Working document QAS/18.773 Rev. 1
July 2018
Draft document for comments
GUIDELINES ON IMPORT PROCEDURES 1
FOR MEDICAL PRODUCTS 2
(July 2018) 3
DRAFT FOR COMMENTS 4
5
6
7
8
9
10
11 © World Health Organization 2018 12 13 All rights reserved. 14 15 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The 16 draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, 17 in any form or by any means outside these individuals and organizations (including the organizations' concerned staff and 18 member organizations) without the permission of the World Health Organization. The draft should not be displayed on any 19 website. 20 21 Please send any request for permission to: 22 23 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential 24 Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland, fax: (41 22) 791 4856; email: 25 [email protected] 26 27 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 28 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or 29 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate 30 border lines for which there may not yet be full agreement. 31 32 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 33 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors 34 and omissions excepted, the names of proprietary products are distinguished by initial capital letters. 35 36 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this 37 draft. However, the printed material is being distributed without warranty of any kind, either expressed or implied. The 38 responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health 39 Organization be liable for damages arising from its use. 40 41 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 42 43
Please send any comments you may have to Dr S. Kopp, Group Lead, Medicines Quality Assurance,
Technologies Standards and Norms ([email protected]), with a copy to Mrs Xenia Finnerty
([email protected]) by 30 September 2018.
Medicines Quality Assurance working documents will be sent out electronically only. They will
also be placed on the Medicines website for comment under “Current projects”. If you have not
already received our draft working documents, please send your email address (to
[email protected]) and we will add you to our electronic mailing list.
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44
SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/18.773: 45
46
GUIDELINES ON IMPORT PROCEDURES FOR MEDICAL PRODUCTS 47
48
Proposal for the revision of WO Guidelines on Import
Procedures for Pharmaceutical Products during the
consultation onGood Practices for Health Products
Manufacture and Inspection.
25–28 April 2017
Presentation of a proposal to update to the 52nd WHO
Expert Committee on Specifications for Pharmaceutical
Preparations (ECSPP).
16–22 October 2017
Preparation of draft for revision by Dr V. Gigante, WHO
Medicines Quality Assurance Group. February 2018
Review of draft by Dr A. J. Van Zyl, member of the Expert
Advisory Panel for the International Pharmacopoeia and
Pharmaceutical Preparations.
April 2018
Finalization of draft for mailing and public consultation. May–June 2018
Consolidation of comments received. Beginning of July 2018
Discussion of working document and feedback received
during the informal consultation on Good Practices for
Health Products Manufacture and Inspection. Revision of
the title to align it to the WHO terminology “WO
Guidelines on Import Procedures for Medical Products”.
10–12 July 2018
Revision based on feedback received during the informal
consultation on Good Practices for Health Products
Manufacture and Inspection.
July 2018
Mailing for public consultation. August–September 2018
Consolidation of comments received during public
consultation. September 2018
Presentation to the 53rd ECSPP. 22–26 October 2018
Any other follow-up action as required
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GUIDELINES ON IMPORT PROCEDURES FOR MEDICAL PRODUCTS1 49
50
1. INTRODUCTORY NOTE 51
52
1.1 Public health considerations demand that medical products should not be treated in 53
the same way as ordinary commodities. Their manufacturing and subsequent handling within 54
the distribution chain, both nationally and internationally, must conform to prescribed 55
standards and be rigorously controlled. These precautions serve to assure that patients 56
receive quality-assured medical products, and to prevent the infiltration of substandard and 57
suspected falsified medical products into the supply system. 58
59
1.2 The availability of medical products is sometimes limited due to economic constraints, 60
difficulty in meeting norms and standards in their production, and lack of resources in their 61
supply chain. The market penetration by substandard and suspected falsified medicines poses 62
hazards for public health and forces the diversion of public health resources from other uses. 63
In light of this, investments towards strengthening strategies at the customs level are deemed 64
crucial to ensure quality-assured medical products to patients (1, 2). 65
66
1.3 The global economy of scale and scope that characterizes modern trade requires 67
continuous improvement in border control. This includes a departure from the traditional 68
reactive control system to a risk-based and pro-active approach. The risk-based surveillance 69
scheme should identify risks and define the controls that will protect patients from 70
substandard, falsified and unregulated medical products. A risk-based approach can improve 71
the cost-benefit ratio with existing or reduced resources through more effective and efficient 72
controls. 73
74
1.4 Within the context of its revised medicines strategy adopted in 1986 by the Thirty-75
ninth World Health Assembly in resolution WHA39.27, the World Health Organization 76
(WHO) developed Guiding Principles for Small National Drug Regulatory Authorities (3) 77
which established a regulatory approach in line with the resources available within a small 78
national regulatory authority (NRA), and were intended to assure not only the quality, but 79
also the safety and efficacy of pharmaceutical products distributed under its aegis. 80
1 This was first published in 1996 in the WHO Technical Report Series (TRS), No. 863, Annex 12.
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81
1.5 The principles emphasize the need for the effective use of the WHO Certification 82
Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (4, 5). 83
This constitutes a formal agreement between participating Member States to provide 84
information on any medical products under consideration for export, notably on its marketing 85
authorization in the country of origin and whether or not the manufacturer complies with the 86
WHO Guidelines on Good Manufacturing Practices for Pharmaceutical Products (6). 87
88
1.6 To be fully effective, the WHO Certification Scheme needs to be complemented by 89
administrative and other safeguards aimed at ensuring that imported products are in 90
conformity with all particulars with the relevant marketing authorization or specific intended 91
use, such as clinical trial, named patient programmes, emergencies or other means, as 92
appropriate, within the importing country and that they remain secure within the distribution 93
chain. Storage and transit facilities must provide protection against tampering and adverse 94
conditions and relevant controls must be applied at every stage of transportation (7, 8). 95
96
1.7 Medical products containing substances controlled under international conventions 97
have long been subjected to rigorous border control. Some of these controls, and particularly 98
those designed to prevent the diversion and illicit interchange of products during transit, are 99
relevant to all pharmaceutical products and are therefore included in these guidelines. Only 100
those pharmaceutical products falling under the category of narcotic and psychotropic 101
substances which are permitted by the relevant authorities shall be allowed to be imported as 102
foreseen in the national and regional legislations and international treaties signed by the 103
country. 104
105
2. OBJECTIVES AND SCOPE 106
107
2.1 These guidelines, which stem from the above considerations, had been developed first 108
in 1996 in consultation with NRAs, the pharmaceutical industry, the World Customs 109
Organization, and the United Nations International Drug Control Programme.2 110
111
2 Since 1997, part of the UN Office for Drug Control and Crime
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2.2 These guidelines are directed to all parties involved in the importation of medical 112
products, including NRAs, competent trade ministries, customs authorities, port authorities 113
and importing agents. 114
115
2.3 They are intended to promote efficiency in applying relevant regulations, to simplify 116
the checking and handling of medical products for import, inter alia, to provide a basis for 117
collaboration between the various interested parties. 118
119
2.4 They are applicable to medical products destined for use within the country of import 120
and are intended to be adopted into prevailing national procedures and legal requirements. 121
122
3. GLOSSARY 123
124
The definitions given apply to the terms used in these guidelines. They may have different 125
meanings in other contexts. 126
127
falsified medical products. 128
Medical products that deliberately or fraudulently misrepresent their identity, composition or 129
source. Any consideration related to intellectual property rights does not fall within this 130
definition. Such deliberate or fraudulent misrepresentation refers to any substitution, 131
adulteration or reproduction of an authorized medical product or the manufacture of a 132
medical product that is not an authorized product. 133
134
import authority. 135
The national agency responsible for authorizing imports (for example, the ministry or 136
department of trade or of imports and exports). 137
138
importation. 139
The act of bringing or causing any goods to be brought into a customs territory (national 140
territory, excluding any free zone). 141
142
143
144
145
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importer. 146
An individual or company or similar legal entity importing or seeking to import a 147
pharmaceutical product. A “licensed” or “registered” importer is one who has been granted a 148
licence for the purpose. 149
150
marketing authorization (product license, registration certificate). 151
A legal document issued by the competent medicines regulatory authority that authorizes the 152
marketing or free distribution of a pharmaceutical product in the respective country after 153
evaluation for safety, efficacy and quality. In terms of quality, it establishes, inter alia, the 154
detailed composition and formulation of the pharmaceutical product and the quality 155
requirements for the product and its ingredients. It also includes details of packaging, 156
labelling, storage conditions, shelf life and approved conditions of use. 157
158
national regulatory authority. 159
The national agency responsible for the marketing authorization of, and other regulatory 160
activities concerning pharmaceutical products. 161
162
pharmaceutical product. 163
Any medicine intended for human or veterinary use, presented in its finished dosage form, 164
that is subject to control by pharmaceutical legislation in both the exporting state and the 165
importing state. 166
167
screening technologies. 168
The qualitative and/or semi-quantitative technologies which could rapidly acquire the 169
analytical information or data for preliminary identification of suspect medical products in 170
the field. 171
172
standard operating procedure. 173
An authorized written procedure giving instructions for performing standardized operations 174
both general and specific. 175
176
starting material. 177
Any substance of defined quality used in the production of a pharmaceutical product, but 178
excluding packaging materials. 179
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substandard product. 180
A substandard product is an authorized product that fails to meet either its quality standards 181
or its specifications, or both. 3 182
183
unauthorized product. 184
An unauthorized product that has not undergone evaluation and/or approval by the NRA for 185
the market in which it is marketed/distributed or used, subject to permitted conditions under 186
national or regional regulation and legislation. 187
188
These medical products may or may not have obtained the relevant authorization from the 189
national/regional regulatory authority of its geographical origin. 190
191
4. LEGAL RESPONSIBILITIES 192
193
4.1 The importation of medical products should be done in accordance with national and 194
regional legislation and should be enforced by the NRA and other relevant authorities. 195
196
National and regional guidelines providing recommendations on the implementation of 197
legislation should be drawn up by the NRA or the Ministry of Health, if a NRA is not 198
formally established, in collaboration with the customs authority and other responsible 199
agencies and organizations. 200
201
4.2 The import of pharmaceutical products should be undertaken by an importer or 202
agency authorized by the NRA as per national and regional legislation. This normally does 203
not include pharmaceutical products in transit. 204
205
4.3 The import of all medical products should be channelled exclusively through custom 206
posts or ports specifically authorized for this purpose. This is also applicable to medical 207
products moving through the networking global commerce (such as, the World Wide 208
Web/Internet). 209
210
3 These standards and specifications are normally reviewed, assessed and approved by the applicable national or
regional medicines regulatory authority before the product is authorized for marketing..
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4.4 All formalities on importation of medical products should be coordinated by the 211
customs authority in close collaboration with the NRAs or the Ministry of Health if a NRA is 212
not formally established. When justified by the workload, NRA officials may be stationed in 213
a full-time position at such designated ports of entry. In carrying out the duties and 214
formalities, the impact of possible delays on, for example, access to medicines and storage 215
conditions of medical products, should be considered (for storage facilities, please see chapter 216
9 of this document). 217
218
5. LEGAL BASIS OF CONTROL 219
220
5.1 Subject to the exemptions specified in the national and regional legislation, and 221
mentioned in paragraph 5.5 below, only medical products proved by appropriate 222
documentation to be duly authorized for marketing should be cleared by customs. 223
224
5.2 The NRA should publish an updated list of authorized pharmaceutical products and 225
authorized importers permitted to import into the country for marketing. This does not 226
include a list of exempted products and importers as per national or regional legislation. In 227
all cases, close collaboration with the NRA is needed to verify that the product is authorized 228
for importation and that there are no restrictions, temporary suspensions or withdrawals of 229
marketing authorizations. 230
231
5.3 NRAs should be empowered to take legal actions and should collaborate closely with 232
customs, police, judiciary and others to detect substandard and falsified products and to avoid 233
the import of such products. Efficient and confidential channels for communicating 234
information on these products and other illicit activities should be established between all 235
responsible official bodies. 236
237
5.4 In countries where no formal system of product marketing authorization has been 238
established, the importation of products is most effectively controlled by issuing permits in 239
the name of the NRA to the authorized importing agency or agent. Within the framework of 240
the WHO Certification Scheme, WHO provides a list with names and full addresses of those 241
government organizations authorized to sign and issue a certificate of a pharmaceutical 242
product (CPP). NRAs receiving a CPP can use this list to check and verify if the certificate 243
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they are receiving has been issued by the authorized organization (4, 5). Additional measures 244
that may be taken under these conditions include: 245
246
the provision by the NRA to the customs authorities and to the importing agency 247
and agents of official lists of pharmaceutical products permitted and/or prohibited 248
to be imported; and 249
the provision by the importing agent of certified information to establish that the 250
product is authorized by license for sale in the country of export. 251
252
5.5 The NRA should reserve discretionary powers to waive product authorization 253
requirements in respect of consignments of pharmaceutical products imported in response to 254
emergency situations, specific intended use as in clinical trials and in response to requests 255
from clinicians for limited supplies of an unlicensed product needed for the treatment of a 256
specific named patient. 257
258
6. REQUIRED DOCUMENTATION 259
260
6.1 As a prerequisite to customs clearance, the importing agency or agent should be 261
required to furnish the customs authority with the following documentation in respect of each 262
consignment, except in cases of exemptions as per national or regional legislation (see also 263
5.5.): 264
documents issued by the NRA in the importing country, attesting that: 265
266
(a) the importer is duly authorized to import the medical products;, and 267
(b) the product is duly authorized to be marketed or permitted to be imported 268
into the importing country; 269
a batch release certificate issued by the manufacturer; 270
safety data sheet; 271
relevant invoice, bill or delivery slip for the batch, including product name, batch 272
number, quantity and expiry date; and 273
any other documentation required by national or regional legislation for customs 274
clearance, for example a certificate in accordance with the WHO Certification 275
Scheme. 276
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277
6.2 The NRA may grant exemptions to the above if the distribution is taking place 278
through regional hubs or by international organizations, for example, in case of emergencies. 279
280
7. IMPLEMENTATION OF CONTROLS 281
282
7.1 A visual examination should be routinely undertaken by the customs authorities. 283
Where possible, this should be done in collaboration with an inspector or enforcement officer 284
of the NRA. The size of the consignment should be checked against invoices, bills or 285
delivery slips, and attention should be given to the nature and conditions of the packaging and 286
labelling. The external package should be compared with a standard when this is possible. 287
(NOTE: spelling errors, low-quality printing and other defects may be signs of a substandard 288
or falsified product. The external package should be intact and should not show any signs of 289
damages or infiltrations that may change the inner content (2, 13,14,15).) 290
291
7.2 Arrangements should be made by the NRA for the sampling and subsequent physical 292
and chemical analysis of medical products based on established procedures following a risk-293
based approach. 294
295
7.3 When samples, prior to the release of the consignment as per national and regional 296
legislation, are taken for analysis to a governmental or other accredited quality control 297
laboratory, the consignment should be placed in quarantine at approved sites. During this 298
procedure, and throughout the time that the consignment is held legally under customs 299
control, particular care must be taken to ensure that packages do not come into contact with 300
potential contaminants. In addition, the package should be stored under appropriate 301
conditions as recommended on the label or in the safety data sheet such as temperature, light 302
and humidity limits (13, 14, 15). 303
304
7.4 A consignment suspected of being substandard, falsified or not authorized should be 305
placed in quarantine pending the analysis of samples and forensic investigation. During this 306
procedure, particular care must be taken to ensure that packages do not come into contact 307
with potential contaminants. In addition, the package should be stored under appropriate 308
conditions as recommended on the label or in the safety data sheet such as temperature, light, 309
and humidity limits (13, 14, 15). Time is often saved if materials and reagents needed to 310
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undertake simple analytical tests and screening technologies are available at the customs 311
border. The consignee should immediately be informed of such action, ideally the authorized 312
manufacturer or importer should also be promptly involved in the investigation. 313
314
7.5 National or regional regulations should define the responsibilities of the respective 315
parties and the precise procedures to be followed by representatives from the NRA, police, 316
border control, or Ministry of Health, as appropriate, for the relevant investigation and legal 317
actions. 318
319
7.6 Falsified medical products and other products which have been imported in 320
contravention of the law must be forfeited and destroyed, or otherwise dealt with in 321
accordance with the procedures established by national and regional legislation, the records 322
of which should be appropriately archived (9). The relevant authorities must be indemnified 323
against any consequent legal actions and proceedings. 324
325
7.7 NRAs should notify other national or regional authorities and the WHO Global 326
Surveillance and Monitoring System4 of confirmed cases of imported substandard or falsified 327
products without delay on the appropriate form. 328
329
7.8 The WHO Member State mechanism has prepared an overview on the different field 330
screening devices, authentication and verification technologies, and “track and trace” models 331
that can facilitate responses (11). Overt/covert technologies, forensic chemical markers, bar-332
coding and other forms of serializations can support the seamless tracking of products 333
through the supply chain. The implementation of these and upcoming new technologies is 334
considered one of the most prominent preventive measures to tackle substandard and falsified 335
medical products. 336
337
338
339
4 The WHO Global Surveillance and Monitoring System collects reports from focal points in the NRAs and
international procurement agencies which will forward the report via email to [email protected] where
necessary. Focal points are encouraged to send any photographs, laboratory reports or other relevant
documents as attachments.
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8. PROCEDURES APPLICABLE TO PHARMACEUTICAL STARTING 340
MATERIALS 341
342
8.1 When considering finished pharmaceutical products, the responsibility for the quality 343
assurance of starting materials (active pharmaceutical ingredients (APIs) and excipients) used 344
in that product is vested in the manufacturer of the finished pharmaceutical product (FPP). 345
Few NRAs have introduced authorization requirements for APIs and excipients (8). 346
347
8.2 Some national and regional authorities also exercise documentary and (in some cases) 348
quality control through laboratory testing of APIs as a prerequisite to customs clearance. 349
350
8.3 Each imported pharmaceutical starting material should be accompanied by a warranty 351
(or batch certificate) prepared by the manufacturer, for example, as recommended by the 352
WHO pharmaceutical starting materials certification scheme (SMACS) (10). 353
354
9. STORAGE FACILITIES 355
356
9.1 Many medical products tend to degrade during storage and some need to be stored 357
under specified conditions, such as 2–8 degree Celsius. All customs posts designated to 358
handle consignments of medical products should be provided with secure storage facilities, 359
with the required conditions including cold storage areas. 360
361
Customs and NRA officials shall ensure that the appropriate environmental conditions are 362
maintained for storage and shall monitor that the equipment is maintained and in good 363
working order. The facilities should be inspected periodically by the NRA. 364
365
9.2 The importer should inform the customs authorities in advance of the anticipated 366
arrival of medical products in order that they may be transferred from the international carrier 367
to the designated storage facility without delay and, in appropriate cases, without breaking 368
the cold chain. 369
370
9.3 Consignments of medical products and pharmaceutical starting materials, especially 371
those requiring cold chain, should be accorded high priority for clearance through customs to 372
avoid extended storage. 373
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10. TRAINING REQUIREMENTS 374
375
10.1 When implementing these guidelines, the performance of the established procedures 376
(including but not limited to personnel, documentation, procedures, and equipment) should be 377
reviewed on an open-ended basis and improved in the light of on-site monitoring and 378
evaluation. Workshops designed to facilitate efficient implementation of the guidelines and 379
established procedures, and to foster collaborative approaches between the various 380
responsible parties, should be organized at intervals by the NRA in collaboration with the 381
customs authority and other parties. 382
383
REFERENCES 384
385
1. Guidelines on the Conduct of Surveys of the Quality of Medicines (WHO TRS, No. 386
996, 2016, Annex 7). 387
388
2. WHO Guidance on Testing of “Suspect” Falsified Medicines (WHO TRS, No. 1010, 389
Annex 5, 2018). 390
391
3. National Drug Regulatory Legislation: Guiding Principles for Small Drug Regulatory 392
Authorities (WHO TRS, No. 885, 1999, Annex 8). 393
394
4. WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in 395
International Commerce. In: Fiftieth World Health Assembly, Resolution WHA50.3, 396
Geneva. 397
398
5. Guidelines on the Implementation of the WHO Certification Scheme on the Quality of 399
Pharmaceutical Products Moving in International Commerce (in Working document 400
QAS/18.768 April 2018) 401
http://www.who.int/medicines/areas/quality_safety/quality_assurance/WHOCertificati402
onScheme-QAS18-768_06042018-wb-09042018.pdf?ua=1. 403
404
6. WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles 405
(WHO TRS, No. 986, 2014, Annex 2). 406
407
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7. WHO Good Distribution Practices for Pharmaceutical Products (WHO TRS, No. 957, 408
2010, Annex 5). 409
410
8. Good Trade and Distribution Practices for Starting Materials (Revision) (WHO TRS, 411
No. 996, 2016, Annex 6). 412
413
9. Guidance on Good Data and Record Management Practices (WHO TRS, No. 996, 414
2016, Annex 5). 415
416
10. WHO Pharmaceutical Starting Materials Certification Scheme (SMACS) 417
(WHO TRS, No 917, 2003, Annex 3). 418
419
11. Member State Mechanism on Substandard/Spurious/Falsely-Labelled/Falsified/ 420
Counterfeit Medical Products (Seventieth World Health Assembly A70/2320, 421
Appendix 2). 422
423
12. Considerations for Requesting Analysis of Medicines Samples (WHO TRS, No. 1010 , 424
2018, Annex 3). 425
426
13. WHO Guide to Good Storage Practices for Pharmaceutical (WHO TRS, No. 908, 427
2003, Annex 9). 428
429
14. Technical supplements to Model Guidance for the Storage and Transport of Time and 430
Temperature-Sensitive Pharmaceutical Products (WHO TRS, No. 992, 2015, Annex 5). 431
432
15. Model Guidance for the Storage and Transport of Time- and Temperature-Sensitive 433
Pharmaceutical Products (jointly with the Expert Committee on Biological 434
Standardization) (WHO TRS, No. 961, 2011, Annex 9). 435
436
16. Available Authentication Technologies for the Prevention and Detection of SSFFC 437
Medical Products. Appendix 2 of the Report by the Director-General on Member 438
State Mechanism on Substandard/Spurious/Falsely-Labelled/Falsified/Counterfeit 439
Medical Products (WHA A70/23). 440
441
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17. Good Review Practices: Guidelines for National and Regional Regulatory 442
Authorities, WHO TRS, No. 992, 2015. 443
444
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