ich safety guidelines

ICH GUIDELINES

Submitted to Dr. Ashuthosh Kumar Niper Hyderabad

Submitted BY Jatoth vishnu RT/2016/604 D. Sneha RT/2016/603 Niper Hyderabad

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ICH is the “International Conference on Harmonization of

Technical Requirements for Registration of Pharmaceuticals for

Human Use”

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

WHAT IS ICH

05/02/23 ICH Guidelines

The ICH Secretariat is based in Geneva. The biennial meetings and conferences of the ICH Steering Committee rotate between the EU, Japan, and the USA.

ICH located

05/02/23 ICH Guidelines 3

To increase international harmonization of technical

requirements to ensure that safe, effective and high quality

medicines are developed.

To harmonize technical requirements for registration or marketing

approval.

To develop and register pharmaceuticals in the most efficient and

cost effective manner.

To promote public health.

To prevent unnecessary duplication of clinical trials on humans.

To minimize the use of animal testing without compromising

safety and effectiveness of drug. 4

Objectives of ICH


To promote international harmonization by bringing together

representatives from the three ICH regions (EU, Japan and USA)

To discuss and establish common guidelines.

To make information available on ICH, ICH activities and ICH

guidelines to any country or company that requests the information

To promote a mutual understanding of regional initiatives in order to

facilitate harmonization processes related to ICH guidelines

regionally and globally

To strengthen the capacity of drug regulatory authorities and

industry to utilize them.5

Goal of ICH


ICH is comprised of representatives from six parties that represent the regulatory bodies and research-based industry in the European Union, Japan and the USA.

In Japan, the members are the Ministry of Health, Labour and Welfare (MHLW), and the Japan Pharmaceutical Manufacturers Association (JPMA).

In Europe, the members are the European Union (EU), and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

In the USA, the members are the Food and Drug Administration (FDA), and the Pharmaceutical Research and Manufacturers of America (PhRMA).

Additional members include Observers from the World Health Organization (WHO), European Free Trade Association (EFTA), and Canada. The Observers represent non-ICH countries and regions.

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Members of ICH


ICH structure The ICH structure consists of the ICH Steering Committee, ICH

Coordinators, ICH Secretariat and ICH Working Groups.

ICH Steering Committee The Steering Committee is the body that governs the ICH, determines

the policies and procedures for ICH, selects topics for harmonization and monitors the progress of harmonization initiatives. Each of the six ICH parties has two seats on the ICH Steering Committee.

ICH Coordinators The Coordinators are fundamental to the smooth running of the ICH

and are nominated by each of the six parties. An ICH Coordinator acts as the main contact point with the ICH Secretariat.


ICH Secretariat The Secretariat is primarily concerned with preparations for, and

documentation of, meetings of the Steering Committee as well as coordination of preparations for Working Group and Discussion Group meetings. Information on ICH Guidelines and the general ICH process can be obtained from the ICH Secretariat.

ICH Working Group Depending on the type of harmonization activity needed, the Steering

Committee will endorse the establishment of one of three types of working group i.e., Expert Working Group (EWG), Implementation Working Group (IWG) or Informal Working Group.


ICH operates through the ICH Steering Committee with

administrative support from the ICH Secretariat and ICH

Coordinators.

The Steering Committee meets at least twice a year .

During these meetings, new topics will be considered for adoption,

reports are received on the progress of existing topics, and

maintenance and implementation of the guidelines are discussed.

The topics identified for harmonization by the Steering Committee

are selected from Safety, Quality, Efficacy, and Multidisciplinary

matters.905/02/23 ICH Guidelines

ICH OPERATION

Step-1: Drafts are prepared and circulated through many revisions

until a "final harmonized draft" is completed

Step-2: This draft is signed by the EWG as the agreed-upon draft and

forwarded to the Steering Committee for signing which signifies

acceptance for consultation by each of the six co-sponsors

Step-3: The three regulatory sponsors initiate their normal consultation

process to receive comments.


Steps in the ICH process

• Step-4 is reached when the Steering Committee agrees that there

is sufficient scientific consensus on the technical issues. This

endorsement is based on the signatures from the three regulatory

parties to ICH affirming that the Guideline is recommended for

adoption by the regulatory bodies of the three regions.

• Step-5: The process is complete when the guidelines are

incorporated into national or regional internal

procedures(implementation in the 3 ICH regions.)


GUIDELINES

MULTIDISCIPLINARY

EFFICACY

SAFETY

QUALITY


• "Quality" Topics i.e., those relating to chemical and pharmaceutical

Quality Assurance (Stability Testing, Impurity Testing, etc.)

• Efficacy" Topics, i.e., those relating to clinical studies in human

subject (Dose Response Studies, Good Clinical Practices, etc.)

• Safety" Topics, i.e., those relating to in vitro and in vivo pre-clinical

studies (Carcinogenicity Testing, Genotoxicity Testing, etc.)

• Multidisciplinary" Topics, i.e., cross-cutting Topics which do not fit

uniquely into one of the above categories.


http://www.ich.org/UrlGrpServer.jser?@_ID=363&@_TEMPLATE=272



http://www.ich.org/UrlGrpServer.jser?@_ID=2196&@_FORCETEMPLATE=272

S1A: Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals

Carcinogenicity studies should be performed for any

pharmaceutical whose expected clinical use is continuous for at

least 6 months.

This document provides a consistent definition of the

circumstances under which it is necessary to undertake

carcinogenicity studies on new drugs. These recommendations

take into account the known risk factors as well as the intended

indications and duration of exposure.


Carcinogenicity studies(S1A-S1C)

The objectives of carcinogenicity studies are to identify a tumorigenic potential in animals and to assess the relevant risk in humans.

S1B: Testing for Carcinogenicity of PharmaceuticalsThis document provides guidance on the need to carry out

carcinogenicity studies in both mice and rats, and guidance is also given on alternative testing procedures which may be applied without jeopardizing safety.

S1C(R2): Dose Selection for Carcinogenicity Studies of Pharmaceuticals

This document addresses the criteria for the selection of the high dose to be used in carcinogenicity studies on new therapeutic agents to harmonize current practices and improve the design of studies.


S2(R1): Guidance on Genotoxicity Testing and Data Interpretation for

Pharmaceuticals Intended for Human Use

• This guidance is a combination of ICH S2A and S2B guidelines:

S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for

Pharmaceuticals;

• This document provided specific guidance and recommendations for in

vitro and in vivo tests and on the evaluation of test results. It includes

terms related to genotoxicity tests to improve consistency in applications.


S2– Genotoxicity:

• S2B: A Standard Battery for Genotoxicity Testing for Pharmaceuticals :

This document addresses two fundamental areas of genotoxicity

testing:

1.the identification of a standard set of assays to be conducted for

registration, and the extent of confirmatory experimentation in any

particular genotoxicity assay in the standard battery.

2.Registration of pharmaceuticals requires a comprehensive

assessment of their genotoxic potential. It is clear that no single test

is capable of detecting all relevant genotoxic agents. Therefore, the

usual approach should be to carry out a battery of in vitro and in vivo

tests for genotoxicity1805/02/23 ICH Guidelines

The purpose of this guideline is to optimize the standard genetic

toxicology battery for prediction of potential human risks, and for

interpretation of results, with the ultimate goal of improving risk

characterization for carcinogenic effects that have their basis in

changes in the genetic material.


• S3A: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies

• ICH guidelines do not require toxicokinetic studies to be conducted,

except in pregnant, lactating animals, before initiating reproductive

studies.

• In this context, toxicokinetics is defined as the generation of

pharmacokinetic data, either as an integral component in the conduct

of non-clinical toxicity studies or in specially designed supportive

studies, in order to assess systemic exposure.


S3A-S3B Toxicokinetics and Pharmacokinetics:

This document gives guidance on developing test strategies in

toxicokinetics and the need to integrate these pharmacokinetics into

toxicity testing, in order to aid in the interpretation of the toxicology

findings and and their relevance to clinical safety issues

The primary objective of toxicokinetics is: to describe the systemic

exposure achieved in animals and its relationship to dose level and

the time course of the toxicity study.


S3B: Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution Studies

• Tissue distribution studies are essential in providing information on

distribution and accumulation of the compound and/or metabolites,

especially in relation to potential sites of action; this information may

be useful for designing toxicology and pharmacology studies and for

interpreting the results of these experiments.

• This document gives guidance, when the repeated dose tissue

distribution studies should be considered (i.e., when appropriate

data cannot be derived from other sources). It also gives

recommendations on the conduct of such studies


S4: Duration of Chronic Toxicity Testing in Animals (Rodent and Non-Rodent Toxicity Testing)

The objective of this guidance is to set out the considerations that

apply to chronic toxicity testing in rodents and non rodents as part of

the safety evaluation of a medicinal product

• Rodents (a study of 6 months duration)

• Non-rodents (a study of nine months duration).


• S5: Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility

• This document provides guidance on tests for reproductive toxicity.

• It defines the periods of treatment to be used in animals to better

reflect human exposure to medical products and allow more specific

identification of stages at risk.

• It should encourage the full assessment on the safety of chemicals

on the development of the offspring.


• S6: Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals

This document covers the pre-clinical safety testing requirements for biotechnological products. It addresses the use of animal models of disease, determination of when genotoxicity assays and carcinogenicity studies should be performed, and the impact of antibody formation on duration of toxicology studies.

The primary goals of preclinical safety evaluation are:

1) to identify an initial safe dose and subsequent dose in humans;

2) to identify potential target organs for toxicity and for the study of whether such toxicity is reversible;

3) to identify safety parameters for clinical monitoring.


• This guideline was developed to protect clinical trial participants and

patients receiving marketed products from potential adverse effects of

pharmaceuticals

• This document addresses the definition, objectives and scope of

safety pharmacology studies.

• It also addresses which studies are needed before initiation of Phase

1 clinical studies as well as information needed for marketing.


S7A: Safety Pharmacology Studies for Human Pharmaceuticals

• This guideline describes a non-clinical testing strategy for assessing

the potential of a test substance to delay ventricular repolarization.

• This guideline includes information concerning non-clinical assays

and integrated risk assessments.


S7B : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) By Human Pharmaceuticals

• This guideline addresses the recommendations on nonclinical

testing for immunosuppressant.

• The guideline might also apply to drugs in which clinical signs of

immunosuppressant are observed during clinical trials and following

approval to market.

• The term immunotoxicity in this guideline will primarily refer to

immunosuppressant, i.e. a state of increased susceptibility to

infections or the development of tumors.


S8 : Immunotoxicity Studies for Human Pharmaceuticals

• S9: Nonclinical Evaluation for Anticancer Pharmaceuticals

• This guideline provides information for pharmaceuticals that are

only intended to treat cancer in patients with late stage or advanced

disease regardless of the route of administration, including both

small molecule and biotechnology-derived pharmaceuticals.

• It describes the type and timing of nonclinical studies in relation to

the development of anticancer pharmaceuticals and references

other guidance as appropriate.

• This guideline aims to facilitate and accelerate the development of

anticancer pharmaceuticals and to protect patients from

unnecessary adverse effects, while avoiding unnecessary use of

animals and other resources2905/02/23 ICH Guidelines

These guideline applies to new APIs . New excipients clinical

formulations for dermal application and photodynamic therapy

products.

It is an integrated process that can involve an evaluation of

photochemical characteristics, data from non clinical studies and

human safety information.

The photo safety assessment aims to determine weather risk

minimization measures are warranted to prevent adverse events in

humans.

In-vitro assay for photo-toxicity is the 3T3 neutral red uptake assay.

in vivo for species selection irradiation sensitivity, heat tolerance,

performance of reference substance should be considered.


S10 guidelines-Photo safety evaluation of pharmaceuticals

S11-FOR NON CLINICAL SAFETY TESTING IN SUPPORT OF DEVELOPMENT OF PRDIATRIC MEDICINES

This guideline is needed to recommended standards for the

conditions under which non clinical juvenile animal testing is

considered informative and support pediatric clinical trails .

The expert working group (EWG) Will consist of two nonclinical

experts nominated by EU,EFPIA,FDA, PhRMA, MHLW, JPMA,

HEALTH Canada and Swiss medic. One member can also be

nominated by WHO Observer, as well as RHIs, DRAs/doH


• The ICH M3 (R2) Guideline state, the conduct of any juvenile animal

toxicity studies should be considered when pervious animal data

and human safety data ,including effects from other drugs of

pharmacological class, are judged to be sufficient to support

pediatric studies


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ich safety guidelines

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