Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French] View the PDF document
Table of Contents
Open this folder and view contentsIntroduction
Open this folder and view contents1. National drug regulation
Close this folder2. Product assessment and registration
View the documentGuidelines for the assessment of herbal medicines1,2
Open this folder and view contentsStability of drug dosage forms1
Open this folder and view contentsGuidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms1
Close this folderMultisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability1
View the documentIntroduction
View the documentGlossary
Open this folder and view contentsPart One. Regulatory assessment of interchangeable multisource pharmaceutical products
Open this folder and view contentsPart Two. Equivalence studies needed for marketing authorization
Close this folderPart Three. Tests for equivalence
View the document10. Bioequivalence studies in humans
View the document11. Pharmacodynamic studies
View the document12. Clinical trials
View the document13. In vitro dissolution
View the documentPart Four. In vitro dissolution tests in product development and quality control
View the documentPart Five. Clinically important variations in bioavailability leading to non-approval of the product
View the documentPart Six. Studies needed to support new post-marketing manufacturing conditions
View the documentPart Seven. Choice of reference product
View the documentAuthors
View the documentReferences
View the documentAppendix 1. Examples of national requirements for in vivo equivalence studies for drugs included in the WHO Model List of Essential Drugs (Canada, Germany and the USA, December 1994)
View the documentAppendix 2. Explanation of symbols used in the design of bioequivalence studies in humans, and commonly used pharmacokinetic abbreviations
View the documentAppendix 3. Technical aspects of bioequivalence statistics
Open this folder and view contents3. Distribution
Open this folder and view contents4. The international pharmacopoeia and related activities
Open this folder and view contents5. Basic tests
Open this folder and view contents6. Laboratory services
Open this folder and view contents7. International trade in pharmaceuticals
Open this folder and view contents8. Counterfeit products
Open this folder and view contents9. Training
View the documentSelected WHO publications of related interest
View the documentBack cover

Part Three. Tests for equivalence

The bioequivalence studies, pharmacodynamic studies and clinical trials should be carried out in accordance with the provisions and prerequisites for a clinical trial, as outlined in the guidelines for good clinical practice for trials on pharmaceutical products (5) (see box), with GMP (2) and with good laboratory practice (GLP) (6).

1. Provisions and prerequisites for a clinical trial

1.1 Justification for the trial

It is important for anyone preparing a trial of a medicinal product in humans that the specific aims, problems and risks or benefits of a particular clinical trial be thoroughly considered and that the chosen options be scientifically sound and ethically justified.

1.2 Ethical principles

All research involving human subjects should be conducted in accordance with the ethical principles contained in the current version of the Declaration of Helsinki. Three basic ethical principles should be respected, namely justice, respect for persons, and beneficence (maximizing benefits and minimizing harms and wrongs) or non-maleficence (doing no harm), as defined by the current revision of the International Ethical Guidelines for Biomedical Research Involving Human Subjects1 or the laws and regulations of the country in which the research is conducted, whichever represents the greater protection for subjects. All individuals involved in the conduct of any clinical trial must be fully informed of and comply with these principles.

1 These guidelines are updated regularly by the Council for International Organizations of Medical Sciences (CIOMS).

1.3 Supporting data for the investigational product

Pre-clinical studies that provide sufficient documentation of the potential safety of a pharmaceutical product for the intended investigational use are a prerequisite for a clinical trial. Information about manufacturing procedures and data from tests performed on the actual product should establish that it is of suitable quality for the intended investigational use. The pharmaceutical, pre-clinical and clinical data should be appropriate to the phase of the trial, and the amount of supporting data should be appropriate to the size and duration of the proposed trial. In addition, a compilation of information on the safety and efficacy of the investigational product obtained in previous and ongoing clinical trials is required for planning and conducting subsequent trials.

1.4 Investigator and site(s) of investigation

Each investigator should have appropriate expertise, qualifications and competence to undertake the proposed study. Prior to the clinical trial, the investigator(s) and the sponsor should establish an agreement on the protocol, standard operating procedures (SOP), the monitoring and auditing of the trial, and the allocation of trial-related responsibilities. The trial site should be adequate to enable the trial to be conducted safely and efficiently.

1.5 Regulatory requirements

Countries in which clinical trials are performed should have regulations governing the way in which these studies can be conducted. The pre-trial agreement between the sponsor and investigator(s) should designate the parties responsible for meeting each applicable regulatory requirement (e.g. application to or notification of the trial to the relevant authority, amendments to the trial protocol, reporting of adverse events and reactions, and notifications to the ethics committee). All parties involved in a clinical trial should comply fully with the existing national regulations or requirements. In countries where regulations do not exist or require supplementation, relevant government officials may designate, in part or in whole, these Guidelines as the basis on which clinical trials will be conducted. The use of these Guidelines should not prevent their eventual adaptation into national regulations or laws. Neither should they be used to supersede an existing national requirement in countries where the national requirement is more rigorous.

2. The protocol

The clinical trial should be carried out in accordance with a written protocol agreed upon and signed by the investigator and the sponsor. Any change(s) subsequently required must be similarly agreed on and signed by the investigator and sponsor and appended to the protocol as amendments.

The protocol, appendices and any other relevant documentation should state the aim of the trial and the procedures to be used; the reasons for proposing that the trial should be undertaken on humans; the nature and degree of any known risks; the groups from which it is proposed that trial subjects be selected; and the means for ensuring that they are adequately informed before they give their consent.

The protocol, appendices and other relevant documentation should be reviewed from a scientific and ethical standpoint by one or more (if required by local laws and regulations) review bodies (e.g. institutional review board, peer review committee, ethics committee or drug regulatory authority), constituted appropriately for this purpose and independent of the investigator(s) and sponsor.

For additional information, see the guidelines for good clinical practice for trials on pharmaceutical products (5), from which the above text has been taken.

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