WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 885 - Thirty-fifth Report: Annex 3. General guidelines for the establishment, maintenance and distribution of chemical reference substances: Part A. Primary chemical reference substances: 5. Assignment of content

WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 885 - Thirty-fifth Report
(1999; 168 pages) [Spanish]

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Good Manufacturing Practices: Supplementary Guidelines for the Manufacture of Pharmaceutical Excipients. WHO Technical Report Series, No. 885, 1999, Annex 5

Índice de contenido

WHO Expert Committee on Specifications for Pharmaceutical Preparations
1. Introduction
2. The international pharmacopoeia and related issues
	2.1 Quality specifications for drug substances and dosage forms
	2.2 Simple test methodology
3. International Chemical Reference Substances and Infrared Reference Spectra
	3.1 Establishment of International Chemical Reference Substances
	3.2 International Infrared Reference Spectra
	3.3 Use of International Chemical Reference Substances and Infrared Reference Spectra
	3.4 Guidelines for the establishment, maintenance and distribution of chemical reference substances
4. Quality control - national laboratories
	4.1 Good laboratory practices in government drug quality control laboratories
	4.2 Information on external quality assessment
5. Good manufacturing practices
	5.1 Adoption of additional guidelines
	5.2 Good manufacturing practices for sterile products
	5.3 Relationship between pharmacopoeial requirements and manufacturers' internal specifications
6. Quality systems and inspection
	6.1 Quality systems for GMP inspectorates
	6.2 Pre-approval inspection
	6.3 Guidelines for inspection of drug distribution channels
	6.4 Use of simple test methods by inspectors
7. Other quality assurance topics
	7.1 Compendia
	7.2 Packaging for pharmaceutical products
	7.3 Multisource pharmaceutical products
	7.4 Guidelines for good pharmacy practice
8. Nomenclature and terminology
	8.1 International Nonproprietary Names for pharmaceutical substances
	8.2 Terminology
9. Legal aspects of pharmaceuticals
	9.1 Drug regulatory legislation
	9.2 National implementation guidelines for combating counterfeit pharmaceuticals
10. Regulatory issues
	10.1 WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce
		10.1.1 Finished pharmaceutical products
		10.1.2 Active pharmaceutical ingredients
	10.2 WHO model system for computer-assisted drug registration
	10.3 Model guidelines for the international provision of controlled medicines for emergency medical care
11. Training activities
	11.1 Training programmes for drug regulators and related activities
	11.2 Training programmes for the detection of counterfeit pharmaceutical products
12. Pharmaceuticals contaminated with diethylene glycol
Acknowledgements
References
Annex 1. List of available International Chemical Reference Substances¹
Annex 2. List of available International Infrared Reference Spectra¹
Annex 3. General guidelines for the establishment, maintenance and distribution of chemical reference substances
	Introduction
	Part A. Primary chemical reference substances
		1. Assessment of need for the establishment of chemical reference substances
		2. Obtaining source material
		3. Evaluation of chemical reference substances
			3.1 Use in identification tests
			3.2 Use in purity tests
			3.3 Use in assays
			3.4 Use in the calibration of an instrument
		4. Chemical and physical methods used in evaluating chemical reference substances
			4.1 Methods used to verify the identity of chemical reference substances
			4.2 Methods used to determine the purity of chemical reference substances
		5. Assignment of content
		6. Handling and distribution of chemical reference substances
			6.1 Packaging operations
			6.2 Storage
			6.3 Stability
			6.4 Information to be supplied with chemical reference substances
			6.5 Distribution and supply
			6.6 Period of use
	Part B. Secondary chemical reference substances
	References
Annex 4. Good manufacturing practices: authorized person - role, functions and training
	1. The role and position of the authorized person in the company
	2. Implementation of the quality system
	3. Routine duties of an authorized person
	4. Education and training
	5. Selected references
Annex 5. Good manufacturing practices: supplementary guidelines for the manufacture of pharmaceutical excipients
	1. General considerations
	2. Glossary
	3. Self-inspection and quality audits
	4. Equipment
		4.1 Use of equipment
		4.2 Cleaning programme
			4.2.1 Detailed cleaning procedure
			4.2.2 Sampling plan
			4.2.3 Analytical methods/cleaning limits
	5. Materials
		5.1 General
		5.2 Starting materials
		5.3 Rejected and recovered materials
		5.4 Returned excipients
		5.5 Storage practices
	6. Documentation
		6.1 General
		6.2 Specifications
		6.3 Batch production records
		6.4 Other documents
	7. Good practices in production and quality control
		7.1 Change control and process validation
		7.2 Good practices in production
			7.2.1 Prevention of cross-contamination
			7.2.2 In-process blending/mixing
			7.2.3 Control of microbial contamination
			7.2.4 Water systems/water quality
			7.2.5 Packaging operations
			7.2.6 Delivery
		7.3 Good practices in quality control
			7.3.1 General
			7.3.2 Control of starting materials
			7.3.3 In-process testing
			7.3.4 Quality records and retention samples
			7.3.5 Stability studies
			7.3.6 Expiry/re-evaluation dating
			7.3.7 Calibration of measuring and test equipment
Annex 6. Guidelines for inspection of drug distribution channels
	Introductory note
	General considerations
	Glossary
	1. Drug inspectors
		1.1 Qualifications
		1.2 Organizational aspects
		1.3 Methods of inspection
		1.4 Reference/information sources
	2. Inspection of establishments in the drug distribution chain
		2.1 Broad objectives
		2.2 Establishments
		2.3 Inspections
		2.4 Special categories of drugs
	References
	Selected further reading
	Appendix 1. Checklist for inspection and the preparation of a report
	Appendix 2. Guidance on sampling
	Appendix 3. Guidance for inspection when pharmaceutical products are suspected to be counterfeit, spurious or substandard
	Appendix 4. Sample receipt form
Annex 7. Good pharmacy practice in community and hospital pharmacy settings
Annex 8. National drug regulatory legislation: guiding principles for small drug regulatory authorities
	Introduction
	Drafting national legislation: points for consideration
	Defining the scope of the marketing authorization procedure for medicinal products
	Example of a legislative scheme for regulating medicinal products
		General considerations
		Potential value of the scheme
		Model legislative text and commentary
			Part A. Administration
			Part B. Provisional registration/marketing authorization and inventory of medicinal products
			Part C. Screening of products and issuance of product licences/authorizations
			Part D. Other activities requiring authorization/licensing
			Part E. General provisions
			Part F. Interpretation
	References
	Selected bibliography
	Appendix 1. Provisional legislative scheme for registration of pharmacy personnel
	Appendix 2. Guidelines, documents and other regulatory instruments established by WHO to support drug regulatory authorities
Annex 9. Provisional guidelines for developing training programmes: inspection and examination of counterfeit pharmaceuticals
	1. General remarks
		1.1 Introduction
		1.2 Requirements and goals of the training programmes for inspection and examination
		1.3 Prerequisites
	2. Training programme for inspection
		2.1 Course objectives
		2.2 Types of training
		2.3 Educational background of trainees and trainers
		2.4 Course programme items
		2.5 Duration of training course
		2.6 Reiterative training
		2.7 Assessment
		2.8 Certificate
		2.9 Evaluation of the programme
	3. Training programme on examination
		3.1 Course objectives
		3.2 Types of training
		3.3 Educational background of trainees and trainers
		3.4 Course programme items
		3.5 Duration of course
		3.6 Reiterative training
		3.7 Assessment
		3.8 Certificate
		3.9 Evaluation of the programme
	References
	World Health Assembly resolutions
	Appendix 1 The practical issues of organizing and implementing the programme
	Appendix 2 Thin-layer chromatography and its application
World Health Organization Technical Report Series
Selected WHO Publications of Related Interest
Back Cover

5. Assignment of content

If a content is to be assigned to a chemical reference substance, it should be borne in mind that the value is based on the results of a collaborative interlaboratory programme using different analytical methods. This experimentally obtained value represents the best estimate of the true value. In general, the assignment of content for a chemical reference substance is 100% minus the content of water and volatiles, and when a substance is intended for use as an assay standard based on a separation technique the impurity content, as determined by that method, must also be subtracted. Sometimes the chemical reference substances must be dried before use, in which case the content is expressed on the basis of the dried material.