A Project Work

(Pharmaceutical Regulatory Science)

A Project Report Submitted in
“The role of ICH guideline in Harmonization global pharmaceutical
regulation” (BP814PW)

Is In the fulfilment of the requirements

For the degree of
BACHELOR OF PHARMACY
By
SURAJ YADAV
2102030500096
B. pharm 4th year

Name of Supervisor
Sir Vipin Rao Sonkar
(Asst. Professor)
Rameshwaram Institute of Technology & Management

To the
Faculty of Pharmacy
(Affiliated to Dr. A.P.J. Abdul Kalam Technical University, Lucknow)
2024-2025
 Rameshwaram Institute of Technology and Management
Affiliated to Dr. APJ AKTU, Lucknow and approved by PCI, New Delhi
NH24, Govind Puram, Sitapur Road, Lucknow, 226021
Web: www.ritm.in
Email: [email protected]

CERTIFICATE

This is to certify that Tarannum Fatma student of B. Pharm 8th semester

has completed his project report on the topic of “The role of ICH
guideline in Harmonisation global pharmaceutical regulation”
(BP814PW) for the award of bachelor of pharmacy under the
supervision of Sir Vipin Rao Sonkar (Asst. Professor) as per the
norms of Dr. A.P.J. Abdul Kalam Technical University, Lucknow.

Date: SUPERVISOR
Sir Vipin Rao Sonkar
(Asst. Professor)
RITM, Lucknow
 Rameshwaram Institute of Technology and Management
Affiliated to Dr. APJ AKTU, Lucknow and approved by PCI, New Delhi
NH24, Govind Puram, Sitapur Road, Lucknow, 226021
Web: www.ritm.in
Email: [email protected]

CERTIFICATE

This is to certify that Suraj Yadav student of B. Pharm 8th semester has
completed his project report on the topic of “The role of ICH guideline in
Harmonisation global pharmaceutical regulation” (BP814PW) for the
award of bachelor of pharmacy under the supervision of Sir Vipin Rao
Sonkar (Asst. Professor) as per the norms of Dr. A.P.J. Abdul Kalam
Technical University, Lucknow.

Date: Signature of
External Examiner
 DECLARATION
I hereby declare that the Rameshwaram Institute of Technology and
Management, Lucknow shall have the right to preserve, use and
disseminate the report or electronic format for academic/ research
purpose

Place: Lucknow Student Name:

Date: Suraj Yadav
Roll no. 2102030500096
 ACKNOWLEDGEMENT

I would like to express my special thanks of gratitude to our Honourable

Director Prof. Dr. Umesh Pratap Singh Who gave me the golden
opportunity to do this wonderful project of subject "A Project Work
(Pharmacetical Regulatory Science)" Which also helped me in doing a lot
of research and I came to know about so many new things I am really
thankful to them. I am also grateful to our subject teacher Asst. Prof.
Vipin Rao Sonkar for his enthusiasm, patience, insightful comments,
helpful information, practical advice and unceasing ideas that have
helped me tremendously at all times in my works and writing of this
thesis.
Finally, last but by no means least, I would like to thank my parents and
friends who helped me a lot in finalizing this project within the limited
time frame.

Suraj Yadav
2102030500096
 CONTENT OF TABLE

S.NO CONTENT PAGE NO.

1 Introduction 1-2

2 Objectives f ICH 2-3

Organisations Association
3 3

4 Active Members 3

4
5 Structure of ICH

6 ICH Guidelines 4-6

7 Quality Guidelines 6-11

8 Safety Guidelines 11-14

9 Efficacy Guidelines 15-17

10 Multidisciplinary Guidelines 18-19

11 Process Harmonising 19-20

Conclusion 21
12

13 References 22
 ABSTRACT

International council for harmonization of technical requirements for

pharmaceuticals for human use (ICH) is a joint initiative founded to

collaborate regulatory authorities with the authorities of industries for taking

part in scientific and technical discussions of testing procedures that help in

ensuring efficacy and safety of the medications. The major contribution in

developing ICH guidelines was by the regulatory and industrial authorities of

Europe, Japan and the United States. Many other countries also have now

joined hands with them to harmonise drug regulation worldwide. ICH has

made very remarkable progress since its initiation. Most of the guidelines were

implemented and maintained since the first ten years and thus they hold a

solid foot without drifting between regions using the guidelines, which

evidently shows why ICH still stands intact. ICH provides guidelines for

quality, safety, efficacy and multidisciplinary aspects. This article will review

the history, need for harmonisation, initiation and establishment of ICH,

objectives, process of harmonisation, associated organisations and the

guidelines.
INTRODUCTION
New drugs are developed within the laboratories by scientists including chemists,
pharmacologists who identify the cellular and genetic factors associated with the disease
and make target molecules that have therapeutic value. In the beginning thousands of
compounds are discovered, from which 4 to 5 are safe to be tested on humans after the
preclinical trials. After 5 to 7 years of continuous clinical trials, on an average, only one
compound among them reaches the market. The pharmaceutical industry is one among
the largest global businesses. It is associated with constant innovation in terms of
development of new drugs, adhering to safety, quality and efficacy and resolving issues
related to profits, patent rights and protection. At present, it is considered as the most
highly regulated industry worldwide. Earlier, variation in technical requirements from
country to country led to the necessity of duplicating many time-consuming and expensive
test procedures to release new medicines. This resulted in shooting up of the cost of
research. Therefore, a need to rationalize and harmonize drug regulation came into
existence, in order to make safe and efficacious treatments delivered to patients in the
minimum amount of time. The regulatory authorities fill this position. The purpose of
regulatory agencies is to ensure the efficacy, safety, and quality of drugs and medical
equipment. They also harmonise the legal processes involved in drug development and
monitor and ensure that laws are being followed. They also play a crucial role in ensuring
and boosting the application of regulations in unregulated regions of the world for the
protection of those who live there. This is an innovative project for the registration of
pharmaceutical products intended for human use. To debate the scientific and
technological facets of product registration, this brings together regulatory authorities
from Europe, Japan, and the United States with specialists from the pharmaceutical
business in those three countries.

NEED FOR HARMONISATION

The insight for having independent evaluation for every new drug and drugs that already
existing the market was developed after witnessing several medical tragedies such as
thalidomide in the late 1950S and early 1960s [3]. Cautious testing procedures began and
escalated during the 1960s and 1970s. Both time and cost required for drug development
shooted up dramatically in the two decades [4]. This instigated economic risks in drug
development and the rate of attrition were estimated to be as high as 1:5,000-10,000 [5].
The creation of regulatory bodies followed, with the intention of offering strategic,
tactical, and operational guidance and support for operating within the law to hasten the
development and distribution of secure and efficient healthcare goods to people all over
the world [2]. The industry at the time was expanding internationally and looking for new
markets, but because technical standards varied so greatly from nation to nation, it
became necessary for the industry to duplicate numerous time- consuming and expensive
test procedures in order to market new products internationally. Standardized procedures
would facilitate communication with corporations at the
1
INITIATION AND ESTABLISHMENT
European Union developed the idea of harmonising regulatory requirements in the 1980s. they
looked forward to developing single market for pharmaceuticals. It was evident that the
harmonisation was realistic after remarkable success of the EU. Soon in the 1989, Europe,
Japan and the United States discussed about the potentials of harmonization in April 1990, at
the WHO conference of drug regulatory authorities (ICDRA) in Paris hosted by EFPIA, at
Brussels. The International Conference on Harmonization (ICH) was founded shortly after
the experts from the three areas approached the International Federation of Pharmaceutical
Manufacturers and Associations (IFPMA) to develop a collaborative regulatory industry
initiative on global harmonisation. Industry and regulatory agencies no longer have to
assemble and evaluate distinct submissions for each region thanks to ICH's harmonised
submission standards and standardised submission format. The International Council for
Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH)
underwent a number of changes in 2015 and changed its name. This action was taken as a
result of a 25-year history of successfully delivering harmonised rules for international
pharmaceutical development and regulation, as well as a longer history of recognising the
need for harmonisation. This elevated it to a worldwide endeavour. ICH, thus, became a legal,
non-profit entity in Switzerland. On 23rdOctober 2015, ICH held its inaugural assembly
establishing itself as a legal international association under Swiss law.
OBJECTIVES OF ICH
The goal of this harmonisation is to use human, animal, and material resources more sparingly
and to stop needless delays in the global development and accessibility of new medicines while
upholding regulatory requirements for the protection of public health and safeguards on
product quality, safety, and efficacy. It establishes a setting that gives all significant
pharmaceutical regulatory agencies and industry stakeholders the chance to participate more
actively in the process of pharmaceutical harmonisation [10]. By promoting higher economies of
scale and creating a level playing field for regulatory compliance, it attempted to standardise the
standards, format, and content of regulatory documentation. This reduces the pressure on drug
prices.
By 2015, the ICH's goal was stated in its Articles of Incorporation as follows:
To provide proposals towards greater harmonisation in the interpretation and execution
of technical standards and procedures for pharmaceutical product registration and the
maintenance of such registrations;
Maintaining a venue for productive communication on scientific concerns between
regulatory bodies and the pharmaceutical sector on the standardisation of technical
criteria for pharmaceutical goods;

2
 To add value to the international protection of public health in the interest of patients; To
monitor and update harmonised specifications resulting in greater mutual acceptance of
the results of research and development data;
To prevent diverging future requirements by harmonisation of chosen issues required as a
result of therapeutic advancements and the development of new technologies for the
manufacturing of pharmaceutical goods; To enable the adoption of new or improved
technical research and development techniques that update or replace present ones;
To promote the appropriate application and integration of common standards through
the distribution of, transmission of information about, and integration of training on,
harmonised guidelines and their usage; and to formulate policy for the ICH Medical
Dictionary for Regulatory Activities Terminology (MedDRA) while assuring the
technical and scientific maintenance, growth, and promotion of MedDRA as a
standardised glossary that enables the exchange of information.
ORGANISATIONS ASSOCIATED
The European Union, European Federation of Pharmaceutical Industries and Associations,
Ministry of Health, Labour and Welfare, Japan, Japan Pharmaceuticals Manufacturer's
Association, Food and Drug Administration, USA, Pharmaceutical Research and
Manufacturers of America, Swissmedic, and Health Canada comprise the Steering Committee
that controls ICH's actions. The World Health Organization is present as an observer, while the
International Federation of Pharmaceutical Manufacturers and Associations is a non-voting
member.

ACTIVE MEMBERS:
Founding regulatory members include FDA (United States), EC (Europe), MHLW/PMDA
(Japan). Founding industry members include JPMA, EFPIA, phRMA. Standing regulatory
members include Health Canada (Canada), Swissmedic (Switzerland). Regulatory Members
include MFDS (Republic of Korea), ANVISA (Brazil), HSA (Singapore), TITCK (Turkey),
NMPA (China), SFDA (Saudi Arabia), TFDA (Chinese Taipei). Industry members include
Global Self-care Federation, BIO, IGBA.

OBSERVERS:
Standing observers include IFPMA, WHO. Legislative or Administrative Authorities include
CECMED (Mexico), AEC(Azerbaijan), CDSCO (India), ANMAT (Argentina), CPED (Israel),
INVIMA (Colombia), SAHPRA (South Africa), JFDA (Jordan), MHRA (UK), MMDA
(Moldova), Roszdravnadzor (Russia), MOPH (Lebanon), National Center (Kazakhstan), NRA
(Iran), SCDMTE (Armenia), TGA (Australia). Regional harmonisation initiatives (RHIs) include
APEC, ASEAN. EAC, GHC, PANDRH, SADC. International Pharmaceutical Industry
Organisation include APIC. International Organisation regulated or affected by ICH Guideline(s)
include Bill & Melinda Gates Foundation,EDQM, CIOMS, IPEC, PIC/S, USP.

3
Structure of ICH
1. ICH Assembly
2. ICH Management Committee
3. MedDRA Management Committee
4. ICH Secretariat
ICH Assembly
The ICH Assembly works in bringing together all Members and Observers of the ICH
Association as the overarching governing body of ICH. It takes decisions on particular matters
such as on the adoption of ICH Guidelines, admission of new Members and Observers, and the
ICH Association‟s work plans and budget. Member representatives appointed by the Assembly
are supported by ICH Coordinators who represent each Member to the ICH Secretariat on a
daily basis.
ICH Management Committee
The ICH Management Committee (MC) is that body which supervises the operational aspects
of ICH on behalf of all Members, including administrative and financial matters and oversight
of the Working Groups (WGs).
MedDRA Management Committee
The MedDRA Management Committee (MC) has responsibility for providing direction of
MedDRA, ICH‟s standardised medical terminology. The MedDRA MC is responsible for
managing, supporting, and facilitating the maintenance, development, and dissemination of
MedDRA.
ICH Secretariat
The ICH Secretariat is responsible for day-to-day management of ICH, coordinating ICH
activities as well as providing support to the Assembly, the MC and Working Groups. The ICH
Secretariat also provides support to the MedDRA MC. The ICH Secretariat is located in
Geneva, Switzerland.

Selection of New Topic for Harmonization

Consensus on draft Technical document

Endorsement by the Assembly

Assembly adoptio n of ICH Guidelines

Regulatory Consu ltation and Discussion

Imple mentation
4
Figure1. Flowchart showing ICH Harmonization Process
ICH Guidelines
The objective of ICH is to increase international harmonization of technical requirements to
ensure that safe, effective, and higher quality medicines are developed and registered in the
most efficient and cost effective manner. ICH has developed over 45 harmonized guidelines.
There are four major categories into which the ICH guidelines are divided:

5
The creation of ICH guidelines is a step-by-step procedure. In the first stage, the EWG creates
a "final harmonised copy." Stage two is to forward the document to the Steering Committee for
signing, indicating acceptability for comment. Stage three is a six-month or longer procedure of
meetings and discussions with regulatory agencies in the three regions. Stage three also includes
the publishing of the stage two guideline for public discussion. As a consequence of the
consultation, fourth stage develops the Experts Document, which is subsequently forwarded to
the Steering Committee. Stage four is accomplished when the Steering Committee approves the
guideline's adoption by the regulatory bodies of the main regions. The process is finished in the
last stage (stage five), when the recommendations are incorporated into national or regional
internal processes.

QUALITY GUIDELINES
Q1A-Q1F stability Q1A (R2) Stability Testing of New Drug Substances and Products This
guideline recommends stability testing techniques for climatic zones I and II, including
temperature, humidity, and trial length. Additionally, the amended protocol considers the criteria
for stability testing in climatic zones III and IV, in minimising the varied storage conditions for
worldwide dossier submission.

Q1B Stability Testing: Photostability Testing of New Drug Substances and Products
This document provides guidelines on the fundamental testing technique necessary to assess the
light sensitivity and stability of novel medications and goods.

Q1C Stability Testing for New Dosage Forms This expands the principal stability guideline for
novel preparations from already authorised drugs and describes the conditions within which
lower stability data can be approved. Q1D Bracketing and Matrixing Designs for Stability Testing
of New Drug Substances and Products This is aimed at addressing recommendations on the use of
bracketing and matrixing to stability studies conducted in compliance with the concepts indicated
in the primary stability guideline.

Q1E Evaluation of Stability Data This explains how extrapolation of retest intervals of shelf life
might occur. Beyond real-time data may be relevant. It also includes instances of statistical
techniques to stability data analysis.

Q1F Stability Data Package for Registration Applications in Climatic Zones III And IV This leaves
the specification of storage conditions in climatic zones II and IV. to various regions and WHO

6
Q2- Analytical Validation Q2 (R1) Validation of Analytical Procedures: Text and Methodology
This gives the validating conditions necessary for a range of analysing techniques and also
addresses the qualities that must be regarded during the validation of the analytical processes
contained in submissions.

Q2(R2)/Q14EWG Analytical Procedure Development and Revision of

Q2 (R1 Analytical Validation)
Q3A- Q3E Impurities
Q3A (R2) Impurities in New Drug Substances
This guideline covers the chemical and hazard concerns of impurities, such as the inclusion of
impurities in specifications, and establishes the reporting, identification, and qualification limits.

Q3B (R2) Impurities in New Drug Products It supplements the information on contaminants in
new medication substances and offers suggestions on contaminants in products containing new
chemically produced medicinal compounds.

Q3C (R8) Guidelines for Residual Solvents This suggests using less harmful solvents in the
manufacturing of medicine and dosage forms, as well as establishing pharmaceutical thresholds
for residual solvents (organic volatile contaminants) in pharmaceutical formulations.

Q3D (R1) Guideline for Elemental Impurities This regulates elemental contaminants in new
pharmaceutical drugs and prescribes permitted daily exposures (PDEs) for 24 elemental
impurities (EIs) for pharmaceutical drugs taken via the oral, parenteral, and inhalational routes.

Q3E EWG Impurity: Assessment and Control of Extractables and Leachable for Pharmaceuticals
and Biologics It benefits both registrants and policymakers by focusing on therapeutic
considerations and increasing openness in medicinal product criteria, including drug delivery
device components.

Q4A-Q4B Pharmacopoeias Q4A Pharmacopeial Harmonisation Q4B Evaluation and

Recommendation of Pharmacopeial Texts for Use in The ICH Regions. This guideline specifies a
method for the Q4B EWG to evaluate and endorse chosen pharmacopeial literature for
recognition by regulatory bodies as interchangeable in the ICH areas. The ICH decided to
provide topical clauses containing information regarding the rules and its application.

8
Q5A-Q5E Quality of Biotechnological Products Q5A (R1) Viral Safety Evaluation of
Biotechnology Products Derived from Cell Lines of Human or Animal Origin. This section
identifies the examination and assessment of the viral safety of biotechnology goods produced
from human and animal cell lines, as well as the details which ought to be part of the marketing
application or registration package. The goal of this guideline is to offer a basic framework for
virus screening, experiments for viral clearance evaluation, and a suggested strategy for the
designing of viral tests and viral clearance research.

Q5A (R2) EWG Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of
Human or Animal Origin. Q5B Analysis of The Expression Construct in Cells Used for
Production Of rDNA Derived Protein Products. This section is designed to detail the kinds of
data that are regarded to be useful in evaluating the structure of the expression construct used
to make recombinant DNA derived proteins.

Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/ Biological

Products This publication addresses the specific features of the stability testing process required to
cater for the unique properties of proteins and/or polypeptides derived products.

Q5D Derivation and Characterisation of Cell Substrates Used for Production of

Biotechnological/Biological Products This document provides general guidelines on suitable
standards for the synthesis of animal and human cell lines and cells derived from microbes, used
to produce bioengineered products, as well as the production and assessment of cell banks for
manufacturing.

Q5E Comparability of Biotechnological/ Biological Products Subject to Changes in Their

Manufacturing Process This paper outlines the guidelines for determining the comparability of
biotechnological/ biological products before and after alterations to the production method of the
pharmaceutical products. As a result, the purpose of this guideline is to aid in the collecting of
important technical details that will provide proof that modifications to the manufacturing
process will have no unfavourable effect on the quality, safety, and effectiveness of the medicine.

Q6A-Q6B Specifications Q6A Specifications: Test Procedures and Acceptance Criteria for New
Drug Substances and New Drug Products: Chemical Substances This guideline acts as a guide for
the establishment and rationale of acceptance criteria, as well as the choosing of testing methods
for new synthetic chemically derived pharmaceutical formulations and novel therapeutic
products derived from them that haven't already been registered in the ICH areas.

9
Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological
Products This document establishes broad principles for the development and validation of a
consistent collection of global standards for proteins and polypeptides derived from recombinant
or non- recombinant cultured cells production methods [36].

Q7 Good Manufacturing Practice

Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
This paper provides GMP recommendations for the manufacture of therapeutic ingredients in
accordance with an adequate quality management system. It is also meant to assist in ensuring
that APIs fulfil the quality and purity standards that they reflect onto the process.

Q8 Pharmaceutical Development
Q8 (R2) Pharmaceutical Development
This section guides on the topics of section 3.2.P.2 (pharmaceutical development) for
pharmaceutical products, as described in the framework of module 3 of the common technical
document.

Q9 Quality Risk Management

This guideline presents concepts and instances of quality risk management methods that may be
used to many elements of biopharmaceutical quality. These facets usually involve the
innovation, production, distribution, and evaluation and audit procedures for drugs and
biotechnological products (which includes the utilization of raw resources, solvents, inactive
ingredients, packaging, and labelling materials in drug (medicinal) products, biomedical, and
biotechnological products).

Q9 (R1) EWG Quality Risk Management

This focuses on the harmonising activities listed below:
Implement only minor and targeted changes to particular sections and annexes of the
present ICH Q9 guideline and quality risk management (QRM)
Provide customised training resources (with cases) to strengthen the preexisting ICH
briefing package on ICH Q9, and also to discuss and assist the suggested modifications'
implementation and use.

Q10 Pharmaceutical Quality System

During the lifecycle of a product, this guideline is applicable to systems that assist the research
and production of medications and biomedical products, including biotechnology and
biological goods.

Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological
or Biological Substances)
This guideline covers techniques to establishing and comprehending the drug substance
production methods, as well as suggestions on what information should be supplied in module 3
of the common technical document (CTD).
10
Q12 Life Cycle Management
Q12 Technical and Regulatory Considerations for Pharmaceutical Products Life Cycle
Management
This new guideline is suggested to offer a structure to handle post-approval chemistry,
manufacture, and controls (CMC) modifications in an easier, more
foreseeable and equitable way throughout the lifecycle of a product.

Q12 IWG Training of Regulatory and Technical Considerations for Pharmaceutical Products Life
Cycle Management
The Q12 IWG was formed to provide a detailed education program and relevant documentation
to assist and harmonise the comprehension and execution of ICH Q12 in ICH and non-ICH
locations.

Q13 Continuous Manufacturing of Drug Substances and Drug Products

This new guideline is recommended to:
Incorporate essential legal and technical factors that support uniformity, including
particular current good manufacturing practices (CGMP) aspects relevant to continuous
manufacturing (CM)
Enable drugs companies to use flexible techniques to design, execute, or incorporate CM for
the synthesis of small molecules and therapeutic proteins for new and current
pharmaceuticals (drug substances and drug products).
Give regulatory expectations on the innovation, deployment, and evaluation of CM systems
used in the manufacture of drugs and their products to the pharmaceutical industry and
regulatory bodies [44].

Q14 Analytical Procedure Development

The new guidelines aim to harmonise scientific methodology to analytical procedure
development and to give rules for describing the analytical procedure
development process. It seeks to improve regulatory engagement among companies and
regulators, in addition to attempting to promote more effective,
proper empirical risk-based approvals and post-approval management of change of analysis
tools.

SAFETY GUIDELINES
S1A-S1C Carcinogenicity Studies
S1A Need for Carcinogenicity Studies in Pharmaceuticals
This covers the scenarios under which carcinogenicity research on new medications are required.
It contains identified risk factors, specified indications,
and length of exposure

S1B testing for carcinogenicity of Pharmaceuticals

This provides information on methods for assessing a pharmaceutical's carcinogenic risk.
11
S1C (R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals
This guideline assists in harmonising existing practises and improving research methodology by
addressing the requirements to choose the highest dosage
to be utilised in carcinogenicity studies on a novel medicinal drug.

S2 Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for
Human Use
This guideline discusses in vitro and in vivo test protocols and assessment. It includes a
dictionary of words related to genotoxicity testing to improve
application dependability.

S2(R1) Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended
for Human Use
This guideline addresses two critical aspects of genotoxicity testing: the recognition of a series
of standards tests which must be performed for registration
and the extent of conclusive experimental research in any particular test in the standard battery.

S3A Note for Guidance on Toxicokinetic: The Assessment of Systemic Exposure in Toxicity
Studies
This acts as a guide for obtaining toxicokinetic testing methods and highlights the importance
of incorporating pharmacokinetics into toxicological analysis, assisting in the inference of study
results, and promoting rational research methodology

S3B Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution Studies

This recommendation specifies the circumstances in which repetitive dosage tissue distribution
experiments must be performed, such as when existing data resources are insufficient. It also
makes advice on how such research should be carried out.

S4 Duration of Chronic Toxicity Testing in Animals (Rodent and Non-Rodent Toxicity Testing)
This act as a guide for the development of medical goods that are not previously provided by the
ICH guideline on safety evaluations for biotechnological products including recombinant DNA
proteins and monoclonal antibodies.

S5 (R3) Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human

Pharmaceuticals
This guideline incorporates expertise gained from assessing medications utilising existing and
innovative research approaches, as well as recent breakthroughs in scientific, technical, and
regulatory understanding. It also guarantees at least the same degree of human safety as current
testing paradigms.

S6 (R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals

This covers the standards for preclinical safety assessment for biotechnological products. It
specifies how to employ animal models of illness, the timing of genotoxicity testing and
carcinogenicity studies, and the effect of antibody production on the length of treatment. 13
S7A Safety Pharmacology Studies for Human Pharmaceuticals
It defines pharmacological and toxicological safety assessment, as well as basic concepts and
suggestions. This policy applies to novel chemical substances and bioengineered goods for
human use in general. It may be employed with marketed medications in suitable instances, for
example when serious adverse events, a new patient group, or a novel dosage form create
significant concerns.

S7B The non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval
prolongation) by human pharmaceuticals
This paper describes a non-clinical assessment approach for determining a test substance's ability
to delay ventricular repolarization. This recommendation includes information on non-clinical
testing and integrated risk evaluations

S8 immunotoxicity studies for human pharmaceuticals

This paper provides guidelines on nonclinical testing methodologies for identifying chemicals
with immunotoxic potential, as well as information on a weight-of-evidence decision making
strategy for immunotoxicity evaluation. It applies to both novel medications and existing drugs
recommended for various conditions or other alterations on the present product label when the
change may result in unresolved and significant immunotoxicity problems.

S9 non-clinical evaluation for anticancer pharmaceuticals

This guideline covers medications aimed at treating cancer in individuals having late-stage or
severe illness, irrespective of how they are administered, and includes both small molecule and
biotechnology-derived drugs. It defines the nature and timing of non-clinical investigations in the
development of cytotoxic pharmaceuticals and refers to further recommendations as needed.

S10 Photo-safety evaluation of pharmaceuticals

This guideline establishes worldwide standards for photostability analysis and harmonises such
evaluations in conjunction with human clinical studiesand medical and health care approvals.

S11 Non-clinical Safety testing in support of development of paediatric medicines

It specifies standards for the situations in which non-clinical juvenile animal experimentation is
deemed useful and required to assist paediatric clinical studies, as well as guidelines for study
design.

S12 EWG Non-clinical Biodistribution considerations for gene therapy products

The S12 EWG is developing a new S12 Guideline on Non-Clinical Biodistribution Factors for
Gene Therapy Products, with the objective of offering guidance on the components of non-
clinical research conducted that cover Biodistribution evaluation, and will make a contribution to
the refined innovation of regenerative medicinal products while maintaining scientific credibility
and reducing the superfluous usage of animals.

14
EFFICACY GUIDELINES
E1Clinical Safety for Drugs Used in Long Term Treatment
It guides on the patient population and period of exposure for evaluating the safety of
medications designed for the long-term treatment of not-lifethreatening illnesses.

E2A-E2FPharmacovigilance
E2AClinical Safety Data Management: Definitions and Standards for Expedited Reporting
Standardized definitions and terminology for important elements of clinical safety reporting are
provided in this guideline. Furthermore, it provides instructions on how to handle accelerated
(quick) reporting of adverse drug responses throughout the research stage of product
development.

E2B(R3) Clinical Safety Data Management: Data Elements for Transmission of Individual Case
Safety Report ICSR)
Implementation guide for ICH E2B (R3) Electronic transmission of individual case safety
reports (ICSRs) - data components and message specification.

E2C(R2) Periodic Benefit-Risk Evaluation Report

When a medication has been launched, regulatory bodies must be periodically updated with
safety data, which is outlined in this regulation. The goal of the directive is to prevent repetition
of work and guarantee that the regulators get information on the overall safety expertise at
predetermined intervals following commercialization.

E2D Post Approval Safety Data Management: Definition and Standards for Expedited Reporting
The guidelines for obtaining and reporting information is provided in this paper, together with a
standard operating procedure for post-approval safety data management.

E2E Pharmacovigilance Planning

This recommendation is meant to help in the implementation of drug safety operations,
particularly in advance of the early post-marketing phase of a novel drug (in this
recommendation, the term drug denotes chemical entities, biotechnology-derived products, and
vaccines).

E2F Development Safety Update Report

The development Safety Update (DSUR) that is suggested in this policy is meant to serve as a
uniform protocol for regular reporting on pharmaceuticals that are either in development or that
have already been approved but are undergoing additional research throughout the ICH zones.

E3 Clinical Study Reports

The structure and information of a clinical trial report acceptable to all regulatory agencies
within the ICH territories are described in this document.

15
E4 Dose-Response Studies
Throughout the clinical development of a novel medicine, this document makes guidelines on
the planning and execution of studies to evaluate the correlations between dosage,
biodistribution in blood, and therapeutic effects.

E5(R1) Ethic Factors in The Acceptability of Foreign Clinical Data

This clarifies the idea of the bridging analysis that a new region may require to ascertain as to if
statistics of another region are relevant to its cohort. It also discusses the intrinsic factors of the
drug recipient; cultural and environmental factors which might influence the outcomes of
clinical research done in regions.

E6 Good Clinical Practice (GCP)

It outlines the obligations and demands placed on each everyone involved with the execution of
clinical trials, including investigators, monitors, sponsors, and IRBs. GCP comprises addenda on
the key documents as well as the investigator's brochure and addresses topics of surveillance,
reporting, and recordkeeping of clinical studies.

E7 Clinical Trials in Geriatric Population

This paper offers suggestions on the unique attributes that should be taken into account when
designing and carrying out clinical testing for drugs that are anticipated to be useful for the
geriatric population.

E8 General Considerations for Clinical Trials

The proposed revision would discuss a greater variety of trial designs and information sources,
suggest the identification of a fundamental set of criticalto-quality factors adaptable to various
trial forms, and offer a revised cross-referencing of all the other pertinent ICH guidelines that
must be consulted while organising research studies.

E9 Statistical Principles for Clinical Trials

The statistical technique used in clinical testing for commercial applications submitted in the
ICH areas is outlined in this. The guidelines provided here are particularly applicable to clinical
studies that are carried out in the latter stages of development, which include a lot of efficacy
confirmation trials.

E10 Choice of Control Groups in Clinical Trials

This article discusses the selection of control groups for therapeutic studies while taking into
account their differing moral, interferential, and functional characteristics. It draws attention to
the test sensitivity issue that impacts the efficacy of study protocol in many situations in active
control equivalence/non-inferiority studies..

E11 (R1) Clinical Trials in Paediatric Population

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Regulatory standards for paediatric research plans, frameworks for conducting sophisticated
experiments in paediatric patient populations, and focused scientific and technical problems
pertaining to these groups have progressed significantly over the past ten years without
corresponding progress in unified guidance.

E12 Clinical Evaluation by Therapeutic Category

The therapeutic area guideline includes the clinical assessment of novel antihypertensive
medications. It offers a set of guidelines for outcomes and study designs on which all ICH regions
generally adhere.

E14 Clinical Evaluation Of QT

With respect to the planning, execution, assessment, and interpretation of clinical trials to evaluate
a drug's capacity for delaying cardiac repolarization, this document offers advice to the sponsor.

E15 Definitions in pharmacogenetics/ pharmacogenomics

Key words in the fields of pharmacogenomics and pharmacogenetics, such as molecular
diagnostics, pharmacogenomics, pharmacogenetics, and genetic information and specimen
encoding classes, are defined within this guideline.

E16 Qualification of Genomic Biomarkers

In accordance with ICH E15 [79], the regulation makes advice for the background, organization,
and structure of regulatory submissions for the qualifying of genetic biomarkers.

E17 Multi-Regional Clinical Trials

This recommendation offers advice on fundamental designs and planning concepts for multi-
regional clinical trials (MRCT).

E18 Genomic Sampling

In clinical trials, this article offers standardised guidelines for genetic information handling and
sampling. By establishing a shared knowledge of crucial factors for the objective gathering,
preservation, and best utilisation of genetic specimens and information, this approach will make it
easier to conduct genetic research.

E19 Safety Data Collection

In certain late-stage pre-marketing or post-marketing trials, it may be suitable to utilise a focused
approach to safety data gathering. This new guideline is suggested to establish standardised
concepts so that when this could be beneficial and how this type of strategy might be carried out.

E20 Adaptive Clinical Trials

The E20 EWG is developing a new E20 Guideline on Adaptive Clinical Trials to serve as a
straightforward and unified set of guidelines for the regulatoryscrutiny of these research findings in
a worldwide pharmaceutical research programme. This framework will address the layout, conduct,
assessment,and inference of Flexible Drug Trials.
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MULTIDISCIPLINARY GUIDELINES
M1 MedDRA – Medical dictionary for regulatory activities
This comprehensive and thoroughly harmonised medical language was created by the ICH to
assist the international exchange of regulatory data for medicinal goods used among humans.

M2 electronic standards for the transfer of regulatory information

By evaluation and recommendations that were as transparent and generic as feasible, this was
intended to facilitate global digital communications.

M3 non clinical safety studies

The unanimity which exists in relation to the kind, length, and scheduling of non-clinical safety
research to back up the execution of clinical trials on humans and the commercial authorization
of medicines is reflected in this recommendation.

M4 common technical document

The review and evaluation procedures have been revolutionised by the consensus to compile all
quality, safety, and efficacy data in a single framework.
This led to a standardised electronic submission, which in turn made it possible to establish
good critique procedures.

M5 data elements and standards for drug dictionary

The consensus draught guideline includes listings of CVOs for dosage forms and units of
measure, as well as ICH commercial criteria for pharmaceutical product IDs.

M6 gene therapy
This offers advice on the use of testing methods for the identification and description of shed
viruses to industries and regulatory bodies, as well as guidelines on non-clinical and clinical
investigations.

M7 Mutagenic impurities
This manual on structural activity relationships (SAR) assessment for genotoxicity aims to
answer issues if combining contaminants with comparablewarnings that could result in
equivalent warnings that may have equivalent mechanisms of action is a good idea.

M8 electronic common technical document (eCTD)

The ICH M4 CTD Guidelines' usage in the setting of the eCTD raises a number of difficulties
that the M8 EWG reviews technically and evaluates in regard to their effect. The M4 Annex:
Granularity Document will be updated as a component of this project by the relevant M4
Working Group in line with the agreement, although M4 will keep possession of the granularity
document.

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M9 Biopharmaceutics classification system-based biowaivers
It covers biowaivers relying on the Biopharmaceutics Classification System (BCS). Although
BCS-based biowaivers for BCS class I and class III medications may be appropriate, these two
kinds of biowaivers are not universally recognised. As a result, drug companies must adopt
various strategies depending on the location. The report makes suggestions in favour of the
biopharmaceutics categorization of pharmaceuticals and the exemption from bioequivalence
studies.

M10 Bioanalytical Method Validation

The suggestions in this policy addresses the technical regulatory standards for bioanalysis
performed during the development of pharmaceuticals with both organic and chemical roots.

M11 Clinical Electronic Structured Harmonised Protocol (CeSHarP)

It is suggested that this guideline organise treatment protocols thoroughly and uniformly,
including both necessary and discretionary elements. A technical specification that utilises an
accessible, non-proprietary criterion to allow electronic exchange of medical protocol data is one
of two major sets of harmonised strategies that the guideline will outline. The other is a
blueprint which allows detecting headers, common text, and a variety of data fields and
terminologies which will serve as the foundation for efficiency in exchanging data.

M12 Drug Interaction Studies

In order to provide a uniform procedure for designing, conducting, and analysing
Pharmacological And toxicological Studies during the development of a Medicinal Product, the
M12 EWG is focusing on the development of an entirely novel M12 guideline on
pharmaceutical interactions

M13 Bioequivalence for Immediate- Release Solid Oral Dosage Forms

It works on the emergence of the M13 guideline to harmonise bioequivalence study design and
standards, that is envisioned to be advantageous to researchers and generic product developers
because the same suitable methodology will be employed in numerous domains, minimising
duplication of effort.

PROCESS OF HARMONISING
In accordance with the kind of ICH harmonisation effort, there are four different classes: formal
ICH procedure, Q and A procedure, revision procedure, and maintenance procedure. The
official ICH approach consists of 5 phases for developing new harmonised guidelines and
putting them into action.

Step 1: Consensus building

In accordance with the objectives outlined in the Write - up, the WG creates a joint draught of
the Technical Document. The WG's skilled professionals will sign the Step 1 Specialists sign-off
document once the group has agreed on the draught. The Council would then be asked to accept
the Step 1 Experts Technical Document under Step 2 of the ICH procedure. 19
Step 2a: Confirmation of consensus on the Technical Document
Step 2a is achieved once the Council decides that there is enough scientific agreement on the
technical concerns, relying on the WG's report, for the Technical Memorandum to move on to
the following regulatory consultation stage. The Step 2a Technical Document is then approved
by the Council.

Step 2b: Endorsement of draft Guideline by Regulatory Members

When the Statutory Council members further approve the draught Guideline, step 2b is reached.

Step 3: Regulatory consultation and discussion

The Step 3 Specialist Draft Guideline is finalised after three separate stages: regulatory outreach,
review, and discussion.

Stage I - Regional regulatory consultation: The scientifically consensus-based policy exits the
ICH process and is expected to undergo extensive regulatory scrutiny in the ICH areas.
Regulatory agencies and business organisations from other areas are also welcome to offer their
feedback on the draught discussion materials by sending it to the ICH Secretariat.
Stage II - Discussion of regional consultation comments: The EWG works to deal with the
problems obtained and come to an agreement regarding the document called Step 3 Experts
Draft Guideline after collecting all remarks from the discussion phase
Stage III - Finalization of Step 3 Experts Draft Guideline: The Step 3 Expert Draft
Guideline is certified by expertise of the ICH Regulatory Members if, following careful
evaluation of the outcomes of the WG's discussion, the experts agree on a revised version of
the Step 2b draught Guideline. To propose acceptance at Step 4 of the ICH procedure, the
Step 3 Expert Draft Guideline is presented to the Regulatory AssemblyMembers in
accordance with regulatory EWG signatures.

Step 4: Adoption of an ICH Harmonized Guideline

When the Regulatory Representatives of the Assembly concur that the draught guideline has
enough support from the research community, the process moves to step 4 and they endorse the
ICH Harmonized Guideline.

Step 5: Implementation
The regulatory implementation phase of the procedure is promptly followed by the ICH
Harmonized Guideline. This process is executed in accordancewith the exact national/regional
guidelines that are used for other regional regulatory guidelines and norms in the ICH regions.
The ICH Secretariat updates the ICH website with data on the regulatory measures undertaken,
the execution references, and sends it back to the council.

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 CONCLUSION

ICH is a regulatory body formed to collaborate between different countries in setting similar

standards for manufacturing pharmaceutical products. It has succeeded in the process of

harmonisation and has eased the cost of production and duplication of qualitative tests. ICH

guidelines are followed in all the reputed pharmaceutical industries in India. Quality guidelines

are followed in QC and QA departments, Safety guidelines in R&D department, Efficacy

guidelines in the Clinical Trials and Multidisciplinary in the maintenance and transfer of all the

data. ICH shall be implemented in the upcoming industries too, for smooth functioning of

industry and for obtaining quality and safe products.

The ICH is a major global undertaking to affect the harmonization of regulatory requirements

in the 3 major regions involved. The creation of the ICH – the International Conference of

Harmonization, was fuelled by trade reasons, to even out the competition between markets and

end the aforementioned stagnation. ICH was created to deliver health care technology providers

a common, almost global regulatory framework for them to develop their products. The ICH‟s

work is far from over, as more and more regulatory scrutiny is demanded from manufacturers

and investigators and more pressure is applied to Pharmaceutical companies to increase data

transparency, who look up for ICH‟s guidance.

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 REFERENCES

J. Singh, “International conference on harmonisation of technical requirements for

registration of pharmaceuticals for human use,” Journal ofPharmacology and
Pharmacotherapeutics, 2015.

P. T. Geethanjali Sengar, “Pharmaceutical regulatory agencies and organisations around the

world: scope and challenges in drug development,” Pharmatutor, 2012.

“History,” [Online]. Available: https://www.ich.org/page/history.

y. ohno, “ICH guidelines-Implementation of the 3Rs (Refinement, Reduction and

Replacement): incorporating best scientific practices into the regulatory process,” ILAR,
2002.

J. A. DiMasi, “Trends in drug development costs, times and risks,” Sage, 1995.

Z. Brennan, “ICH makes organisational changes,” 2015.

“ICH is now international council for harmonisation- a legal swiss entity,” 2015.

“Members and Observers,” [Online]. Available: https://www.ich.org/page/members-

observers.

“Final concept paper Q5A (R2): Viral safety evaluation of biotechnology products derived
from cell lines of human or animal origin”.

“S10 Photo safety evaluation of pharmaceuticals”.

Final Concept Paper ICH M7(R2) ： Assessment and Control of DNA Reactive
(Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk”.

ICH guideline M7 on assessment and control of DNA reactive (mutagenic) impurities in

pharmaceuticals to limit potential carcinogenic risk”.

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