ICH Guidelines with special emphasis on ICH Q3 Guidelines; M. Pharmacy 1st Semester (Pharmaceutics)

1. GURU GOBIND SINGH COLLEGE OF PHARMACY
Presented To:
Dr. Anjali Sharma
Presented By:
Prabhjot Kaur (M-507)
ICH Guidelines

2. INTRODUCTION
1
2
3
4
CONTENTS
5
PURPOSE
ICH PARTIES
ICH ORGANISATION
BREIF OVWEVIEW OF QSEM
GUIDLINES

3. 1. INTRODUCTION
• Harmonisation : It is the act of making something consistent.
• The International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use is a joint initiative established in 1990
involving both regulatory agencies and research - based industry representatives of the
European Union, Japan, and the United States.
• ICH operates through the ICH Steering Committee with administrative support from
the ICH Secretariat and ICH Coordinators.
• The ICH Steering Committee meets at least twice a year. During these meetings, new
topics will be considered for adoption, reports are received on the progress of existing
topics, and maintenance and implementation of the guidelines are discussed. The topics
identified for harmonisation by the ICH Steering Committee are elected from Safety,
Quality, Efficacy, and Multidisciplinary matters of a pharmaceutical drug product

4. 2. PURPOSE
• Maintaining safeguards on quality, safety, efficacy, and regulatory obligations to
protect public health.
• More economical use of human, animal and material resources.
• Eliminate unnecessary delay in the global development and availability of new
medicines.
• Develop policy for the ICH Medical Dictionary for Regulatory Activities
Terminology (MedRA) which facilitates the sharing of regulatory information
internationally for medicinal products used by humans.
• To encourage implementation and integration of common standards through
communication of information and coordination of training on harmonised guidelines
and their use.
• To monitor and update technical requirements leading to a greater acceptance of
research and data

5. 3. ICH PARTIES
• The six parties to ICH represent the regulatory bodies and research based industry in
the three regions - Europe, Japan, and USA, where the vast majority of new medicines
are currently developed.
1. European Commission – European Union (EU)
2. European Federation of Pharmaceutical Industries and Associations (EFPIA)
3. Ministry of Health, Labour, and Welfare, Japan (MHLW)
4. Japan Pharmaceutical Manufacturers Association (JPMA)
5. US Food and Drug Administration (FDA)
6. Pharmaceutical Research and Manufacturers of America (PHRMA)

6. 4. ICH ORGANISATION
STEERING COMMITTEE
The body that governs the ICH, determines the policies and procedures for
ICH, selects topics for harmonisation and monitors the progress of
harmonisation initiatives. Each of the six parties has two seats on the ICH
steering committee
ICH Secretariat
- Primarily concerned with
preparations and documentation of
meetings of the Steering
Committee as well as coordination
of preparations for Working Groups
and discussion group meetings.
- Information on ICH Guidelines
and the ICH process can be
obtained from the ICH Secretariat.
ICH Coordinators
-These are fundamental
to the smooth running
of the ICH and are
nominated by each of
the six parties. An ICH
Coordinator acts as the
main contact point with
the ICH Secretariat.
ICH Working Group
Depending on the type of
harmonization activity needed,
the Steering Committee will
endorse the establishment of
one of 3 types of working group
- Expert working group (EWG)
- Implementation working
group (IWG)
- Informal working group
(InWG).

7. 5. BREIF OVWEVIEW OF QSEM GUIDLINES
Quality Guidelines
-Topics related to chemical and
pharmaceutical quality assurance.
-Includes Stability Testing, Photostability
Testing of New Drug Substances and
Products, Validation of Analytical
Procedures, Impurities in New Drug
Substances
Efficacy Guidelines
-Concerned with the design, conduct, safety
and reporting of clinical trials (dose response
studies, good clinical studies etc).
-Also covers novel types of medicines
derived from biotechnological processes and
the use of pharmacogenetics to produce
better targeted medicines.
Safety Guidelines
-To uncover the potential risks in the in
vitro and in vivo pre-clinical studies
including Carcinogenecity Studies,
Genotoxicity and Pharmacokinetic Studies
and Reproductive Toxicity Studies.
Multidisciplinary Guidelines
-Include, the ICH medical terminology,
common technical document and
development of electronic standards for the
transfer of regulatory information.

8. 5.1 QUALITY SERIES
 Q1A-Q1F: STABILITY
Q1A (Stability testing of new drug substance and products)
Q1B (Photo stability testing of new drug substance or product)
Q1C (Stability testing of new dosage forms)
Q1D (Bracketing and Matrixing designs for stability testing of new drug substances or
products)
Q1E (Evaluation of Stability Data)
Q1F (Stability data package for registration applications in climatic zones III and IV)
 Q2: ANALYTICAL VALIDATION
Q2(R1)- Validation of analytical procedures- Text and Methodology
Q2(R2)- Analytical Procedure Development and Revision of Q2(R1) Validation of
analytical procedures- Text and Methodology
 Q3A-Q3C: IMPURITIES
Q3A- Impurities in a New Drug Substances
Q3B- Impurities in a New Drug Products
Q3C- Impurities in Residual Solvents

9. Q4(A)-Q4(B): PHARMACOPOEIA
Q4(A) Pharmacopoeial Harmonisation
Q4(B) Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions.
 Q5(A)-Q5(E): QUALITY OF BIOTECHNOLOGICAL PRODUCTS
Q5(A)(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or
Animal Origin Q5A
Q5(B) Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein
Products
Q5(C) Stability Testing of Biotechnological/Biological Products
Q5(D) Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/
Biological Products
Q5(E) Comparability of Biotechnological/ Biological Products subject to Changes in their
Manufacturing Process

10.  Q6A-Q6B: SPECIFICATIONS
Q6(A) Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New
Drug Products: Chemical Substances
Q6(B) Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological
Products
 QQ(7): GOOD MANUFACTURING PRACTICES
 Q(8): PHARMACEUTICAL DEVELOPMENT
 Q(9): QUALITY RISK MANAGEMENT
 QQ(10): PHARMACEUTICAL QUALITY SYSTEM
 Q(11): DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES
 Q(12): LIFECYCLE MANAGEMENT
 Q(13): CONTINOUS MANUFACTURING OF DRUG SUBSTANCE AND DRUG
PRODUCTS
 Q(14): ANALYTICAL PROCEDURE DEVELOPMENT

11. First recommended for adoption on 30 March 1995, the Guideline was revised on 7 October 1999
and finalised on 7 February 2002 [Q3A(R1)]. It includes:
5.1.1 PREAMBLE : This document is intended to provide guidance for registration applications on
the content and qualification of impurities in new drug substances produced by chemical syntheses
and not previously registered in a region or member state.
The following types of drug substances are not covered in this guideline:
Biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation product
and semi-synthetic products derived from, herbal products, and crude products of animal or plant
origin.
ICH guidelines with regard to impurities in API (Q3A)

12. 5.1.2 CLASSIFICATION OF IMPURITIES :
Impurities can be classified into the following categories
Organic impurities (process- and
drug-related)
Inorganic impurities Residual solvents
- Can arise during the
manufacturing process and/or
storage of the new drug
substance.
-They can be identified or
unidentified, volatile or non-
volatile, and include:
• Starting materials
• By-products
• Intermediates
• Degradation products
• Reagents, ligands and
catalysts
- Can result from the
manufacturing process.
They are normally known and
identified and include:
• Reagents, ligands and
catalysts
• Heavy metals or other
residual metals
• Inorganic salts
• Other materials (e.g., filter
aids,
charcoal)
- Residual solvents in
pharmaceuticals are
defined here as organic
volatile chemicals that are
used or produced in the
manufacture of drug
substances or excipients,
or in the preparation of
drug products.
- The solvents are not
completely removed by
practical manufacturing
techniques.

13. 5.1.3 RATIONALE FOR THE REPORTING AND CONTROL OF IMPURITIES:
a) Organic Impurities: The applicant should summarise the actual and potential impurities
most likely to arise during the synthesis, purification, and storage of the new drug
substance. In addition, the applicant should summarise the laboratory studies conducted to
detect impurities in the new drug substance.
b) Inorganic Impurities: Inorganic impurities are normally detected and quantified using
pharmacopoeial or other appropriate procedures. Carry-over of catalysts to the new drug
substance should be evaluated during development.
c) Solvents: The control of residues of the solvents used in the manufacturing process for
the new drug substance should be discussed and presented according to the ICH Q3C
Guideline for Residual Solvents.
5.1.4 ANALYTICAL PROCEDURES : The registration application should include
documented evidence that the analytical procedures are validated and suitable for the
detection and quantification of impurities (ICH Q2A and Q2B Guidelines for Analytical
Validation).

14. 5.1.5 REPORTING IMPURITY CONTENT OF BATCHES
5.1.6 LISTING OF IMPURITIES IN SPECIFICATIONS
5.1.7 QUALIFICATION OF IMPURITIES: The applicant should provide a rationale for
establishing impurity acceptance criteria that includes safety considerations. The level of any
impurity present in a new drug substance that has been adequately tested in safety and/or
clinical studies would be considered qualified.
5.1.8 GLOSSARY
5.1.9 ATTACHMENTS 1 to 3

15. - This Guideline has been first revised and finalised in February 2003.
It complements the Guideline on impurities in new drug substances and provides advice in regard to
impurities in products containing new, chemically synthesized drug substances.
- The Guideline specifically deals with those impurities which might arise as degradation products of
the drug substance, or arising from interactions between drug substance and excipients or
components of primary packaging materials.
- The Guideline sets out a rationale for the reporting, identification and qualification of such
impurities based on a scientific appraisal of likely and actual impurities observed, and of the safety
implications, following the principles elaborated in the parent Guideline.
Threshold values for reporting and control of impurities are proposed, based on the maximum daily
dose of the drug substance administered in the product.
ICH guidelines with regard to impurities in New Drug Product (Q3B)

17. S1(A): Guideline on the need for carcinogenicity studies of pharmaceuticals
• S1(B): Testing for carcinogenicity of pharmaceuticals
• S1(C)(R2): Dose selection for carcinogenicity studies of pharmaceuticals
S2(R1):Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for
human use
S3(A): Note for guidance on toxicokinetics: the assessment of systemic exposure in toxicity studies
S3(B): Pharmacokinetics:guidance for repeated dose tissue distribution studies
S(4): Duration of chronic toxicity testing in animals (rodent and non rodent toxicity testing)
S5(R2): Detection of toxicity to reproduction for medicinal products & toxicity to male fertility
S6(R1): Addendum to ICH
S(6): preclinical safety evaluation of biotechnology-derived pharmaceuticals
S7(A): Safety pharmacology studies for human pharmaceuticals
• S7(B): The non-clinical evaluation of the potential for delayed ventricular repolarization (qt
interval prolongation) by human pharmaceuticals
S(8): Immunotoxicity studies for human pharmaceuticals
S(9): Nonclinical evaluation for anticancer pharmaceuticals
5.2 SAFETY SERIES

18. • E(1): The extent of population exposure to assess clinical safety
• E2(A): clinical safety data management
• E2(B)(R2): maintenance of the ICH guideline on clinical safety data management
• E2(B)(R3): revision of the ICH guideline on clinical safety data management ,Data
elements for transmission of individual case safety reports
• E2(C)(R1): clinical safety data management: periodic safety update reports for marketed
drugs
• E2(D): post-approval safety data management: definitions and standards for expedited
reporting
• E2(E): pharmacovigilance planning
• E2(F): development safety update report
• E(3): structure and content of clinical study reports
• E(4): dose-response information to support drug registration
• E(5)(R1): ethnic factors in the acceptability of foreign clinical data
• E(6)(R1): guideline for good clinical practice
5.3 EFFICACY SERIES

19. • E(7): studies in support of special populations: geriatrics
• E(8): general considerations for clinical trials
• E(9): statistical principles for clinical trials
• E(10): choice of control group and related issues in clinical trials
• E(11): clinical investigation of medicinal products in the pediatric population
• E(12): principles for clinical evaluation of new antihypertensive drugs
• E(14): the clinical evaluation of qt/qtc interval prolongation and proarrhythmic potential for non-
antiarrhythmic drugs
• E(15): definitions for genomic biomarkers, pharmacogenomics,
pharmacogenetics, genomic data and sample coding categories
• E(16): genomic biomarkers Related to drug response

20. • M(1) : Medical Terminology
• M(2): Electronic Standards for the Transfer of Regulatory Information
• M(3)- (R2): Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing
Authorization for Pharmaceuticals
• M(4): The Common Technical Document
• M(5): Data Elements and Standards for Drug Dictionaries
5.4 MULTIDISCIPLINARY SERIES

21. THANK YOU