Working document QAS/16.656/Rev.1

June 2016

Draft document for comment

117

PREQUALIFICATION OF QUALITY CONTROL 118

LABORATORIES. PROCEDURE FOR ASSESSING THE 119

ACCEPTABILITY, IN PRINCIPLE, OF QUALITY CONTROL 120

LABORATORIES FOR USE BY UNITED NATIONS AGENCIES 121

PROPOSAL FOR UPDATE 122

(June 2016) 123

REVISED DRAFT FOR COMMENT 124

125

126

127

128

129 ________________________________________________________________________________ 130

________________________________________________________________________________ 131

© World Health Organization 2016 132

All rights reserved. 133

This draft is intended for a restricted audience only, i.e. the individuals and organizations having 134 received this draft. The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, 135 distributed, translated or adapted, in part or in whole, in any form or by any means outside these 136 individuals and organizations (including the organizations' concerned staff and member 137 organizations) without the permission of the World Health Organization. The draft should not be 138 displayed on any website. 139

Please send any request for permission to: 140

Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms, 141 Department of Essential Medicines and Health Products, World Health Organization, CH-1211 142 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: kopps@who.int. 143

The designations employed and the presentation of the material in this draft do not imply the 144 expression of any opinion whatsoever on the part of the World Health Organization concerning the 145 legal status of any country, territory, city or area or of its authorities, or concerning the delimitation 146 of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which 147 there may not yet be full agreement. 148

The mention of specific companies or of certain manufacturers’ products does not imply that they 149 are endorsed or recommended by the World Health Organization in preference to others of a similar 150 nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are 151 distinguished by initial capital letters. 152

Should you have any comments on the attached text, please send these to Dr S. Kopp, Group Lead,

Medicines Quality Assurance, Technologies, Standards and Norms (kopps@who.int) with a copy to

Ms Marie Gaspard (gaspardm@who.int) by 30 July 2016.

Medicines Quality Assurance working documents will be sent out electronically only and will

also be placed on the Medicines website for comment under “Current projects”. If you do not

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Working document QAS/16.656/Rev.1

page 2

All reasonable precautions have been taken by the World Health Organization to verify the 153 information contained in this draft. However, the printed material is being distributed without 154 warranty of any kind, either expressed or implied. The responsibility for the interpretation and use 155 of the material lies with the reader. In no event shall the World Health Organization be liable for 156 damages arising from its use. 157

This draft does not necessarily represent the decisions or the stated policy of the World 158 Health Organization. 159 160

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PREQUALIFICATION OF QUALITY CONTROL 161 LABORATORIES. PROCEDURE FOR ASSESSING THE 162

ACCEPTABILITY, IN PRINCIPLE, OF QUALITY 163 CONTROL LABORATORIES FOR USE BY UNITED 164

NATIONS AGENCIES 165

Proposal for update 166

167

168 Background information 169 170

Recently there has been a lot of interest in laboratories that belong, are 171

located or linked to manufacturers making enquiries as to whether or not 172 they should submit expressions of interest (EOI). They have been 173

discouraged after being informed that consideration of their application 174 will not be prioritized. 175

176 Annual reports submitted by all prequalified laboratories have shown little 177 activity related to United Nations (UN) agencies and other WHO-related 178

development agencies. Particularly for quality control laboratories (QCLs) 179 linked to manufacturing sites, there has been no activity at all reported and 180

therefore the motive for prequalification or remaining prequalified is not 181 clear. Both manufacturers linked to prequalified QCLs either have 182

products that are prequalified or are in the prequalification pipeline. 183 184

The number of enquiries has been increasing yet there is no agreed policy 185 on how to handle them. There is therefore a need for a clear public and 186 transparent policy. 187

188

Quality control laboratories included in the current (Third) invitation for 189 EOI 190 191 The aim of the 3rd invitation for EOI was to promote testing of 192 pharmaceutical products internationally by QCLs which meet WHO-193

recommended standards and to increase the range of QCLs for which the 194 acceptability for use by UN agencies has been proven. 195 196 Participation in the prequalification procedure is voluntary and any 197 pharmaceutical QCL (governmental or private) may participate. The 198

invitation is open and transparent, inviting all interested QCLs to submit 199 the EOI for prequalification. 200 201

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Current priorities 202 203 Although WHO reserves the right to charge for the quality assessment 204 procedure on a cost-recovery basis, this is not yet practiced for QCLs. 205 There are, however, insufficient resources and time constraints, and 206 therefore WHO has set priorities in the assessment of interested 207

laboratories. Invitations are not limited to QCLs from a specific region. 208 However, priority is currently given to QCLs in areas where UN agencies 209 identify the need for testing of the quality of pharmaceutical products, to 210

national QCLs and laboratories providing testing services to governments. 211 212

In addition there should be a commitment by the laboratory to providing 213

services of testing of pharmaceutical products to UN agencies. This is, 214 however, not required in writing. 215

216 Status of QCLs 217

218 As at 21 March 2016, 39 QCLs are working towards prequalification. 219 Thirty (30) of these are national QCLs with the remaining nine (9) being 220 commercial. None of the nine are located or linked to a pharmaceutical 221

manufacturer. 222 223

Forty-one (41) QCLs are prequalified, of which 16 are commercial (39%). 224

Of the 16 commercial QCLs, two (2) are located/linked to a 225

pharmaceutical manufacturer. 226 227

228

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Distribution by geographical region 229

230 231

There is, therefore, an apparent good distribution of prequalified and 232

pipeline QCLs that are either national or private/commercial. It is, 233 however, not clear if the laboratories are in fact really regional in the sense 234

that it is generally easy for samples to be submitted from nearby countries. 235 This has been noted not to be the case in the south-east region, for 236

example. 237 238

Proposals on way forward 239 240 Continue with the following existing priorities: 241

242

QCLs in areas where UN agencies identify the need for testing of 243

the quality of pharmaceutical products; 244

national QCLs and laboratories providing testing services to 245

governments. 246

Provided there is a commitment by the laboratory to providing services 247

of testing of pharmaceutical products to UN agencies. 248

249 On the basis of the above, the current procedure is proposed to be revised 250 as follows. 251 252

253

AFRO AMRO EMRO EURO SEARO WPRO Subtotal

Prequalified

National 5 6 2 8 2 2 25

Commercial 3 1 1 7 3 1 16

Total 8 7 3 15 5 3 41

Interested

National 17 3 6 2 1 1 30

Commercial 4 1 1 1 2 0 9

Total 21 4 7 3 3 1 39

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254

255 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT 256

QAS/16.656/Rev.1 257

Prequalification of quality control laboratories. Procedure 258 for assessing the acceptability, in principle, of quality control 259

laboratories for use by United Nations (UN) agencies 260 261

262

263 264 265 266 267 268 269

Development of draft by Mr Rutendo Kuwana, PQT,

based on discussions outlined in the background

information

February–March 2016

Circulation for comments March–April 2016

Compilation of feedback May 2016

Review of feedback and comments during the informal

consultation on quality control laboratory tools and

specifications for medicines

9–11 May 2016

Revised version is recirculated for feedback and

comments

June 2016

Compilation of feedback September 2016

Discussion at fifty-first meeting of the WHO Expert

Committee on Specifications for Pharmaceutical

Preparations

17–21 October 2016

Any further action, as necessary

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270 © World Health Organization 271

WHO Technical Report Series, No. 961, 2011 272 273 274 275

Annex 12 276

Prequalification of quality control laboratories. 277

Procedure for assessing the acceptability, 278

in principle, of quality control laboratories 279

for use by United Nations (UN) agencies 280 281 282 [Note from Secretariat: Proposed updates are included in track change.] 283

284 Introduction 285

286 1. Steps of the procedure 287

1.1 Publication of invitation for Expressions of Interest 288 1.2 Submission of Expressions of Interest and laboratory information 289 1.3 Screening of submitted laboratory information 290 1.4 Evaluation of the laboratory information 291 1.5 Site inspection 292 1.6 Report and outcome of inspection 293 1.7 Results of assessment 294 1.8 Monitoring of prequalified quality control laboratories 295 1.9 Monitoring of complaint(s) 296 1.10 Cost recovery 297 1.11 Confidentiality undertaking 298 1.12 Conflict of interest 299

References 300

301

Introduction 302

The World Health Organization (WHO) provides United Nations (UN) 303 agencies, on request, with advice on the acceptability, in principle, of 304 quality control laboratories (QCLs) that are found to meet WHO- 305 recommended quality standards for such laboratories, i.e. Good practices 306 for pharmaceutical quality control laboratories (GPCL) (1) and the 307 relevant parts of good manufacturing practices (GMP) (2). This is done 308 through a standardized quality assessment procedure. The purpose of the 309 quality assessment procedure is to evaluate whether the QCLs to be used 310 for the quality control of pharmaceutical products meet the requirements 311 recommended by WHO for such laboratories. 312

Participation in the prequalification procedure is voluntary and any 313

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pharmaceutical QCL (governmental or private) could participate. 314 Certification such as ISO (in terms of ISO/IEC17025) is encouraged and 315 will also be considered in the prequalification procedure. It is 316 recommended that laboratories should work towards obtaining 317 certification. 318

The quality assessment procedure established by WHO is based on the 319 following principles: 320

‒ commitment of the laboratory to providing services of testing of 321 pharmaceutical products to UN agencies, its partners and international 322 procurers; 323

‒ a general understanding of the quality assurance management and 324 quality control testing activities of the laboratory; 325

‒ evaluation of information submitted by the laboratory; 326 ‒ assessment of compliance with WHO-recommended quality standards 327

for QCLs, i.e. GPCL (1) and the relevant parts of GMP (2); and 328 ‒ monitoring of performance of prequalified laboratories. 329

WHO invites the national medicines regulatory authority (NMRA) having 330 regulatory oversight over a laboratory participating in the prequalification 331 procedure, to join as an observer in the inspection of the laboratory’s 332 compliance with WHO-recommended standards for QCLs. WHO 333 recommends that laboratories expressing an interest in participating in 334 the prequalification procedure, inform the regulatory authority of the 335 country in which they are established as well as relevant networks (e.g. 336 the Official Medicines Control Laboratories (OMCL) network) of their 337 submission for prequalification. 338

This procedure is to be followed for prequalification of quality control 339 laboratories for use by the UN agencies and its partners. 340

341

1. Steps of the procedure 342

WHO requires information related to the activities of, and quality control of 343 pharmaceutical products in, laboratories interested in being assessed under 344 this procedure. Interested QCLs should submit the information about their 345 activities as requested by WHO (see point 1.2 below). In addition to the 346 evaluation of the information submitted, a site inspection (or inspections) 347 may be performed. 348

If, due to insufficient resources and time constraints, WHO has to set 349 priorities in the assessment of interested laboratories, then priority will be 350 given to QCLs in areas where UN agencies identify the need for testing of 351

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the quality of pharmaceutical products, and to national QCLs and 352 laboratories providing testing services to governments. For example, 353 applications from laboratories that belong to or are linked to a 354 manufacturer of pharmaceutical products, particularly those that have an 355 interest to have such products prequalified or are prequalified, are 356 discouraged and will be given low priority. 357

WHO reserves the right to terminate the quality assessment of a laboratory 358 when the laboratory is not able to provide, or fails to provide, the required 359 information, when the information supplied is inadequate to complete 360 the quality assessment effectively, the laboratory fails to collaborate in 361 inspections required by WHO and/or is unable to implement corrective 362 actions which WHO may require within a specified time period. 363

364 1.1 Publication of invitation for Expressions of Interest 365

WHO will publish an invitation to quality control laboratories to submit an 366 Expression of Interest (EOI) to participate in the prequalification procedure. 367 Such an invitation will specify the scope of quality control testing which is 368 subject to prequalification and will be published widely, i.e. on the WHO 369 web site and possibly also through other media, such as the international 370 press. The invitation will be open and transparent, inviting all interested 371 QCLs to submit the EOI for prequalification. 372

373 1.2 Submission of Expressions of Interest and laboratory 374

information 375

Each interested laboratory should provide the WHO focal point indicated in 376 the invitation for EOIs with: 377

— a cover letter expressing interest in participating in the prequalification 378 procedure; and 379

— the relevant laboratory information. 380

WHO will record the receipt of the EOI from each laboratory in a register. 381

Guidelines for the submission of EOIs and for the preparation and 382 submission of the relevant information are available on the WHO website 383 at http://apps.who.int/prequal/ and will be sent to interested laboratories 384 upon request. 385

If the laboratory has documented its quality system as a quality manual, 386 this can be submitted, provided that it is supplemented with the information 387 required for the laboratory information file ((LIF) see below) that is not 388 provided in the quality manual. 389

If there is no quality manual, the information should be submitted as 390

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described in the document Guidelines for preparing a laboratory 391 information file (3) and contain information on the areas listed below: 392

‒ general information on the laboratory, including activities proposed for 393 prequalification; 394

‒ quality management system implemented, and inspections and external 395 audits performed in the laboratory; 396

‒ participation in proficiency testing schemes and/or collaborative trials; 397 ‒ internal audits; 398 ‒ control of documentation and records; 399 ‒ personnel; 400 ‒ premises; 401 ‒ equipment; 402 ‒ reagents, reference substances and reference materials; 403 ‒ subcontracting of testing (where applicable); 404 ‒ handling of samples; 405 ‒ validation and/or verification of analytical procedures; 406 ‒ investigation of out-of-specification (OOS) results; 407 ‒ stability testing (where applicable); 408 ‒ microbiological testing (where applicable). 409

410

1.3 Screening of submitted laboratory information 411

The information submitted by the laboratory will be screened for 412 completeness against the Guidelines for preparing a laboratory information 413 file (3). Incomplete information will not be considered for evaluation. The 414 laboratory will be informed that incomplete information has been received, 415 and be requested to complete it within a specified time period. In the event 416 of noncompliance with this request, the laboratory information will in 417 principle be rejected on grounds of incompleteness and returned to the 418 laboratory. 419

420

1.4 Evaluation of the laboratory information 421

Laboratory information that complies with the requirements set out in 422 section 1.2 above will be evaluated in accordance with a standard operating 423 procedure (SOP) established by WHO to ensure uniformity in evaluation 424 of the information. The information will be evaluated against the WHO-425 recommended quality standards for QCLs, i.e. GPCL 426

(1) and the relevant parts of GMP (2), and the laboratory will be considered 427 for a possible site inspection. 428

A laboratory may submit the report of the inspection or audit performed 429 by a regulatory authority applying standards at least equivalent to WHO 430

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recommended quality standards for QCLs, i.e. GPCL 431

(1) and the relevant parts of GMP (2), and the response of the laboratory 432 to the observations made by the authority during inspection or audit. 433 Based on WHO’s assessment of the report and response, if the laboratory 434 is considered to be operating at an acceptable level of compliance with 435 WHO-recommended standards, WHO may decide that it is not necessary 436 to conduct a site inspection. 437

438 1.5 Site inspection 439

Depending on the outcome of the evaluation of the laboratory information, 440 WHO may plan and coordinate inspections of the laboratory to assess 441 compliance with WHO-recommended quality standards for such 442 laboratories, 443

i.e. GPCL (1) and the relevant parts of GMP (2).1 The inspection will be 444 performed by an inspector, or a team of inspectors, having the relevant 445 qualifications and experience in the field of quality control of medicines. 446 External inspectors will be appointed in accordance with a SOP established 447 by WHO and will act as temporary advisers to WHO. The external inspectors 448 must comply with the confidentiality and conflict of interest rules of 449 WHO, as laid down in the relevant sections of this procedure. A WHO staff 450 member will coordinate the team. The inspector or inspection team will 451 perform the inspections and report on the findings in accordance with 452 SOPs established by WHO to ensure a standard harmonized approach. 453

A representative or representatives of the NMRA having regulatory 454 oversight over a laboratory participating in the prequalification procedure, 455 is invited to accompany the team as an observer. 456

With a view to coordinating inspection activities, avoiding duplication and 457 promoting information sharing without prejudice to the protection of any 458 confidential and proprietary information of the laboratory in accordance 459 with the terms of this procedure, WHO may disclose inspection-related 460 information to regulatory authorities of WHO Member States, UN 461 agencies and to the European Directorate for the Quality of Medicines & 462 HealthCare (EDQM). 463

464 465

466 1 Training modules can be found on the Prequalification website 467 (http://apps.who.int/prequal/). 468

469

1.6 Report and outcome of inspection 470

The inspector or inspection team will finalize a report describing the 471

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findings according to the established WHO SOP and format. The report 472 will be communicated by WHO to the laboratory and a copy will be sent to 473 the NMRA having regulatory oversight over the laboratory. 474

If any additional information is required, or if a corrective action has to be 475 taken by the laboratory, WHO will postpone its decision on the acceptability 476 of the laboratory concerned until the additional information has been 477 evaluated, or the corrective action has been taken, and found satisfactory. If 478 the decision cannot be made based on the information received, a follow-up 479 inspection will be performed. 480

In the event of any disagreement between a laboratory and WHO, an SOP 481 for the handling of such disagreements will be followed to discuss and 482 resolve the issue. 483

As WHO is responsible for the quality assessment procedure, the 484 ownership of the reports lies with WHO (without prejudice, however, to 485 any confidential and proprietary information of the laboratory contained 486 in this report). Thus, WHO shall be entitled to use and publish such 487 reports subject always, however, to the protection of any confidential and 488 proprietary information of the laboratory. “Confidential information” in 489 this context means: 490

‒ confidential intellectual property, “know-how” and trade secrets 491 (including, e.g. programmes, processes or methods, unpublished 492 aspects of trade marks, patents, etc.); 493

‒ commercial confidences (e.g. structures and development plans). 494

Provisions of confidentiality will be contained in the letters exchanged 495 between WHO and the laboratory, to be agreed upon before the evaluation 496 of the information and site inspection. 497

Notwithstanding the foregoing, WHO reserves the right to share the full 498 reports with the relevant authorities of any interested Member State of the 499 Organization and interested UN agencies. 500

501 502

1.7 Results of assessment 503

Once WHO is satisfied that the quality assessment process for the 504 laboratory is complete, and that the laboratory is acceptable in principle 505 for use by UN agencies and its partners (i.e. it has been found to meet the 506 WHO-recommended quality standards for QCLs), the laboratory at the 507 specified site will be included in a list referred to as “List of prequalified 508 quality control laboratories”. 509

510 Laboratories on the list will be considered to be able to test products in 511

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compliance with WHO-recommended quality standards for QCLs. 512 Inclusion in the list does not, however, imply any regulatory approval by 513 WHO of the laboratories (which is the sole prerogative of national 514 authorities). It is, however, an attestation of compliance with GPCL (1) and 515 the relevant parts of GMP (2) based on the most recent inspection and other 516 available information. 517

Each laboratory will receive a letter from WHO informing it of the outcome 518 of the quality assessment process for that particular laboratory. 519

A copy of this letter will be sent to the NMRA of the country where the 520 laboratory is located. The list of prequalified laboratories will be published 521 on the WHO web site and will specify the areas of expertise assessed and 522 considered prequalified. The list will be updated whenever new relevant 523 information is obtained. 524

In accordance with World Health Assembly Resolution WHA57.14 of 525

22 May 2004, WHO will – subject to the protection of any confidential 526

and proprietary information – publish WHO Public Inspection Reports 527 (WHOPIR(s)) on the laboratories considered to meet WHO- 528 recommended quality standards for QCLs. These reports will be published 529 on the WHO website. 530

531 1.8 Monitoring of prequalified quality control laboratories 532

Once the laboratory is included in the list of prequalified QCLs, it should 533 inform WHO without delay about any implemented changes which may 534 have an impact on the prequalification of the laboratory (such as changes to 535 facility, equipment or key personnel) and should submit an updated LIF. 536

Each prequalified QCL will be re-evaluated on a routine basis at regular 537 intervals (annually) or earlier, when information requiring re-evaluation is 538 obtained by WHO. 539

To enable WHO to carry out re-evaluation, all prequalified laboratories 540 are requested to submit a brief annual report on their activities. The report 541 should cover all activities related to quality control of medicines within the 542 preceding calendar year and should be submitted by the end of March of 543 the subsequent year. The following items should be included in the report: 544

‒ a summary of services provided to UN agencies, other public health 545 organizations procuring medicines and other customers; 546

‒ a summary of number of samples analysed, differentiating between 547 compliant and non-compliant samples; 548

‒ a list of analytical methods used; 549 ‒ a summary of complaints concerning results of analyses performed by 550

the laboratory received from customers; 551

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‒ brief details of participation in proficiency testing schemes (organizing 552 party, methods involved, outcomes and, if appropriate, adopted corrective 553 measures); 554

‒ listing of inspections and audits performed by external parties, 555 identifying the party and scope of the inspection and audit; and 556

‒ in the case that changes have been implemented, which have an impact 557 on the content of the LIF, a summary of these changes should be included 558 in the report and an updated LIF should be attached. 559

WHO will conduct re-inspections of prequalified laboratories in 560 accordance with SOPs established by WHO. The frequency of such re-561 inspections depends on WHO’s assessment of the quality risk management 562 factors described below. Normally, however, such re-inspections will take 563 place at least once every three years. The following factors will be taken 564 into account when planning inspections: 565

‒ major changes to, e.g. premises, equipment, key personnel; 566 ‒ the results of previous inspection(s)/audit(s) by WHO or another 567

external party, and history of compliance of the laboratory with 568 WHO-recommended quality standards; 569

‒ the outcomes of participation of the laboratory in proficiency testing 570 schemes; 571

‒ number and significance of known complaints by customers; 572 ‒ laboratory experience with testing of medicines; 573 ‒ WHO experience with testing services provided by the laboratory. 574

WHO reserves the right to proceed with the re-inspection of a prequalified 575 laboratory at any time, when considered necessary based on information or 576 complaints received by WHO. The NMRA which has regulatory oversight 577 over the laboratory will be invited to participate in the re-inspection as an 578 observer. 579

WHO may suspend or withdraw a prequalified quality control laboratory 580 from the List of prequalified QCLs when there is evidence of non-581 compliance with the WHO-recommended quality standards for such 582 laboratories and/or this procedure. In addition WHO may suspend or 583 withdraw a prequalified QCL if the laboratory is considered to no longer 584 serve the objectives of prequalification including, but not limited to, 585 failure to provide regular services to UN agencies and their partners for a 586 continuous period of more than three years. 587

588 589

1.9 Monitoring of complaint(s) 590

Complaint(s) concerning the results of analysis of pharmaceutical 591 product(s) performed by the prequalified laboratory or concerning the 592

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service provided by the prequalified laboratory, which are communicated 593 to WHO, will be investigated in accordance with an SOP established by 594 WHO. The NMRA which has regulatory oversight over the laboratory will 595 be invited to participate in the investigation of the complaint. 596

597

After conducting its investigation, WHO will provide a written report of 598 the problem, which may, where appropriate, include recommendations for 599 action to the laboratory under investigation and to the NMRA having the 600 regulatory oversight over the laboratory. 601

602

1.10 Cost recovery 603

WHO reserves the right to charge for the quality assessment procedure on 604 a cost-recovery basis. 605

606

1.11 Confidentiality undertaking 607

WHO will require any external inspectors (acting as temporary advisers 608 to WHO) to treat all information to which they gain access during the 609 inspections of the laboratory, or otherwise in connection with the discharge 610 of their responsibilities in regard to the prequalification procedure, as 611 confidential and proprietary to WHO or parties collaborating with WHO in 612 accordance with the terms set out below. 613

Such inspectors will be required to take all reasonable measures to ensure 614 that confidential information: 615

‒ is not used for any purpose other than the activities described in this 616 document; 617

‒ is not disclosed or provided to any person who is not bound by similar 618 obligations of confidentiality and non-use as contained herein. 619

External inspectors will not, however, be bound by any obligations of 620 confidentiality and non-use to the extent they are clearly able to demonstrate 621 that any part of the confidential information: 622

— was known to them prior to any disclosure by or on behalf of WHO 623 (including by laboratories); or 624

— was in the public domain at the time of disclosure by or on behalf of 625 WHO (including by laboratories); or 626

— has become part of the public domain through no fault of theirs; or 627 — has become available to them from a third party not in breach of any 628

legal obligations of confidentiality. 629

630

1.12 Conflict of interest 631

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Before undertaking the work, each external inspector will also (in addition 632 to the above-mentioned confidentiality undertaking) be required to sign a 633 declaration of interest. If, based on this declaration of interest, it is felt 634 that there is no risk of a real or perceived conflict of interest (or it is felt 635 that there is only an insignificant and/or irrelevant conflict of interest), and 636

it is thus deemed appropriate for the inspector in question to undertake 637 this work, he/she will discharge his/her functions exclusively as adviser to 638 WHO. In this connection, each inspector is required to confirm that the 639 information disclosed by him/her in the declaration of interest is correct 640 and complete, and that he/she will immediately notify WHO of any change 641 in this information. 642

All external inspectors furthermore agree that, at the laboratory’s request, 643 WHO will advise the laboratory in advance of the identity of each such 644 inspector and the composition of the team performing the site inspection 645 and provide curricula vitae of the external inspectors. The laboratory then 646 has the opportunity to express possible concerns regarding any of the 647 external inspectors to WHO prior to the visit. If such concerns cannot be 648 resolved in consultation with WHO, the laboratory may object to an external 649 inspector’s participation in the site visit. Such an objection must be made 650 known to WHO by the laboratory within 10 days of receipt of the proposed 651 team composition. In the event of such an objection, WHO reserves the 652 right to cancel its agreement with the inspector in question and the activities 653 to be undertaken by that inspector, in whole or in part. 654

655

References 656

1. Good practices for pharmaceutical quality control laboratories. In: WHO 657 Expert Committee on Specifications for Pharmaceutical Preparations. 658 Forty-fourth report. Geneva, World Health Organization, 2010 (WHO 659 Technical Report Series, No. 957), Annex 1. 660

2. Quality assurance of pharmaceuticals. A compendium of guidelines and 661 related materials. Vol. 2, Second updated edition. Good manufacturing 662 practices and inspection. Geneva, World Health Organization, 2007; 663 Quality assurance of pharmaceuticals. A compendium of guidelines 664 and related materials. World Health Organization, 2010 (CD-ROM) 665 (http://apps.who.int/medicinedocs/en/q/). 666

3. WHO guidelines for preparing a laboratory information file. Revision. In: WHO 667 Expert Committee on Specifications for Pharmaceutical Preparations. 668 Thirty-eighth report. Geneva, World Health Organization, 2011 (WHO 669 Technical Report Series, No. 961), Annex 13. 670