 2015

6. Founding
Regulatory
Members
European Commission
(EC), Europe
Food and Drug
Administration (FDA), US
Ministry of Health, Labour
and Welfare (MHLW),
Japan
Founding Industry
Members
European Federation of
Pharmaceutical Industries
and Association (EFPIA)
Japan Pharmaceutical
Manufacturers Association
(JPMA)
Pharmaceutical Research
and Manufacturers of
America (PhRMA)
Standing
Regulatory
Members
Health Canada , Canada
Swissmedic, Switzerland
Members with ICH

7. Brazilian Health
Regulatory Agency
(ANVISA) , Brazil
Federal Committee for
Protection from
Sanitary Risks
(COFEPRIS) , Mexico
Health Sciences
Authority (HSA) ,
Singapore
Ministry of Food &
Drug Safety (MFDS) ,
Republic of Korea
Medicines and
Healthcare Products
Regulatory Agency
(MHRA) , UK
Regulatory
Members National Medical
Products
Administration
(NMPA) , China
Saudi Food and Drug
Authority (SFDA) ,
Saudi Arabia
Tanzania Food and
Drugs Authority
(TFDA) , Chinese
Taipei
Turkish Medicines and
Medical Devices
Authority (TITCK) ,
Turkey
Regulatory
Members
Biotechnological
Innovations
Organization (BIO)
Global Self-care
Federation
International Generic
and Biosimilar
Medicines Association
(IGBA)
Industry
Members

8. Quality:
Conduct of stability studies,
defining relevant thresholds
for impurities testing and a
more flexible approach to
pharmaceutical quality based
on Good Manufacturing
Practice (GMP) risk
management.
Safety:
To uncover potential risks like
carcinogenicity, genotoxicity
and reprotoxicity. A recent
breakthrough has been a
non-clinical testing strategy
for assessing the QT interval
prolongation liability: the
single most important cause
of drug withdrawals in recent
years.
Efficacy:
Concerned with the design,
conduct, safety and reporting
of clinical trials. It also covers
novel types of medicines
derived from
biotechnological processes
and the use of
pharmacogenetics/genomics
techniques to produce better
targeted medicines.
Multidisciplinary:
Cross-cutting topics which do
not fit uniquely into one of
the Quality, Safety and
Efficacy categories. It
includes the ICH medical
terminology (MedDRA), the
Common Technical
Document (CTD) and the
development of Electronic
Standards for the Transfer of
Regulatory Information
(ESTRI).
FOUR PILLARS OF ICH GUIDELINES

9. QUALITY
Q1A –Q1F
Stability
Q4A –Q4B
Pharmacopoeias
Q5A –Q5E
Quality of
Biotechnological
Products
Q6A –Q6B
Specifications
Q7
Good
Manufacturing
Practice
Q2
Analytical
Validation
Q3A –Q3E
Impurities

10. QUALITY
Q8
Pharmaceutical
Development
Q9
Quality Risk
Management
Q10
Pharmaceutical
Quality System
Q11
Development
and
Manufacture
of Drug
Substance
Q12
Life cycle
management
Q13
Continuous
manufacturing
of Drug
substance and
Drug Product
Q14
Analytical
Procedure
Development

11. Q4A
–
Q4B
Q3A
-
Q3E
Q1A
-
Q1F
Q1A (R2) Stability Testing
of new drug substances
and products
Q1B Stability Testing:
PhotostabilityTesting of
new drug substances and
products.
Q1C Stability testing for
new dosage forms
Q1D Bracketing and
MatrixingDesigns for
stability testing of new drug
substances and products
Q1E Evaluation of Stability
Data
Q1F Stability data package
for registration applications
in climatic zones 3 and 4
Q1/Q5C EWG Targeted
revisions of the ICH
stability guideline series
Q3A(R2) Impurities in new dug
substances
Q3B(R2) Impurities in new dug
products
Q3C(R8) Guideline for residual
solvents
Q3C(R9) Maintenance EWG
Maintenance of the guideline
for residual solvent
Q3D(R2) Guideline for elemental
impurities
Q3C(R3) Maintenance EWG
Maintenance of the guideline for
Elemental impurity
Q3D training Implementation of
guideline for Elemental
impurities
Q3E EWG Impurity : Assessment
and control of Extractablesand
Leachable for Pharmaceuticals
and biologics
Q4A Pharmacopeialharmonization
Q4B Evaluation & recommendation of pharmacopeialtext for use in
ICH region
Q4B Annex 1 (R1) Residual on ignition/sulphatedash general chapter
Q4B Annex 2 (R1) Test for extractable values of parentralpreparation
general chapter
Q4B Annex 3 (R1) Test for particulate contamination
Q4B Annex 4A (R1) Microbial examination of non-sterile products :
enumeration test
Q4B Annex 4B (R1) Microbial examination of non-sterile products :
Test for micro-organisms
Q4B Annex 4C (R1) Microbial examination of non-sterile products :
Acceptance criteria for pharmaceutical product
Q4B Annex 5 (R1) Disintegration test general chapter
Q4B Annex 6 Uniformity of dosage units general chapter
Q4B Annex 7 (R2) Dissolution test general chapter
Q4B Annex 8 (R1) Sterility test general chapter
Q4B Annex 9 (R1) Tablet friability general chapter
Q4B Annex 10(R1) Polyacrylamide gel electrophoresis general
chapter
Q4B Annex 11 Capillary Electrophoresis general chapter
Q4B Annex 12 Analytical sieving general chapter
Q4B Annex 13 Bulk & tapped density of powders general chapters
Q4B Annex 14 Bacterial Endotoxin test general chapter
Q4B FAQs
QUALITY GUIDELINES SUBPARTS

12. Q6A
-
Q6B
Q5A
-
Q5E
Q5A (R1) Viral safety and evaluation of
biotechnological product derived from
cell lines of human or animal
Q5A (R2) EWG Viral safety and
evaluation of biotechnological product
derived from cell lines of human or
animal
Q5B Analysis of expression constructed
in cells used for production of rDNA
derived protein products
Q5C Quality of biotechnological
products
Q5D Derivation and characterization of
cell substrates used for production of
biological products
Q5E Comparibilityof Biotechnological
products in respect to changes in its
manufacturing process
Q6A Specifications: Test
procedures and acceptance
criteria for new drug
substances and product:
Chemical substances
Q6B Specifications : Test
procedures and acceptance
criteria for Biotechnological
/biological products
QUALITY GUIDELINES SUBPARTS

13. •Carcinogenicity studiesS1A –S1C
•Genotoxicity StudiesS2
•Toxicokinetics and PharmacokineticsS3A –S3B
•Toxicity testingS4
•Reproductive toxicologyS5
•Biotechnological ProductsS6
SAFETY

14. SAFETY
•Pharmacological StudiesS7A –S7B
•ImmunotoxicologicalStudiesS8
•Non-clinical evaluation for anti-cancer pharmaceuticalsS9
•PhotosafetyevaluationS10
•Non-clinical Pediatric safetyS11
•Non-clinical Biodistributionconsideration for Gene
Therapy ProductsS12

15. S1A-S1C
•S1A Need for carcinogenicity studies of
pharmaceutical products
•S1B (R1) EWG Testing for
carcinogenicity of pharmaceutical
products
•S1C (R2) Dose selection for
carcinogenicity studies for
pharmaceutical
S3A-S3B
•S3A Note for guidance on
toxicokinetics: The assessment of
systemic exposure in toxicity studies
•S3A Q&As Questions and answers -
Note for guidance on toxicokinetics:
The assessment of systemic exposure –
Focus on microsampling
•S3B Pharmacokinetics: Guidance for
repeated dose tissue distribution
studies
S7A –S7B
•S7A Safety pharmacological studies for
human pharmaceuticals
•S7B The non clinical evaluation of the
potential for delayed ventricular
repolarization (QT interval
prolongation) by human
pharmaceuticals
•E14/S7B EWG Questions and answers:
clinical and non clinical evaluation of
QT/QTcinterval prolongation and
proarrhythmicpotential
SAFETY GUIDELINES SUBPARTS

16. •Clinical Safety for Drugs used in long term treatment
E1
•Pharmacovigilance
E2A-E2F
•Clinical Study Reports
E3
•Dose Response Studies
E4
•Ethnic Factors
E5
•Good Clinical Practice
E6
•Clinical Trials in Geriatric Population
E7
EFFICACY

17. EFFICACY
•General Considerations for Clinical Trial
E8
•Statistical Principles for Clinical Trial
E9
•Choice of control group in Clinical Trial
E10
•Clinical Trials in Pediatric Population
E11 –E11A
•Clinical Evaluation by Therapeutic Category
E12
•Clinical Evaluation of QT
E14
•Definitions in Pharmacogenetics/Pharmacogenomics
E15

18. EFFICACY
•Qualification of Genomic Biomarkers
E16
•Multi-regional Clinical Trials
E17
•Genomic Sampling
E18
•Safety Data Collection
E19
•Adaptive Clinical Trials
E20
•Inculsionof pregnant and breastfeeding women in
clinical trials
E21

19. E2A –E2F
•E2A Clinical safety data management: definitions and
standards for reporting
•E2B (R2) Clinical safety data management: Data element
for transmission of Individual Case Safety Reports(ICSRs)
•E2B (R3) Q&As Clinical safety data management: Data
element for transmission of Individual Case Safety Reports
•E2B (R3) EWG/IWG Element for transmission of Individual
Case Safety Reports
•E2C (R2) Periodic benefit risk evaluation reports
•E2C (R2) Q&As Question and answers: Periodic benefit risk
evaluation reports
•E2D Post approval safety data management : Definitions
and standards for expediting reportings
•E2D (R1) EWG Post approval safety data management :
Definitions and standards for expediting reportings
•E2E Pharmacovigilanceplanning
•E2F Development safety update
E11-E11A
•E11 (R1) Addendum: Clinical invstigationof
medicinal products in the pediatric population
•E11A EWG Pediatric extrapolation
EFFICACY GUIDELINE SUBPARTS

20. M1
MedDRA
Terminology
M2
Electronic Standards
M3
Non-clinical Safety
guideline
M4
Common Technical
Document
M5
Data Element and
Standards for Drug
Dictionaries
M6
Gene Therapy
M7
Mutagenic
Impurities
M8
Electronic Common
Technical Document
MULTIDISCIPLINARY

21. MULTIDISCIPLINARY
M9
Biopharmaceutics
Classification System
based -Biowaivers
M10
BioanalyticalMethod
Validation and Study
Sample Analysis
M11
Clinical electronic
Structured Harmonised
Protocol (CeSHarP)
M12
Drug interaction studies
M13
Bioequivalence for
Immediate –Release solid
oral dosage forms
M14
Use of real world data for
Pharmacoepidemiological
studies
M15
General Principles for
Model –Informed Drug
Development

22. Website
ich.org

23. THANK YOU 