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![History–
The International Council for Harmonization (ICH), formerly the International
Conference on Harmonization (ICH) held the inaugural Assembly meetings on 23 October 2015
establishing ICH as an international association, a legal entity under Swiss law. This step built
upon a 25-year track record of successful delivery of harmonized guidelines for global
pharmaceutical development as well as their regulation, and a longer standing recognition of the
need to harmonies. Since ICH's inception in 1990, the ICH process has gradually evolved. ICH's
first decade saw significant progress in the development of ICH Guidelines on Safety, Quality
and Efficacy topics. Work was also undertaken on a number of important multidisciplinary
topics, which included Medora (Medical Dictionary for Regulatory Activities) and the CTD
(Common Technical Document). As ICH started into a new millennium, the need to expand
communication and dissemination of information on ICH Guidelines with non-ICH regions
became a key focus. Attention was also directed throughout the second decade towards
facilitating the implementation of ICH Guidelines in ICH's own regions and maintaining already
existing ICH Guidelines as science and technology continued to evolve. Soon afterwards, the
authorities approached International Federation of Pharmaceutical Manufacturers and
Associations (IFPMA) to discuss a joint regulatory-industry initiative on international
harmonization, and ICH was conceived. The birth of ICH took place at a meeting in April 1990,
hosted by EFPIA in Brussels. Soon afterwards, the authorities approached International
Federation of Pharmaceutical Manufacturers and Associations (IFPMA) to discuss a joint
regulatory-industry initiative on international harmonization, and ICH was conceived. The birth
of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels.
ICH
-ICH is a joint initiative involving both regulators and research-based industry
representatives of the EU, Japan and the US in scientific and technical discussions of
the testing procedures required to assess and ensure the safety, quality and efficacy of
medicines.
Objective-
1] More economical, use of humans, animal and for material resources.
2] Elimination of unnecessary delay in the global development and availability of -new
medicines.](https://image.slidesharecdn.com/ich2-180131092702/85/Ich-2-2-320.jpg)
![3] Maintaining safeguards on quality safety efficacy and regulatory obligation to protect public
health.
Members of ich guidelines -
MEMBERS OBSERVERS
t
Founding Regulatory Members Standing Observers
EC, Europe IFPMA
FDA, US WHO
MHLW/PMDA, Japan Legislative or Administrative Authorities
Founding Industry Members CDSCO, India
Founding Regulatory Members Standing Observers
EC, Europe IFPMA
FDA, US WHO
MHLW/PMDA, Japan Legislative or Administrative Authorities
Founding Industry Members CDSCO, India
EFPIA CECMED, Cuba
JPMA COFEPRIS, Mexico
Parma HSA, Singapore
Standing Regulatory Members MCC, South Africa
Health Canada, Canada National Center, Kazakhstan
Swiss medic, Switzerland Roszdravnadzor, Russia
Regulatory Members TFDA, Chinese Taipei](https://image.slidesharecdn.com/ich2-180131092702/85/Ich-2-3-320.jpg)
![Regions of the EC, Japan and the United States would be mutually acceptable to the other two
Regions, provided the information is consistent with this guideline and the labeling is in
Accord with national/regional requirements.
General
Information on the stability of the drug substance is an integral part of the systematic
Approach to stability evalution.
1] 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 intrinsic stability of the molecule
And validate the stability indicating power of the analytical procedures used. The nature of the
Stress testing will depend on the individual drug substance and the type of drug product
Involved.
Stress testing is likely to be carried out on a single batch of the drug substance.
2] 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.
3] Selection of Batches
Data from formal stability studies should be provided on at least three primary batches of the
Drug substance. The batches should be manufactured to a minimum of pilot scale by the same
Synthetic route as, and using a method of manufacture and procedure that simulates the final
Process to be used for, production batches. The overall quality of the batches of drug
Substance placed on formal stability studies should be representative of the quality of the
Material to be made on a production scale.
Other supporting data can be provided.
4] Specification
Specification, which is a list of tests, reference to analytical procedures, and proposed
Acceptance criteria, is addressed in ICH Q6A and Q6B. In addition, specification for
A degradation product in a drug substance is discussed in Q3A.
5] Evaluation
The purpose of the stability study is to establish, based on testing a minimum of three batches
Of the drug substance and evaluating the stability information (including, as appropriate,
Results of the physical, chemical, biological, and microbiological tests), a re-test period
Applicable to all future batches of the drug substance manufactured under similar
Circumstances. The degree of variability of individual batches affects the confidence that a
Future production batch will remain within specification throughout the assigned re-test](https://image.slidesharecdn.com/ich2-180131092702/85/Ich-2-9-320.jpg)
![Period.
The data may show so little degradation and so little variability that it is apparent from
Looking at the data that the requested re-test period will be granted.
Drug Product-
1] General
The design of the formal stability studies for the drug product should be based on knowledge
Of the behavior and properties of the drug substance and from stability studies on the drug
Substance and on experience gained from clinical formulation studies. The likely changes on
Storage and the rationale for the selection of attributes to be tested in the formal stability
Studies should be stated.
2]. Photo stability Testing
Photo stability testing should be conducted on at least one primary batch of the drug product if
Appropriate. The standard conditions for photo stability testing are described in ICH Q1B.
3] Container Closure System
Stability testing should be conducted on the dosage form packaged in the container closure
System proposed for marketing (including, as appropriate, any secondary packaging and
Container label). Any available studies carried out on the drug product outside its immediate
Container or in other packaging materials can form a useful part of the stress testing of dosage.
4] Drug products packaged in semi-permeable containers
Aqueous-based products packaged in semi-permeable containers should be evaluated for
Potential water loss in addition to physical, chemical, biological, and microbiological
Stability. This evaluation can be carried out under conditions of low relative humidity, as
Discussed below
Study Storage condition Minimum time period
Covered by data at submission
Long term* 25°C ± 2°C/40% RH ± 5% RH
Or
30°C ± 2°C/35% RH ± 5% RH
12 months
Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months
Accelerated 40°C ± 2°C/not more than (NMT)
25% RH
6 months
Specification-
Specification is a list of
• Tests, test attributes
• Reference to analytical procedures
• Proposed acceptance criteria release and shelf life
Test attributes](https://image.slidesharecdn.com/ich2-180131092702/85/Ich-2-10-320.jpg)
![• Attributes susceptible to change during storage
• may influence quality, safety and/or efficacy
• should cover physical, chemical, biological, microbiological Attributes
Evaluation -
Stability information
• Systematic approach in presentation and evaluation of
Stability information.
• Should include results from physical, chemical,
Biological and microbiological tests.
Overview-
Section of stress testing of active substance from glossary to the main text
� Text on test procedures brought in line with Q6A
� Text on testing frequency amended for accelerated conditions
� Storage conditions described in more detail. Testing on low temperatures and
aqueous
Liquid in semi-permeable containers
� Post -approval commitment described unambiguously
� Change 30°C ± 2°C/60% ± 5% to 30°C ± 2°C/65% ± 5%
Reference-
1- Mario ChenFamily Health International Biostatistics Workshop New
Delhi, India, March 2007BriefIntroduction to the ICH Guidelines]
2- Www. Ich.org
3- about/membership.html
4- www.pacificmedicalwriting.com/documents/MEDIA356. List of ICH
5- Reference ikev.org
6- ema europa.eu]
7 - Futscher, N.; Schumacher, P.; Pharm. Ind. 34, 479 - 483 (1972)]](https://image.slidesharecdn.com/ich2-180131092702/85/Ich-2-11-320.jpg)
![ICH [ Q ] Guidelines](https://cdn.slidesharecdn.com/ss_thumbnails/ichabhishek-210812054107-thumbnail.jpg?width=640&height=640&fit=bounds)
Ich 2
- 1. ICH - INTERNATIONAL COUNCILFOR HARMONIZATION Presented by –Punam Sunil Desai M.Pharm .1st year Quality assurance
- 2. History– The International Councilfor Harmonization (ICH), formerly the International Conference on Harmonization (ICH) held the inaugural Assembly meetings on 23 October 2015 establishing ICH as an international association, a legal entity under Swiss law. This step built upon a 25-year track record of successful delivery of harmonized guidelines for global pharmaceutical development as well as their regulation, and a longer standing recognition of the need to harmonies. Since ICH's inception in 1990, the ICH process has gradually evolved. ICH's first decade saw significant progress in the development of ICH Guidelines on Safety, Quality and Efficacy topics. Work was also undertaken on a number of important multidisciplinary topics, which included Medora (Medical Dictionary for Regulatory Activities) and the CTD (Common Technical Document). As ICH started into a new millennium, the need to expand communication and dissemination of information on ICH Guidelines with non-ICH regions became a key focus. Attention was also directed throughout the second decade towards facilitating the implementation of ICH Guidelines in ICH's own regions and maintaining already existing ICH Guidelines as science and technology continued to evolve. Soon afterwards, the authorities approached International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) to discuss a joint regulatory-industry initiative on international harmonization, and ICH was conceived. The birth of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels. Soon afterwards, the authorities approached International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) to discuss a joint regulatory-industry initiative on international harmonization, and ICH was conceived. The birth of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels. ICH -ICH is a joint initiative involving both regulators and research-based industry representatives of the EU, Japan and the US in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines. Objective- 1] More economical, use of humans, animal and for material resources. 2] Elimination of unnecessary delay in the global development and availability of -new medicines.
- 3. 3] Maintaining safeguardson quality safety efficacy and regulatory obligation to protect public health. Members of ich guidelines - MEMBERS OBSERVERS t Founding Regulatory Members Standing Observers EC, Europe IFPMA FDA, US WHO MHLW/PMDA, Japan Legislative or Administrative Authorities Founding Industry Members CDSCO, India Founding Regulatory Members Standing Observers EC, Europe IFPMA FDA, US WHO MHLW/PMDA, Japan Legislative or Administrative Authorities Founding Industry Members CDSCO, India EFPIA CECMED, Cuba JPMA COFEPRIS, Mexico Parma HSA, Singapore Standing Regulatory Members MCC, South Africa Health Canada, Canada National Center, Kazakhstan Swiss medic, Switzerland Roszdravnadzor, Russia Regulatory Members TFDA, Chinese Taipei
- 4. ANVISA, Brazil TGA,Australia CFDA, China Regional Harmonization Initiatives (RHIs) MFDS, Republic of Korea APEC Industry Members ASEAN BIO EAC IGBA GHC WSMI PANDRH SADC International Pharmaceutical Industry Organization APIC International Organizations with an Interest in Pharm CIOMS EDQM IPEC PIC/S USP ICH GUIDLINES–BATCH Q Q1A (R2) Stability Testing of New Drug Substances and Products (Second Revision) Feb. 2003 Q1B Stability Testing: Photo stability Testing of New Drug Substances and Products Nov. 1996 Q1C Stability Testing for New Dosage Forms Nov. 1996 Q1D Bracketing and Martyring Designs for Stability Testing of New Drug Substances and Products Feb. 2002 Q1E Evaluation for Stability Data Feb. 2003 Q1F* Stability Data Package for Registration Applications in Climatic Zones III and IV
- 5. (Guideline withdrawn inJune 2006). Feb. 2003 Q2 (R1) Validation of Analytical Procedures: Text and Methodology (The Addendum dated November 1996 has been incorporated into the core guideline in November 2005). Oct. 1994 Q3A (R2) Impurities in New Drug Substances Oct. 2006 Q3B (R2) Impurities in New Drug Products Jun. 2006 Q3C (R4) Impurities: Guideline for Residual Solvents (including the two Maintenance guidelines PDE For Tetrahydrofuran and PDE for N-Methylpyrrolidone dated September 2002 and Incorporated into the core guideline in November 2005, as well as updates of Table 2, Table 3 and Appendix 1 incorporated in February 2009) Feb. 2009 Q4B Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions Nov. 2007 Q4B Annex 1 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Residue on Ignition/Sulphated Ash General Chapter Nov. 2007 Q4B Annex 2 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Test for Extractable Volume of Parenteral Preparations General Chapter Jun. 2008 Q4B Annex 3 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Test for Particulate Contamination: Sub-Visible Particles General Chapter Jun. 2008 Q4B Annex 4A Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests General Chapter Nov. 2008 Q4B Annex 4B Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-Organisms General Chapter Nov. 2008 Q4B Annex 4C Evaluation and Recommendationof Pharmacopoeia Texts forUse in the ICH Regions on MicrobiologicalExamination ofNon-Sterile Products:Acceptance Criteria for
- 6. PharmaceuticalPreparationsandSubstancesforPharmaceuticalUse GeneralChapter Nov.2008 Q4B Annex 5 Evaluationand Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Disintegration Test General Chapter Jun. 2009 Q4B Annex 7 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Dissolution Test General Chapter Oct. 2009 Q4B Annex 8 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Sterility Chapter General Chapter Jun. 2009 Q4B Annex 9 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Tablet Friability General Chapter Oct. 2009 Q4B Annex 10 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Polyacrylamide Gel Electrophoresis General Chapter Oct. Q4B Annex 11 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Capillary Electrophoresis General Chapter June 2010 Q4B Annex 12 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Analytical Sieving General Chapter June 2010 Q5A (R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Sep. 1999 Q5B Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products Nov. 1995 Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological
- 7. Products Nov. 1995 Q5D Derivationand Characterization of Cell Substrates Used for Production of Biotechnological/ Biological Products Jul. 1997 Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process Nov. 2004 Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Oct. 1999 Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products Mar. 1999 Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Nov. 2000 Q8(R1) Pharmaceutical Development Nov. 2008 Q9 Quality Risk Management Nov. 2005 Q10 Pharmaceutical Quality System Guidelines releasedfor consultation (Step 2) June 2008 Q3C (R4) PDE for Cunene Mar. 2010 Q4B Annex 6 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on University of Dosage Units General Chapter Nov. 2008 Q4B Annex 13 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Bulk Density and Tapped Density of Powders General Chapter June 2010 Q4B Annex 14 Evaluation and Recommendation of Pharmacopoeia Texts for Use in the ICH Regions on Bacterial End toxins Test General Chapter June . ICH TopicQ1 StabilityTestingGuidelines - StabilityTestingOf New Drug Substance
- 8. And Product – STABILITYTESTING OF NEW DRUG SUBSTANCESAND PRODUCTS DRUG SUNSTANCE- - OBJECTIVE - The following guideline is a revised version of the ICH Q1A guideline and defines the Stability data package for a new drug substance or drug product that is sufficient for a Registration application within the three regions of the EC, Japan, and the United States. It Does not seek necessarily to cover the testing for registration in or export to other areas of the World. The guideline seeks to exemplify the core stability data package for new drug substances and Products, but leaves sufficient flexibility to encompass the variety of different practical Situations that may be encountered due to specific scientific considerations and characteristics Of the materials being evaluated. Alternative approaches can be used when there are Scientifically justifiable reasons. Guidelines - Registration application for New Molecular Entity (NME) and associated Drug Product. • Not covered: - Abbreviated or abridged applications, - Variations, - Clinical trial applications General Principles- 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 re-test period for the drug Substance or a shelf life for the drug product and recommended storage conditions. The choice of test conditions defined in this guideline is based on an analysis of the effects of Climatic conditions in the three regions of the EC, Japan and the United States. The mean Kinetic temperature in any part of the world can be derived from climatic data, and the world Can be divided into four climatic zones, I-IV. This guideline addresses climatic zones I and II. The principle has been established that stability information generated in any one of the three
- 9. Regions of theEC, Japan and the United States would be mutually acceptable to the other two Regions, provided the information is consistent with this guideline and the labeling is in Accord with national/regional requirements. General Information on the stability of the drug substance is an integral part of the systematic Approach to stability evalution. 1] 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 intrinsic stability of the molecule And validate the stability indicating power of the analytical procedures used. The nature of the Stress testing will depend on the individual drug substance and the type of drug product Involved. Stress testing is likely to be carried out on a single batch of the drug substance. 2] 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. 3] Selection of Batches Data from formal stability studies should be provided on at least three primary batches of the Drug substance. The batches should be manufactured to a minimum of pilot scale by the same Synthetic route as, and using a method of manufacture and procedure that simulates the final Process to be used for, production batches. The overall quality of the batches of drug Substance placed on formal stability studies should be representative of the quality of the Material to be made on a production scale. Other supporting data can be provided. 4] Specification Specification, which is a list of tests, reference to analytical procedures, and proposed Acceptance criteria, is addressed in ICH Q6A and Q6B. In addition, specification for A degradation product in a drug substance is discussed in Q3A. 5] Evaluation The purpose of the stability study is to establish, based on testing a minimum of three batches Of the drug substance and evaluating the stability information (including, as appropriate, Results of the physical, chemical, biological, and microbiological tests), a re-test period Applicable to all future batches of the drug substance manufactured under similar Circumstances. The degree of variability of individual batches affects the confidence that a Future production batch will remain within specification throughout the assigned re-test
- 10. Period. The data mayshow so little degradation and so little variability that it is apparent from Looking at the data that the requested re-test period will be granted. Drug Product- 1] General The design of the formal stability studies for the drug product should be based on knowledge Of the behavior and properties of the drug substance and from stability studies on the drug Substance and on experience gained from clinical formulation studies. The likely changes on Storage and the rationale for the selection of attributes to be tested in the formal stability Studies should be stated. 2]. Photo stability Testing Photo stability testing should be conducted on at least one primary batch of the drug product if Appropriate. The standard conditions for photo stability testing are described in ICH Q1B. 3] Container Closure System Stability testing should be conducted on the dosage form packaged in the container closure System proposed for marketing (including, as appropriate, any secondary packaging and Container label). Any available studies carried out on the drug product outside its immediate Container or in other packaging materials can form a useful part of the stress testing of dosage. 4] Drug products packaged in semi-permeable containers Aqueous-based products packaged in semi-permeable containers should be evaluated for Potential water loss in addition to physical, chemical, biological, and microbiological Stability. This evaluation can be carried out under conditions of low relative humidity, as Discussed below Study Storage condition Minimum time period Covered by data at submission Long term* 25°C ± 2°C/40% RH ± 5% RH Or 30°C ± 2°C/35% RH ± 5% RH 12 months Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months Accelerated 40°C ± 2°C/not more than (NMT) 25% RH 6 months Specification- Specification is a list of • Tests, test attributes • Reference to analytical procedures • Proposed acceptance criteria release and shelf life Test attributes
- 11. • Attributes susceptibleto change during storage • may influence quality, safety and/or efficacy • should cover physical, chemical, biological, microbiological Attributes Evaluation - Stability information • Systematic approach in presentation and evaluation of Stability information. • Should include results from physical, chemical, Biological and microbiological tests. Overview- Section of stress testing of active substance from glossary to the main text � Text on test procedures brought in line with Q6A � Text on testing frequency amended for accelerated conditions � Storage conditions described in more detail. Testing on low temperatures and aqueous Liquid in semi-permeable containers � Post -approval commitment described unambiguously � Change 30°C ± 2°C/60% ± 5% to 30°C ± 2°C/65% ± 5% Reference- 1- Mario ChenFamily Health International Biostatistics Workshop New Delhi, India, March 2007BriefIntroduction to the ICH Guidelines] 2- Www. Ich.org 3- about/membership.html 4- www.pacificmedicalwriting.com/documents/MEDIA356. List of ICH 5- Reference ikev.org 6- ema europa.eu] 7 - Futscher, N.; Schumacher, P.; Pharm. Ind. 34, 479 - 483 (1972)]