ISO 23419:2021 pdf download – Traditional Chinese medicine — General requirements for manufacturing procedures and quality assurance of granules.
3.8 granulation process of particle enlargement by agglomeration technique with and without small amounts of excipients Note 1 to entry: Granulation involves agglomeration of fine particles into larger granules, typically of between 0,1 mm and 4,0 mm, depending on their subsequent use. The resulting shapes can be balls, spheroids, small cylinders or irregular. 3.9 dry granulation granulation (3.8) without a mixing process of moistening with liquid to bind excipients and drug substances 3.10 compaction agglomeration of dry extracts (3.5) and excipients without adding liquid(s) with high pressure Note 1 to entry: Compaction uses mechanical compression or compaction (roller technic) to facilitate the agglomeration of dry powder into irregularly shaped particles. 3.11 semi-dry granulation granulation (3.8) with a slight amount (1 % to 4 %) of granulating fluid before the granulation step Note 1 to entry: Semi-dry granulation is a variation of the conventional wet granulation technique. 3.12 wet granulation granulation (3.8) with a mixing process of moistening with liquid to bind excipients and drug substance followed by a drying process 3.13 first? pass? yield efficiency index of a process expressed by the ratio of acceptable output to whole input obtained by a single operation Note 1 to entry: First pass yield is a good measure of the efficiency of a process. 3.14 dosage unit dosage amount contained in a single or daily administration Note 1 to entry: Dosage unit of granules means minimum package unit, such as a sachet or bottle. 3.15 uniformity of dosage unit degree of uniformity in the amount of the drug substance among dosage units
c) All critical parameters shall be determined by experiments in laboratories and test plants, then modified for commercial production scale. Thereafter, three lots of repetitive test production in practical production scale is required for verification study. d) The manufacturing processes of granules shall follow the general requirements given in ISO 19617. e) Quality testing of starting raw materials shall be conducted in accordance with the requirements given in ISO 23723. For the production and lot selection of crude drugs as starting materials, see Annex A. f) Powder made by crushing and milling of crude drugs without extraction shall only be used in this manufacturing process instead of dry extracts if this pharmaceutical form is based on traditional usage. g) Simple fractionation, such as two-layer partition, can be applied in the manufacturing procedure. 4.2 Crushing a) Crude drugs shall be cut or crushed into small pieces by devices suitable for the processing of crude drugs. b) The appropriate particle size shall be determined according to the result of equivalency evaluation (5.2). c) In this process, the critical parameter is particle size of herbs (mm). d) When needed, mixing usage of multiple lots of single crude drugs should be considered to avoid batch-to-batch variation and to obtain consistent quality in the final granules, as described in Annex C. 4.3 Extraction a) Crushed drugs shall be extracted using purified water or aqueous ethanol (e.g. white wine, less than 50 % of ethanol) according to traditional methods. b) Acidic or alkaline solvents shall not be used as extraction solvents. c) Supercritical CO 2 gas extraction shall not be used. d) The amount of solvent to be added is 3 to 20 times the weight of crude drugs. NOTE This varies depending on the density and water adsorption capacity of crushed drugs. e) Extract repetition time is set according to the result of equivalency evaluation given in Annex C.