1. Presented by :
MISS HARSHITA SINGHAI
m. Pharm sem. 2
Roll no. Y21254012
DEPARTMENT OF PHARMACEUTICAL SCIENCES
DR. HARISINGH GOUR VISHWAVIDYALAYA SAGAR (M.P.)
( A CENTRAL UNIVERSITY )
3. I N T R O D U C T I O N
In 1989, Europe, Japan, and the United States began creating
plans for harmonisation. The International Conference on
Harmonisation of Technical Requirements for Registration
of Pharmaceuticals for Human Use (ICH) was created in
ICH had the initial objective of coordinating the regulatory
activities of the European, Japanese and United States
regulatory bodies in consultation with the pharmaceutical trade
associations from these regions, to discuss and agree the
scientific aspects arising from product registration.
4. In 2015, ICH underwent several reforms and changed its name
to the International Council for Harmonisation of
Technical Requirements for Pharmaceuticals for Human
Use while becoming a legal entity in Switzerland as a non-
The aim of these reforms was to transform ICH into a truly
global initiative supported by a robust and transparent
5. • Harmonization of legislative and teachnical requirements.
• Mutual acceptance of data between Europe, Japan and US.
• To reduce cost of research work duplication.
• To reduce time frame for global marketing of newer drugs after
• To maintain and formulate guidelines on quality, safety and
efficacy based regulations for consumer and patient benefits.
6. S T R U C T U R E
International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use (ICH)
comprises the following bodies-
1. ICH Assembly
2. ICH Management Committee
3. MedDRA Management Committee
4. ICH Secretariat
7. I C H G U I D E L I N E S
ICH has developed over 45 harmonized guidelines .
The ICH Topics are divided into four major categories:
1. Quality (Q): Related to chemical and pharmaceutical Quality
2. Safety (S): Related to in vitro and in vivo preclinical studies .
3. Efficacy (E): Related to clinical studies in human subject.
4. Multidisciplinary topics (M): Related to cross-cutting topics
which do not fit uniquely into one of the above categories.
8. Q U A L I T Y G U I D E L I N E S
Harmonisation achievements in the Quality area include pivotal
milestones such as the 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.
9. ICH has produced a comprehensive set of safety Guidelines 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
S A F E T Y G U I D E L I N E S
10. E F F I C A C Y G U I D E L I N E S
The work carried out by ICH under the Efficacy heading is 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.
Those are the 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).
11. T H E Q FA M I LY
• Q 1 – Stability Testing
• Q 2 – Analytical Validation
• Q 3 – Impurities
• Q 4 – Pharmacopoeias
• Q 5 – Biotechnological Products
• Q 6 – Specifications
• Q 7 – Good Manufacturing Practices
• Q 8 – Pharmaceutical Development
• Q 9 – Quality Risk Management
• Q 10 – Pharmaceutical Quality System
12. ICH GUIDELINES FOR STABILITY STUDIES
• Q1A(R2)- Stability Testing of New Drug Substances and Products
• 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 & IV
13. PRINCIPLES OF THE GUIDELINE
1. Purpose of stability testing is to provide evidence how quality varies
with time under influence of temperature, humidity and light.
2. Establish re-test period for drug substances
RETEST PERIOD: The period after which samples of the drug
substance should be examined to ensure that the material is still in
compliance with the specification, and thus suitable for use in
manufacturing. A retest period should be proposed on the basis of
stability results and may be extended to five years (e.g., Ethambutol
2HCl, or Isoniazid) .
SHELF LIFE (EXPIRY DATE/EXPIRATION DATING PERIOD): The period
of time during which a pharmaceutical product, if stored correctly, is
expected to comply with the specification as determined by stability
studies on a number of batches of the product.
The shelf-life is used to establish the expiry date of each .
Stability of pharmaceutical product may be defined as the capability of
a particular formulation in a specific container/closure system to
remain within its physical, chemical, microbiological, therapeutic and
toxicological specification. Types stability studies:
1) Long term stability study
2) Intermediate stability study
3) Accelerated stability study
• Assurance to the patient • Economic considerations
• Legal requirement
Information on the stability of the drug substance is an integral part of
the systematic approach to stability evaluation.
Carried out on a single batch and it include the effect of temperature,
humidity where appropriate, oxidation and photolysis on DS.
Scope: These guidelines help to identify the likely degradation
products, to establish the degradation pathway and intrinsic stability
of the molecule.
SELECTION OF BATCHES- At least 3 primary batches of the drug
substance should be selected. The quality should be representative to
quality of material used for production scale.
CONTAINER CLOSURE SYSTEM- Stability study conducted on
the drug substance packed in a container closure system that is same
or simulate packaging proposed for storage and distribution.
SPECIFICATION- These guidelines states the list of test, references
to analytical procedure and proposed acceptance criteria.
STATEMENT AND LABELLING- A storage statement established
for labelling in relevant national/regional requirements based on the
stability evaluation of the drug substance.
Terms such as “ambient conditions” or “room temperature” should be
Retest date for DS and Expiry date for DP should be displayed on the
container label if appropriate.
21. ICH GUIDELINES Q1B
• To demonstrate that light exposure does not result in unacceptable
• Testing is carried out on a single batch
• Testing carried out on:
Exposed drug product outside of the immediate pack
Drug product in the immediate pack
Drug product in the marketing pack
Artificial daylight fluorescent lamp combining visible and
ultraviolet (UV) outputs, xenon or metal halide lamp.
22. ICH GUIDELINES Q1C
• New dosage forms
• Same active substance
• Different administration route
• New specific functionality/delivery systems
• Reduced stability database
• Different dosage forms of same administration route.
Stability Testing for New Dosage Forms
23. ICH GUIDELINES Q1C
Only samples on the extremes of certain design factors are tested at
all time points as in a full design. Design Factors : >Strength >
Container Closure Sizes and/or Fills .
• Matrixing is t he statistical design of a stability schedule.
• Each storage condition should be treated separately under its own
• At a given time point (other than the initial or final ones) not every
batch on stability needs to be tested.
• Full testing must be performed at the maximum storage period at
the time of submission
25. ICH GUIDELINES Q1E
Objectives of the Guideline : It describes:
How to propose a retest period for drug substances and a shelf life for
drug products in the registration application .
When and how a extrapolation beyond available data can be
Stability Data Package for Registration Applications in Climatic
Zones III and IV
Objectives of the Guideline
Application of ICH Q1A(R) in countries of Climatic zones III and IV
ICH GUIDELINES Q1F
26. THE S FAMILY
S1A=Need for Carcinogenicity Studies of Pharmaceuticals
S1B=Testing for Carcinogenicity of Pharmaceuticals
S1C (R2)=Dose Selection for Carcinogenicity Studies of
S2 (R1)=Guidance on Genotoxicity Testing and Data
Interpretation for Pharmaceuticals intended for Human Use
S3A=Note for Guidance on Toxicokinetics: The Assessment of
Systemic Exposure in Toxicity Studie
S4=Duration of Chronic Toxicity Testing in Animals ( Rodent
and Non-Rodent Toxicity Testing) S5 (R2)
S5A, S5B (M)=Detection of Toxicity to Reproduction for
Medicinal Products & Toxicity to Male Fertility
27. S6 (R1)=Preclinical Safety Evaluation of Biotechnology-
S7A=Safety Pharmacology Studies for Human
S7B=The Non-Clinical Evaluation of the Potential for
Delayed Ventricular Repolarization (QT Interval
Prolongation) by Human Pharmaceuticals
S8=Immunotoxicity Studies for Human Pharmaceuticals
S9=NonClinical Evaluation for Anticancer Pharmaceuticals
S10=Photosafety Evaluation of Pharmaceuticals
S11=Nonclinical Safety Testing in Support of Development
of Paediatric Medicines
THE S FAMILY
The work carried out by ICH under the Efficacy
heading is 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/ pharmacogenomics techniques
to produce better targeted medicines.
29. THE FAMILY OF EFFICACY
E1 - E2F Clinical Safety
E3 Clinical Study Reports
E4 Dose-Response Studies
E5 Ethnic Factors
E6 Good Clinical Practice
E7 - E11 Clinical Trials
E12 Clinical Evaluation by Therapeutic Category
E14 Clinical Evaluation
E15 - E16 Pharmacogenomics
30. Those are the 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
ICH Multidisciplinary Guidelines from M1 to M13
31. ICH 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 Mutagenic Impurities
• M8 Electronic Common Technical Document (eCTD)
• M9 Biopharmaceutics Classification System-based Biowaivers
• M10 Bioanalytical Method Validation
• M11 Clinical electronic Structured Harmonised Protocol (CeSHarP)
• M12 Drug Interaction Studies
• M13 Bioequivalence for Immediate-Release Solid Oral Dosage Forms