Why Stability Testing is So much Important?

Why Stability Testing is So much Important (Climatic Zone & Conditions)?


Q1A(R2)& WHO;

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 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.

Stability Testing Study should be perform as per Climatic zone conditions specified by as per given below;

Sr No         Zone                      Type of Climate
1                 Zone I                    Temperate Zone
2                 Zone II                  Mediterranean/Subtropical Zone
3                 Zone III                 Hot Dry Zone
4                 Zone IVa               Hot Humid/Tropical Zone
5                 Zone IVb               Hot/Higher Humidity

Accelerated and Intermediate Testing Conditions.

Sr. No Climatic Zone Temperature Humidity Minimum Duration
1 Accelerated Ambient 40ºC ± 2ºC 75% RH ± 5% RH 6 Months
2 Accelerated Refrigerated 25ºC ± 2ºC 60% RH ± 5% RH 6 Months
3 Accelerated Frozen 5ºC ± 3ºC No Humidity 6 Months
4 Intermediate 30ºC ± 2ºC 65% RH ± 5% RH 6 Months

Long Term Stability Testing Criteria as per Given Below;

Sr No Zone Temperature Humidity Minimum Duration
1 Zone I 21ºC ± 2ºC RH 45% RH ± 5% 12 Months
2 Zone II 25ºC ± 2ºC RH 60% RH ± 5% 12 Months
3 Zone III 30ºC ± 2ºC 35% RH ± 5% RH 12 Months
4 Zone IVa 30 ± ºC 2ºC 65% RH ± 5% RH 12 Months
5 Zone IVb 30ºC ± 2ºC 75% RH ± 5% RH 12 Months
6  Refrigerated  5 ºC ± 3ºC  No Humidity 12 Months
 7  Frozen  -15 ºC ± 5ºC  No Humidity 12 Months

Classification of countries according to climatic zones

Region zone i and ii countries zone iii and iv countries
Europe all countries
America Argentina, Bolivia, Chile, Canada,

Mexico, Peru, Uruguay, USA

Barbados, Belize, brazil, costa Rica, Dominican republic,

Ecuador, el Salvador, Guatemala, Guyana, haita,

Honduras, Jamaica, Columbia, Cuba, Nicaragua, Dutch

Antilles, panama, Paraguay, Puerto rico, Venezuela. all

of these countries are assigned to cz iv.

Asia Afghanistan, Armenia,

Azerbaijan, china, Georgia, Iran,

Israel, Japan, Kazakhstan,

Kirghizia, Korea, Lebanon, Nepal,

Syria, Tadzhikistan, turkey,

Turkmenia, Uzbekistan

Bahrain, Bangladesh, Hong Kong, India, Indonesia, Iraq

(iii), Jordan (iii), Kampuchea, Qatar, Kuwait, Laos,

Malaysia, Maldives islands, Myanmar, Oman, Pakistan,

Philippines, Saudi Arabia, Singapore, Sri-Lanka, Taiwan,

Thailand, United Arab Emirates, Vietnam, Yemen

Africa Egypt, Algeria, Tunisia, Libya,

morocco, Namibia, Ruanda,

south Africa, tunesia, Zambia,



Angola, Ethiopia, Benin, Botswana (iii), burkino faso,

burundi, djibouti, ivory coast, gabon, gambia, ghana,

guinea, cameroon, kenya, longo, liberia, madagascar,

malawi, mali, mauritania, mozambique, niger, nigeria,

senegal, sierra leone, somalia, sudan, tanzania, togo,

Chad (iii), uganda, zaire, central african republic.



Australia, new Zealand. figi. society islands, Marshall islands, new Caledonia,

Papua-new guinea, Samoa, Tonga.

Pharmaceutical Quality System Elements & Change Management System (ICHQ10)

Pharmaceutical Quality System Elements & Change Management System As per ICH Q10

The elements described below might be, required in part under regional GMP
regulations. However, the Q10 model’s intent is to enhance these elements in order to
promote the lifecycle approach to product quality. These four elements are:
• Process performance and product quality monitoring system;
• Corrective action and preventive action (CAPA) system;
• Change management system;                                                                                                        • Management review of process performance and product quality.
These elements should be applied in a manner that is appropriate and proportionate
to each of the product lifecycle stages, recognising the differences among, and the
different goals of, each stage. Throughout the product lifecycle, companies are
encouraged to evaluate opportunities for innovative approaches to improve product
quality. Each element is followed by a table of example applications of the element to the
stages of the pharmaceutical lifecycle.

Process Performance and Product Quality Monitoring System

Pharmaceutical companies should plan and execute a system for the monitoring of
process performance and product quality to ensure a state of control is maintained. An
effective monitoring system provides assurance of the continued capability of
processes and controls to produce a product of desired quality and to identify areas for
continual improvement. The process performance and product quality monitoring
system should:
(a) Use quality risk management to establish the control strategy. This can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, inprocess controls, finished product specifications, and the associated methods and frequency of monitoring and control. The control strategy should facilitate timely feedback / feed forward and appropriate corrective action and preventive action;
(b) Provide the tools for measurement and analysis of parameters and attributes identified in the control strategy (e.g., data management and statistical tools);
(c) Analyse parameters and attributes identified in the control strategy to verify continued operation within a state of control;
(d) Identify sources of variation affecting process performance and product quality for potential continual improvement activities to reduce or control variation;
(e) Include feedback on product quality from both internal and external sources,
e.g., complaints, product rejections, non-conformances, recalls, deviations,
audits and regulatory inspections and findings;
(f) Provide knowledge to enhance process understanding, enrich the design space
(where established), and enable innovative approaches to process validation

Table I: Application of Process Performance and Product Quality Monitoring System throughout the Product Lifecycle

Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation
Process and product knowledge generated and process and product monitoring conducted throughout development can be used to establish a control strategy for manufacturing Monitoring during scale-up activities can provide a preliminary indication of process performance and the successful integration into manufacturing. Knowledge obtained during transfer and scale up activities can be useful in further developing the control strategy. A well-defined system for process performance and product quality monitoring should be applied to assure performance within a state of control and to identify improvement areas. Once manufacturing ceases, monitoring such as stability testing should continue to completion of the studies. Appropriate action on marketed product should continue to be executed according to regional regulations.

Corrective Action and Preventive Action (CAPA) System

The pharmaceutical company should have a system for implementing corrective
actions and preventive actions resulting from the investigation of complaints, product
rejections, non-conformances, recalls, deviations, audits, regulatory inspections and
findings, and trends from process performance and product quality monitoring. A
structured approach to the investigation process should be used with the objective of
determining the root cause. The level of effort, formality, and documentation of the
investigation should be commensurate with the level of risk, in line with ICH Q9.
CAPA methodology should result in product and process improvements and enhanced
product and process understanding.

Table II: Application of Corrective Action and Preventive Action System throughout the Product Lifecycle

Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation
Product or process variability is explored. CAPA methodology is useful where corrective actions and preventive actions are incorporated into the iterative design and development process. CAPA can be used as an effective system for feedback, feedforward and continual improvement. CAPA should be used and the effectiveness of the actions should be evaluated CAPA should continue after the product is discontinued. The impact on product remaining on the market should be considered as well as other products which might be impacted.

Change Management System

Innovation, continual improvement, the outputs of process performance and product
quality monitoring and CAPA drive change. In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. There is generally a difference in formality of change management processes prior to the initial regulatory submission and after submission, where changes to the regulatory filing might be required under regional requirements.
The change management system ensures continual improvement is undertaken in a timely and effective manner. It should provide a high degree of assurance there are no
unintended consequences of the change.
The change management system should include the following, as appropriate for the
stage of the lifecycle:

(a) Quality risk management should be utilised to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk;
(b) Proposed changes should be evaluated relative to the marketing authorisation, including design space, where established, and/or current product and process understanding. There should be an assessment to determine whether a change to the regulatory filing is required under regional requirements. As stated in ICH Q8, working within the design space is not considered a change (from a regulatory filing perspective). However, from a pharmaceutical quality system standpoint, all changes should be evaluated by a company’s change management system;
(c) Proposed changes should be evaluated by expert teams contributing the appropriate expertise and knowledge from relevant areas (e.g., Pharmaceutical Development, Manufacturing, Quality, Regulatory Affairs and Medical), to ensure the change is technically justified. Prospective evaluation criteria for a proposed change should be set;
(d) After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and that there was no deleterious impact on product quality.

Table III: Application of Change Management System throughout the Product Lifecycle.

Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation
Change is an inherent part of the development process and should be documented; the formality of the change management process should be consistent with the stage of pharmaceutical development. The change management system should provide management and documentation of adjustments made to the process during technology transfer activities. A formal change management system should be in place for commercial manufacturing. Oversight by the quality unit should provide assurance of appropriate science and risk based assessments. Any changes after product discontinuation should go through an appropriate change management system.

Management Review of Process Performance and Product Quality

Management review should provide assurance that process performance and product
quality are managed over the lifecycle. Depending on the size and complexity of the
company, management review can be a series of reviews at various levels of
management and should include a timely and effective communication and escalation
process to raise appropriate quality issues to senior levels of management for review.
(a) The management review system should include:
(1) The results of regulatory inspections and findings, audits and other
assessments, and commitments made to regulatory authorities;
(2) Periodic quality reviews, that can include:
(i) Measures of customer satisfaction such as product quality
complaints and recalls;
(ii) Conclusions of process performance and product quality
(iii)The effectiveness of process and product changes including those
arising from corrective action and preventive actions.
(3) Any follow-up actions from previous management reviews.
(b) The management review system should identify appropriate actions, such as:
(1) Improvements to manufacturing processes and products;
(2) Provision, training and/or realignment of resources;
(3) Capture and dissemination of knowledge.

Table IV: Application of Management Review of Process Performance and Product Quality throughout the Product Lifecycle.

Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation
Aspects of management review can be performed to ensure adequacy of the product and process design. Aspects of management review should be performed to ensure the developed product and process can be manufactured at commercial scale. Management review should be a structured system, as described above, and should support continual improvement Management review should include such items as product stability and product quality complaints.



Leadership is essential to establish and maintain a company-wide commitment to quality and for the performance of the pharmaceutical quality system.

Resource Management

(a) Management should determine and provide adequate and appropriate resources (human, financial, materials, facilities and equipment) to implement and maintain the pharmaceutical quality system and continually improve its effectiveness.
(b) Management show specific product, process or site.

Internal Communication

(a) Management should ensure appropriate communication processes are established and implemented within the organisation.
(b) Communications processes should ensure the flow of appropriate information between all levels of the company.
(c) Communication processes should ensure the appropriate and timely escalation of certain product quality and pharmaceutical quality system issues.

Management Review

(a) Senior management should be responsible for pharmaceutical quality system governance through management review to ensure its continuing suitability and effectiveness.
(b) Management should assess the conclusions of periodic reviews of process performance and product quality and of the pharmaceutical quality system, as described in Sections of ICH Q10.

Management of Outsourced Activities and Purchased Materials

The pharmaceutical quality system, including the management responsibilities described in this section, extends to the control and review of any outsourced activities and quality of purchased materials. The pharmaceutical company is ultimately responsible to ensure processes are in place to assure the control of outsourced activities and quality of purchased materials. These processes should incorporate quality risk management and include:
(a) Assessing prior to outsourcing operations or selecting material suppliers, the suitability and competence of the other party to carry out the activity or provide the material using a defined supply chain (e.g., audits, material evaluations, qualification);
(b) Defining the responsibilities and communication processes for quality-related activities of the involved parties. For outsourced activities, this should be included in a written agreement between the contract giver and contract acceptor;
(c) Monitoring and review of the performance of the contract acceptor or the quality of the material from the provider, and the identification and implementation of any needed improvements;
(d) Monitoring incoming ingredients and materials to ensure they are from approved sources using the agreed supply chain.

Management of Change in Product Ownership

When product ownership changes, (e.g., through acquisitions) management should consider the complexity of this and ensure:
(a) The ongoing responsibilities are defined for each company involved;ld ensure that resources are appropriately applied to ab) The necessary information is transferred.


This section describes the lifecycle stage goals and the four specific pharmaceutical quality system elements that augment regional requirements to achieve the ICH Q10 objectives, as defined in Section of ICH Q10. It does not restate all regional GMP requirements.

Lifecycle Stage Goals

The goals of each product lifecycle stage are described below.

Pharmaceutical Development

The goal of pharmaceutical development activities is to design a product and its manufacturing process to consistently deliver the intended performance and meet the needs of patients and healthcare professionals, and regulatory authorities and internal customers’ requirements. Approaches to pharmaceutical development are described in ICH Q8. The results of exploratory and clinical development studies, while outside the scope of this guidance, are inputs to pharmaceutical development.

Technology Transfer

The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realisation. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach and ongoing continual improvement.

Commercial Manufacturing

The goals of manufacturing activities include achieving product realisation, establishing and maintaining a state of control and facilitating continual improvement. The pharmaceutical quality system should assure that the desired product quality is routinely met, suitable process performance is achieved, the set of controls are appropriate, improvement opportunities are identified and evaluated, and the body of knowledge is continually expanded.

Product Discontinuation

The goal of product discontinuation activities is to manage the terminal stage of the product lifecycle effectively. For product discontinuation, a pre-defined approach should be used to manage activities such as retention of documentation and samples and continued product assessment (e.g., complaint handling and stability) and reporting in accordance with regulatory requirements.

Most Important Definitions In Clinical Trials.

Most Important Definitions In Clinical Trials.



What is Clinical Trials? What are all terms used in Clinical Trials? How ICH Guideline Define all these terms? ICH has mentioned all clinical study related terms in ICH HARMONISED TRIPARTITE GUIDELINE  GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R1)


  • Clinical Trial/Study

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous.


  • Adverse Drug Reaction (ADR)

In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out. Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).

  • Adverse Event (AE)

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).


  • Amendment (to the protocol) See Protocol Amendment.

  • Applicable Regulatory Requirement(s)

 Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.

  • Approval (in relation to Institutional Review Boards)

The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and the applicable regulatory requirements.


A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

  • Audit Certificate

A declaration of confirmation by the auditor that an audit has taken place.

  • Audit Report

A written evaluation by the sponsor’s auditor of the results of the audit.

  • Audit Trail

Documentation that allows reconstruction of the course of events.

  • Blinding/Masking

 A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).

  • Case Report Form (CRF)

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

  • Clinical Trial/Study Report

A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report (see the ICH Guideline for Structure and Content of Clinical Study Reports).


  • Comparator (Product)

An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.


  • Compliance (in relation to trials)

Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements.


  • Confidentiality

Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary information or of a subject’s identity.


  • Contract

A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.


  • Coordinating Committee

A committee that a sponsor may organize to coordinate the conduct of a multicentre trial


  • Coordinating Investigator

An investigator assigned the responsibility for the coordination of investigators at different centres participating in a multicentre trial.


  • Contract Research Organization (CRO)

A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.


  • Direct Access

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor’s monitors and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information.

All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

  • Essential Documents

 Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced (see 8. Essential Documents for the Conduct of a Clinical Trial).

  • Good Clinical Practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

  • Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)

An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.

  • Impartial Witness

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.


  • Independent Ethics Committee (IEC)

An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving / providing favourable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects. The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP as described in this guideline.


  • Informed Consent

A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form.

  • Inspection

The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). 1.30 Institution (medical) Any public or private entity or agency or medical or dental facility where clinical trials are conducted.


  • Institutional Review Board (IRB)

An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.


  • Interim Clinical Trial/Study Report

A report of intermediate results and their evaluation based on analyses performed during the course of a trial.


  • Investigational Product

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.


  • Investigator

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. See also Subinvestigator


  • Investigator / Institution

An expression meaning “the investigator and/or institution, where required by the applicable regulatory requirements”.


  • Investigator’s Brochure

A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects (see 7. Investigator’s Brochure).


  • Legally Acceptable Representative

An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject’s participation in the clinical trial.


  • Monitoring

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).


  • Monitoring Report

A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor’s SOPs.


  • Multicentre Trial

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.


  • Nonclinical Study

Biomedical studies not performed on human subjects.

  • Opinion (in relation to Independent Ethics Committee)

The judgment and/or the advice provided by an Independent Ethics Committee (IEC).


  • Original Medical Record See Source Documents.


  • Protocol

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guideline the term protocol refers to protocol and protocol amendments.


  • Protocol Amendment

A written description of a change(s) to or formal clarification of a protocol.

Quality Assurance (QA) All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

  • Quality Control (QC)

The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled.


  • Randomization

The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.


  • Regulatory Authorities

Bodies having the power to regulate. In the ICH GCP guideline the expression Regulatory Authorities includes the authorities that review submitted clinical data and those that conduct inspections  These bodies are sometimes referred to as competent authorities.


  • Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)

Any untoward medical occurrence that at any dose: – results in death, – is life-threatening, – requires inpatient hospitalization or prolongation of existing hospitalization, – results in persistent or significant disability/incapacity, or – is a congenital anomaly/birth defect (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).


  • Source Data

All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies).


  • Source Documents

Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).


  • Sponsor

An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial


  • Sponsor-Investigator

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

  • Standard Operating Procedures (SOPs)

Detailed, written instructions to achieve uniformity of the performance of a specific function.


  • Subinvestigator

Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows). See also Investigator.


  • Subject/Trial Subject

An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.


  • Subject Identification

Code A unique identifier assigned by the investigator to each trial subject to protect the subject’s identity and used in lieu of the subject’s name when the investigator reports adverse events and/or other trial related data.


  • Trial Site

The location(s) where trial-related activities are actually conducted.

  • Unexpected Adverse Drug Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product) (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).


  • Vulnerable Subjects

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.


  • Well-being (of the trial subjects)

The physical and mental integrity of the subjects participating in a clinical trial.


Reference :-




Current Step 4 version

dated 10 June 1996