WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 885 - Thirty-fifth Report
(1999; 168 pages) [Spanish] View the PDF document
Table of Contents
View the documentWHO Expert Committee on Specifications for Pharmaceutical Preparations
View the document1. Introduction
Open this folder and view contents2. The international pharmacopoeia and related issues
Open this folder and view contents3. International Chemical Reference Substances and Infrared Reference Spectra
Open this folder and view contents4. Quality control - national laboratories
Open this folder and view contents5. Good manufacturing practices
Open this folder and view contents6. Quality systems and inspection
Open this folder and view contents7. Other quality assurance topics
Open this folder and view contents8. Nomenclature and terminology
Open this folder and view contents9. Legal aspects of pharmaceuticals
Open this folder and view contents10. Regulatory issues
Open this folder and view contents11. Training activities
View the document12. Pharmaceuticals contaminated with diethylene glycol
View the documentAcknowledgements
View the documentReferences
View the documentAnnex 1. List of available International Chemical Reference Substances1
View the documentAnnex 2. List of available International Infrared Reference Spectra1
Open this folder and view contentsAnnex 3. General guidelines for the establishment, maintenance and distribution of chemical reference substances
Open this folder and view contentsAnnex 4. Good manufacturing practices: authorized person - role, functions and training
Close this folderAnnex 5. Good manufacturing practices: supplementary guidelines for the manufacture of pharmaceutical excipients
View the document1. General considerations
View the document2. Glossary
View the document3. Self-inspection and quality audits
Open this folder and view contents4. Equipment
Open this folder and view contents5. Materials
Open this folder and view contents6. Documentation
Close this folder7. Good practices in production and quality control
View the document7.1 Change control and process validation
Close this folder7.2 Good practices in production
View the document7.2.1 Prevention of cross-contamination
View the document7.2.2 In-process blending/mixing
View the document7.2.3 Control of microbial contamination
View the document7.2.4 Water systems/water quality
View the document7.2.5 Packaging operations
View the document7.2.6 Delivery
Open this folder and view contents7.3 Good practices in quality control
Open this folder and view contentsAnnex 6. Guidelines for inspection of drug distribution channels
View the documentAnnex 7. Good pharmacy practice in community and hospital pharmacy settings
Open this folder and view contentsAnnex 8. National drug regulatory legislation: guiding principles for small drug regulatory authorities
Open this folder and view contentsAnnex 9. Provisional guidelines for developing training programmes: inspection and examination of counterfeit pharmaceuticals
View the documentWorld Health Organization Technical Report Series
View the documentSelected WHO Publications of Related Interest
View the documentBack Cover
 
7.2.2 In-process blending/mixing

Some processes require blending or mixing. Such in-process blending is acceptable provided it is adequately documented in batch production records. Examples include:

• Collection of multiple batches or continuous accumulation of batches with defined endpoint in a single holding tank (with a new batch number).

 

• Recycling material from one batch for further use in a subsequent batch.

• Repeated crystallizations of the same mother liquor for better yield of crystals.

• Collecting several centrifuge loads in a single drier/blender.

 

Incidental carry-over is another type of in-process mixing that frequently occurs. Examples include:

• Residue adhering to the wall of a micronizer used for milling the finished excipient.

 

• Residual layer of damp crystals remaining in a centrifuge bowl after discharge of the bulk of the crystals from a prior batch.

• Incomplete discharge of fluids, crystals or particles from a processing vessel upon transfer of the material to the next step in the process.

 

These residues are usually acceptable since clean-up between successive batches of the same excipient is not normally required during production. However, in the case of non-dedicated production units, complete cleaning procedures designed to prevent contamination that would alter the quality of the substance must be employed when changing from one excipient to another. Checking the effectiveness of these cleaning procedures may require the use of analytical testing for the substances involved.

In contrast to in-process blending and incidental carry-over discussed above, other blending operations should be directed towards achieving homogeneity of the finished excipient batch. Three areas in the processing of finished batches of an excipient which should be examined carefully and critically are:

- the final blending operation to produce the finished batch;

 

- the point in the process at which the batch number is assigned;

- the sampling procedure used to obtain the sample that is intended to be representative of the batch.

 

Blending of excipient batches to salvage adulterated material is not an acceptable practice.

Mother liquors containing recoverable amounts of excipients are frequently reused. Secondary recovery procedures for such excipients are acceptable, if the recovered excipient meets its specifications and if recovery procedures are indicated in batch production records. Secondary recovery procedures for reactants and intermediates are acceptable provided that the recovered materials meet suitable specifications.

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