Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1: 7. International trade in pharmaceuticals: Guidelines for implementation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce 1 : Appendix 4. Glossary and index [not intended to be a formal part of the Scheme]

Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French]

Table of Contents

Introduction
	National drug regulation
	Product assessment and registration
	Good manufacturing practices and inspection
	Distribution
	The international pharmacopoeia and related activities
	Basic tests
	Laboratory services
	International trade in pharmaceuticals
	Counterfeit products
	Training
	Conclusion
1. National drug regulation
	Guiding principles for small national drug regulatory authorities^1,2
		1. General considerations
			1.1 The scope of drug control
			1.2 Basic responsibilities
			1.3 Licensing functions
			1.4 Product licences
			1.5 Manufacturers’ and distributors’ licences
			1.6 New drug assessments
			1.7 Authorization of clinical trials
			1.8 Terms of reference of the regulatory authority
			1.9 Powers of enforcement
			1.10 Technical competence
			1.11 Advisory bodies
			1.12 Independence of operation
		2. Administrative aspects of the licensing process
			2.1 Provisional registration of existing medicinal products
			2.2 Screening of provisionally registered products
			2.3 New product licences
			2.4 Renewal and variation of licences
		3. Technical aspects of the licensing process
			3.1 General considerations
			3.2 Products containing long-established chemical entities
			3.3 Products containing new chemical entities
			3.4 Herbal products
			3.5 Combinations of potent, therapeutically active substances
			3.6 Generic products
2. Product assessment and registration
	Guidelines for the assessment of herbal medicines^1,2
	Stability of drug dosage forms¹
		1. Introduction
		2. General considerations
		3. Responsibility of parties involved in the assurance of drug stability
			3.1 Manufacturers
			3.2 Drug regulatory authorities
			3.3 Procurement agencies
			3.4 Pharmacists and other workers in the supply system
		4. Use of terms
		5. Less stable drug substances
		References
	Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms¹
		General
		Definitions
		1. Stability testing
		2. Intended market
		3. Design of stability studies
		4. Analytical methods
		5. Stability report
		6. Shelf-life and recommended storage conditions
		References
		Official, international and national guidelines
		Appendix 1. Survey on the stability of pharmaceutical preparations included in the WHO Model List of Essential Drugs: answer sheet
		Appendix 2. Stability testing: summary sheet
	Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability¹
		Introduction
		Glossary
		Part One. Regulatory assessment of interchangeable multisource pharmaceutical products
			1. General considerations
			2. Multisource products and interchangeability
			3. Technical data for regulatory assessment
			4. Product information and promotion
			5. Collaboration between drug regulatory authorities
			6. Exchange of evaluation reports
		Part Two. Equivalence studies needed for marketing authorization
			7. Documentation of equivalence for marketing authorization
			8. When equivalence studies are not necessary
			9. When equivalence studies are necessary and types of studies required
		Part Three. Tests for equivalence
			10. Bioequivalence studies in humans
			11. Pharmacodynamic studies
			12. Clinical trials
			13. In vitro dissolution
		Part Four. In vitro dissolution tests in product development and quality control
		Part Five. Clinically important variations in bioavailability leading to non-approval of the product
		Part Six. Studies needed to support new post-marketing manufacturing conditions
		Part Seven. Choice of reference product
		Authors
		References
		Appendix 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)
		Appendix 2. Explanation of symbols used in the design of bioequivalence studies in humans, and commonly used pharmacokinetic abbreviations
		Appendix 3. Technical aspects of bioequivalence statistics
3. Distribution
	Quality assurance in pharmaceutical supply systems¹
		1. Introduction and general considerations
		2. Elements of quality assessment and assurance
			2.1 Legal base
			2.2 Regulatory elements
			2.3 Technical elements
		3. Pre-marketing quality assessment
			3.1 Drug notification, authorization and registration
			3.2 Drug nomenclature
		4. Drug quality surveillance during marketing
			4.1 Quality surveillance during manufacture
			4.2 Quality surveillance of imported drugs
			4.3 Quality surveillance during distribution
		References
4. The international pharmacopoeia and related activities
	Guidance for those preparing or commenting on monographs for preparations to be included in The international pharmacopoeia¹
	Validation of analytical procedures used in the examination of pharmaceutical materials¹
	General guidelines for the establishment, maintenance, and distribution of chemical reference substances¹
		1. Criteria for determining the need for the establishment of chemical reference substances
		2. Evaluation of reference substances
		3. Chemical and physical methods used in evaluating reference substances
			3.1 Methods useful for verifying the identity of reference substances
			3.2 Purity requirements for reference substances
			3.3 Methods used in determining the purity of reference substances
		4. Handling and distribution of reference substances
			4.1 Packing and storage
			4.2 Stability and periodic re-evaluation
			4.3 Information to be supplied with reference substances
			4.4 Expiry of reference substances
			4.5 Distribution problems
		5. Reference materials calibrated against International Chemical Reference Substances
		6. Means of promoting effective exchange of information and ensuring cooperation between organizations establishing reference substances
	General recommendations for the preparation and use of infrared spectra in pharmaceutical analysis¹
	List of available International Chemical Reference Substances¹
	List of available International Infrared Reference Spectra¹
5. Basic tests
	Collaboration within the basic test programme¹
6. Laboratory services
	National laboratories for drug quality surveillance and control¹
		1. Introduction
		2. First-stage laboratory for drug surveillance
		3. Medium-size drug control laboratory
			3.1 Capability
			3.2 Premises
			3.3 Staff
			3.4 Equipment
		4. Scope of activity
		5. Factors influencing the size and location of a laboratory
		6. Implementation of control laboratory projects
			6.1 Feasibility study
			6.2 Phasing of development
			6.3 Programme support
	Good laboratory practices in governmental drug control laboratories¹
		1. General
		2. Management and operational issues
			2.1 Organizational structure
			2.2 Staffing
			2.3 Incoming samples
			2.4 Analytical worksheet
			2.5 Testing
			2.6 Evaluation of test results
			2.7 Retention samples
			2.8 Specifications repertory
			2.9 Reagents
			2.10 Reference materials
			2.11 Instruments and their calibration
			2.12 Safety in drug control laboratories
		References
	Sampling procedure for industrially manufactured pharmaceuticals¹
		1. General considerations
			1.1 Purpose of sampling
			1.2 Types of controls
			1.3 Classes and types of materials
			1.4 Parties concerned with sampling procedures
		2. Use of terms
			2.1 Sampling operations
			2.2 Samples
			2.3 Quantities of material
			2.4 Personnel
		3. General precautions to be taken during sampling operations
		4. Packaging and labelling of samples
		5. Sampling during pharmaceutical inspections
		6. Sampling of pharmaceutical dosage forms in regular surveillance programmes on drug quality during marketing
		7. Sampling of pharmaceutical dosage forms for acceptance of consignments
		8. Sampling of starting materials
			8.1 General considerations
			8.2 Sampling plans for consignments of starting materials supplied in several sampling units
7. International trade in pharmaceuticals
	Guidelines for implementation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce¹
		1. Provisions and objectives
		2. Eligibility for participation
		3. Requesting a certificate
		4. Issuing a certificate
		5. Notifying and investigating a quality defect
		References
		Appendix 1. Model Certificate of a Pharmaceutical Product
		Appendix 2. Model Statement of Licensing Status of Pharmaceutical Product(s)
		Appendix 3. Model Batch Certificate of a Pharmaceutical Product
		Appendix 4. Glossary and index
	World Health Assembly resolution WHA50.3: Guidelines on the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce
	Guidelines on import procedures for pharmaceutical products¹
8. Counterfeit products
	Observations and recommendations on counterfeit drugs^1,2
9. Training
	Training programme in drug analysis^1,2
	Places of training in drug quality control offered by the International Federation of Pharmaceutical Manufacturers Associations¹
Selected WHO publications of related interest
Back cover

Appendix 4. Glossary and index

In order to facilitate understanding, terms used in the guidelines are explained here and/or reference is made to relevant sections. This appendix provides supplementary information and is not a formal part of the Scheme.

For the sake of clarity, all definitions taken from the glossary of “Good manufacturing practices for pharmaceutical products” (1) are preceded by an asterisk.

abuse of Scheme

See sections 4.9 and 5.2 of the guidelines.

active ingredients

See sections 1.5, 4.4 and 4.5 of the guidelines.

addresses of competent authorities

See sections 2.2 and 3.3 of the guidelines.

applicant

The party applying for a Product Certificate. This is normally the product-licence holder. Because certain data are confidential for commercial reasons, the competent authority in the exporting country must always obtain permission to release these data from the product-licence holder or, in the absence of a product licence, from the manufacturer.

authentication of certificates

See section 4.9 of the guidelines.

^*batch (or lot)

A defined quantity of a starting material, packaging material, or product processed in a single process or series of processes so that it can be expected to be homogeneous. In the case of continuous manufacture, the batch must correspond to a defined fraction of the production, characterized by its intended homogeneity. It may sometimes be necessary to divide a batch into a number of sub-batches, which are later brought together to form a final homogeneous batch.

batch certificate

A document containing information, as set out in Appendix 3 of the guidelines, will normally be issued for each batch by the manufacturer. Furthermore, a batch certificate may exceptionally be validated or issued by the competent authority of the exporting country, particularly for vaccines, sera and other biological products. The batch certificate accompanies every major consignment (see also section 3.14 of the guidelines).

^*batch number

A distinctive combination of numbers and/or letters which specifically identifies a batch on the labels, the batch records, and the certificates of analysis, etc.

^*bulk product

A product that has completed all processing stages up to, but not including, final packaging.

certifying authority

The competent authority that issues product certificates. It must ensure that it possesses the capacities listed in section 2.4 of the guidelines.

charges for product certificates

See section 3.11 of the guidelines.

competent authority

The national authority as identified in the formal letter of acceptance in which each Member State informs WHO of its intention to participate in the Scheme. The extent of its participation should be indicated in the letter of acceptance (see section 2.1 of the guidelines). The competent authority can issue or receive certificates.

WHO makes available on request a continuously updated list of addresses of competent authorities and, when applicable, the specific conditions for participation.

competence and evaluation of national authority

See sections 2.4, 2.5 and 4.2 of the guidelines.

dosage form

The form of the completed pharmaceutical preparation, e.g. tablet, capsule, elixir, suppository.

drug regulatory authority

An authority appointed by the government of a Member State to administer the granting of marketing authorizations for pharmaceutical products in that country.

^*finished product

A product that has undergone all stages of production, including packaging in its final container and labelling.

free sale certificate

See section 3.2 of the guidelines.

GMP certificate

See section 3.2 of the guidelines.

importing agents, guidelines for

See section 3.4 of the guidelines.

language of product certificate

See section 3.10 of the guidelines.

licence holder

An individual or a corporate entity possessing a marketing authorization for a pharmaceutical product.

licensee

An individual or corporate entity responsible for the information and publicity on, and the pharmacovigilance and surveillance of batches of, a pharmaceutical product and, if applicable, for their withdrawal, whether or not that individual or corporate entity is the holder of the marketing authorization.

limits of certificate by competent authority

See sections 3.12 and 4.8 of the guidelines.

lot

See batch.

^*manufacture

All operations of purchase of materials and products, production, quality control, release, storage, shipment of finished products, and related controls.

^*manufacturer

A company that carries out at least one step of manufacture. (For the different categories of manufacturer, see Appendix 1, explanatory note no. 8.)

marketing authorization

See product licence.

pharmaceutical product

Any medicine intended for human use or administered to food-producing animals, presented in its finished dosage form or as an active ingredient for use in such dosage form, that is subject to control by pharmaceutical legislation in both the exporting state and the importing state.

product

See pharmaceutical product.

product certificate

A document containing the information as set out in Appendix 1 of the guide- lines that is validated and issued for a specific product by the competent authority of the exporting country and intended for use by the competent authority in the importing country or - in the absence of such an authority - by the drug procurement authority (see also section 3.5 of the guidelines).

Transmission of product certificate: see sections 3.8 and 4.9 of the guidelines.

Validity of product certificate: see section 3.9 of the guidelines.

When to request a product certificate: see section 3.5 of the guidelines.

product information

The approved product information referred to in section 4.7 of the guidelines and item 2A.5 of the Product Certificate. It normally consists of information for health professionals and the public (patient information leaflets), as approved in the exporting country and, when available, a data sheet or a Summary of Product Characteristics (SPC) approved by the regulatory authority.

product licence

An official document issued by the competent drug regulatory authority for the purpose of the marketing or free distribution of a product. It must set out, inter alia, the name of the product, the pharmaceutical dosage form, the quantitative formula (including excipients) per unit dose (using International Nonproprietary Names or national generic names, where they exist), the shelf-life and storage conditions, and packaging characteristics. It also contains all the information approved for health professionals and the public (except promotional information), the sales category, the name and address of the licence holder, and the period of validity of the licence.

product-licence holder

See licence holder.

^*production

All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing and packaging, to completion of the finished product.

registration

Any statutory system of approval required at national level as a precondition for introducing a pharmaceutical product on to the market.

registration certificate

See product licence.

specifications

See Appendix 3, explanatory note 7.

statement of licensing status

See section 3.13 of the guidelines and Appendix 2.

Summary Basis of Approval

The document prepared by some national regulatory authorities that summarizes the technical basis on which the product has been licensed (see section 4.7 of the guidelines and explanatory note 10 of the Product Certificate contained in Appendix 1).

Summary of Product Characteristics (SPC)

Product information as approved by the regulatory authority. The SPC serves as the basis for production of information for health personnel as well as for consumer information on labels and leaflets of medicinal products and for control of advertising (see also Product information).

tenders and brokers

See section 4.6 of the guidelines.

WHO responsibility

See section 5.4 of the guidelines.

Reference

1. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva, World Health Organization, 1992:18-22 (WHO Technical Report Series, No. 823).