WHO Herbal Extraction Guidelines

- Do not distribute without permission from WHO R-Draft WHO guidelines for comments, March 2017 -
- WHO guidelines on good herbal processing practices (GHPP) for herbal medicines -
1
2 WHO/SDS/TCM
3 R-Draft WHO guidelines for comments
4 March 2017
5 Distribution: Restricted
6 Revised Draft:
7 WHO guidelines on good herbal processing practices (GHPP)
8 for herbal medicines
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10 REVISED DRAFT FOR COMMENTS
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Please address any comments on this revised draft WHO guidelines by 31 May 2017, to:
Ms Yukiko Maruyama, Scientist, Traditional and Complementary Medicine, Service Delivery and
Safety Department, World Health Organization, 1211 Geneva 27, Switzerland, at the email address
below:
E-mail: trmdocuments@who.int
12
13 Traditional and Complementary Medicine (TCM)
14 Service Delivery and Safety Department (SDS)
15 World Health Organization (WHO)
16
17 TITLE: R-Draft: WHO guidelines on good herbal processing practices (GHPP) for herbal medicines –
18 Revised draft for comments, March 2017
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20 © World Health Organization 2017
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22 All rights reserved.
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24 This revised draft is intended for a restricted audience only, i.e. the individuals and organizations having received this revised
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29 Please send any request for permission to:
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31 Ms Yukiko Maruyama, Scientist, Traditional and Complementary Medicine, Service Delivery and Safety Department, World
32 Health Organization, 1211 Geneva 27, Switzerland. E-mail: trmdocuments@who.int
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34 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion
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45 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DRAFTDOCUMENT:

46 WHO GUIDELINES FOR GOOD HERBAL PROCESSING PRACTICES FOR HERBAL
47 MEDICINES
Need for a WHO technical guidance on processing to produce herbal July 2001
materials, and to produce herbal preparations for quality control of herbal
medicines at different stages of their production, was stated during the
WHO informal meeting on methodologies for quality control of finished
herbal products (Ottawa, Canada) as a recommendation to WHO for
development/action.
Reported to the 37th session of the WHO Expert Committee on 22-26 October 2001
Specifications for Pharmaceutical Preparations (ECSPP), Geneva, on the
output of the WHO informal meeting (July 2001) and informed the
Committee that WHO planned to develop new technical guidelines on
processing of herbal medicines; the Committee noted the proposal.
Needs for good processing practices for herbal medicines were also stated Hong Kong SAR, China,
during the International Conferences of Drug Regulatory Authorities November 2002
(ICDRAs) Madrid, Spain, February 2004
Drafting of the proposal on the development of WHO guiding document 2003
on good processing practices for medicinal plant materials
Obtained WHO’s internal approval in developing a WHO guiding November 2003
document on good processing practices for medicinal plant materials
(title: tentative)
Identification, collection, collation and compilation of technical 2008
information and reference materials for formulating draft synopsis and
annotated content table
Development of concept paper on scope and background as well as the 2008
document development plan
Further identification, collection, collation and compilation of technical 2012
information and reference materials for revising draft synopsis and
annotated content table.
Revision of draft concept paper on scope and background as well as the 2012 – 2013
document development plan
Revision and elaboration of the draft synopsis and content table for 2012 – 2013
drafting the first working draft guidelines
Meeting proposal development and search for potential host of the 2012 – 2013
meeting (2nd WHO consultation on quality control of herbal medicines)
Further collection and collation of technical information and reference 2013 – 2014
materials for the preparation of the first working draft guidelines
Formulating the first working draft WHO guidelines on good processing 2014
practices for herbal medicines
Formation of initial drafting group 2014
Reported on the progress to the 49th session of the WHO ECSPP, October 2014
Geneva, October 2014
2
Distribution of the first working draft WHO guidelines to the participants October – November 2014
of the 2nd WHO consultation on quality control of herbal medicines for
discussion at the 2nd WHO consultation meeting
Reported on the progress to the 37th Annual meetings of national centres October 2014
participating in the WHO international drug monitoring programme,
Tianjin, China, October 2014
At the 2nd WHO consultation meeting held in Hong Kong SAR, China, in 17-19 November 2014
November 2014, the first working draft WHO guidelines on good
processing practices for herbal medicines were reviewed and discussed;
and the objectives, scope and proposed contents were discussed
intensively, and agreed. The draft synopsis and table of content of the
proposed guidelines were further refined and agreed; it was also agreed to
revise the first working draft WHO guidelines based on the discussion
and agreed guidelines’ objectives, scope, and contents at the 2nd WHO
consultation meeting.
Reported on the progress of the guidelines development at the 7th annual December 2014
meeting of International Regulatory Cooperation for Herbal Medicines
(IRCH), Lisbon, Portugal, December 2014
Further identification, collection and collation of relevant technical 2015 – 2016
information for revision of the first working draft guidelines
Revision of the first working draft WHO guidelines 2015 – 2016
Reported on the progress at the 8th annual meeting of IRCH, Riyadh, 8-10 December 2015
Saudi Arabia, December 2015
Formulation of the draft WHO guidelines on good herbal processing 2016
practices for herbal medicines for a global review
Reported on the progress to the 51st session of the WHO ECSPP, Geneva, 17-21 October 2016
October 2016
Reported on the progress at the 9th annual meeting of IRCH, New Delhi, 9-11 November 2016
India, November 2016
First global review on the draft WHO guidelines on good herbal December 2016 – February
processing practices for herbal medicines 2017
Meeting proposal development and search for potential host of the December 2016 – February
meeting (3rd WHO consultation on quality control of herbal medicines) 2017
Compilation of comments received and revision of the draft February – March 2017
The second global review on the revised draft April – May 2017
Compilation of comments received and revision of the revised draft (to June – July 2017
form the 2nd revised draft)
Review and discussion of feedback received on the 2nd revised draft at 4-6 September 2017
the 3rd WHO consultation on quality control of herbal medicines, Hong
Kong SAR, China, September 2017
Finalization of the manuscript based on the discussion at the 3rd WHO September 2017
consultation meeting
Update to the 10th annual meeting of IRCH, Bonn, Germany, September 11-13 September 2017
2017
Update to the 52nd session of the WHO ECSPP, Geneva, October 2017 October 2017
Any follow-up action, as needed
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48 Table of Contents
49
50 1. INTRODUCTION…………………………………………………………………...………………7
51 1.1 Background of guidelines development………………………………………………...…7
52 1.2 Scope………………………………………………………………...…………………….9
53 1.2.1 Processing of herbs into herbal materials……………………………………...….9
54 1.2.2 Processing of herbal materials into herbal preparations……………………..……9
55 1.2.3 Processing of herbal materials or herbal preparations into herbal dosage forms..10
56 1.3 Objectives of guidelines………………………………………………………...……..…10
57 1.4 Definitions of terms………………………………………………..…….…………….…11
58 1.4.1 Terms relating to herbal medicines…………………………………..….………11
59 1.4.2 Terms related to herbal processing practices……………………….……….…..13
60 1.4.3 Terms relating to quality control……………………………………………..….13
61
62 2. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF HERBAL
63 MATERIALS…………………………………………………………………………………...….15
64 2.1 General information………………………………………………………………….…..15
65 2.2 Purposes and functions of processing……………………………………………….…...16
66 2.3 Processing techniques and procedures……………………………………………….…..17
67 2.3.1 Preparation of harvested/collected medicinal plant part for processing………..17
68 2.3.2 Primary processing procedures………………………...………………..………18
69 2.3.2.1 Sorting………………………………………………………………18
70 2.3.2.2 Washing………………………………………………..……………19
71 2.3.2.3 Parboiling (Blanching) ……………………………………………..19
72 2.3.2.4 Leaching…………………………………………………….………19
73 2.3.2.5 Drying…………………………………………………….…………19
74 2.3.3 Secondary processing procedures………………………………….……………20
75 2.3.3.1 Cutting, sectioning, and comminution……...………………….……21
76 2.3.3.2 Aging/Sweating…………………………………………………….21
77 2.3.3.3 Baking/Roasting……………………………………………………22
78 2.3.3.4 Boiling/Steaming………………………………………………….22
79 2.3.3.5 Stir-frying…………………………………………………………22
80 2.3.3.6 Fumigation …………………………………………………….……23
81 2.3.3.7 Irradiation………………………………………………………….23
82 2.3.3.8 Selection of processing method ………...…..………………….……23
83 2.3.3.9 Temperature………………………………………………....………23
84 2.3.3.10 Duration of procedure/treatment………….………………………..24
85 2.3.3.11 Use of adjuvants…………………………………….……...………..24
86 2.3.4 Special processing procedures………………………..……………….…………24
87 2.3.4.1 Detoxification…………………….………………..………………..24
88 2.3.4.2 Modification of therapeutic properties……….…………...…………25
89 2.3.4.3 Use of adjuvants……………………………..………………………25
90 2.3.5 Documentation………………….…………………….…………………………25
91
93 PREPARATIONS………………………………………………………………………………….26
94 3.1 General information…………………………………….……..……………………….26
95 3.1.1 Preparation of herbal materials for processing……………………………..……27
96 3.2 Processing techniques and procedures…………………………………………..……….27
97 3.2.1 Extraction…………………………………..……….…………………...………27
98 3.2.1.1 Common methods of extraction……………………………….…...27
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99 3.2.1.2 Steps involved in the extraction of herbs and herbal materials…..….29

100 3.2.1.3 Common herbal preparations prepared by extraction………...……..30
101 3.2.1.4 Factors influencing extraction of herbal materials……….……….…31
102 3.2.1.5 Selection of extraction methods…………………………………….31
103 3.2.1.6 Extraction conditions and procedures………………………….……31
104 3.2.2 Distillation……………………………………..…………….…………………33
105 3.2.2.1 Distillation procedures……………………………….……………33
106 3.2.3 Fractionation and purification…………………………………………...………34
107 3.2.3.1 Liquid-liquid partition……………………………………….………34
108 3.2.3.2 Chromatography………………………………………………….….34
109 3.2.3.3 Fractionation and purification procedures………………….……….34
110 3.2.4 Concentration and drying…….………………………………………………….35
111 3.2.4.1 Concentration and drying procedures……………………………….35
112 3.2.5 Fermentation……………………………………………………….……….……35
113 3.2.5.1 Fermentation procedures…………………………………….………36
114 3.2.6 Powdering………………………………………………………………………..36
115 3.2.6.1 Powdering procedures………………………………………….…36
116 3.3 Documentation………………………………………..……………………….………....36
117
119 DOSAGE FORMS…………………………………………...……………………………….……37
120 4.1 General information………………………………………………………….………..…37
121 4.2 Processing techniques and procedures…………………………………………………...37
122 4.2.1 Liquid herbal dosage forms…………………………………….…………..…....38
123 4.2.1.1 Fludiextracts…………………………………………………………38
124 4.2.1.2 Infusions……………………………………………………………38
125 4.2.1.3 Decoctions…………………………………………………………38
126 4.2.1.4 Liquid (fluid) extracts……………………………………..…………38
127 4.2.1.5 Tinctures…………………………………………………………….38
128 4.2.1.6 Syrups……………………………………………………………….38
129 4.2.1.7 Oral emulsions………………………………………………….……38
130 4.2.2 Solid herbal dosage forms……………..…………………….………………..…38
131 4.2.2.1 Herbal tea bags………………………………………………………38
132 4.2.2.2 Plant powders………………………………………………………..38
133 4.2.2.3 Powdered extracts…………………………………………………..38
134 4.2.2.4 Granules……………………………………………………………..39
135 4.2.2.5 Pills…………………………………………………………………39
136 4.2.2.6 Capsules…………………………………………………………….39
137 4.2.2.7 Tablets………………………………………………………………39
138 4.2.2.8 Lozenges……………………………………………………………39
139 4.2.3 Other herbal dosage forms…………………………………………………….39
140 4.2.3.1 Ointments/creams……………………………………………………39
141 4.2.3.2 Inhalations……………………………………………………...……39
142 4.2.3.3 Plasters and patches…………………………………………….……39
143 4.2.3.4 Aromatic waters……………………………………………………..40
144 4.2.3.5 Gel capsules………………………………………………...……….40
145
146 5. T E C H N I C A L I S S U E S S U P P O R T I N G G O O D H E R B A L P R O C E S S I N G
147 PRACTICES…………………………………………………….…………………………….……40
148 5.1 Processing facilities………………………………………………………………….…...40
149 5.2 Packaging and labelling……………………………………………………………….…40
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150 5.3 Storage and transportation……………………………………………………….…….…41

151 5.4 Equipment………………………………………………………………………….….…42
152 5.5 Quality assurance and quality control…………………………………………….……...42
153 5.6 Documentation……………………………………………………………….……..……43
154 5.7 Personnel……………………………………….…………………….……………….….43
155 5.7.1 General…………………………………….…………….……………………….43
156 5.7.2 Health, hygiene and sanitation…………………………………….……………..43
157
158 6. OTHER RELEVANT ISSUES………………………………………………………….………….44
159 6.1 Ethical and legal considerations……………………………………………….…………44
160 6.2 Research, research training and information sharing……………………………….……44
161 6.3 Adoption of good herbal processing practices………………….…………….………….45
162 6.4 Intellectual property rights and benefits-sharing……………………...………….………45
163 6.5 Threatened and endangered species……………………………………………………...45
164
165 7. REFERENCES……………………………………………………………………………….….....45
166
167 Annex 1: Example of a model format of good herbal processing practices monograph/SOP protocol to
168 produce a herbal material………………………….…..………………………..………..…47
169
170 Annex 2: Example of a model format of good herbal processing practices monograph/SOP protocol to
171 produce a herbal preparation…..…………..…………………………………………….…..50
172
173 Annex 3: Example of general rules for preparations/monographs of herbal preparations and herbal
174 dosage forms …………………………………………………………………………….…53
175
176 Annex 4: Processing facilities…………………….…..………………………………………..…….59
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177 1. INTRODUCTION
178
179 1.1 Background of guidelines development
180
181 Needs
182 Over the past three decades, there has been a constant, and at times, exponential growth in
183 global interest in the use of herbal medicines. This increase in popularity and usage of herbal
184 medicines is evidenced by the global market which also experienced similar growth. Herbal
185 medicines, including not only finished herbal products but also their starting materials for
186 production, such as medicinal plants, herbal materials, and herbal preparations, are moving
187 into the international commerce and the global trade arena, which indicates increased
188 economic value and importance. When adverse events are reported to the regulatory
189 authorities in relation to the use of herbal products, a large portion of them are attributable to
190 poor quality of products, which may involve a variety of factors, including those due to
191 natural (e.g. source material) and human (e.g. manufacturing/processing) factors. Hence, the
192 safety and quality of herbal medicines at every stage of its production process, have become a
193 major concern to health authorities, healthcare providers, the herbal industries and the public.
194
195 The safety and efficacy of herbal medicines largely depend on their quality. Unlike other
196 pharmaceutical products, which are formulated from single molecule chemicals produced
197 synthetically or by isolation from natural source materials employing reproducible methods,
198 herbal medicines consist of simple processed herbs or finished herbal products prepared from
199 source materials containing a multiplicity of chemical constituents, the quality and quantity of
200 which can vary from batch to batch due to intrinsic and extrinsic factors. Consequently, the
201 quality of finished herbal products is greatly influenced by the quality of the raw materials
202 and the intermediates; and the requirements and methods for quality control of finished herbal
203 products, particularly for mixed herbal preparations, are far more complex than those
204 employed for single molecule chemical drugs.
205
206 A number of World Health Assembly (WHA) resolutions relating to traditional medicine has
207 requested WHO to provide technical support to develop methodology to monitor or ensure the
208 quality, efficacy and safety of herbal medicines. The International Conferences of Drug
209 Regulatory Authorities (ICDRAs), and annual meetings of International Regulatory
210 Cooperation for Herbal Medicines (IRCH), as well as the Meetings of the National Centres
211 Participating in the WHO International Drug Monitoring Programme have also requested
212 WHO to develop and continuously update the technical guidelines on quality, safety, and
213 efficacy of herbal medicines.
214
215 Process and context
216 Participants of the WHO Informal Meeting on Methodologies for Quality Control of Finished
217 Herbal Products (held in Ottawa, Canada, July 2001) looked at the overall picture of herbal
218 medicines: from raw materials to the distribution and supply of finished herbal products,
219 including key steps where quality control is required.
220
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221 One of the main recommendations of the meeting was that WHO should prepare a series of
222 technical guidelines and documents covering quality control issues (from raw materials to
223 finished herbal products), as well as to update other existing documents.
224
225 Following the meeting’s recommendations, and as a part of the implementation of relevant
226 WHO strategies (notably, WHO traditional medicine strategies and WHO medicines
227 strategies) and WHA resolutions, WHO, since then, undertook the development of four new
228 guidelines and to update other existing documents in order to provide technical guidance for
229 quality control required at key steps in the production of herbal medicines to support Member
230 States in their efforts to ensure the quality of herbal medicines. These cover:
231
232  WHO guidelines on good agricultural and collection practices (GACP) for medicinal
233 plants (published in 2003) [WHO, 2003a];
234  WHO guidelines on assessing quality of herbal medicines with reference to contaminants
235 and residues (published in 2007) [WHO, 2007b];
236  WHO guidelines for selecting marker substances of herbal origin for quality control of
237 herbal medicines (in press) [WHO, 2017]; and
238  WHO guidelines on good herbal processing practices (GHPP) for herbal medicines
239 (present document).
240
241 WHO has also updated two key technical guiding documents:
242
243  WHO guidelines on good manufacturing practices (GMP) for herbal medicines (published
244 in 2007) [WHO, 2007a]; and
245  Quality control methods for herbal materials (published in 2011) [WHO, 2011], which
246 includes the WHO good practices for pharmaceutical quality control laboratories as an
247 annex.
248
249 GACP for medicinal plants are only the first step in quality assurance. The next important
250 phase involves the GHPP of herbal materials. The processed materials are herbal materials or
251 herbal preparations, which may be used as a starting source material for the GMP production
252 of finished herbal products, or directly employed as herbal medicines in various herbal dosage
253 forms. For this reason, GHPP for herbal medicines is integrally linked to GACP for
254 medicinal plants and GMP for herbal medicines in the quality assurance and control of herbal
255 medicines.
256
257 The present guidelines are intended to complement, and should be read in conjunction with,
258 those guidelines provided in WHO guidelines on GACP for medicinal plants [WHO, 2003a]
259 and WHO guidelines on GMP for herbal medicines [WHO, 2007b]. Altogether, the present
260 guidelines plus the above-mentioned three new and two updated WHO guidelines form the
261 core technical guidance for the overall quality assurance and control of herbal medicines.
262
263 Preparation of the guidelines
264 The original title suggested for these guidelines was “Good processing practices for herbal
265 materials”. In November 2014, WHO convened the second WHO consultation on quality
266 control of herbal medicines with financial support of Department of Health of Hong Kong
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267 SAR, China, in Hong Kong SAR, during which the working draft guidelines were reviewed
268 and discussed, and the objectives, scope and proposed contents were discussed and agreed.
269 First draft guidelines were revised through global review process.
270
271 1.2 Scope
272
273 Processing refers to the unique procedures of preparing herbal materials, herbal preparations
274 and herbal dosage forms for therapeutic applications. The process concerns ensuring the
275 quality of the herbal materials, herbal preparations and herbal dosage forms produced. The
276 safety and efficacy are strictly related to the intrinsic properties of the herbal materials.
277
278 These guidelines will provide technical guidance on good processing practices in the:
279 (1) processing of herbs into herbal materials;
280 (2) processing of herbal materials into herbal preparations; and
281 (3) processing of herbal materials or herbal preparations into herbal dosage forms.
282
283 In the case of processing herbs into herbal materials, the “primary” process is involved;
284 whereas in the case of processing of herbal materials into herbal preparations, “secondary” or
285 “special” processes are involved. On the other hand, for processing herbal materials or herbal
286 preparations into herbal dosage forms, the processing procedures involve the good practice of
287 the preparation or GMP for the production.
288
289 An outline of the major processes and examples of procedures are given below.
290
291 1.2.1 Processing of herbs into herbal materials
292
293 Primary processing encompasses the immediate post-harvest treatments accorded to herbs
294 obtained from cultivation or by wild crafting or field collection intended to free them from
295 foreign matters, untargeted plant materials and other contaminants, and includes, for example,
296 the procedures of sorting (garbling), washing, drying, cooling and freezing, where
297 appropriate. Primary processing is applied to herbs in the preparation of herbal materials.
298
299 1.2.2 Processing of herbal materials into herbal preparations
300
301 Secondary processing is the next step concerned with converting the primary processed herbs
302 (herbal materials) into herbal preparations by various additional procedures, including, for
303 example, cutting, sectioning, comminution (fragmentation), aging/sweating; baking/roasting;
304 boiling/steaming; and stir-frying.
305
306 Secondary processing may also involve special processing, an extension, in which a
307 specialized method is employed to treat selected herbs with the view of reducing the contents
308 of toxic ingredients or altering the chemical composition in order to modify their therapeutic
309 activity. Examples of herbs so processed include Aconitum, nux-vomica and Panax species.
310
311 The herbal preparations described above may serve as crude materials for use as herbal
312 medicines. In many cases, they will undergo further treatment procedures before being used
9
313 to manufacture the finished herbal products. The active ingredients are usually not purified
314 but rather are obtained along with other components of the medicinal plant part. Sometimes
315 the active ingredients are further concentrated by the removal of inactive and/or undesirable
316 substances. The herbal preparations thus obtained include extracts, decoctions, tinctures,
317 essential oils, and others. The processes involved include extraction, distillation,
318 fractionation, purification, concentration, fermentation, or other chemical/biological methods.
319
320 1.2.3 Processing of herbal materials or herbal preparations into herbal dosage forms
321
322 Depending on the intended use, herbal materials could be regarded as starting materials and
323 herbal preparations could be regarded as intermediates in the process of producing finished
324 products or as final dosage forms for therapeutic applications. In the latter case, it is not
325 uncommon that simple dosage forms are prepared from either herbal materials (such as
326 unprocessed seeds or plant exudates) or herbal preparations (such as ground powders and
327 dried extracts) ready for administration to the patients. These herbal dosage forms, produced
328 under GMP conditions, include liquid extracts, decoction, tea bags, granules, syrups,
329 ointments/creams, inhalations, patches, among others.
330
331 1.3 Objectives of guidelines
332
333 These new guidelines will provide technical guidance on good herbal processing practices
334 (GHPP) for the production of herbal materials, herbal preparations and finished herbal dosage
335 forms. Under the overall context of quality assurance and control of herbal medicines, the
336 main objectives of these guidelines are to:
337
338  provide general and specific technical guidance on GHPP for herbal medicines;
339  provide technical information on general as well as specific good herbal processing
340 techniques and procedures applied for the preparation of herbal materials from
341 herbs/medicinal plant;
342  provide technical information on good herbal processing techniques and procedures
343 applied for the production of herbal preparations from herbal materials;
344  provide technical information on good herbal processing techniques and procedures
345 applied for the production of dosage forms of herbal medicines;
346  provide a model for the formulation of national and/or regional good herbal processing
347 practice guidelines and monographs for herbal materials, as well as for herbal preparations,
348 and related standard operating procedures (SOP); and
349  contribute to the quality assurance and control of herbal materials, herbal preparations and
350 herbal dosage forms, and to promote safety, efficacy and sustainability of herbal
351 medicines.
352
353 Use of these guidelines
354 These guidelines should be considered in conjunction with the existing WHO technical
355 documents and publications relating to the quality assurance of herbal medicines and
356 medicinal plants (for details, see References), for example:
357
358  WHO guidelines on good agricultural and collection practices (GACP) for medicinal
10
359 plants [WHO, 2003a];

360  WHO guidelines on good manufacturing practices (GMP) for herbal medicines [WHO,
361 2007a];
362  Good Manufacturing Practices for pharmaceutical products: main principles [WHO,
363 2014];
364  Quality control methods for herbal materials [WHO, 2011];
365  WHO guidelines on assessing quality of herbal medicines with reference to contaminants
366 and residues [WHO, 2007b];
367  Safety issues in the preparation of homeopathic medicines [WHO, 2010];
368  WHO guidelines for selection of substances of herbal origin for quality control of herbal
369 medicines [in press, WHO, 2017];
370  WHO monographs on selected medicinal plants, Vol. 1-4 [WHOM-1999, WHOM-2002,
371 WHOM-2007, WHOM-2009];
372  WHO monographs on selected medicinal plants commonly used in the Newly Independent
373 States (NIS) [WHOM-2010]; and
374  General guidelines for methodologies on research and evaluation of traditional medicine
375 [WHO, 2000].
376
377 The WHO guidelines on good herbal processing practices (GHPP) for herbal medicines is
378 one of a series of guidance documents concerned with control measures necessary to produce
379 quality herbal medicines for safe and efficacious use as directed by the appropriate authority
380 body. The present document concerns the assurance of the quality of the herbal materials
381 being prepared through various methods and steps of processing of the medicinal plant and its
382 medicinal plant part obtained under GACP; and of the herbal preparations being prepared
383 through various methods and steps of processing of the herbal materials. Herbal materials can
384 be used directly as herbal medicines or to serve as source materials for the GMP production of
385 finished products. These guidelines are applicable to the processing operations from post-
386 harvest to finished herbal products. The processing of medicinal plants or plant parts should
387 meet all applicable national and/or regional quality standards. The guidelines therefore may
388 need to be adjusted according to local legislation and practice in each Member State. Each
389 Member State should develop its own national guidelines on good herbal processing practices
390 for herbal medicines that are appropriate to the country’s actual situation.
391
392 1.4 Definitions of terms
393
394 The terms used in these guidelines are defined below. The terms and their definitions have
395 been selected and adapted from other WHO documents and guidelines that are widely used by
396 WHO Member States, as well as from other reference sources (reference source is indicated
397 with [ ]). These definitions may differ from those included in national regulations, and are
398 therefore, for reference only.
399
400 1.4.1 Terms related to herbal medicines
401
402 Herbal medicines include herbs and/or herbal materials and/or herbal preparations and/or
403 finished herbal products in a form suitable for administration for patients. [WHO, 2017, in
404 press]
11
405 Note: In some countries herbal medicines may contain, by tradition, natural organic or
406 inorganic active ingredients that are not of plant origin (e.g. animal and mineral
407 materials). [WHO, 2017, in press]
408
409 Herbs [WHO, 2017, in press]
410 Herbs are crude plant material which may be entire, fragmented or powdered. Herbs
411 include, e.g. the entire aerial part, leaves, flowers, fruits, seeds, roots, barks (stems) of
412 trees, tubers, rhizomes or other plant parts.
413
414 Herbal materials [WHO, 2017, in press]
415 Herbal materials include, in addition to herbs, other crude plant materials. Examples
416 of these other plant materials include gums, resins, balsams, exudates.
417
418 Herbal preparations [WHO, 2017, in press]
419 Herbal preparations are produced from herbal materials by physical or biological
420 processes.
421 These processes may be extraction (with water, alcohol, supercritical carbon dioxide
422 (CO2)), fractionation, purification, concentration, fermentation, and other processes.
423 They also include processing herbal materials with a natural vehicle or steeping or
424 heating them in alcoholic beverages and/or honey, or in other materials.
425 The resulting herbal preparations include, among others, simply comminuted
426 (fragmented) or powdered herbal materials as well as extracts, tinctures, fatty (fixed)
427 or essential oils, expressed plant juices, decoctions, cold and hot infusions.
428
429 Finished herbal products [WHO, 2017, in press]
430 Finished herbal products consist of one or more herbal preparations made from one or
431 more herbs (i.e. from different herbal preparations made of the same plant as well as
432 herbal preparations from different plants. Products containing different plant materials
433 are called “mixture herbal products”).
434
435 Finished herbal products and mixture herbal products may contain excipients in
436 addition to the active ingredients. However, finished products or mixture herbal
437 products to which chemically defined active substances have been added, including
438 synthetic compounds and/or isolated constituents from herbal materials, are not
439 considered to be “herbal”.
440
441 Herbal dosage forms
442 Herbal dosage forms are herbal products in the forms in which they are marketed for use or
443 taken by the patient. They are produced either from herbal materials (such as dried roots or
444 leaves) or herbal preparations (such as freeze-dried extracts). The herbal dosage forms may
445 contain substances originated from a single herb or a combination of herbs.
446
447 Medicinal plants are plants (wild or cultivated) used for medicinal purposes [WHO, 2003a];
448 [WHO, 2007a].
449
450 Medicinal plant materials: see Herbal materials
12
451
452 1.4.2 Terms related to herbal processing practices
453
454 Processing
455 The processing of herbal materials refers to a series of post-harvest treatments applied to the
456 crude medicinal plant materials. For the purpose of the present guidelines, “processing”
457 includes primary processing, such as sorting, removal of untargeted plant materials, cleaning,
458 and drying as described in the WHO guidelines on GACP for medicinal plants [WHO, 2003a];
459 it also includes secondary and special processing as defined in the present guidelines.
460
461 Primary processing
462 Primary processing refers to a series of simple preparatory procedures that may be performed
463 at the harvest/collection site, including sorting, removal of untargeted plant materials,
464 cleaning, drying, and where appropriate, cooling and freezing.
465
466 Secondary processing
467 Secondary processing refers to the preparative steps applied to herbs in addition to the
468 primary processing before they can be used as materials for therapeutic treatment or as
469 intermediate materials for manufacturing of finished herbal products. They are considered
470 important pharmaceutical techniques in the herbal industry, through which purity of raw herbs
471 is assured (such as removal of foreign matter, prevention of microbial and insect
472 infection/infestation), and the therapeutic properties of raw herbs are altered (such as
473 enhancement of effectiveness or reduction of toxicity). The secondary processing procedures
474 may vary from one herbal material to another, depending on the characteristics of the active
475 ingredients as well as the therapeutic purposes. These processes, along with below described
476 “Special Processing”, have been grouped under the term “specific processing” in the WHO
477 guidelines on GACP for medicinal plants [WHO, 2003a].
478
479 Special processing
480 Special processing is an extension of the secondary processing by further treatments using a
481 series of well-defined special procedures after the general secondary processing, for the
482 purpose of further detoxification of some toxic herbs (e.g. aconite) or further enhancement of
483 the therapeutic properties (e.g. ginseng). It is often practiced by the herbal industry according
484 to traditional medicine knowledge and customs.
485
486 Adjuvants
487 Adjuvants are adjunctive substances used during the herbal processing procedures alongside
488 the herbal materials, included for the purpose of altering the pharmacological/therapeutic
489 properties of the herbal preparations or neutralizing/reducing toxicity. Common adjuvants
490 include wine, vinegar, honey, milk, and clarified butter, among other materials.
491
492 1.4.3 Terms relating to quality control
493
494 For a comprehensive list of terms on quality control of herbal medicines, please refer to the
495 WHO guidelines on GMP for herbal medicines [WHO, 2007a], Good Manufacturing
496 Practices for pharmaceutical products: main principles [WHO, 2014]; Quality control
13
497 methods for herbal materials [WHO, 2011], and WHO guidelines for selection of substances
498 of herbal origin for quality control of herbal medicines [WHO, 2017]. The following terms
499 are more directly or indirectly applicable to the present guidelines than others.
500
501 Batch (or lot) [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
502 A defined quantity of starting material, packaging material or product processed in a single
503 process or series of processes so that it is expected to be homogeneous. It may sometimes be
504 necessary to divide a batch into a number of sub-batches which are later brought together to
505 form a final homogeneous batch. In the case of terminal sterilization the batch size is
506 determined by the capacity of the autoclave. In continuous manufacture the batch must
507 correspond to a defined fraction of the production, characterized by its intended homogeneity.
508 The batch size can be defined either as a fixed quantity or as the amount produced in a fixed
509 time interval.
510
511 Batch number (or lot number) [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
512 A distinctive combination of numbers and/or letters which uniquely identifies a batch on the
513 labels, its batch records and corresponding certificates of analysis, etc.
514
515 Contamination [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
516 The undesired introduction of impurities of a chemical or microbiological nature, or of
517 foreign matter, into or on to a starting material or intermediate during production, sampling,
518 packaging or repackaging, storage or transport.
519
520 Cross-contamination [WHO, 2007a- WHO, 2003b]; [WHO, 2014]
521 Contamination of a starting material, intermediate product or finished product with another
522 starting material or product during production.
523
524 Good manufacturing practice (GMP) [WHO, 2014]
525 GMP is that part of quality management which ensures that products are consistently
526 produced and controlled according to the quality standards appropriate to their intended use
527 and as required by the marketing authorization, clinical trial authorization or product
528 specification. GMP is concerned with both production and quality control. GMP is aimed
529 primarily at managing and minimizing the risks inherent in pharmaceutical manufacture to
530 ensure the quality, safety and efficacy of products.
531
532 In-process control [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
533 Checks performed during production in order to monitor and, if necessary, to adjust the
534 process to ensure that the product conforms to its specifications. The control of the
535 environment or equipment may also be regarded as a part of in-process control.
536
537 Master formula [WHO, 2007a – WHO, 2003b];[WHO, 2014]
538 A document or set of documents specifying the starting materials with their quantities and the
539 packaging materials, together with a description of the procedures and precautions required to
540 produce a specified quantity of a finished product as well as the processing instructions,
541 including the in-process controls.
542
14
543 Chemical reference substance (or standard) [WHO, 2007c]

544 An authenticated, uniform material that is intended for use in specified chemical and physical
545 tests, in which its properties are compared with those of the product under examination, and
546 which possesses a degree of purity adequate for its intended use.
547
548 Specification [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
549 A list of defined requirements with which the products or materials used or obtained during
550 manufacture have to conform. They serve as a basis for quality evaluation.
551
552 Standard operating procedure (SOP) [WHO, 2007a – WHO, 2003b]; [WHO, 2014]
553 An authorized written procedure giving instructions for performing operations not necessarily
554 specific to a given product or material (e.g. equipment operation, maintenance and cleaning;
555 validation; cleaning of premises and environmental control; sampling and inspection).
556 Certain SOPs may be used to supplement product-specific master and batch production
557 documentation.
558
559 2. GOOD HERBAL PROCESSING PRACTICES FOR THE PRODUCTION OF
560 HERBAL MATERIALS
561
562 2.1 General information
563
564 Processing for the preparation of herbal materials from medicinal plants is often specific to
565 the medicinal plant and to the part and may involve unique procedures. The particular
566 processing methods may have a history as old as the use of medicinal plants, and they are
567 sometimes proprietary procedures. Many of the traditional processing procedures are subject
568 to standardization in modern settings.
569
570 When the medicinal plant and its parts are obtained through wild collection or cultivation
571 under GACP for medicinal plants [WHO, 2003a], they must be subjected to a series of good
572 practice of post-harvest processing procedures. The exact processing procedures may vary
573 from one herbal material to another. Some consist of only a few simple steps such as sorting,
574 cleaning and drying, and they are generally referred to as the “primary processing”. Others
575 may require some more complicated steps such as cutting, sectioning, comminuting,
576 aging/sweating, baking/roasting, boiling/steaming, and stir-frying, for the purpose of
577 improving the purity, preventing damage from mould and other microorganisms, detoxifying
578 intrinsic toxic ingredients, or enhancing therapeutic efficacy. Such processing procedures are
579 referred to as the “secondary processing” in these guidelines. They may have a significant
580 impact on the quality of the resulting herbal preparations.
581
582 Special processing is an extension of the secondary processing by further treatments using a
583 series of well-defined special treatment procedures applied to the herbs for specific purposes
584 such as reduction of toxicity or alteration/modification of therapeutic properties. Examples of
585 herbs (medicinal plants) using special processing include Aconitum, nux-vomica and Panax
586 species.
587
588 The safety and efficacy of herbal medicines are closely dependent on the quality of the
15
589 starting and processed source materials. To assure their quality, the good practices for
590 processing herbal materials may be considered. In general, good practices for processing
591 herbal materials mirror the good manufacturing practices for herbal medicine as delineated in
592 the WHO guidelines on GMP for herbal medicines [WHO, 2007a], with the first step being
593 the post-harvest handling and preparation of the starting medicinal plant materials under
594 sanitary conditions. All critical equipment for processing must be qualified; all processing
595 methods and procedures are standardized (SOP); master formulae, master and batch records
596 documented; and quality control parameters established and adhered to. GHPP
597 monograph/SOP protocol on specific herbal material should be developed and implemented.
598
599 2.2 Purposes and functions of processing
600
601 Through experiences gained over the centuries, knowledge has been acquired for the
602 development of processing procedures for maximizing the quality and therapeutic value of
603 herbal materials. The final form of a herbal medicine depends upon the nature of the herb and
604 its intended use. In general, the traditional processing of herbal materials serves several
605 purposes, such as concentrating the components, removing undesirable substances, modifying
606 the therapeutic properties, facilitating dispensing and compounding, and facilitating storage.
607 Thus, the major objectives for the processing of herbal materials are summarized as below.
608
609 Neutralization of toxicity and diminishing side effects
610 Herbal materials that possess significant levels of toxicity, highly potent pharmacological
611 activity or being known to cause severe side effects must be pre-treated in certain specific
612 manners in order to neutralize the toxicity or to reduce the side effects prior to use. Such a
613 detoxifying process is particularly important for those medicinal plants that are known to
614 contain toxic or undesirable chemical components; they must be properly processed to
615 remove those unwanted substances. Through the pre-treatment processes such as “steaming”
616 and “frying”, the heat-sensitive toxic components will be degraded. In other cases, processes
617 such as “sweating” and “aging” would result in enzymatic degradation of the toxic
618 ingredients. For example, raw aconite (Aconitum species) root, containing significant
619 amounts of toxic alkaloids such as aconitine, must be boiled or steamed for hours to hydrolyse
620 aconitine into less toxic derivatives. In the case of cascara (Frangula purshiana, synonym
621 Rhamnus purshiana) bark, they have to be aged for at least one year before use, to allow
622 oxidation to occur, by which the strongly laxative hydroxyanthracene glycosides are
623 converted to oxidized compounds of lower laxative potencies.
624
625 Modification of therapeutic properties
626 Some herbal materials require specific processing to alter their therapeutic properties. For
627 example, rhubarb (Rheum palmatum) in its raw form possesses purgative action and is useful
628 as a cathartic. After being steamed with wine, however, the purgative action is attenuated and
629 the processed rhubarb can be used for other purposes such as reducing inflammation.
630
631 The specific action of some herbal materials may be changed through processing. For
632 example, the unprocessed raw rehmannia (Rehmannia glutinosa) root is used to treat fever,
633 hypertension and skin eruptions; whereas after being cooked in wine, the processed
16
634 rehmannia is often used for tonic and anti-aging purposes in some traditional medicine
635 context.
636
637 In the case of ginseng (Panax ginseng) roots, different post-harvest processing procedures
638 give rise to several processed products, such as "white ginseng" and "red ginseng". "White
639 ginseng" is the material dried by the sun or heat, whereas “red ginseng” is prepared through a
640 series of steaming and cooking steps. These two types of ginseng products have found
641 different uses in some traditional medicine context, the former can nourish the Yin function
642 while the latter supports Yang.
643
644 Enhancing efficacy and reinforcing therapeutic effects
645 The therapeutic efficacy of certain herbal materials can be augmented through specific
646 methods of preparation. For instance, the pain-relieving property of corydalis (Corydalis
647 yanhusuo) rhizomes is believed to increase when they are stir-fried with rice vinegar.
648 Similarly the honey-treated ephedra (Ephedra species) is regarded to possess stronger
649 antitussive and anti-asthma properties than the unprocessed ephedra, which is mostly used as
650 a diaphoretic.
651
652 2.3 Processing techniques and procedures
653
654 Appropriate measures of general processing are dependent on the individual materials. These
655 processes should be carried out in conformity with state/provincial, national and/or regional
656 quality standards, regulations and norms. These protocols should also comply with the
657 regulatory requirements that apply in the producer and the purchaser countries. The SOP of
658 processing should describe in detail the various operations to be performed on the medicinal
659 plant material, such as sorting, washing, drying, crushing, milling, pulverization and sifting.
660 They should also include the length of time and temperature, among others. As much as
661 possible, the SOP should be followed. If modifications are made, they should be justified by
662 adequate test data demonstrating that the quality of the herbal materials is enhanced and/or
663 not compromised.
664
665 2.3.1 Preparation of harvested/collected medicinal plant part for processing
666
667 Harvested or collected raw medicinal plant materials should be promptly unpacked upon
668 arrival at the processing facility. Prior to processing, they should be protected from rain,
669 excessive sunlight, moisture and any other conditions that might cause microbial growth,
670 mould, aflatoxin formation, fermentation and thermal degradation. The unprocessed raw
671 medicinal plant materials should be stored in appropriate containers under adequate and
672 ventilated environmental conditions (special conditions of humidity and temperature may be
673 required and monitored); as well as protected from insects, rodents, birds, livestock, domestic
674 animals, and other pests.
675
676 Consistent quality for the finished herbal products can only be assured if the starting raw
677 medicinal plant materials are defined in a rigorous and detailed manner. For this reason, the
678 crude/raw medicinal plant materials must be adequately documented prior to the secondary
679 processing procedures to include, as far as possible, the following information;
17
680
681  Botanical name (Binomial), synonyms, and applicable variety, local name; plant part(s) of
682 the medicinal plant;
683  Source (cultivation/wild growing region);
684  Accession number/information;
685  Name and affiliation of collector or supplier;
686  Batch (or lot) number and size;
687  Collection (harvest) conditions (e.g. season/month and date; plant part; wet/dry
688 environment);
689  State of the plant material (e.g. fresh or dried);
690  Botanical authentication of the source medicinal plant materials;
691  Physical appearance such as colour, odour, form, shape, size and texture;
692  Suitable identification tests such as thin-layer chromatography (TLC) or other
693 chromatographic fingerprints;
694  Assay results, where appropriate, of active ingredient(s) or chemical reference standard(s);
695  Limit tests such as ash value, water content, and extractives; and
696  Determination of possible contaminants such as pesticides and heavy metals, mycotoxins,
697 microbiological load, and where appropriate, fumigation sulphur residue, and radioactivity.
698
699 2.3.2 Primary processing procedures
700
701 Harvested/collected medicinal plants and/or their parts undergo a series of post-harvest (and
702 post-collection) good practice of processing procedures, which in the broadest sense include
703 all steps from the immediate on-site primary clean-up of the desired medicinal plant part to its
704 being processed into a form (herbal materials) ready for therapeutic use or as a starting source
705 material for the production of a finished herbal products. While the exact processing methods
706 may differ from one herbal material to another, the procedures shall be adopted from those
707 good practice protocols specified in the national pharmacopoeia or recommended by other
708 authoritative documents of the end-user’s country. In the event that no acceptable good
709 processing procedures are available, or that modification of existing or reference cited
710 protocols are required, they should be justified by adequate quality control test data that the
711 quality of the herbal material is not diminished. In the absence of national/regional
712 procedures or protocols, international guidelines, such as WHO guidelines on GACP for
713 medicinal plants [WHO, 2003a], and the present guidelines, may be consulted.
714
715 2.3.2.1 Sorting (Garbling)
716 The sorting process serves as the first step to ensure the purity and cleanness of the medicinal
717 plant materials. After the bulk amount of the desired plant part is harvested or collected, all
718 extraneous and unwanted matters including dirt (e.g. soil, dust, mud, stones), impurities (e.g.
719 insects, rotten tissues, untargeted medicinal plants and/or plant parts), and residual non-
720 medicinal parts must be separated from the medicinal part(s). The process may involve,
721 depending on the plant material, procedures such as removing dirt and foreign substances,
722 discarding damaged parts, peeling (to separate unwanted plant parts from the medicinal plant
723 parts such as removing unwanted root bark from the roots or collecting stem bark from the
724 stem), sieving, trimming, singeing (to remove hairs or rootlets), removal of residuals of
725 unwanted plant parts (e.g. removing unwanted seeds from fruits and stripping leaves from
18
726 stems). Although sorting may be done by mechanical means in some cases, it is usually
727 performed by hand operation. Only suitably trained and equipped (e.g. gloves, dust mask, etc.
728 as appropriate) staff should carry out this work.
729
730 2.3.2.2 Washing
731 Raw medicinal plant materials, especially roots, rhizomes and tubers, are usually washed with
732 clean water, dried soon after harvest/collection. During the washing process, scraping and
733 brushing may be necessary. It is generally recommended not to soak the medicinal plant
734 materials in water for an unnecessarily long period of time. Change water frequently as
735 required.
736
737 2.3.2.3 Parboiling (Blanching)
738 After washing, certain raw medicinal plant materials may undergo a parboiling or blanching
739 process in which they are put into boiling water for a brief period of time without being fully
740 cooked. Such a heating procedure may serve several purposes, such as improving storage life
741 of the processed materials by gelatinizing the starch and preventing mould/insect
742 contamination, and facilitating further processing such as removal of the seed coat of
743 almonds.
744
745 2.3.2.4 Leaching
746 Some impurities can be removed by the action of running water over the raw medicinal plant
747 materials. The length of leaching has to be controlled in order to prevent excessive loss of
748 other ingredients.
749
750 2.3.2.5 Drying
751 Unless used in the fresh state, the raw medicinal plant materials are to be dried after being
752 sorted and washed. In general, they must be dried as soon as possible in order to reduce
753 damage from mould and other microbial infestation. Drying will also avoid tissue
754 deterioration and phytochemical alteration caused by the actions of enzymes and microbial
755 organisms; and will also facilitate grinding and milling, and convert the herbal materials into a
756 convenient form for further processing.
757
758 The final moisture content for dried herbal materials varies depending on the tissue structure,
759 but should generally be below 10-12%. Information on the appropriate moisture content for
760 particular herbal material may be available from pharmacopoeias or other authoritative
761 monographs.
762
763 Proper drying involves three major aspects: control of temperature, humidity and air flow.
764 The drying conditions are determined by the nature of the raw medicinal plant material to be
765 dried (tissue structure and chemical composition) and by the desired appearance of the final
766 form. The drying method used may have considerable impact on the quality of the resulting
767 herbal materials. Hence, the choice of proper operational procedure is crucial. Information
768 on the appropriate drying methods and procedures for particular herbal materials may be
769 available from pharmacopoeias or other authoritative monographs. In general, raw medicinal
770 plant materials are most often dried by sun-drying, shade-drying, or by artificial heat.
771
19
772 The drying conditions chosen should be appropriate to the type of the medicinal plant
773 material. They are dependent on the characteristic (e.g. volatility, stability) of the ingredients
774 and the texture of the plant part collected (e.g. root, leaf or flower). In general, the following
775 drying processes can be adapted.
776
777 Sun-drying
778 Some medicinal plant materials can be dried in the open air under direct sunlight, provided
779 the climate is suitable for such a practice. The duration of the drying process depends largely
780 on the physical state of the medicinal plant material and the weather conditions.
781
782 In the case of natural drying in the open air, medicinal plant materials should be spread out in
783 thin layers on drying frames and kept away from possible contaminations such as vehicle
784 exhaust, heavy dusts, and rain, as well as protected from insects, rodents, birds and other
785 pests, livestock and domestic animals. The material should be turned periodically to achieve
786 uniform drying. The drying frames should be located at least 15 cm above the ground.
787 Efforts should be made to achieve uniform drying within the shortest period of time to avoid
788 mould formation.
789
790 Shade-drying
791 Some medicinal plant materials can be dried in the shade with or without artificial air flow to
792 avoid direct exposure to strong sunlight. The drying process is slow, but it is preferred to
793 maintain (or minimize loss of) colour of leaves and flowers. Low temperatures (relative to
794 heat-drying) will also preserve most of the volatile and aromatic components by reducing
795 evaporation.
796
797 Drying by artificial heat
798 Drying by artificial heat can be more rapid than open-air drying and is often necessary on
799 rainy days or in regions where the humidity is high. Medicinal plant materials may be dried
800 by means of ovens, stoves, rack dryer, tunnel dryer, belt driers, other heating devices or with
801 open fires. The use of open fire should be avoided as much as possible, as residues of
802 combustion may introduced contamination. When open fire is used, the area must be well
803 ventilated.
804
805 For artificial-heat drying, the temperature, humidity and other conditions should be governed
806 by the physical nature of the drug and the physical/chemical properties of its active
807 ingredients. Over-heating may lead to an excessive loss of the volatile components and/or
808 decomposition of chemical ingredients. In general, the temperature should be kept below
809 65°C for barks and root and below 40°C for leaves, herbs and flowers.
810
811 2.3.3 Secondary processing procedures
812
813 In addition to the primary processing, the WHO guidelines on GACP for medicinal plants
814 [WHO, 2003a] also addressed, albeit very briefly, the fact that some herbal materials require
815 “specific” processing to improve their purity and quality. In the current guidelines, this term
816 is delineated into “secondary” and “special” processing. This section highlights the principles
817 and practice of the commonly used secondary processing techniques. In all cases, good in-
20
818 process control measures must be employed to assure the quality of the end product. National
819 and/or regional botanical and chemical quality standards for each processed herbal material
820 must be met. In absence of national standards, regional or international pharmacopoeial
821 standards may be adopted. Guidance for compliance measures can be found in the annex to
822 the Quality control methods for herbal materials [WHO, 2011], WHO guidelines for selection
823 of substances of herbal origin for quality control of herbal medicines [WHO, 2017], WHO
824 guidelines on GMP for herbal medicines [WHO, 2007a], and the present guidelines. An
825 example of a model format of good herbal processing practices monograph/SOP protocol on
826 secondary processing is given as Annex 1.
827
828 The applicable procedures of the secondary processing nature are as follows:
829
830 2.3.3.1 Cutting, sectioning, and comminution (see also section 3.2.1.2 for Comminution
831 (fragmentation)/grinding/milling)
832
833 When thoroughly dried, the herbal materials are processed by cutting and sectioning into
834 convenient or specific sizes and shapes or forms for storage or direct use as decoction
835 slices/pieces, and/or further processing for the manufacture of herbal preparations or finished
836 herbal products. Decoction slices or pieces are available in many Member States for direct
837 use as herbal medicines. Where applicable, the entire, sectioned or cut herbal materials are
838 comminuted/pulverized into powder form according to common practice found in herbal
839 medicines for use as a finished herbal products.
840
841 White and/or red ginseng products presented as root pieces, slices, or in powder form
842 prepared from naturally dried roots of Panax ginseng, marketed as herbal medicines, are good
843 examples of herbal materials derived from simple processing procedures.
844
845 2.3.3.2 Aging/Sweating
846 The aging (or wilting) process refers to storing the herbal materials for a period of time after
847 being harvested or collected from the field prior to use. It is generally done under the sun or
848 in the shade for up to a year, depending on the specific herbal material. During the process of
849 aging, excessive water is evaporated and enzymatic reactions (such as hydrolysis of the
850 glycone portion from glycosides) may occur to alter the chemical composition of the herbal
851 material. For example, cascara (Frangula purshiana, synonym Rhamnus purshiana) bark
852 should be aged for at least one year (or artificially heated to speed up the process) prior to use
853 in medicinal preparations, for the purpose of curtailing the strong irritating effects that may
854 cause vomiting and upset stomach.
855
856 A similar process known as sweating involves keeping the herbal materials at a temperature
857 of 45-65 °C with high humidity for an extended period of time, from one week to a couple of
858 months, depending on the plant species. The herbal materials are usually densely stacked
859 between woollen blankets or other kinds of cloth. The sweating process is considered a
860 hydrolytic and oxidative process in which some of the chemical ingredients within the herbal
861 materials are hydrolysed and/or oxidized.
862
863 For example, vanilla beans (Vanilla planifolia) are well known to undergo repeated sweating
21
864 between woollen blankets in the sun during the day and packing in wool-covered boxes at
865 night for about two months, during which the vanilla pods lose up to 80% of weight and take
866 on the characteristic colour and odour of the commercial drug.
867
868 2.3.3.3 Baking/Roasting
869 The baking/roasting process is a dry-heating using indirect, diffused heat, where the herbal
870 materials are put in a heating device, often embedded in bran or magnesium silicate (talc)
871 powder to ensure even heating on the entire surface at an elevated temperature for a specified
872 period of time. Some herbal materials are wrapped in moistened papers during the roasting
873 process. The exact temperature used and duration of baking/roasting vary from one herbal
874 material to another. Some are baked or roasted until the surface colour turns yellowish
875 brown; some may be further heated until charred.
876
877 For example, the processing procedure of nutmeg (Myristica fragrans) and kudzu (Pueraria
878 montana var. lobata) root requires being roasted with bran.
879
880 2.3.3.4 Boiling/Steaming
881 The boiling process involves cooking the raw medicinal plant materials in water or another
882 liquid solvent such as vinegar, wine, milk or other vehicles.
883
884 In the steaming process, raw medicinal plant materials and/or herbal materials are kept
885 separate from the boiling water but have direct contact with the steam, resulting in a moist
886 texture to the herbal materials. Such treatment is often done by placing the herbal materials in
887 a steamer or in a special utensil equipped with a flat frame hanging over boiling water. In
888 some cases, the herbal materials are pre-mixed with excipient substances such as wine, brine,
889 or vinegar before being steamed. The boiling/steaming process serves to soften plant tissues,
890 to denature enzymes present in the herbal materials, and/or to thermally degrade selected
891 chemical constituents. At the same time, the excipient, if used, is absorbed into the plant
892 tissues to become an integral part of the processed herbal materials.
893
894 For example, Reynoutria multiflora (synonym Polygonum multiflorum) root is often steamed
895 in the presence of a black-bean decoction in order to enhance its tonic effects. Boiling the
896 raw medicinal plan materials such as Croton tiglium, Abrus precatorius, Nerium oleander
897 (synonym N. indicum), and Gloriosa superba, in cow’s milk is practiced in some traditional
898 medicine context to reduce the levels of their toxic ingredients and thus diminish the toxicity
899 of the herbal materials.
900
901 2.3.3.5 Stir-frying
902 Stir-frying is a process in which the herbal materials are put in a pot or frying pan,
903 continuously stirred or tossed for a period of time under heating, until the external colour
904 changes, charred, or even carbonized. Depending on the medicinal plant species, the stir-
905 drying process may require the addition of adjuvants such as wine, vinegar, honey, saline, and
906 ginger juice, which would be infused into the herbal matrix to become an integral part of the
907 processed herbal material.
908
909 To ensure even heating on the surface of the herbal materials, sand, rice, bran, talc or clay can
22
910 be admixed with the herbal material during stir-frying.

911
912 For example, liquorice (Glycyrrhiza glabra) root and rhizome and Astragalus mongholicus
913 (synonym A. membranaceus) roots are often stir-fried with honey for the preparation of
914 decoction slices, whereas the Salvia miltiorrhiza root is stir-fried with wine. In the case of
915 ginger, fresh ginger is often stir-fried together with sand until the surface colour turns brown.
916 In other instances, ginger can be further stir-fried over intense fire to a carbonized state for
917 use as decoction pieces.
918
919 2.3.3.6 Fumigation
920 Fumigation by sulphur dioxide has been employed in post-harvest handling of some
921 medicinal herbs for the purpose of preserving colour, improving fresh-looking appearance,
922 bleaching, preventing the growth of insect and overcoming decays caused by moulds. Thus
923 the process has been frequently applied to herbal materials of light and bright colours to avoid
924 “browning”. Due to concerns about the undesirable residues, this process should be avoided
925 as much as possible. When a real need is identified, treatment should be carried out at the
926 earliest possible stage and exclusively by adequately trained and qualified personnel,
927 according to the specific recommendations for use. All relevant regulations (e.g. limits on
928 sulphur residue) should be complied with.
929
930 2.3.3.7 Irradiation
931 In some cases, infrared or ultraviolet lights can be used to eliminate or reduce microbial load
932 of the medicinal plant materials. The use of these procedures has to comply with the national
933 and/or regional regulations.
934
935 2.3.3.8 Selection of processing method
936 Herbal materials derived from the same species but processed by different methods may show
937 significant differences in quality and therapeutic properties, owing to the influence of the
938 treatment process on the chemical composition.
939
940 It is not uncommon to find different processing methods for the same medicinal plant/plant
941 part, depending on intended use. For example, raw (unprocessed) liquorice is used as an
942 antitussive and expectorant; but after being stir-fried with honey or ghee, the processed
943 liquorice becomes a tonic drug to be used for replenishing body strength.
944
945 Prior to processing, consult the national or regional regulatory standards and other literature
946 sources to decide on the most appropriate method to use. Once a method is adopted, adhere to
947 the SOP to ensure batch-to-batch consistency. For industrial production, method validation
948 should be adopted as part of the SOP.
949
950 Only suitably trained staff should carry out the work, which should be conducted in
951 accordance with the SOP and national and/or regional regulations in both the
952 grower/collector, manufacturer and the end-user countries.
953
954 2.3.3.9 Temperature
23
955 With in-processing procedures that involve heating, the temperature used is critical. Ensure
956 that the required temperature is achieved during the process. In some cases, pre-heating the
957 equipment (e.g. oven, frying pan and steamer) and/or the additives (such as sand, bran and
958 rice) is required before putting in the herbal materials. When heating equipment (e.g. electric
959 oven) is used, the heating device should be regularly calibrated.
960
961 2.3.3.10 Duration of procedure/treatment
962 It is also critical to control the duration of the procedure/treatment of the herbal materials.
963 Both over- and under- treatment will affect the quality of the resulting materials. Duration of
964 procedure/treatment should be monitored through adequate in-process controls performed on
965 the basis of organoleptic alterations (such as changes in colour, odour, and texture) or changes
966 in the contents of constituents with appropriate instruments or testing.
967
968 2.3.3.11 Use of adjuvants
969 Any adjuvant (e.g. wine, vinegar, salt, ginger juice and honey) used in the processing
970 procedures should be of the required/appropriate quality. The quality of adjuvants must be
971 clearly defined and controlled (according to pharmacopoeial requirements and/or relevant
972 regulatory requirements). The exact amounts and quality of these adjuvants used (the ratio of
973 herbal material and the adjuvant) should also be consistent from batch to batch.
974
975 2.3.4 Special processing procedures
976
977 For herbal materials derived from toxic medicinal plants, general primary and/or secondary
978 processing might be insufficient to reduce or attenuate their adverse effects. Such herbal
979 materials require further special processing procedures before they can be used for therapeutic
980 purpose. These special processing procedures serve as a means to detoxify or neutralize the
981 toxicity, or to reduce the side effects. Such processes are particularly important for those
982 medicinal plant parts that are known to contain toxic or undesirable chemical components;
983 they must undergo proper processes in order to have the unwanted substances degraded. On
984 the other hand, a number of herbal materials require special methods of processing in order to
985 enhance their therapeutic efficacy or to modify their therapeutic properties for the treatment of
986 other disease conditions. The following are examples of special herbal material processing
987 used in some traditional medicine context.
988
989 2.3.4.1 Detoxification
990  Aconite (Aconitum species) root is a highly toxic substance and should not be taken in the
991 crude form. Only after proper processing procedures can the toxicity of aconite root be
992 reduced so that it becomes suitable for use in herbal medicine by trained practitioners. The
993 specific process generally involves boiling in water or steaming, or both, to significantly
994 reduce the content of aconitine and related alkaloids.
995  Nux-vomica (Strychnos nux-vomica) seeds are specifically processed by frying in
996 ghee/clarified butter or boiling in water or other media such as cow’s milk to reduce the
997 content of their toxic ingredients, strychnine and brucine.
998  Pinellia ternata tuber: To reduce the gastrointestinal irritant property, the raw herb is
999 soaked in a solution containing glycyrrhiza and calcium oxide at a pH ≥ 12. Another way
1000 of reducing the irritant property is soaking in water together with potassium aluminum
24
1001 sulphate, or boiled in water together with ginger and potassium aluminum sulphate.
1002  Arisaema erubescens rhizome: The raw medicinal plant material is first soaked in water
1003 together with potassium aluminum sulphate for several days, followed by cooking with
1004 ginger and potassium aluminum sulphate to reduce the strong irritant effect on the
1005 respiratory and gastrointestinal tracts. An alternate method for processing Arisaema
1006 rhizome is by steaming with animal bile.
1007  Euphorbia kansui and E. pekinensis herb: Processing by frying with vinegar is needed to
1008 degrade the toxic components that cause severe vomiting and diarrhoea, and central
1009 nervous system poisoning.
1010  Seeds of Xanthium strumarium (synonym X. sibiricum), Ricinus communis and Croton
1011 tiglium are often processed by stir-frying for the purpose of degrading their contained toxic
1012 proteins.
1013  Cascara sagrada (Frangula purshiana, synonym Rhamnus purshiana) bark: Following
1014 primary post-harvest processing, the bark is aged (stored) for at least one year prior to use
1015 as a laxative. During the aging period, natural enzymatic action reduces the drastic
1016 cathartic potency of its active glycoside constituents to a non-toxic level.
1017
1018 2.3.4.2 Modification of therapeutic properties
1019  Ginseng (Panax ginseng and Panax quinquefolius): Fresh ginseng is converted to red
1020 ginseng through a series of repeated steaming procedures to afford a product with altered
1021 medicinal properties.
1022  Corydalis yanhusuo rhizomes are stir-fried or cooked with rice vinegar to enhance their
1023 analgesic property.
1024  Rehmannia glutinosa root: The unprocessed herbal material is used to treat fever,
1025 hypertension and skin eruptions; whereas after being cooked in wine, the processed
1026 rehmannia is used as a tonic and anti-aging drug in some traditional medicine context.
1027
1028 2.3.4.3 Use of adjuvants
1029 Common adjuvants used during the special processing procedures include wine (e.g. rice
1030 wine, wheat wine, and sorghum wine), vinegar, honey, ginger juice, liquorice extract, cow
1031 milk, ghee and brine, etc. Under special circumstances, other auxiliaries such as, other animal
1032 derived materials including their tissues and secretions (e.g. goat milk, animal bile, goat fat,
1033 cow’s urine), butter, black bean extract, coconut water, tamarind juice, turmeric, lemon juice
1034 and mineral materials (e.g. borax) have been used. The quality of adjuvants must be clearly
1035 defined and controlled (according to pharmacopoeial requirements and/or relevant regulatory
1036 requirements).
1037
1038 In addition, the use of any materials derived from animal/animal products in any processing
1039 procedures should be evaluated for safety and contamination, especially of pathogens, prior to
1040 use. General guidance could be found e.g. in Safety issues in the preparation of homeopathic
1041 medicines [WHO, 2010].
1042
1043 2.3.5 Documentation
1044
1045 All processing procedures that could affect quality and safety of herbal materials should be
1046 documented. Guidance for good documentation can be found in the Good Manufacturing
25
1047 Practices for Pharmaceutical Products: main principle [WHO, 2007a -WHO, 2003b];
1048 [WHO, 2014], as well as WHO guidelines on good agricultural and collection practices for
1049 medicinal plants [WHO, 2003a]. Thus it is important to establish a record keeping system so
1050 that all records are up-to-date, maintained and traceable for the entire processing procedures
1051 for each batch of herbal materials.
1052
1053 Written processing records should include, but not be limited to, the following information;
1054
1055  Botanical (scientific) and the local/common names of the source medicinal plant material;
1056 and plant part(s) being processed;
1057  Site and time of harvesting/collection;
1058  Batch number and any other identification code;
1059  State of the plant (e.g. fresh or dried);
1060  Dates of receipt of the material, processing of the material, and completion of the process;
1061  Name of person in charge of the processing;
1062  General processes that the plant material has already undergone (drying, washing, cutting,
1063 for example., including drying time and temperatures, and size of herbal material);
1064  Gross weight of the plant material before and after processing;
1065  Method used for special processing;
1066  Details of the procedures (master formula), including descriptions of the utensil and
1067 equipment used, steps of operation, amount and quality grade of the auxiliary (e.g. wine,
1068 vinegar) and/or other substances (e.g. sand, bran) used, temperature control, length of
1069 processing time, after-process steps (e.g. cooling, drying, cutting), and other relevant
1070 information;
1071  Batch production detail deviations/modifications of the master formula;
1072  In-process control, e.g. organoleptic changes of the plant material after processing (such as
1073 change in colour, shape, texture, odour and taste);
1074  Quality control parameters, specifications, and assay results, where appropriate, of active
1075 ingredient(s) or Chemical reference standard(s); and
1076  Shelf-life/retest period.
1077
1079 HERBAL PREPARATION
1080
1082
1083 The herbal materials described in Section 2 of these guideline may be ready to serve as the
1084 starting materials for use as herbal medicines. In some cases, they are cut into sections or
1085 ground into powder and used directly as the final dosage form. But in many other cases, the
1086 herbal materials will undergo further treatment processes before being used to manufacture
1087 the finished herbal products. The ingredients are usually not purified and the extracts are
1088 further concentrated by the removal of inactive and/or undesirable substances.
1089
1090 Herbal preparations are thus obtained by subjecting the herbal materials to treatments such as
1091 extraction, distillation, fractionation, purification, concentration, fermentation, or other
1092 chemical/biological methods. These include extracts, decoctions, tinctures, essential oils, and
26
1093 others.
1094
1095 3.1.1 Preparation of herbal materials for processing
1096
1097  Authentication of herbal materials should be performed prior to extraction. Purity (devoid
1098 of contaminants) should also be ensured.
1099  Proper documentation on the herbal material should be available as recommended in
1100 Section 2.3.5.
1101  The herbal material should be cleaned, dried (unless fresh material is required), and
1102 comminuted into an optimal size for extraction.
1103  The herbal materials should be processed as soon as possible after arrival at the processing
1104 facility. Otherwise they must be properly stored to avoid contamination, damage, and
1105 deterioration.
1106  All operational steps should be reproducible and performed hygienically, forming parts of
1107 the processing SOP.
1108
1110
1111 In general, for processes such as extraction, fractionation, purification and fermentation, the
1112 rationale for the guidelines should be established on a case-by-case basis. An example of a
1113 model format of good herbal processing practice monograph/SOP protocol to produce a
1114 herbal preparation is given as Annex 2. The general guidance is provided below.
1115
1116 3.2.1 Extraction
1117
1118 Extraction is a process in which soluble plant chemical constituents (including those which
1119 have therapeutic activity) are separated from insoluble plant metabolites and cellular matrix,
1120 by the use of selective solvent (which is sometimes called the menstruum). The purpose of
1121 extraction of medicinal plant matrix is to eliminate unwanted materials and to concentrate
1122 other constituents in a soluble form. Herbal extracts include decoctions, liquid extracts, soft
1123 extract, fluidextracts, tinctures, oleoresins, dry extracts, and others. The herbal preparations
1124 so obtained may be ready for use as a medicinal agent, or it may be further processed into
1125 finished herbal products such as tablets and capsules.
1126
1127 Various techniques are used for extraction, including maceration, infusion, digestion,
1128 percolation, and decoction. Modern separation techniques can also be applied, e.g. counter-
1129 current extraction, microwave-assisted extraction, ultrasonic extraction (sonication), and
1130 supercritical fluid extraction.
1131
1132 3.2.1.1 Common methods of extraction
1133 In order to produce herbal preparations of defined quality, the use of appropriate extraction
1134 technology, extraction solvents, and type of equipment are crucial. Some common methods
1135 of extraction are illustrated below.
1136
1137 Maceration
27
1138 Maceration involves the procedures of mixing the properly comminuted herbal materials with
1139 the solvent and allowing the mixture to stand at a certain temperature (in most cases at room
1140 temperature) for a defined period of time with frequent agitation. During the maceration
1141 process, chemical constituents are separated from the plant tissues through a dissolution
1142 process into the liquid solvent. A common practice is to put the herbal material in a container
1143 and add solvent until the herbal powder is thoroughly moistened. An additional amount of
1144 solvent is then introduced. The mixture is agitated at regular intervals for a defined period of
1145 time, strained, and the marc (the solid materials) is pressed. All liquids are collected,
1146 combined, and separated by decantation, centrifugation, straining or filtration. The
1147 maceration process may be repeated if desirable. In the process of maceration, the herbal
1148 materials are macerated in definite quantities of a solvent (at an optimal ratio of the amounts
1149 of herbal material and solvent), and a definite duration should be specified. Exhaustive bulk
1150 extractions can be quite time-consuming and require large volumes of solvent.
1151
1152 In a special case, a modified maceration procedure involves pre-soaking the herbal material in
1153 water for a period of time to induce fermentation. In other cases, maceration can be
1154 performed by gentle heating in order to enhance the extraction efficiency in a process known
1155 as “digestion”.
1156
1157 “Sonication-assisted extraction” and “microwave-assisted extraction” are modified methods
1158 of maceration, in which ultrasound or microwave is utilized to enhance the extraction
1159 efficiency, to reduce the amount of solvent used, and to shorten the extraction time. For
1160 sonication, the herbal material is placed in a container together with a solvent, which is in turn
1161 put in an ultrasonic bath. The ultrasound provides sufficient power to breakdown the cell
1162 walls of the herbal material and facilitates the solubilization of metabolites into the solvent.
1163 The frequency of ultrasound, length of treatment, and temperature of sonication are important
1164 factors affecting the extraction yield. For microwave-assisted extraction, the herbal material
1165 is placed in a container together with water and subjected to microwave treatment. Heat
1166 generated by the microwave energy facilitates the dissolution of compounds from the herbal
1167 matrix into the solvent. Sonication-assisted and microwave-assisted extraction are rarely
1168 applied to large-scaled extraction; they are used mostly for the initial extraction of a small
1169 amount of material.
1170
1171 Infusion
1172 Infusion refers to an extraction procedure in which the herbal material is immersed in hot
1173 liquid for a brief period of time to produce a dilute liquid preparation. Typically, the herbal
1174 material is steeped in hot water and allowed to stand for some time (15-20 minutes).
1175 Sometimes another part of hot water is added and allowed to stand for additional time. The
1176 extracted plant material is removed by straining and the infusion is ready for use. Infusion is
1177 commonly employed to make herbal teas.
1178
1179 Percolation
1180 Percolation is the procedure in which the solvent is allowed to continuously flow through the
1181 herbal material in a percolator (a vessel with an outflow at the bottom ends). Typically, the
1182 properly comminuted herbal material is moistened with an appropriate amount of solvent and
1183 allowed to stand (macerate) for a few hours before being packed into the percolator.
28
1184 Additional solvent is added to totally wet the plant powder for a day or two. The bottom end
1185 (valve) of the percolator is then opened (adjusted), with fresh solvent being replenished from
1186 the top of the percolator to maintain a steady flow of solvent through the bed of herbal
1187 materials. The flow rate of the liquid is controlled by adjusting the valve of the outlet. The
1188 extraction liquid is collected from the bottom outlet of the percolator. When the process is
1189 completed, the marc is pressed and all liquids are pooled to obtain the percolate. In addition
1190 to the solvent used for the extraction, the flow rate and the temperature would influence the
1191 extraction yields and they have to be carefully controlled. Percolation is often used for an
1192 exhaustive extraction of the herbs and is applicable to both initial and large-scale extraction.
1193 In some cases, the process of percolation can be modified by applying vacuum to increase the
1194 flow of solvent.
1195
1196 Decoction
1197 Decoction is the most common method to make herbal preparations in various traditional
1198 medicine context. It involves boiling the herbal material in water, during which time the
1199 chemical ingredients are dissolved into the hot liquid. This procedure is suitable for
1200 extracting water-soluble and heat-stable ingredients of the medicinal plant and/or herbal
1201 materials.
1202
1203 A special technique of decoction is the “hot continuous (Soxhlet) extraction” using the
1204 Soxhlet apparatus. Typically, the Soxhlet instrument includes an extraction chamber with
1205 reflux condenser and a collection flask. The chamber is placed between the collection flaks
1206 and the condenser. The herbal powder or pieces are kept inside the extraction chamber. A
1207 suitable solvent is added to the flask and heated under refluxing. The solvent will first be
1208 evaporated up into the condenser, then liquefied and drops into the chamber and covers up the
1209 herbal powder. When the condensed solvent in the chamber reaches a certain height, it is
1210 siphoned back into the flask, and the next cycle of extraction starts. Usually, 50-60 times of
1211 recycling are necessary for an extraction to complete. Due to continuous extraction, this
1212 method is more efficient than simple decoction with less consumption of solvent. However,
1213 due to continuous heating at the boiling point of the solvent used, thermolabile compounds
1214 may be damaged and/or artefacts may be formed. Besides the laboratory scale setup for
1215 continuous extraction, industrial scale stainless steel extractors and high pressure extraction
1216 are commonly used in many manufacturing facilities.
1217
1218 Supercritical fluid extraction
1219 Supercritical fluid extraction is a modern technique making use of the solvating property of a
1220 supercritical fluid (carbon dioxide is the most common supercritical solvent) to dissolve the
1221 chemical constituents in herbal materials. The density of the supercritical fluid (thus its
1222 solvating property) can be adjusted by altering the temperature and pressure, or by the
1223 addition of modifiers (e.g. ethanol) to change the polarity of the supercritical fluid.
1224
1225 3.2.1.2 Steps involved in the extraction of herbs and herbal materials
1226 The following steps are generally involved in the extraction procedures.
1227
1228 Comminution (fragmentation)/grinding/milling (see also section 2.3.3.1)
29
1229 Prior to extraction, the medicinal plant part is generally dried and reduced to a size of 30-40
1230 mesh (the actual size can be adjusted as the need arises). If fresh material is used for
1231 extraction, it is necessary to perform extraction as soon as possible after the material is
1232 collected to avoid deterioration (microbial fermentation). The purpose of powdering the plant
1233 material is to rupture its tissues and cell structures so that the chemical ingredients are more
1234 readily exposed to the extraction solvent. Moreover, size reduction increases the surface area,
1235 which in turn enhances the mass transfer of chemical ingredients from plant tissue to the
1236 solvent. However, excessive grinding can degrade the herbal material through mechanical
1237 heating and oxidation from exposure to the air, and an excessively fine powder will block the
1238 pores of the extraction filter, slowing or preventing the passage of the filtrate.
1239
1240 Extraction
1241 The extraction process is carried out in the selected solvent at a desirable temperature for an
1242 optimal period of time. Depending on the polarity of the desirable chemical components,
1243 water or other solvents can be used, either at room temperature (“cold” extraction) or at an
1244 elevated temperature (“hot” extraction).
1245
1246 Filtration
1247 After the completion of extraction, the liquid so obtained is separated from the marc by
1248 filtration through a filter cloth or filter paper to remove any particulate insoluble residues.
1249 Other filtering devices/methods, including decantation, centrifugation, or straining, may be
1250 used depending on the method of extraction and matrix.
1251
1252 Concentration
1253 The extract is often concentrated by the removal of excessive solvent to a thick concentrated
1254 extract or to a solid mass. The concentration procedures may involve evaporation under
1255 reduced pressure, freeze-drying or spray-drying.
1256
1257 3.2.1.3 Common herbal preparations prepared by extraction
1258 Decoction
1259 A water-based herbal preparation made by boiling herbal materials with water, and is most
1260 common utilized in various traditional medicine context. Generally, it is recommended that
1261 only freshly prepared decoctions should be used. However, decoctions may be prepared by a
1262 programmable decocting machine that processes the herbal material at a specific temperature
1263 for a specific duration and then dispenses the decoction in hermetically sealed plastic pouches
1264 of a specified single-dosage volume that can be refrigerated for subsequent reheating and
1265 consumption. The amounts of herbal materials and water used, as well as the length of the
1266 decocting process, should be specified.
1267
1268 Infusion
1269 A dilute solution prepared by steeping the herbal materials in hot (sub-boiling) water over a
1270 short period of time. Infusions prepared in edible oil or vinegar are also available.
1271
1272 Extract
1273 A preparation of liquid, semi-solid or solid consistency obtained from herbal materials by an
1274 extraction process using suitable solvents. “Liquid (fluid) Extract” is a liquid preparation of
30
1275 herbal materials obtained using water, alcohol or other extraction solvents. When the
1276 evaporation of the solvent leads to a semi-solid extract composed of a resin in solution of an
1277 essential and/or fatty oil, it is called “Oleoresin”. In some cases, the solvent is partially
1278 evaporated to afford a semi-solid preparation called “Soft Extract”. When the solvent is
1279 completely removed, “Dry Extract” is obtained as a solid preparation. Dry extract can also be
1280 prepared by spray-drying with or without the use of an adsorbent (such as methyl cellulose),
1281 or by drying and milling to produce a powder. This may be further processed by compression
1282 or with use of a binding agent or granulation liquid to produce multi-particulate granules.
1283
1284 Fluidextract
1285 An aqueous alcoholic preparation typically made in a ratio of one part (e.g. one millilitre) of
1286 liquid to one part (one gram) of the extract of the original herbal materials.
1287
1288 Tincture
1289 An ethanol extract of herbal materials, typically made up of 1 part of herbal material and 5-10
1290 parts of solvent. Tinctures can be prepared by extracting herbal materials with ethanol of a
1291 suitable concentration or a spirit (an alcoholic beverage). The ratio of water to alcohol should
1292 be recorded.
1293
1294 Macerate
1295 A liquid preparation extemporaneously prepared by soaking the herbal material(s), reduced to
1296 a suitable size, in water at room temperature for a defined period of time, usually for 30
1297 minutes, when not otherwise specified.
1298
1299 3.2.1.4 Factors influencing extraction of herbal materials
1300 There are a number of factors that would influence the efficiency and reproducibility of the
1301 extraction process. A few issues to consider include the solvent used to make an extract,
1302 particle size of the herbal material, the herb-to-solvent ratio, kind of extraction process (e.g.
1303 percolation or maceration), extraction time, temperature and other relevant conditions. All
1304 these factors should be optimized and incorporated into the SOP, and be strictly adhered to.
1305
1306 3.2.1.5 Selection of extraction methods
1307  The choice of extraction method is governed by the nature (stability, solubility, etc.) and
1308 amount of material to be extracted. For large amounts, the feasibility of extracting in bulk
1309 scale should be considered.
1310  The extraction method should be as exhaustive as possible, i.e. removing as much of the
1311 desired ingredients as possible from the plant matrix.
1312  It should be fast, simple, economical, environment-friendly, and reproducible.
1313
1314 3.2.1.6 Extraction conditions and procedures
1315 Solvent
1316  Depending on the nature of the target compounds or undesirable compounds, an
1317 appropriate solvent (or solvent mixture) should be selected for use. While water has been,
1318 and is, most commonly used as a solvent, organic solvents of varying polarities are
1319 generally selected in modern methods of extraction to exploit the various solubilities of
1320 plant constituents. For example, an aqueous solution of alcohol (e.g. 60-80% aqueous
31
1321 ethanol) can extract the majority of organic secondary metabolites from herbal materials.
1322 Other solvents may apply for the extraction of specific types of ingredients (such as
1323 proteins and polysaccharides).
1324  When selecting a solvent or solvent mixture, the following factors should be considered:
1325 solubility of the target compounds, stability and reactivity of the solvent, safety (low
1326 toxicity, low flammability, non-corrosiveness), cost, ease of subsequent solvent removal
1327 and solvent recovery (low boiling point), and environmental friendliness.
1328  Before using a solvent, the material safety data sheet (MSDS) should be reviewed and
1329 appropriate protective measures should be used. Precautions must be taken to minimize
1330 the risk of fire and explosion. Care should be taken to reduce environmental
1331 contamination and to protect the workers and other people in the vicinity from exposure to
1332 chemical hazards.
1333  Toxic solvents and those detrimental to the environment, e.g. benzene, toluene, and carbon
1334 tetrachloride, must not be used. Diethyl ether should be avoided as it is highly flammable
1335 and can lead to the formation of explosive peroxides. The use of chlorinated solvents is
1336 discouraged; if used, dichloromethane is preferred to chloroform, the latter being more
1337 toxic. Ethanol is preferred over methanol; the latter has higher toxicity.
1338  Solvents are classified by ICH (CPMP/ICH 238/95), according to their potential risk, into:
1339 o class 1 (solvents to be avoided such as benzene);
1340 o class 2 (limited toxic potential such as methanol or hexane); and
1341 o class 3 (low toxic potential such as ethanol) [WHO, 2007b].
1342  Solvents of general-purpose grade available in plastic containers are often contaminated by
1343 plasticizers, and minimizing contamination is especially important when bulk extraction is
1344 carried out requiring large volumes of solvent. It is advisable to distil solvents prior to use.
1345  The amounts of solvent used must be optimized to ensure batch-to-batch conformity.
1346  The quality and specification of solvent used should be specified and controlled.
1347  Solvents should be properly stored in non-plastic containers in a well ventilated, fire and
1348 explosion containable area; and away from direct exposure to sun light.
1349  When solvents are recycled, strength and purity must be confirmed prior to re-use.
1350 Recycled solvent should be used in the same extraction process only.
1351  Waste solvents must be disposed safely and properly. Guidelines from national, local, or
1352 institutional regulations of waste solvent disposal must be strictly observed and followed.
1353  Limits for solvent residue may be important to observe especially when the solvent is not
1354 considered safe for general consumption.
1355
1356 Temperature
1357  To avoid thermal degradation of the chemical constituents, extractions are preferably
1358 performed under 40 °C, unless evidence is available for the use of higher temperatures.
1359  For heat stable constituents, Soxhlet extraction or decocting in boiling water can be used.
1360 In any case, higher than required temperatures should be avoided.
1361  Temperature during the entire extraction process should be controlled and recorded.
1362
1363 Length of treatment
1364  The length of extraction time depends on the purpose for which the extraction is performed
1365 and the nature of the active constituents. Insufficient time will result in incomplete
32
1366 extraction, but prolonged extraction will lead to excessive extraction of the unwanted
1367 constituents and/or degradation of active chemical ingredients.
1368  The number of repeated extraction cycles required for the complete removal of the
1369 desirable constituents is as important as the length of time per each extraction.
1370  The length of extraction time and the number of cycles should be controlled and recorded.
1371
1372 3.2.2 Distillation
1373
1374 For the extraction of volatile components of the herbal materials, such as essential (volatile)
1375 oils, the odorous and volatile principles of plants, techniques such as distillation, expression
1376 and enfleurage may be employed.
1377
1378 Water or steam distillation is a method of choice for extracting volatile ingredients from
1379 medicinal plants. In brief, the herbal material is packed in a still, a sufficient amount of water
1380 is added and brought to a boil (water distillation). Alternatively a stream of steam is
1381 introduced to the herbal material pre-soaked in water (water-steam distillation), or a stream of
1382 steam is introduced to medicinal plant materials without water being added (direct steam
1383 distillation). The method of distillation depends on the condition of the herbal materials.
1384 Water distillation can be applied to fresh plant materials to avoid steam to penetrate into the
1385 materials such as rose flowers, while direct steam distillation is often used for fresh or dried
1386 medicinal plant materials. Freed from the plant tissue, the essential oil is carried away with
1387 the steam. Upon condensation, both water and oil are collected in the liquid form, and the
1388 latter separates from the former into two immiscible layers.
1389
1390 The yield and quality of essential oil obtained by distillation is affected by the process
1391 parameters. It is advisable to design the most optimal conditions in order to obtain the best
1392 results. Among the contributing factors are: mode of distillation, condition of raw medicinal
1393 plant materials, loading of raw medicinal plant materials, steam pressure and temperature, and
1394 length of time for distillation.
1395
1396 For volatile oils that may be decomposed during distillation, they can be obtained by
1397 expression (mechanical pressing), solvent extraction, supercritical carbon dioxide extraction,
1398 or by the enfleurage process for delicate flowers of which volatile chemicals may decompose
1399 during distillation.
1400
1401 3.2.2.1 Distillation procedures
1402  The distillation apparatus must be set up properly and safely according to the
1403 manufacturer’s instructions.
1404  Distillation should be carried out in a well ventilated room.
1405  Optimum distillation conditions, e.g. heating rate and distilling rate, have to be specified
1406 and controlled.
1407  The equipment employed should be in conformance with the official safety standards and
1408 all procedures must conform to the operational instructions and safety requirements.
1409  The water used for distillation should at least comply with local requirements for drinking
1410 water.
1411
33
1412 3.2.3 Fractionation and Purification

1413
1414 Fractionation is a separation process in which a mixture is divided into a number of smaller
1415 quantities (fractions) with higher content of target substances (compounds). The crude
1416 extracts of herbal materials contain complex mixtures of secondary metabolites with
1417 diversified chemical and physical characteristics. It is often desirable to divide the chemical
1418 constituents into different groups based on their similarities in chemical and physical
1419 properties, such as a flavonoid-rich preparation, total glycosides, or an alkaloid fraction.
1420 Fractional separation of an herbal extract can be achieved by subjecting the extract to a
1421 variety of fractionation techniques such as liquid-liquid partition and various forms of
1422 chromatography. The method can be applied to produce semi-purified preparations in order
1423 to enrich active constituents, to remove inactive and/or toxic constituents.
1424
1425 3.2.3.1 Liquid-liquid partition
1426 The liquid-liquid partition (or solvent partition) method involves the use of a series of liquid
1427 solvents. The herbal extract is usually dissolved or suspended in water and partitioned with
1428 organic solvents successively in a sequence of increasing polarities, e.g. n-hexane,
1429 dichloromethane, ethyl acetate, and water-saturated n-butanol. As a result, chemical
1430 compounds possessing different polarities are transferred from the water portion to different
1431 solvent fractions according to the principle of “like dissolves like”. For example, the initial
1432 step of partition using non-polar solvents (such as n-hexane or petroleum ethers) removes
1433 lipophilic substances (such as alkanes, fatty acids, sterols) from the herbal mixture, and such a
1434 process is sometimes referred to as “defatting”. The compounds with intermediate polarity
1435 (such as flavonoids and quinones) will dissolve in the medium-polarity solvents (such as
1436 dichloromethane and ethyl acetate), whereas more polar compounds (such as glycosides,
1437 polyphenols) will be concentrated in the more polar solvents (such as butanol) or retained in
1438 the water phase.
1439
1440 The counter-current extraction technique can be applied for fractionation and purification
1441 purposes, where applicable.
1442
1443 3.2.3.2 Chromatography
1444 Further purification of the extract fractions can be achieved by various chromatographic
1445 techniques, of which column chromatography is commonly employed, particularly in the
1446 preparative scale. Column chromatography can be carried out using materials based on
1447 different mechanisms. Common modes are adsorption, partition, size exclusion, affinity and
1448 ion-exchange. The most frequently used stationary phases (sorbents) are silica gel and
1449 alumina in adsorption chromatography; in size exclusion and ion-exchange chromatography,
1450 polymeric gels and ion-exchange resins, respectively, are used. A proper column packed with
1451 the appropriate stationary phase and eluted by a mobile phase with suitable elution power is
1452 crucial to obtain optimized separation of constituents in the herbal extract.
1453
1454 3.2.3.3 Fractionation and purification procedures
1455 Liquid-liquid partition
1456  The storage, use, and disposal of solvents must be handled with care and in conformance
1457 with the national/local/institutional regulations.
34
1458  The experimental procedures should be carried out in certified facilities with sufficient
1459 ventilation and safety measures. They are preferably performed inside fume hoods.
1460
1461 Column chromatography
1462  The choice of stationary phase depends on the polarity, molecular size, or the charge of the
1463 desired ingredients. It should be supported by a good rationale.
1464  The choice of mobile phase (solvent system) must be optimized.
1465  Column operation and development procedures (e.g. column length and inner diameter,
1466 amount of stationary phase used, column packing, particle or bead size or macropore size,
1467 porosity and surface area, phase, and support, sample application, elution gradient
1468 formation, flow rate, temperature, fraction collection, and detection method), should be
1469 specified and standardized.
1470
1471 3.2.4 Concentration and drying
1472 The herbal extracts or semi-purified extracts are often concentrated to produce a concentrated
1473 liquid preparation by the removal of excessive solvent. This can be achieved through
1474 evaporation or vaporization. Solvent (single) can be recovered and may be reused provided
1475 that appropriate quality control is ensured. Mixed or mixture of solvents are not reusable.
1476 The degree of concentration depends on the desired end product.
1477
1478 Equipment for concentration may include descending film, thin layer or plate concentrators.
1479 Any method used to concentrate the extracts must avoid excessive heat because the active
1480 compounds may be subject to degradation. The liquid preparation so obtained may be used as
1481 is or further processed into a dry extract.
1482
1483 When complete drying is required, the drying process can make use of vacuum freeze dryers,
1484 cabinet vacuum dryers, continuously operating drum or belt dryers, microwave ovens, or
1485 atomizers. The technique for drying depends on the stability of the product and the amount of
1486 moisture that must be removed. The total removal of solvent results in a dry extract, which is
1487 less subject to microbial contamination than are liquid extracts. Powdered extracts are often
1488 produced by drying the extract onto an inert carrier, such as methyl cellulose, to facilitate
1489 processing into the final finished product.
1490
1491 3.2.4.1 Concentration and drying procedures
1492 • The minimization of loss and/or damage to the chemical constituents of interest is critical
1493 to ensuring the effectiveness of the preparation. Therefore, the preservation of the active
1494 ingredients is of paramount importance during the concentration stage when heat is often
1495 applied to evaporate the solvent. Any concentration process should ensure minimal
1496 thermal decomposition and chemical reactions (such as oxidation) to occur. For organic
1497 solvents, evaporation under reduced pressure at a temperature below 40 °C is preferred.
1498 • Solvent removal should be done as soon as possible after extraction. Prolonged exposure
1499 to sunlight should also be avoided.
1500 • While evaporation is the most common and the most applied technique for concentration,
1501 other approaches such as membrane technology and freeze concentration are available.
1502
1503 3.2.5 Fermentation
35
1504
1505 In some cases, herbal preparation is obtained after undergoing through a fermentation process
1506 of the plant powder or decoction. Fermentation can be either natural (“self-fermentation”)
1507 involving microbial cultures already present on the herb, enzymes naturally occurring in the
1508 herb (which may be activated by bruising the herb), or both, or by introducing an appropriate
1509 microbial organism (e.g. Lactobacillus bacteria).
1510
1511 For natural fermentation, the dry plant powder, a decoction, or an extract of herbal material is
1512 often mixed with the juice of sugarcane, brown sugar or honey, and the mixture is kept in an
1513 airtight utensil for several weeks for anaerobic fermentation to occur.
1514
1515 In some cases, herbal materials are mixed with a small amount of water and shaped into
1516 bricks, followed by microbial cultivation in an incubation room for a week or so, letting the
1517 mould grow on the surface of the herbal materials.
1518
1519 3.2.5.1 Fermentation procedures
1520 • When fermentation is required to produce a herbal preparation, all utensils should be
1521 completely cleaned. A non-corrosive fermentor is required.
1522 • The water to be used should comply with local requirement for potable water, not be
1523 alkaline and should be free of inorganic matters (deionized water).
1524 • The temperature and length of fermentation should be optimized and controlled.
1525 • When fermentation is complete, the solution is filtered and stored in suitable containers.
1526
1527 3.2.6 Powdering
1528
1529 Content needs to be developed.
1530 We kindly request reviewers to provide us with suggested input, as well as, any relevant
1531 technical information for formulating description on this sub-section.
1532 Thank you very much.
1533
1534 3.2.6.1 Powdering procedures
1539
1540 3.3 Documentation
1541
1542 The general principles for documentation are set out in the GMP for pharmaceutical
1543 products: main principles [WHO, 2007a – WHO, 2003b]; [WHO, 2014].
1544
1545 In addition to the data called for in the above guidelines, the documentation for herbal
1546 preparations should as far as possible include, as a minimum, the following information:
1547
1548  Botanical (scientific) name and the taxonomic authority (abbreviation if used should be
1549 according to internationally-accepted rules), the plant family name, any synonyms for the
36
1550 scientific name that are well established in the literature or in commerce, and the
1551 local/common name and well-established synonyms of the source medicinal plant material;
1552 and plant part(s) being processed;
1553  Site and time of harvest/collection of the plant;
1554  State of the plant (e.g. fresh or dried);
1555  Batch number, batch size, and any other identification code;
1556  Supplier;
1557  Dates of receipt of the herbal material, retained sample identifier, processing of the
1558 material, and completion of the process;
1559  Name of person in charge of the processing;
1560  Previous processes that the herbal material has already undergone;
1561  Characteristics of the herbal preparation (such as type of the preparation, ratio of the herbal
1562 material to the herbal preparation, organoleptic characters);
1563  Methods used for processing to produce herbal preparation;
1564  Details of the procedures (master formula), including quantity of herbal materials,
1565 extraction solvent, additive, descriptions of the steps of operation, operational conditions
1566 used during the process, and other relevant information;
1567  Batch production detail deviations/modifications of the master formula; and
1568  Quality control parameters (such as identification tests, tests on water content, impurities,
1569 residual solvents, microbial limits, shelf-life) and assay results, where appropriate, of
1570 active ingredient(s) or Chemical reference standard(s).
1571
1572 The SOP including all processing steps should be adopted and documented in the Master
1573 Record. Batch records should be kept and any deviations from the SOP should be fully
1574 recorded and investigated. Name(s) of all operators, and the dates and time on which each
1575 step/stage are carried out should be documented.
1576
1578 HERBAL DOSAGE FORMS
1579
1581
1582 In contrast to synthetic pharmaceutical drugs, many herbal materials and herbal preparations
1583 may undergo simpler good practice processes to become suitable dosage forms and final
1584 products for administration. However, these dosage forms should be produced under
1585 applicable Good Manufacturing Practices (WHO, 2007a). Starting materials for the
1586 preparation/production of various herbal dosage/final dosage forms should consist of good
1587 practice processed herbal materials or herbal preparations as described previously (Sections 2
1588 and 3).
1589
1590 Examples of a number of herbal dosage forms are presented in the Japanese Pharmacopoeia
1591 (16th Edition) (see Annex 3).
1592
1593 The following describes some common dosage forms of herbal medicines.
1594
37
1596
1597 4.2.1 Liquid herbal dosage forms
1598
1599 Liquid herbal dosage forms as described herein pertains to oral preparations, including, but
1600 not limited to the following product types/categories:
1601
1602 4.2.1.1 Fluidextracts
1603 For description, see section 3.2.3.
1604
1605 4.2.1.2 Infusions
1607
1608 4.2.1.3 Decoctions
1610
1611 4.2.1.4 Liquid (fluid) extracts
1612 For description, see section 3.2.3
1613
1614 4.2.1.5 Tinctures
1615 For description, see section 3.2.3
1616
1617 4.2.1.6 Syrups
1618 Syrups are viscous liquid containing sugars or other sweetening agents. They are prepared by
1619 dissolving, mixing, suspending or emulsifying herbal extracts or decoctions in a solution of
1620 honey, sucrose or other sweetening agents. When necessary, the mixture is boiled and
1621 filtered.
1622
1623 4.2.1.7 Oral emulsions
1624 Oral emulsions are liquid oil-in-water preparations that are rendered homogeneous by the
1625 addition of emulsifying agent. For example, an oil obtained from herbs (e.g. castor oil) is
1626 dispersed in water and emulsified with an emulsifying agent such as gum acacia.
1627
1628 4.2.2 Solid herbal dosage forms
1629
1630 4.2.2.1 Herbal tea bags
1631 Herbal tea bags are prepared by placing finely ground herbal materials (such as dried roots,
1632 leaves or flowers) into paper or cloth bags. When used, boiling water is poured into the vessel
1633 containing the bag to make an infusion.
1634
1635 4.2.2.2 Plant powders
1636 Powders are prepared by grinding/pulverizing herbal materials to a suitable particle size.
1637
1638 4.2.2.3 Powdered extracts
1639 Powdered extracts are prepared by spray-drying with or without the use of an adsorbent (such
1640 as methyl cellulose), or by drying and milling to produce a powder.
1641
38
1642 4.2.2.4 Granules

1643 Granules are dried liquid (fluid) extracts in the form of spherical particles. They are prepared
1644 by adding diluents, binders or other suitable excipients to extract powders, mixed to
1645 homogeneity and granulated by a suitable method. Typically, granules are dissolved in hot
1646 water to make a “herbal tea” for administration.
1647
1648 4.2.2.5 Pills
1649 Pills are dried extracts or decoctions in the form of small, spherical solids, similar to granules.
1650 They may be prepared by adding suitable excipients to extract powders, mixed to homogenize
1651 and granulated by a suitable method. Typically, pills are swallowed with warm water.
1652
1653 4.2.2.6 Capsules
1654 Capsules are prepared by enclosing herbal powder or dry/powder extract in capsule shells or
1655 in a suitable capsule base such as gelatine in a particular shape and size.
1656
1657 4.2.2.7 Tablets
1658 Tablets are solid preparations having a defined shape and size. They are usually prepared by
1659 mixing the homogenous dry/powder extract with excipients such as diluents and binders,
1660 followed by compression into a defined shape and size.
1661
1662 4.2.2.8 Lozenges
1663 Lozenges are solid dosage forms that are designed to dissolve slowly in the mouth to provide
1664 local action in the oral cavity or the throat, such as cough drops or pastilles. In addition to
1665 herbal ingredient, lozenges often contain flavouring agents and sweetened bases.
1666
1667 4.2.3 Other herbal dosage forms
1668
1669 4.2.3.1 Ointments/creams
1670 Ointments/creams are topical preparations for application to the skin. They are usually semi-
1671 solid emulsions dissolved or dispersed in a suitable base. Alongside with the herbal
1672 ingredients, they may contain emulsifiers or thickening agents.
1673
1674 4.2.3.2 Inhalations
1675 Inhalations are preparations intended for administration as aerosols to the bronchial tubes or
1676 lungs. They are usually either dry powder inhalers or inhalation liquid preparations. For
1677 administration of inhalations, suitable devices or apparatus are required.
1678
1679 Dry powder inhalers are prepared by pulverizing dried extracts into fine particles. When
1680 necessary, lactose or other suitable excipients are added to make a homogenous mixture.
1681 Inhalation liquid preparations are usually prepared by mixing dried herbal extracts with a
1682 vehicle and suitable pH adjusting agents to make a solution or suspension. Suitable
1683 preservatives may be added to prevent the growth of microorganisms.
1684
1685 4.2.3.3 Plasters and patches
1686 Plasters and patches contain herbal preparations such as dry or soft extracts on pieces of fabric
1687 or plastic sheets. When applied topically to the skin, they deliver the herbal ingredients
39
1688 through the skin to underlying tissues, usually for the relief of pain, backache, or sore
1689 muscles.
1690
1691 4.2.3.4 Aromatic waters
1692 Aromatic waters are water preparations containing saturated essential oils or other volatile
1693 substances. Usually, an essential oil (1 part) is shaken in water (999 parts) and set aside for
1694 12 hours or longer after mixing with 10 parts of talcum powder. The solution is filtered and
1695 made up to a certain volume with water. Aromatic waters have a characteristic odour of the
1696 essential oil or volatile substances used.
1697
1698 4.2.3.5 Gel capsules
1703
1704 5. TECHNICAL ISSUES SUPPORTING GOOD HERBAL PROCESSING
1705 PRACTICES
1706
1707 In the formulation of a good practice protocol for processing herbal materials, a number of
1708 supporting technical issues must be considered and adopted. Since the primary objective is to
1709 produce quality processed herbal materials and preparations, many of the same technical
1710 issues associated with the GACP, GMP and quality control (QC) methods are applicable to
1711 GHPP.
1712
1713 Therefore, these guidelines have been consulted for applicable good practice items for
1714 adoption. Moreover, the same technical issues on the post-harvest processing of cultivated
1715 and collected medicinal plant materials were addressed in section 4 of the WHO guidelines on
1716 GACP for medicinal plants [WHO, 2003a]. Thus, the applicable good practice guidelines
1717 have been adopted in whole or modified as appropriate for the present guidelines.
1718
1719 5.1 Processing facilities
1720
1721 The ideal design and construction of a herbal material processing facility incorporating the
1722 most appropriate location, buildings, medicinal plant material handling and processing areas,
1723 water supply, effluent and waste disposal, changing facilities and toilets, hand-washing
1724 facilities in processing areas, disinfection facilities, lighting, ventilation, dust and storage of
1725 waste and unusable materials, have already been fully described in Sections 4.1.5 (pages 19-
1726 23) of the WHO guidelines on GACP for medicinal plants [WHO, 2003a]. Therefore, they
1727 are adopted for the present guidelines and the descriptions are excerpted and presented in
1728 Annex 4 for easy reference.
1729
1730 5.2 Packaging and labelling
1731
1732 Processed herbal materials or herbal preparations should be packaged as quickly as possible to
1733 preserve their quality by preventing deterioration of the herbal medicines and to protect
40
1734 against unnecessary exposure to pest infestations and other sources of contamination.
1735
1736 Continuous in-process quality control measures should be implemented to eliminate sub-
1737 standard materials, contaminants and foreign matter prior to and during the final stages of
1738 packaging. Processed medicinal plant materials should be packaged in clean, dry boxes,
1739 sacks, breathable bags or other containers in accordance with standard operating procedures
1740 and meeting national and/or regional regulations of the producer and the end-user countries.
1741 Materials used for packaging should be non-polluting, clean, dry and in undamaged condition
1742 and should conform to the quality requirements for the processed herbal materials or herbal
1743 preparations concerned. Fragile medicinal plant materials should be packaged in rigid
1744 containers. Wherever possible, the packaging used should be agreed upon between the
1745 supplier and buyer.
1746
1747 A label affixed to the packaging should clearly indicate the scientific name, usual common
1748 name, brand name, the processed plant part with date, the processing techniques used, the
1749 name and address of the processor, finished product manufacturer, importer or distributor, i.e.
1750 the entity who should be responsible for receiving consumer complaints and conducting a
1751 recall should the need arise, as well as information on the potency or strength of the medicinal
1752 ingredient if applicable (e.g., for an extract the drug extract ratio (DER) of herbal material to
1753 extract, or the concentration of active or marker substance(s) used for standardization), net
1754 amount in the immediate container in terms of weight, measure or number, and in the case of
1755 a prepared dosage form the quantity of each medicinal ingredient per dosage unit, list of
1756 excipients, recommended storage conditions, and expiry date. Retail labelling should also
1757 provide the recommended use or purpose, the recommended dose and frequency per day,
1758 recommended duration of use, and cautionary information (e.g., known side effects, warnings
1759 regarding interactions, contraindications). The label should also contain information
1760 indicating quality approval and compliance with other national and/or regional labelling
1761 requirements. The label should bear a number that clearly identifies the production batch.
1762 Additional information about the production and quality parameters of the medicinal plant
1763 materials may be added in a separate certificate, which is clearly linked to the package
1764 carrying the same batch number.
1765
1766 Records should be kept of batch packaging, and should include the product name, place of
1767 origin, batch number, weight, assignment number and date. The records should be retained
1768 for a period of three years or as required by national and/or regional authorities.
1769
1770 5.3 Storage and transportation
1771
1772 All processed herbal materials or herbal preparations should be properly stored and preserved
1773 before use. They must be protected from microbial and insect contaminations, and rodents
1774 and other pests. Every effort should be tried to use the type of packaging that provides ample
1775 protection against physical damages to the materials and to keep away, as much as possible,
1776 from exposure to moisture, light, heat, and insect attack.
1777
1778 Substandard herbal medicines should be kept in a separate designated area, clearly labelled
1779 and with specified handling period. Toxic or specific herbal medicines should be checked,
41
1780 labelled and stored according to the government’s regulations.

1781
1782 Storage areas should be of sufficient capacity to allow orderly storage of the various types of
1783 processed herbal materials and herbal preparations with proper separation and segregation. In
1784 particular, they should be clean, dry, sufficiently lit and maintained within acceptable
1785 temperature and humidity limits, and controlled, monitored and recorded where appropriate to
1786 ensure good storage conditions.
1787
1788 Conveyances used for transporting processed herbal materials and herbal preparations from
1789 the place of processing to storage should be clean and, where appropriate, well ventilated to
1790 keep an appropriate level of air flow and to prevent condensation.
1791
1792 Fumigation against pest infestation in conveyances and in storage areas should be carried out
1793 only when necessary, and should be carried out by licensed or trained personnel. Only
1794 registered chemical agents authorized by the regulatory authorities of the source country and
1795 the countries of intended end-use should be used. All fumigation, fumigation agents, and
1796 dates of application should be documented. When freezing or saturated steam is used for pest
1797 control, the humidity of the materials should be checked after treatment.
1798
1799 5.4 Equipment
1800
1801 All equipment, including tools and utensils used in the processing of herbal materials and
1802 herbal preparations should be made of materials that do not transmit toxic substances, odour
1803 or taste; are non-absorbent; are resistant to corrosion and are capable of withstanding repeated
1804 cleaning and disinfection. The use of wood and other materials that cannot be adequately
1805 cleaned and disinfected should be avoided, except when their use would clearly not be a
1806 source of contamination. The use of metals known to cause corrosion should be avoided.
1807
1808 All equipment and utensils should be designed and constructed so as to prevent hygienic
1809 hazards and permit easy and thorough cleaning and disinfection. Where practicable, they
1810 should be accessible for visual inspection. Stationary equipment should be installed in such a
1811 manner as to permit easy access and thorough cleaning.
1812
1813 Containers for unusable materials or waste should be leak-proof, constructed of metal or other
1814 suitable impervious materials, should be easy to clean or be disposable, and should close
1815 securely.
1816
1817 All refrigerated spaces should be equipped with temperature measurement or recording
1818 devices.
1819
1820 5.5 Quality assurance and quality control
1821
1822 Quality assurance system is essential to ensure that herbal processing practice is consistently
1823 executed and controlled. Compliance with quality assurance measures should be verified
1824 through regular internal oversight personnel (QA manager) and external auditing visits to
1825 processing facilities by expert representatives of buyers and other stake holders and through
42
1826 inspection by national and/or local regulatory authorities. No processed herbal material or
1827 processed herbal preparation shall be released until its quality complies or conforms with
1828 standard specifications.
1829
1830 5.6 Documentation
1831
1832 The SOP should be adopted and documented. All methods and procedures involved in the
1833 processing of herbal materials and herbal preparations and the dates on which they are carried
1834 out should be documented.
1835
1836 The types of information that should be collected include the items described in Sections 2.3.5
1837 and 3.3 above. Additionally, documentation on post-processing transportation and storage of
1838 processed products should be prepared.
1839
1840 Where applicable, the results of inspection should be documented in an inspection report
1841 which contains copies of all documents, (QC) analysis reports, and local, national and/or
1842 regional regulations, and which are stored according to their requirements.
1843
1844 5.7 Personnel
1845
1846 5.7.1 General
1847
1848 All personnel should receive proper post-harvest handling and herbal processing training. All
1849 personnel required to handle chemical solvents and adjuvants should receive adequate training
1850 and possess sufficient knowledge and appropriate techniques employed for their safe handling
1851 and proper use. Training records should be signed by the trainer and trainee and documented.
1852
1853 Local, national and/or regional regulations governing labour should be respected in the
1854 employment of staff for all phases of herbal processing.
1855
1856 5.7.2 Health, hygiene and sanitation
1857
1858 All personnel involved in the pre-processing and during processing handling of herbal
1859 materials should be trained and perform tasks in compliance with local, national and/or
1860 regional regulations on safety, materials handling, sanitation and hygiene.
1861
1862 All personnel should be protected from contact with toxic or potentially allergenic herbs by
1863 means of adequate protective clothing, including gloves and masks.
1864
1865 Health status
1866 All personnel known, or suspected to be suffering from or to be a carrier of a disease or illness
1867 likely to be transmitted, should not be allowed to enter any processing area, and should
1868 immediately be reported to the management, and suspended from work as deemed medically
1869 appropriate.
1870
1871 Health conditions that should be reported to the management for consideration regarding
43
1872 medical examination and/or possible exclusion from handling of medicinal plant and
1873 processing/processed herbal materials and associated equipment including but not limited to:
1874 such as jaundice, diarrhoea, vomiting, fever, sore throat with fever, visibly infected lesions
1875 (boils, cuts, among other conditions) and discharges from the ear, nose or eye. Any personnel
1876 who have cuts or wounds and are permitted to continue working should cover their injuries
1877 with suitable waterproof dressings.
1878
1879 Personal hygiene and behaviours
1880 Personnel who handle processing/processed herbal materials should be trained to maintain a
1881 high degree of personal cleanliness, and, where appropriate, wear suitable protective clothing
1882 and gloves, including head/hair covering and footwear.
1883
1884 Personnel should always wash their hands at the start of handling activities, after using the
1885 toilet, and after handling medicinal plant materials or any contaminated material.
1886
1887 Smoking, drinking, and eating should not be permitted in medicinal plant processing areas.
1888
1889 Visitors
1890 Visitors to processing and handling areas should wear appropriate protective clothing and
1891 adhere to all of the personal hygiene provisions mentioned above [WHO, 2003a].
1892
1893 6. OTHER RELEVANT ISSUES
1894
1895 6.1 Ethical and legal considerations
1896
1897 All herbal processing must be carried out in accordance with applicable legal and
1898 environmental requirements and with the ethical codes or norms of the community and
1899 country in which the activities take place.
1900
1901 6.2 Research, research training and information sharing
1902
1903 Research to understand and gain knowledge on the mechanism and scientific basis of
1904 processing procedures as traditional or historical methods is needed; Research to find
1905 alternate processing procedures to achieve the same therapeutic effect as traditional or
1906 historical methods is also needed. Additionally, research to determine the chemical
1907 conversion process and mechanism involved in the qualitative and quantitative alteration of
1908 the biologically active chemical constituents following processing is also needed and
1909 encouraged.
1910
1911 Technical information resulting from processing method research is useful for promoting
1912 technical advancement, and should be shared through publication, conferences or otherwise
1913 conveyed to interested stakeholders.
1914
1915 As in all technical endeavours, education and research training are essential to preserve
1916 technical expertise and to promote innovation in development of new and better techniques
1917 and procedures in herbal processing.
44
1918
1919 Research to develop good herbal processing practices for individual medicinal plant part and
1920 document each in a monograph.
1921
1922 6.3 Adoption of good herbal processing practices
1923
1924 Member States or nations that have not adopted good herbal processing practices for herbal
1925 medicines are encouraged to establish or adopt such practices as part of quality assurance and
1926 control measures, as well as a part of their regulatory requirements for herbal medicines.
1927
1928 6.4 Intellectual property rights and benefits-sharing
1929
1930 Agreements on intellectual property rights and the return of benefits and compensation for the
1931 use of source herbal materials or herbal preparations concluded in writing by the sourcing
1932 contractor, shall be acknowledged and followed by the processor as appropriate.
1933
1934 6.5 Threatened and endangered species
1935
1936 When obtaining medicinal plants that are protected by national and international laws, such as
1937 those listed in national “red” lists, for processing, the processor shall ascertain and obtain
1938 appropriate documentation from the sourcing contractor that said materials were acquired
1939 only by relevant permission according to national and/or international laws, and that the
1940 provisions of the Convention on International Trade in Endangered Species of Wild Fauna
1941 and Flora (CITES) have been complied with.
1942
1943 7. REFERENCES
1944
1945 WHO, 2000:General guidelines for methodologies on research and evaluation of traditional medicine
1946 WHO/EDM/TRM/2000.1, Geneva, World Health Organization, 2000.
1947
1948 WHO, 2003a:WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants.
1949 Geneva, World Health Organization, 2003.
1950
1951 WHO, 2003b: Good Manufacturing Practices for pharmaceutical products: main principles In: WHO
1952 Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-seventh report. Geneva,
1953 World Health Organization, 2003 (WHO Technical Report Series, N0. 908), Annex 4.
1954
1955 WHO, 2007a: WHO guidelines on good manufacturing practices (GMP) for herbal medicines. Geneva,
1956 World Health Organization, 2007.
1957
1958 WHO, 2007b:WHO guidelines on assessing quality of herbal medicines with reference to contaminants
1959 and residues, Geneva, World Health Organization, 2007.
1960
1961 WHO, 2007c:General guidelines for the establishment, maintenance and distribution of chemical reference
1962 substances. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-first
1963 report. Geneva, World Health Organization, 2007 (WHO Technical Report Series, No. 943), Annex 3.
1964
1965 WHO, 2010: Safety issues in the preparation of homeopathic medicines, Geneva, World Health
1966 Organization, 2010.
45
1967 WHO, 2011:Quality control methods for herbal materials. Geneva, World Health Organization, 2011.
1968
1969 WHO, 2014:Good Manufacturing Practices for pharmaceutical products: main principles In: WHO Expert
1970 Committee on Specifications for Pharmaceutical Preparations. Forty-eighth report. Geneva, World Health
1971 Organization, 2014 (WHO Technical Report Series, N0. 986), Annex 2.
1972
1973 WHO, 2017:WHO guideline for selecting marker substances of herbal origin for quality control of herbal
1974 medicines. Geneva, World Health Organization, 2017 (in press).
1975
1976 WHOM-1999:WHO monographs on selected medicinal plants, Volume 1, Geneva, World Health
1978
1981
1984
1987
1988 WHOM-2010:WHO monographs on selected medicinal plants commonly used in the Newly Independent
1989 States (NIS), Geneva, World Health Organization, 2010.
1990
46
1991 Annex 1: Example of a model format of good herbal processing practices

1992 monograph/SOP protocol to produce a herbal material
1993
1994 TITLE of the monograph/protocol:
1995
1996 Processing of [name of the plant] (Scientific name of the medicinal plant; medicinal plant part)
1997
1998 1. Objective of the SOP Protocol
1999
2000 2. Scope
2001
2002 3. Procedures
2003
2004 3.1 Sampling
2005
2006 Sampling of herbal materials should follow applicable national or regional specifications. In absence
2007 of appropriate specifications, the following method may be considered: When a batch consists of five
2008 containers or packaging units, take a sample from each one. From a batch of 6-50 units, take a sample
2009 from five. In the case of batches of over 50 units, sample 10%, rounding up the number of units to the
2010 nearest multiple of ten (WHO, 2011).
2011
2012 Quality testing of the raw material
2013 Perform morphological identification/validation by macroscopic and microscopic examinations and
2014 physicochemical tests by following the procedures set out in the national pharmacopoeia or other
2015 authoritative documents.
2016
2017 The following requirements must be fulfilled.
2018  Morphology: Conform with the national pharmacopoeial standards
2019  Identification (including macroscopic, microscopic examination, and/or chromatographic tests):
2020 Conform with the pharmacopoeial standards
2021  Water content: ≤ xxx %
2022  Total ash: ≤ xxx %
2023  Acid-insoluble ash: ≤ xxx %
2024  Extractive: ≥ xxx %
2025
2026 3.2 Quality control assay
2027
2028 3.2.1 Marker compound
2029 Compound “Z” is used as the marker compound for plant X..y.. for quality control purpose. Obtain
2030 analytical grade Compound Z (≥ 98% purity) from a reliable source to serve as Chemical reference
2031 substance.
2032
2033 3.2.2 High-performance liquid chromatographic (HPLC) analysis
2034 Set up the HPLC system. Perform system suitability test to ensure suitability of the instrument and
2035 method.
2036 Under the recommended HPLC conditions, establish calibration curves by injecting an appropriate
2037 amount of the chemical reference (marker) standard solution in a series of concentrations.
2038 Obtain HPLC chromatogram of the herbal material. Identify the analyte signal in the chromatogram
2039 by comparing the retention time with that of the peak of the chemical reference substance obtained
2040 under same HPLC conditions.
2041 Calculate the percentage content of the analyte in the sample using the calibration curve.
47
2042 Determine the percentage content of the marker compound again after final drying of the processed
2043 herbal material (section 3.10 below).
2044
2045 The following requirement must be fulfilled.
2046  Content of Compound Z before processing: ≥ xxx % calculated with reference to the dry weight of
2047 the starting material
2048  Content of Compound Z after processing: ≥ xxx % calculated with reference to the dry weight of
2049 the processed material
2050
2051 3.3 Testing of the excipient*
2052 (*This step is not required if excipient(s) are not employed in the processing protocol)
2053
2054 Perform tests by following the procedures set out in the SOP document. The following requirements
2055 must be fulfilled.
2056  Appearance: Conform with internal standards
2057  Total excipient content: ≥ xxx %
2058
2059 3.4 Initial sorting of the plant material for processing
2060
2061 The source herbal materials are manually sorted by trained personnel according to the requirements
2062 specified in the SOP. Impurities (e.g. dirt and non-medicinal plant parts) should be removed, and any
2063 materials of non-uniformed sizes should be excluded.
2064
2066  Impurity: ≤ xxx %
2067  Size uniformity: ≥ xxx %
2068  Total recovery: ≥ xxx % (Recovery = Weight after sorting / Weight before sorting X 100%)
2069
2070 3.5 Washing
2071
2072 Washing should be performed by following the procedures set out in the SOP document. Pay attention
2073 to the quality of water used, the length of washing time, and any precautions applicable to the specific
2074 herb.
2075
2077  Appearance after washing: in conformance with the SOP standard
2078  Recovery: xxx-xxx % (Recovery = Weight after washing/Weight before washing X 100%)
2079
2080 3.6 Steaming (or other treatment)
2081
2082 The procedures set out in the SOP document should be strictly followed. All equipment should be
2083 properly maintained, clean, and performing at optimal and safe conditions.
2084
2086  Appearance after steaming/treatment: in conformance with the SOP standard
2087  Recovery: ≥ xxx % (Recovery = Weight after steaming/Weight before steaming X 100%)
2088
2089 3.7 Semi-drying
2090
2091 If required, dry the samples according to SOP guideline, either by sunlight or by artificial heating.
2092
48

2094  Appearance after semi-drying : in conformance with the SOP standard
2095  Recovery: xxx-xxx% (Recovery = Weight after drying/Weight before drying X 100%)
2096
2097 3.8 Cutting/sectioning/comminuting
2098
2099 The processed material should be comminuted into the required size and shape in conformance with
2100 the SOP standard.
2101
2103  Non-conformed pieces: ≤ xxx %
2104  Powder fineness:
2105  Recovery: ≥ xxx % (Recovery = Weight after cutting/Weight before cutting X 100%)
2106
2107 3.9 Final drying of processed herbal material
2108
2109 The cut materials should be thoroughly dried according to the SOP requirement.
2110
2112  Water content of the final product: xxx-xxx %
2113  Recovery: ≥ xxx % (Recovery = Weight after drying/Weight before drying X 100%)
2114
2115 3.10 Final sorting
2116
2117 The dried material should be carefully inspected by trained personnel, with impurities removed, and
2118 sorted into specific grades in accordance with the pharmacopoeial or trading standard.
2119
2121  Impurity: ≤ xxx %
2122  Grade-1 pieces: ≥ xxx%
2123  Grade-2 pieces: xxx –xxx%
2124  Recovery: ≥ xxx % (Recovery = Weight after sorting/Weight before sorting X 100%)
2125
2126 3.11 Packaging, labelling, and storage
2127
2128 3.11.1 Packaging
2129 Processed materials should be packaged quickly and appropriately in appropriate, non-corrosive
2130 containers, and protected from light to preserve quality, prevent deterioration and to protect against
2131 contamination.
2132
2133 3.11.2 Labelling
2134 Labels affixed to each package should clearly indicate the scientific name of the medicinal plant, the
2135 plant part, the processing method, the date of processing, the batch number, quality specification and
2136 compliance, quantitative and other relevant information.
2137
2138 3.11.3 Storage
2139 The packaged products must be stored in a clean, dry and well-ventilated area, at a constant
2140 temperature appropriate for the proper maintenance of the final product, and protected against
2141 microbial and other sources of contaminations and free from insects and animal pest attacks.
49
2142 Annex 2: Example of a model format of good herbal processing practices

2143 monograph/SOP protocol to produce a herbal preparation
2144
2145 TITLE of the monograph/protocol
2146
2147 Processing of [name of the plant] (Scientific name of the medicinal plant; medicinal plant part)
2148
2149 1. Objective of the SOP Protocol
2150 The objective of this protocol is to establish a procedure for preparation of the finished product.
2151
2152 2. Scope
2153 This procedure applies to processes required in the preparation of the fluidextract of the herb of X…y...
2154
2155 3. Procedures
2156 This protocol should be carried out in accordance with the standard operating procedures (SOP) for
2157 the processing of material X…y... as described in this document, the SOP for equipment operation and
2158 maintenance, as well as those for facility management and cleaning. Any other relevant requirements
2159 may also apply.
2160
2161 The protocol should be adhered to in conjunction with relevant internal standards of the processing
2162 facility.
2163
2164 After the completion of each processing step, the products should be inspected by qualified personnel.
2165 All inspection records should be properly filed and retained for a period of three years or as required
2166 by national and/or regional authorities.
2167
2168 4. Plant substance
2169 The identity of the raw plant material should be confirmed using morphological
2170 identification/validation by macroscopic and microscopic examinations and physicochemical tests by
2171 following the procedures set out in the pharmacopoeia or other authoritative documents.
2172
2173 Specifications such as those below should be in place.
2174
2175  Origins of the plant material (natural state/cultivation): Describe appropriate origins of the
2176 plant material
2177  Plant part: Describe the desired plant part/parts (i.e. flowers)
2178  Growing conditions:
2179 o Climatic conditions: length of day, rainfall, field temperature (coldness/warmth)
2180 o Soil conditions: soil type, drainage/moisture retention, fertility
2181 o Shade level
2182 o Fertilizers: Specify allowable fertilizers in compliance with applicable regulations
2183 o Pest controls: Specify allowable pesticides and/or biological pest controls, in compliance
2184 with applicable regulations
2185 o Fungicides: Specify allowable fungicides (if any) in compliance with applicable regulations
2186 o Fumigants: Specify allowable fumigants (if any) in compliance with applicable regulations
2187  Harvest time: Describe the appropriate months for harvest (i.e. during flowering (June-July)
2188  Harvesting: Describe the process for harvesting (i.e. mechanical process)
2189  Drying conditions: Describe the process for drying, if applicable
2190  Purification: Describe the process for inspection and removal of impurities
50
2191  Storage conditions: Specify the storage conditions. In general, the plant material should be
2192 stored in a clean, dry and well-ventilated area, at a constant, appropriate temperature, protected
2193 against microbial and other sources of contaminations, free from attack by insects and animal
2194 pests.
2195  Transportation conditions: Commercial vehicles should be clean, dry, deprived of any foreign
2196 matter. Conditions should ensure protection against moisture and contamination. Baskets, chests
2197 and jute bags can be used as containers. Each container should be labelled with the name of the
2198 material, date of harvest, harvesting site, net and gross weight and the name of the supplier.
2199
2200 5. Processing
2201 Descriptions of the processing facility requirements should be maintained, i.e. certification of the site
2202 as a good practice facility. Details are given here for the raw components to be used in the production
2203 of the final herbal preparation.
2204
2205 As an example, raw X...y... material to be processed into X...y... juice are detailed in the table below.
2206 In this example, the plant material is extracted using ethanol 95% (V/V) and water as needed. The
2207 drug extract ratio (DER) is 1:1.
2208
2209 Raw Material Components in the Production of X...y...juice
Raw Materials Function Amount per 100 kg Standard
Fresh X...y... herb Plant material 100.0 kg Standard specification
Ethanol 95% Extraction solvent Xx litres Pharmacopoeia .XYZ
Extraction water Extraction solvent quantum satis Pharmacopoeia .XYZ
2210
2211 Raw materials accepted for processing must meet specifications for identity and quality.
2212 Specifications include appearance/description of the plant material(s), water content, total ash, as well
2213 as appropriate chemical assays. These criteria may follow criteria detailed in pharmacopoeial
2214 monograph(s).
2215
2216 The steps below describe the preparation of the juice of the herb of X..y..
2217  Step 1. The fresh fragmented plant material is stabilized with the vapours of boiling 95% ethanol
2218 in an autoclave. The duration, temperature and vapour pressure are specified in the SOP. When
2219 the process is completed, the fluid separates from the plant material.
2220  Step 2. The stabilized plant material is placed in a macerator with post-stabilization fluid and
2221 water. The maceration process lasts for a period of time (n days) specified. At the end of the
2222 extraction process, the extract is separated from the plant matter in a manner specified by the SOP.
2223 The ethanol content of the extract and density of the extract are specified.
2224  Step 3. The resulting extract is stored in a stainless steel container for a minimum time
2225 (days/weeks) specified. The process ensures sedimentation of inorganic residual waste.
2226  Step 4. The extract is filtered using a pressurized process. The filter size and input pressure are
2227 selected as specified by the manufacturer or manufacturer’s catalogue of the filtering unit.
2228
2229 6. Process controls
2230 Controls for tests conducted during the process should be described. A description of the tests, their
2231 methods and the acceptance criteria should be given. These include appearance (i.e. colour), particle
2232 size (amount expected to pass through a specified sieve size), water or alcohol content, and/or relative
2233 density.
2234
2235 7. Release specifications of final product
51
2236 Identify criteria that must be met for release of the final product. These criteria generally include
2237 appearance, relative density, and specified quantities for chemical constituent(s), as well as limits for
2238 heavy metals, microbial content and residual matter.
2239
2240  Chemical profile: i.e. TLC/HPLC fingerprint of chemical constituents
2241  Pharmacopoeial/standard quantitation of chemical markers, where applicable
2242  Heavy metals: limits defined
2243  Microbial: limits defined
2244  Residuals: limits for pesticides, fertilizers, foreign matter, solvent residue, mycotoxins, etc.
2245
2246 8. Certificate of analysis
2247 A certificate of analysis should be generated following completion of quality control testing. This
2248 document should include the assay methods as well as the results obtained using those methods.
2249
2250 9. Packaging
2251 The appropriate packaging of the containers should be described. Processed materials should be
2252 packaged quickly and appropriately in air-tight, non-corrosive containers, and protected from light to
2253 preserve quality, prevent deterioration and to protect against contamination.
2254
2255 10. Labelling
2256 Labels affixed to each package should clearly indicate the scientific name of the medicinal plant, the
2257 plant part, the processing method, the date of processing, the batch number, quality specification and
2258 compliance, quantitative and other relevant information.
2259
2260 11. Storage conditions
2261 The packaged products must be stored in a clean, dry and well-ventilated area, at a constant
2262 temperature appropriate for the proper maintenance of the final product, and protected against
2263 microbial and other sources of contaminations and free from insects and animal pest attacks.
2264
2265 12. Stability
2266 Stability testing should be conducted to determine an appropriate shelf-life.
2267
2268 13. Retained samples
2269 Sufficient materials (raw material and finished goods) must be retained in proper storage conditions to
2270 allow for future verification of identity and quality.
52
2271 Annex 3: Example of general rules for preparations/monographs of herbal

2272 preparations and herbal dosage forms
2273
2274 [Reference Source: Japanese Pharmacopoeia 16th edition, Ministry of Health, Labour and Welfare, Mach 2011]
2275
2276 Japanese Pharmacopoeia, 16th Edition (2011):
2277 General Rules for Preparations/Monographs for Preparations Related to Crude Drugs
2278
2279 Monographs for Preparations Related to Crude Drugs
2280
2281 Preparations Related to Crude Drugs
2282
2283 (1) Preparations related to crude drugs are preparations mainly derived from crude drugs. Extracts,
2284 Pills, Spirits, Infusions and Decoctions, Teabags, Tinctures, Aromatic Waters, and Fluidextracts are
2285 included in this category.
2286
2287 Definitions, methods of preparations, test methods, containers and packaging, and storage of these
2288 preparations are described in this chapter.
2289
2290 (2) The descriptions of the test methods and the containers and packaging in this chapter are
2291 fundamental requirements, and the preparation methods represent commonly used methods.
2292
2293 1. Extracts
2294 (1) Extracts are preparations, prepared by concentrating extractives of crude drugs. There are
2295 following two kinds of extracts.
2296 (i) Viscous extracts
2297 (ii) Dry extracts
2298
2299 (2) Unless otherwise specified, Extracts are usually prepared as follows.
2300 (i) Crude drugs, pulverized to suitable sizes, are extracted for a certain period of time with
2301 suitable solvents by means of cold extraction or warm extraction, or by percolation as directed in (ii)
2302 of (2) under 6. Tinctures. The extractive is filtered, and the filtrate is concentrated or dried by a
2303 suitable method to make a millet jelly-like consistency for the viscous extracts, or to make crushable
2304 solid masses, granules or powder for the dry extracts. Extracts, which are specified the content of
2305 active substance(s), are prepared by assaying active substance(s) in a portion of sample and adjusting,
2306 if necessary, to specified strength with suitable diluents.
2307 (ii) Weigh crude drugs, pulverized to suitable sizes, according to the prescription and heat for a
2308 certain period of time after adding 10 ñ 20 times amount of water. After separating the solid and liquid
2309 by centrifugation, the extractive is concentrated or dried by a suitable method to make a millet jelly-
2310 like consistency for the viscous extracts, or to make crushable solid masses, granules or powder for the
2311 dry extracts.
2312
2313 (3) Extracts have odour and taste derived from the crude drugs used.
2314
2315 (4) Unless otherwise specified, Extracts meet the requirements of Heavy Metals Limit Test <1.07>1
2316 (for detail of test methods, procedure, and regents and solutions, see end note of this annex), when
2317 the test solution and the control solution are prepared as follows.
2318
2319 Test solution: Ignite 0.30 g of Extracts to ash, add 3mL of dilute hydrochloric acid, warm, and filter.
2320 Wash the residue with two 5-mL portions of water. Neutralize the combined filtrate and washings
53
2321 (indicator: a drop of phenolphthalein TS) by adding ammonia TS until the color of the solution
2322 changes to pale red, filter where necessary, and add 2mL of dilute acetic acid and water to make
2323 50mL.
2324
2325 Control solution: Proceed with 3mL of dilute hydrochloric acid in the same manner as directed in the
2326 preparation of the test solution, and add 3.0mL of Standard Lead Solution and water to make 50mL.
2327
2328 (5) Tight containers are used for these preparations.
2329
2330 2. Pills
2331 (1) Pills are spherical preparations, intended for oral administration.
2332
2333 (2) Pills are usually prepared by mixing drug substance(s) uniformly with diluents, binders,
2334 disintegrators or other suitable excipient(s) and rolling into spherical form by a suitable method. They
2335 may be coated with a coating agent by a suitable method.
2336
2337 (3) Unless otherwise specified, Pills comply with Disintegration Test.
2338
2339 (4) Well-closed or tight containers are usually used for these preparations.
2340
2341 3. Spirits
2342 (1) Spirits are fluid preparations, usually prepared by dissolving volatile drug substance(s) in ethanol
2343 or in a mixture of ethanol and water.
2344
2345 (2) Spirits should be stored remote from fire.
2346
2348
2349 4. Infusions and Decoctions
2350 (1) Infusions and Decoctions are fluid preparations, usually obtained by macerating crude drugs in
2351 water.
2352
2353 (2) Infusions and Decoctions are usually prepared by the following method.
2354  Cut crude drugs into a size as directed below, and transfer suitable amounts to an infusion or
2355 decoction apparatus.
2356  Leaves, flowers and whole plants: Coarse cutting
2357  Woods, stems, barks, roots and rhizomes: Medium cutting
2358  Seeds and fruits: Fine cutting
2359
2360 (i) Infusions: Usually, damp 50 g of crude drugs with 50mL of water for about 15 minutes, pour
2361 900 mL of hot water to them, and heat for 5 minutes with several stirrings. Filter through a cloth after
2362 cooling.
2363 (ii) Decoctions: Usually, heat one-day dose of crude drugs with 400 ñ 600mL of water until to
2364 lose about a half amount of added water spending more than 30 minutes, and filter through a cloth
2365 while warm. Prepare Infusions or Decoctions when used.
2366
2367 (3) These preparations have odour and taste derived from the crude drugs used.
2368
2369 (4) Tight containers are usually used for these preparations.
2370
54
2371 5. Tea bags

2372 (1) Tea bags are preparations, usually packed one day dose or one dose of crude drugs cut into a size
2373 between coarse powder and coarse cutting in paper or cloth bags.
2374
2375 (2) Teabags are usually used according to the preparation method as directed under 4. Infusions and
2376 Decoctions.
2377
2378 (3) Well-closed or tight containers are usually used for these preparations.
2379
2380 6. Tinctures
2381 (1) Tinctures are liquid preparations, usually prepared by extracting crude drugs with ethanol or with a
2382 mixture of ethanol and purified water.
2383
2384 (2) Unless otherwise specified, Tinctures are usually prepared from coarse powder or fine cuttings of
2385 crude drugs by means of either maceration or percolation as described below.
2386
2387 (i) Maceration: Place crude drugs in a suitable container, and add an amount of a solvent,
2388 equivalent to the same volume or about three-fourths of the volume of the crude drugs. Stopper
2389 container, and allow the container to stand for about 5 days or until the soluble constituents have
2390 satisfactorily dissolved at room temperature with occasional stirring. Separate the solid and liquid by
2391 centrifugation or other suitable methods. In the case where about three-fourths volume of the solvent is
2392 added, wash the residue with a suitable amount of the solvent, and squeeze the residue, if necessary.
2393 Combine the extract and washings, and add sufficient solvent to make up the volume. In the case
2394 where the total volume of the solvent is added, sufficient amounts of the solvent maybe added to make
2395 up for reduced amount, if necessary. Allow the mixture to stand for about 2 days, and obtain a clear
2396 liquid by decantation or filtration.
2397
2398 (ii) Percolation: Pour solvent in small portions to crude drugs placed in a container, and mix well
2399 to moisten the crude drugs. Stopper container, and allow it to stand for about 2 hours at room
2400 temperature. Pack the contents as tightly as possible in an appropriate percolator, open the lower
2401 opening, and slowly pour sufficient solvent to cover the crude drugs. When the percolate begins to
2402 drip, close the opening, and allow the mixture to stand for 2 to 3 days at room temperature. Then, open
2403 the opening, and allow the percolate to drip at a rate of 1 to 3mL per minute. Add an appropriate
2404 quantity of the solvent to the percolator, and continue to percolate until the desired volume has passed.
2405 Mix thoroughly, allow standing for 2 days, and obtain a clear liquid by decantation or filtration. The
2406 time of standing and the flow rate may be varied depending on the kind and amount of crude drugs to
2407 be percolated.
2408
2409 Tinctures, prepared by either of the above methods and specified the content of marker constituent or
2410 ethanol, are prepared by assaying the content using a portion of the sample and adjusting the content
2411 with a sufficient amount of the percolate or solvent as required on the basis of the result of the assay.
2412
2413 (3) Tinctures should be stored remote from fire.
2414
2416
2417 7. Aromatic Waters
2418 (1) Aromatic Waters are clear liquid preparations, saturated essential oils or other volatile substances
2419 in water.
2420
2421 (2) Unless otherwise specified, Aromatic Waters are usually prepared by the following process. Shake
55
2422 thoroughly for 15 minutes 2mL of an essential oil or 2 g of a volatile substance with 1000 mL of
2423 lukewarm purified water, set the mixture aside for 12 hours or longer, filter through moistened filter
2424 paper, and add purified water to make 1000 mL. Alternatively, incorporate thoroughly 2 mL of an
2425 essential oil or 2 g of a volatile substance with sufficient talc, refined siliceous earth or pulped filter-
2426 paper, add 1000 mL of purified water, agitate thoroughly for 10 minutes, and then filter the mixture.
2427 To obtain a clear filtrate repeat the filtration if necessary, and add sufficient purified water passed
2428 through the filter paper to make 1000mL.
2429
2430 (3) Aromatic Waters have odour and taste derived from the essential oils or volatile substances used.
2431
2433
2434 8. Fluidextracts
2435 (1) Fluidextracts are liquid percolates of crude drugs, usually prepared so that each mL contains
2436 soluble constituents from 1 g of the crude drugs. Where the content is specified, it takes precedence.
2437
2438 (2) Unless otherwise specified, Fluidextracts are usually prepared from coarse powder or fine cutting
2439 of crude drugs by either of following maceration or percolation.
2440
2441 (i) Maceration: Place a certain amounts of crude drugs in a suitable vessel, add a solvent to cover
2442 the crude drugs, close the vessel, and allow the vessel to stand at room temperature with occasional
2443 stirring for about 5 days or until the soluble constituents have satisfactorily dissolved. Separate the
2444 solid and liquid by centrifugation or other suitable method. Usually, reserve a volume of the liquid
2445 equivalent to about three-fourths of the total volume, and use it as the first liquid. Wash the residue
2446 with appropriate amount of the solvent, combine the washings and the remaining of the first liquid,
2447 concentrate if necessary, mix with the first liquid, and use it as solution (A). To the solution (A) add
2448 the solvent, if necessary, to make equal amount of the mass of the crude drugs. Allow the mixture to
2449 stand for about 2 days, and collect a clear liquid by decantation or filtration.
2450
2451 (ii) Percolation: Mix well 1000 g of the crude drugs with the first solvent to moisten them, close
2452 the container, and allow it to stand for about 2 hours at room temperature. Transfer the content to a
2453 suitable percolator, stuff it as tightly as possible, open the lower opening of the percolator, and slowly
2454 pour the second solvent to cover the crude drugs. Close the lower opening when the solvent begins to
2455 drop, and allow the mixture to stand for 2 to 3 days at room temperature. Open the lower opening, and
2456 allow the percolate to run out at the rate of 0.5 to 1.0mL per minute. Set aside the first 850 mL of the
2457 percolate as the first percolate. Add the second solvent to the percolator, then drip the percolate, and
2458 use it as the second percolate.
2459
2460 The period of standing and the flow rate during percolation may be varied depending on the kind and
2461 the amount of crude drugs used. The flow rate is usually regulated as follows, depending on the using
2462 amount of crude drugs.
2463
Volume of solution running per
Mass of crude drug minute
Not more than 1000 g 0.5 - 1.0mL
Not more than 3000 g 1.0 - 2.0mL
Not more than 10000g 2.0 - 4.0mL
2464
2465 Concentrate the second percolate, taking care not to lose the volatile substances of the crude drug, mix
2466 with the first percolate, and use it as solution (A). To the solution (A) add the second solvent to make
56
2467 1000 mL, and allow the mixture to stand for about 2 days. Decant the supernatant liquid or filter the
2468 liquid to obtain a clear solution.
2469
2470 Fluidextracts for which the content of marker constituent or ethanol is specified are obtained by
2471 adjusting the content with a sufficient amount of the second solvent as required on the basis of the
2472 result of the assay made with a portion of the solution (A).
2473
2474 (3) Fluidextracts have odour and taste derived from the crude drugs used.
2475
2476 (4) Unless otherwise specified, Fluidextracts meet the requirements of Heavy Metals Limit Test
2477 <1.07>1 when the test solution and the control solution are prepared as follows.
2478
2479 Test solution: Ignite 1.0 g of Fluidextracts to ash, add 3 mL of dilute hydrochloric acid, warm, and
2480 filter. Wash the residue with two 5-mL portions of water. Neutralize the combined filtrate and
2481 washings (indicator: a drop of phenolphthalein TS) by adding ammonia TS until the colour of the
2482 solution changes to pale red, filter if necessary, and add 2 mL of the dilute acetic acid and water to
2483 make 50 mL.
2484
2485 Control solution: Proceed with 3 mL of dilute hydrochloric acid in the same manner as directed in the
2486 preparation of the test solution, and add 3.0 mL of Standard Lead Solution and water to make 50 mL.
2487
2489
1
2490 Test <1.07> 1.07 Heavy Metal Limit test (JP 16, pp21-23)
2491 Heavy Metals Limit Test is a limit test of the quantity of heavy metals contained as impurities in drugs. The heavy metals
2492 are the metallic inclusions that are darkened with sodium sulfide TS in acidic media, as their quantity is expressed in terms of
2493 the quantity of lead (Pb). In each monograph, the permissible limit for heavy metals (as Pb) is described in terms of ppm in
2494 parentheses.
2495
2496 Procedure:
2497 Add 1 drop of sodium sulfide TS to each of the test solution and the control solution, mix thoroughly, and allow to stand for 5
2498 minutes. Then compare the colors of both solutions by viewing the tubes downward or transversely against a white
2499 background. The test solution has no more color than the control solution.
2500
2501 Solutions and Reagents:
2502 Standard Lead Solution
2503 Measure exactly 10 mL of Standard Lead Stock Solution, and add water to make exactly 100 mL. Each mL of this solution
2504 contains 0.01 mg of lead (Pb). Prepare before use.
2505
2506 Standard Lead Stock Solution
2507 Weigh exactly 159.8 mg of lead (II) nitrate, dissolve in 10 mL of dilute nitric acid, and add water to make exactly 1000 mL.
2508 Prepare and store this solution using glass containers, free from soluble lead salts.
2509
2510 Ammonia solution (28)
2511 NH4OH [K 8085, Ammonia Water, Special class, Density: 0.90 g/mL, Content: 28- 30%]
2512
2513 Ammonia TS
2514 To 400 mL of ammonia solution (28) add water to make 1000 mL (10%).
2515
2516 Acetic acid, dilute
2517 Dilute 6 g of acetic acid (100) with water to make 100 mL (1 mol/L).
2518
2519 Acetic acid (100)
2520 CH3COOH [K 8355, Acetic Acid, Special class]
2521
2522 Dilute acetic acid
2523 See acetic acid, dilute.
57
2524
2525 Dilute hydrochloric acid
2526 See hydrochloric acid, dilute.
2527
2528 Hydrochloric acid, dilute
2529 Dilute 23.6 mL of hydrochloric acid with water to make 100mL (10%).
2530
2531 Hydrochloric acid
2532 HCl [K 8180, Special class]
2533
2534 Phenolphthalein TS
2535 Dissolve 1 g of phenolphthalein in 100 mL of ethanol (95).
2536
2537 Phenolphthalein
2538 C20H14O4 [K 8799, Special class]
2539
2540 Ethanol (95)
2541 C2H5OH [K 8102, Special class]
2542
2543 Sodium sulfide enneahydrate
2544 Na2S.9H2O [K 8949,Special class]
2545
2546 Sodium sulfide TS
2547 Dissolve 5 g of sodium sulfide enneahydrate in a mixture of 10 mL of water and 30 mL of glycerin. Or dissolve 5 g of
2548 sodium hydroxide in a mixture of 30 mL of water and 90 mL of glycerin, saturate a half volume of this solution with
2549 hydrogen sulfide, while cooling, and mix with the remaining half. Preserve in well-filled, light-resistant bottles. Use within 3
2550 months.
2551
2552 Sodium hydroxide
2553 NaOH [K 8576, Special class]
2554
2555 Glycerin
2556 C3H8O3 [K 8295, Glycerol, Special class. Same as the monograph Concentrated Glycerin]
2557
2558 Hydrogen sulfide
2559 H2S Colorless, poisonous gas, heavier than air. It dissolves in water. Prepare by treating iron (II) sulfide heptahydrate with
2560 dilute sulfuric acid or dilute hydro chloric acid. Other sulfides yielding hydrogen sulfide with
2561 dilute acids may be used.
2562
2563 Sulfuric acid
2564 H2SO4 [K 8951, Special class]
2565
2566 Sulfuric acid, dilute
2567 Cautiously add 5.7 mL of sulphuric acid to 10 mL of water, cool, and dilute with water to make 100 mL (10%).
2568
2569 Iron (II) sulfate heptahydrate
2570 FeSO4.7H2O [K 8978, Special class]
58
2571 Annex 4: Processing facilities

2572
2573 The following is extracted from Section 4.1.5 of the WHO guidelines on good agricultural and collection
2574 practices (GACP) for medicinal plants (WHO, 2003) (pages 19-23).
2575
2576 4.1 Processing facilities
2577
2578 In constructing or designing a processing facility, the following elements should be considered that
2579 will allow the establishment of a quality assurance system adaptable to the different types and steps of
2580 processing to yield the desired end products.
2581
2582 Location
2583 Facilities should preferably be located in areas that are free from objectionable odours, smoke, dust or
2584 other contaminants, and are not subject to flooding or other natural adverse conditions.
2585
2586 Buildings
2587 Buildings should be of sound construction and maintained in good repair. Filthy areas must be isolated
2588 from clean processing areas. All construction materials should be such that they do not transmit any
2589 undesirable substance including toxic vapours to medicinal plant materials. Electrical supply, lighting,
2590 and ventilation should be appropriately installed.
2591
2592 Buildings should be designed to:
2593  provide adequate working space and storage room to allow for satisfactory performance of all
2594 operations;
2595  to ensure the logical flow of materials and personnel;
2596  facilitate efficient and hygienic operations by allowing a regulated flow in processing from the
2597 arrival of the raw medicinal plant materials at the premises to the dispatch of the processed
2598 medicinal plant materials;
2599  permit appropriate control of temperature and humidity;
2600  permit control of access to different sections, where appropriate;
2601  permit easy and adequate cleaning and facilitate proper supervision of hygiene;
2602  prevent the entry of environmental contaminants such as smoke, dust, the entrance and harbouring
2603 of pests, livestock and domesticated animals.
2604
2605 Medicinal plant material handling and processing areas
2606 The layout and design of the work area should be such as to minimize the risk of errors and permit
2607 effective cleaning and maintenance in order to avoid cross contamination, and otherwise avoid any
2608 adverse effect on the quality of the processed product.
2609
2610  Windows and other openings should be constructed so as to avoid accumulation of dirt, and where
2611 appropriate, those that open should be fitted with insect-proof screens. Screens should be easily
2612 removable for cleaning and kept in good repair. Internal window sills, if present, should be sloped
2613 to prevent use as shelves.
2614  Doors should have smooth, non-absorbent surfaces and, where appropriate, be self-closing and
2615 close-fitting.
2616  Overhead structures and fittings should be installed in such a manner as to avoid contamination of
2617 medicinal plant materials (both raw and processed) by condensation and drippings, and should be
2618 protected to prevent contamination in case of breakage. They should be insulated, where
2619 appropriate, and be designed and finished so as to prevent the accumulation of dirt and to
2620 minimize condensation, mould development and flaking. They should be easy to clean.
59
2621  Food preparation and eating areas, changing facilities, toilets should be completely separated from
2622 and not open directly onto medicinal plant material processing areas.
2623
2624 Water supply
2625  An ample supply of potable water, under adequate pressure and at suitable temperature, used for
2626 processing medicinal plant materials, should be available with appropriate facilities for its storage,
2627 where necessary, and distribution, and with proper protection against contamination.
2628  Ice should be made from potable water; it should be manufactured, handled and stored so as to
2629 protect it against contamination.
2630  Unless there is a post water filtration or treatment system, non-potable water used for steam
2631 production, refrigeration, fire control and other similar purposes not connected with processing
2632 should be carried in completely separate pipes, identifiable preferably by colour, and with no
2633 cross-connection with or back siphonage into the system carrying potable water.
2634
2635 Effluent and waste disposal
2636 Facilities should have an effective effluent and waste disposal system, which should at all times be
2637 maintained in good order and repair; and should be constructed so as to avoid contamination of
2638 potable water supplies.
2639
2640 Changing facilities and toilets
2641 Adequate, suitable and conveniently located changing facilities and toilets should be provided. Hand-
2642 washing facilities with warm or hot and cold water, a suitable hand-cleaning preparation and hygienic
2643 means of drying should be provided adjacent to toilets and located so that employees have to pass
2644 them when returning to the processing area. Notices should be posted directing personnel to wash
2645 their hands after using the toilet.
2646
2647 Hand-washing facilities in processing areas
2648 Adequate and conveniently located facilities for hand-washing and a hygienic means of drying should
2649 be provided whenever the process demands. Where appropriate, facilities for hand disinfection should
2650 also be provided.
2651
2652 Disinfection facilities
2653 Where appropriate, adequate facilities for cleaning and disinfection of working implements and
2654 equipment should be provided. These facilities should be constructed of corrosion-resistant materials,
2655 should be easy to clean, and should be fitted with hot and cold water supplies.
2656
2657 Lighting
2658 Adequate natural or artificial lighting should be fitted throughout the facility. Where appropriate, the
2659 lighting should not alter colours of the medicinal plants undergoing processing.
2660
2661 Ventilation
2662 Adequate ventilation should be provided to prevent excessive heat, steam condensation and dust and
2663 to remove contaminated air from both the processing and storage areas/facilities.
2664
2665 Storage of waste and unusable materials
2666 Facilities should be provided for the storage of waste and unusable materials prior to removal from the
2667 premises.
60

WHO Herbal Extraction Guidelines

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- Do not distribute without permission from WHO R-Draft WHO guidelines for comments, March 2017 -

45 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DRAFTDOCUMENT:

Any follow-up action, as needed

99 3.2.1.2 Steps involved in the extraction of herbs and herbal materials…..….29

150 5.3 Storage and transportation……………………………………………………….…….…41

359 plants [WHO, 2003a];

543 Chemical reference substance (or standard) [WHO, 2007c]

910 be admixed with the herbal material during stir-frying.

1412 3.2.3 Fractionation and Purification

1642 4.2.2.4 Granules

1780 labelled and stored according to the government’s regulations.

1991 Annex 1: Example of a model format of good herbal processing practices

2093 The following requirements must be fulfilled.

2142 Annex 2: Example of a model format of good herbal processing practices

2271 Annex 3: Example of general rules for preparations/monographs of herbal

2371 5. Tea bags

2571 Annex 4: Processing facilities

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