1. INTERNATIONAL CONFERENCE FOR HORMONIZATION
INTEGRAL UNIVERSITY, LUCKNOW
INTERNATIONAL CONFERENCE FOR HORMONIZATION
(ICH) GUIDELINES & QSEM
PRESENTED BY
Mr. ABDURRAHMAN

2. PURPOSE/INTENT
 To harmonize i.e. to equalize the technical requirements for pharmaceuticals
for human use.
 The allopathic doctor there is engaged in the development of drugs. Drugs at
the market developed and in the meantime such an incident has happened
that shock the whole of West Germany, Europe. It was Thalidomide, a
anticancerous drug . That accident popularly called Thalidomide tragedy.
 Shortly after the drug was sold in Germany, between 5000 and
 Shortly after the drug was sold in Germany, between 5000 and
7000 infants were born with Phocomelia (malformation of the limbs).
 So they decide to make a guideline that all the companies will have bring it
under the ambit of a guideline that all the manufacturing companies should
follow this guideline and according to the same guideline make the product
basically this guideline.
- Safety
- Efficacy
- Quality

3. OBJECTIVES
 Harmonization of legislative & technical requirements
 Mutual acceptance of data between Europe, Japan & US
 To reduce cost of research work duplications
 To reduce time-frame for global marketing of newer drugs after approval
 To maintain & formulate guidelines on quality, safety & efficacy-based
regulations, for consumer & patient benefits

4. LOCATION
 The ICH Secretariat is based in Geneva Switzerland.
 Biennial meetings & conferences of ICH Steering Committee
shuffle between the European Union, Japan & the US.

5. ICH MEMBERS
These six committee members are core members
Japan
1. Ministry of Health, Labour & Welfare (MHLW)
2. Japan pharmaceutical manufacture association (JPMA)
Europe
1. Europian Union
2. Europian Federation of association (EFPIA)
USA
USA
1. Food and Drug Administration (FDA)
2. Pharmaceutical Research and Manufacturers of America (PhRMA)
Additional
1. Observers from the WHO (represent non-ICH countries & regions)
2. European Free Trade Association (EFTA)
3. Canada

6. STEPS IN THE ICH PROCESS
 ICH operates through the Steering Committee, with administrative support
from Secretariat & Coordinators .
 Steering committee meets at least twice a year.
 Topics identified for harmonization by Steering Committee selected
from Safety, Efficacy, Quality & Multidisciplinary matters.
 There are 5 steps involved
STEP 1: Drafts are prepared and circulated through many revisions until a "final
harmonized draft" is completed.
STEP 2: This draft is signed by the EWG as the agreed-upon draft and forwarded to
the Steering Committee for signing which signifies acceptance for consultation
by each of the six co-sponsors.
STEP 3: The three regulatory sponsors initiate their normal consultation process to
receive comments.

7. STEPS IN THE ICH PROCESS
STEP 4: This step reached when the Steering Committee agrees that there
is sufficient scientific consensus on the technical issues. This
endorsement is based on the signatures from the three regulatory
parties to ICH affirming that the guideline is recommended for adoption
by the regulatory bodies of the three regions.
STEP 5: The process is complete when the guidelines are incorporated into
STEP 5: The process is complete when the guidelines are incorporated into
national or regional internal procedures (implementation in the 3 ICH
regions.)

8. QSEM
The ICHtopics are dividedinto the four categories belowand ICHtopiccodes are
assignedaccordingto these categories.
“Quality” i.e., those relating to chemical and pharmaceutical Quality Assurance
(it will talk about Stability Testing, Impurity Testing, GMP etc.)
 Total 14 guidelines – Q1 to Q14
“Safety” i.e., those relating to in vitro and in vivo pre-clinical studies (it will talk
about Carcinogenicity Testing, Genotoxicity Testing, Reprotoxicity etc.)
 Total 11 guidelines – S1 to S11
 Total 11 guidelines – S1 to S11
“Efficacy” i.e., those relating to clinical studies in human subject (Dose
Response Studies, Good Clinical Practices, etc.)
 Total 18 guidelines – E1 to E18
“Multidisciplinary” i.e., cross-cutting Topics which do not fit uniquely into
one of the above categories. (it will talk about Med DRA Terminology, Gene
therapy, Mutagenic impurities, Bioanalytical Method Validation etc.)
 Total 10 guidelines – M1 to M10

10. QUALITY GUIDELINES
This guideline covers those relating to chemical and pharmaceutical quality
Assurance, stability studies, impurities testing etc.
Q1A – Q1F: Stability
Q2: Analytical Validation
Q3A – Q3E: Impurities
Q4A – Q4B: Pharmacopoeias
Q5A – Q5E: Quality of Biotechnological Products
Q6A – Q6B: Specifications
Q6A – Q6B: Specifications
Q7: Good Manufacturing Practice
Q8: Pharmaceutical Development
Q9: Quality Risk Management
Q10: Pharmaceutical Quality System
Q11: Development and Manufacturing of Drug Substances
Q12: Lifecycle Management
Q13: Continuous Manufacturing of Drug Substances and Drug Products
Q14: Analytical Procedure Development

11. Q1A - Q1F STABILITY
Q1A(R2) - Stability Testing Of New Drug Substances And Products
 This Guideline provides recommendations on stability testing protocols including
temperature, humidity and trial duration for Climatic Zone I and II. Furthermore, the revised
document takes into account the requirements for stability testing in Climatic Zones III and IV
in order to minimise the different storage conditions for submission of a global dossier.
Q1B - Photostability Testing of New Drug Substances and Products
 This guidelines gives guidance on the basic testing protocol required to evaluate the light
sensitivity and stability of new drugs and products.
Q1C - Stability Testing for New Dosage Forms
 Gives guideline for new formulations of already approved medicines, and defines the
circumstances under which reduced stability data can be accepted.
Q1D - Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and
Products

12. Q1E - Evaluation of Stability Data
 This guideline addresses the evaluation of stability data that should be submitted in
registration applications for new molecular entities and associated drug products. The
guideline provides recommendations on establishing shelf lives for drug substances and drug
products intended for storage at or below “room temperature”.
Q1F - Stability Data Package for Registration Applications in Climatic Zones III and IV
 Describes harmonized global stability testing requirements in order to facilitate access to
medicines by reducing the number of different storage conditions. WHO conducted a survey
amongst their member states to find consensus on 30°C/65% RH as the long term storage
conditions for hot-dry and hot-humid regions.
Q2 ANALYTICAL VALIDATION
Q2(R1) - Validation of Analytical Procedures: Text and Methodology
 The objective of validation of an analytical procedure is to demonstrate that it is suitable
for its intended purpose.
 Gives validation parameters needed for a variety of analytical methods.
 Its purpose is to provide some guidance and recommendations on how to consider the
various validation characteristics for each analytical procedure.

13. Q3A – Q3E IMPURITIES
Q3A(R2) - Impurities in new drug substances
Q3B(R2) - Impurities in new drug products
Q3C(R8) - Guideline for Residual Solvents
Q3C(R9) - Maintenance of the guideline for Residual Solvents
Q3D(R2) - Guideline for Elemental Impurities
Q3D(R3) - Maintenance of the Guideline for Elemental Impurities
Q3E EWG - Impurity: Assessment and Control of Extractables and Leachables for
Pharmaceuticals and Biologics
Q4A – Q4B PHARMACOPOEIAS
Q4A – Q4B PHARMACOPOEIAS
 This document describes a process for the evaluation and recommendation given by the
Q4B Expert Working Group (EWG) for selecting pharmacopoeial texts to facilitate their
recognition by regulatory authorities for use, interchangeable in the ICH regions.
Q4A – Pharmacopoeial Harmonisation
Q4B – Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions
Q4B Annex 1(R1) – Residue on Ignition/Sulphated Ash General Chapter
Q4B Annex 2(R1) – Test for Extractable Volume of Parenteral Preparations General Chapter
Q4B Annex 3(R1) – Test for Particulate Contamination: Sub-Visible Particles General Chapter

14. Q4A – Pharmacopoeial Harmonisation
Q4B – Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions
Q4B Annex 1(R1) – Residue on Ignition/Sulphated Ash General Chapter
Q4B Annex 2(R1) – Test for Extractable Volume of Parenteral Preparations General Chapter
Q4B Annex 3(R1) – Test for Particulate Contamination: Sub-Visible Particles General Chapter
Q4B Annex 4A(R1) – Microbiological Examination of non-sterile Products: Microbial
Enumeration Tests General Chapter
Q4B Annex 4C(R1) - Microbiological Examination of non-sterile Products: Acceptance Criteria
for Pharmaceutical Preparations and Substances for Pharmaceutical use
General Chapter
Q4B Annex 5(R1) – Disintegration test General Chapter
Q4B Annex 6 - Uniformity of Dosage Units 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 Density and Tapped Density of Powders General Chapter
Q4B Annex 14 – Bacterial Endotoxins Test General Chapter

15. Q1A(R2) Stability Testing Of New Drug Substances And Products
 The purpose of stability testing is to provide evidence on how the quality of a
drug substance or drug product varies with time under the influence of a variety
of environmental factors such as temperature, humidity, and light, and to
establish a retest period for the drug substance or a shelf life for the drug product
and recommended storage conditions.
Stress Testing
• Stress testing of the drug substance can help identify the likely degradation
products, which can in turn help establish the degradation pathways and the
products, which can in turn help establish the degradation pathways and the
intrinsic stability of the molecule.
• Stress testing is likely to be carried out on a single batch of the drug substance. It
should include the effect of temperatures, humidity, oxidation, and photolysis on
the drug substance.
• The testing should also evaluate the susceptibility of the drug substance to
hydrolysis across a wide range of pH values when in solution or suspension.
Selection of Batches
• Data from formal stability studies should be provided on at least three primary
batches of the drug substance.

16. Q1A(R2) Stability Testing Of New Drug Substances And Products
• and using a method of manufacture and procedure that simulates the final
process to be used for, production batches.
Container Closure System
• The stability studies should be conducted on the drug substance packaged in a
container closure system that is the same as or simulates the packaging proposed
for storage and distribution.
Specification
• Specification, which is a list of tests, reference to analytical procedures, and
proposed acceptance criteria.
proposed acceptance criteria.
• Stability studies should include testing of those attributes of the drug substance
that are susceptible to change during storage and are likely to influence quality,
safety, and/or efficacy.
Testing Frequency
• For long term studies, frequency of testing should be sufficient to establish the
stability profile of the drug substance.
• For drug substances with a proposed re-test period of at least 12 months, the
frequency of testing at the long term storage condition should normally be every
3 months over the first year, every 6 months over the second year, and annually
thereafter through the proposed re-test period.

17. Q1A(R2) Stability Testing Of New Drug Substances And Products
Storage Conditions
• In general, a drug substance should be evaluated under storage conditions (with
appropriate tolerances).
• The storage conditions and the lengths of studies chosen should be sufficient to
cover storage, shipment, and subsequent use.
• Long term, accelerated, intermediate storage conditions for drug substances are
detailed in the sections below.

18. Thank You
Thank You