GUIDELINES ON IMPORT PROCEDURES FOR MEDICAL PRODUCTS

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

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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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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

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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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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