Ich guidelines syllabus accor. to PCI

1. As Per PCI Regulations /B. Parm. VI
Sem./Pharmaceutical Quality
Assurance
UNIT-1
ICH Guideline
Presented By: VIVEK JAIN
M.Pharm. (Pharmaceutical Analysis)
Associate Professor
ADINA Institute Of Pharmaceutical
Sciences, Sagar (M.P.)
EMAIL:pharmamakers2010@gmail.com

3. ICH (April 1990)
• International Conference on Harmonisation (ICH) was created in
april 1990
• The European Medicines Agency publishes scientific guidelines
that are harmonised between Europe, Japan and the United
States of America
• ICH guidelines are provided for: Quality. Safety and Efficacy of
medicines.

4. MISSION
Harmonisation for Better Health
To make recommendations towards achieving
greater harmonisation in the interpretation and
application of technical guidelines and requirements
for pharmaceutical product registration and the
maintenance of such registrations

5. PURPOSE
 To Harmonize of technical requirements for registration or
marketing approval
 To Ensure quality, safety, efficacy of medicines
 To prevent unnecessary duplication of clinical trials on
humans
 To Minimize the use of animal testing without compromising
safety and effectiveness
 To promote public health

6. history
Need to harmonize, Because of the following reasons:
1. Industry becoming global
2. Duplicate test procedures
 time consuming
 expensive
3. Increase R &D costs
4. Meeting public demand
• Initiation of ICH
• 1980s Formulate European community
• 1989s WHO conference on DRA, Paris
• 1990s birth of ICH (created by all three Japan, USA & Europe)
• Topic of harmonization divided into : safety, quality and
efficacy

7. ICH structure
region Regulatory body
Japan MHLW ( ministry of health, labour and
welfare)
Europe EU (European unions)
US FDA

8. ICH members

10. Process of Harmonisation
ICH harmonisation activities fall into 4 categories;
1.Formal ICH Procedure
2.Q&A Procedure
3.Revision Procedure
4,.Maintenance Procedure

12. BRIEF OVERVIEW OF QSEM WITH SPECIAL EMPHASIS ON Q-
SERIES GUIDELINES
The ICH topics are divided into four categories
•Q – QUALITY GUIDELINES
•S – SAFETY GUIDELINES
•E - EFFICACY GUIDELINES
•M - MULTIDISCIPLINARY GUIDELINES
•Carcinogenicity (carcinogen any
substance that produce cancer)
•Genotoxicity (genetic toxicity)
•Reprotoxicity toxicity related to
reproduction
•ICH medical terminology (MedDRA)
•Common Technical Document (CTD)
•The development of Electronic
Standards for the Transfer of Regulatory
Information (ESTRI).

13. Q – QUALITY GUIDELINES
Q 1 S Stability
Q 2 A Analytical validation
Q 3 I Impurities
Q 4 P Pharmacopoeias
Q 5 B Quality of Biotechnology Products
Q 6 S Specifications
Q 7 API Good Manufacturing Guide for Active Pharmaceutical Ingredients
Q 8 PD Pharmaceutical Development
Q 9 QRM Quality Risk Management
Q 10 PQS Pharmaceutical Quality System
Q 11 DMDS Development and Manufacture of Drug Substances (Chemical
Entities Biotechnological/Biological Entities)
Q 12 LCM Life Cycle Management

14. Q – QUALITY GUIDELINES
Q 1 A – Q 1 F Stability
• Q1A – Stability Testing of New Drug Substances and
Products
• Q1 B – Stability Testing : Photo Stability 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 Application in
Climatic Zones III and IV
Q2 (R1) – Validation of Analytical Procedures: Text and
Methodology

15. Q3A- Q3D Impurities
• Q3A - Impurities in New Drug Substances
• Q3B – Impurities in New Drug Products
• Q3C– Impurities : Guideline for Residual Solvents
• Q3D – Impurities : Guideline for Elemental Impurities
• Q4 – Pharmacopoeias
• Q4A – Pharmacopoeial Harmonisation
• Q4B – Evaluation and Recommendation of Pharmacopoeial Text for
use in the ICH Regions
•
• Q4B Annex 2(R1) – Test for Extractable Volume of Parenteral
Preparation General Chapter
• Q4B – Annex 3(R1) – Test for Particulate Contamination : Sub-
Visibal Particales General Chapter

16. • Q4B – Annex 4A(R1) – Microbiological Examination of Non-
Sterile Products : Microbial Enumeration Tests General
Chapter
• Q4B – Annex 4B(R1) – Microbiological Examination of Non-
Sterile Products : Test for Specified Micro-Organism 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

17. • Q4B Annex 6 (R1) – Uniformity of Dosage Units General
Chapter
• Q4B Annex 7(R2) – Dissolution Test General Chapter
• Q4B Annex 8(R1) – Stability 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 Endotoxin Test General Chapter

18. Q5A-Q5E Quality of Biotechnology Products
• Q5A (R1) – Viral Safety Evaluation of Biotechnology Products
Derived from Cell Lines of Human or Animal Origin
• Q5B – Quality of Biotechnology Products :
• Q5C – Quality of Biotechnology Products :Quality of
Biotechnological
• Q5D – Derivation and Characterisation of Cell Substrates
used for Production of Biotechnological/Biological Products
• Q5E – Comparability of Biotechnological/Biological Products
Subject to Changes in their Manufacturing Process

19. • Q6A-Q6B Specifications
• Q6A – Specifications : Test Procedure and Acceptance
Criteria for New Drug Substances and New Drug Products:
Chemical Substances
• Q6B – Specifications : Test Procedure and Acceptance
Criteria for Biotechnological/Biological
• Q7 – Good Manufacturing Guide for Active
Pharmaceutical Ingredients
• Q8(R2) – Pharmaceutical Development
• Q9 – Quality Risk Management
• Q10 – Pharmaceutical Quality System
• Q11 – Development and Manufacture of Drug Substances
(Chemical Entities Biotechnological/Biological Entities)
• Q12 – Life Cycle Management

20. S – 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 Photo safety evaluation
• S11 Nonclinical paediatric safety

21. E - EFFICACY GUIDELINES
• E1 Clinical Safety For Drugs Used In Long-Term Treatment.
• E2A - E2F Pharmacovigilance.
• E3 Clinical Study Reports.
• E4 Dose-Response Studies.
• E5 Ethnic Factors. Code.
• E6 Good Clinical Practice.
• E7 Clinical Trials In Geriatric Population.
• E8 General Considerations For Clinical Trials
• E9 Statistical Principles For Clinical Trials
• E10 Choice Of Control Group In Clinical Trials
• E11 Clinical Trials In Paediatric Population
• E12 Clinical Evaluation By Therapeutic Category
• E14 Clinical Evaluation Of QT
• E15 Definitions Of Pharmacogenetics
• E16 Qualification Of Genomic Biomarkers
• E17 Multiregional Clinical Trials
• E18 Genomic Sampling
• E19 Safety Data Collection

22. M - MULTIDISCIPLINARY GUIDELINES
• M1 MedDRA Terminology
• M2 Electronic Standards
• M3 Nonclinical Safety Studies
• M4 Common Technical Document
• M5 Data Elements and Standards for
Drug Dictionaries
• M6 Gene Therapy
• M7 Genotoxic Impurities
• M8 Electronic Common Technical
Document (eCTD)
• M9 Biopharmaceutics Classification
System-based Biowaivers
• M10 Bioanalytical Method Validation

23. Stability guideline
• General:
• Definition: Stability of pharmaceutical product may be
defined as the ability of pharmaceutical dosage form to
maintain the physical, chemical, microbiological and
therapeutics properties during the time of storage and
usage by the patient
• 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 re-test period for the drug
substance or a shelf life for the drug product and
recommended storage conditions.

24. Stability protocol For Drug Substance
• General
• Stress testing
• Selection of batches
• Container and closure system
• Specifications
• Testing frequency
• Storage conditions
• Stability Commitment
• Evaluation
• Statements/Labeling

25. Stress Testing
• It is also known as force degradation study
• Stress testing of the drug substance can help identify
the likely degradation products, which can in turn
help establish the degradation pathways and the
intrinsic/natural 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 (e.g., 75% RH or greater) where appropriate
oxidation, and photolysis on the drug substance.

26. Selection of Batches
• At least three primary batches of the drug substance
should be representative to quality of the material
used for production scale.
• Container Closure System
• The stability studies should be conducted on the drug
substance packaged in a container closure system that
is the same as the packaging proposed for storage and
distribution.
• Specification
• Specification, which is a list of tests, reference to
analytical procedures, and proposed acceptance
criteria, is addressed in ICH Q6A and Q6B.

27. Testing Frequency
frequency of testing should be sufficient to establish the
stability profile of the drug substance.
• For long-term studies, (For drug substances with a
proposed re-test period) 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.
• At the accelerated storage condition, a minimum of
three time points, including the initial and final time
points (e.g., 0, 3, and 6 months), from a 6-month study is
recommended.
• For intermediate studies: Min. 4 time points (0, 6, 9, 12
months) for a 12 months study

28. Storage Conditions General case
• .
•
Study
Long term*
Storage conditions
25°C ± 2°C
60% RH ± 5% RH
Minimum
time period
12
months
Intermediate
**
30°C ± 2°C/65% RH ± 5% RH 6 months
Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months

29. . Drug substances intended for storage in a
refrigerator
Long term 5°C ± 3°C 12 months
Accelerated 25°C±2°C 6 months

30. Drug substances intended for storage in a
freezer
Long term - 20°C ± 5°C 12 months

31. Stability Commitment
• In case where data submitted for registration do not cover
the proposed shelf life it is necessary to give commitment
to continue the stability studies post approval in order to
firmly establish the shelf life.
• Where the submission includes long term stability data
from three production batches covering the proposed shelf
life, a post approval commitment is considered
unnecessary.

32. Evaluation
• The purpose of the stability study is to establish re-test
period for DS and shelf life for drug product for future
batched based on evaluation of results obtained from
chemical, physical, biological, microbiological tests
• A systematic approach should be adopted in the
presentation and evaluation of the stability information,
which should include, as appropriate, results from the
physical, chemical, biological, and microbiological tests,
including particular attributes of the dosage form (for
example, dissolution rate for solid oral dosage forms).

33. Statements/Labeling
• A storage statement should be established for the labeling
in accordance with relevant national/regional
requirements.
• The statement should be based on the stability evaluation
of the drug product.
• There should be a direct link between the label storage
statement and the demonstrated stability of the drug
product.
• An expiration date should be displayed on the container
label.