GUIDELINES ON VALIDATION APPENDIX 6 VALIDATION ON ...
36
Working document QAS/16.673 June 2016 Draft document for comment 1 GUIDELINES ON VALIDATION – APPENDIX 6 2 VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES 3 AND EQUIPMENT 4 (June 2016) 5 DRAFT FOR COMMENTS 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 © World Health Organization 2016 26 All rights reserved. 27 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 28 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 29 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 30 organizations) without the permission of the World Health Organization. The draft should not be displayed on any website. 31 Please send any request for permission to: 32 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms, Regulation of Medicines and 33 other Health Technologies, Department of Essential Medicines and Health Products, World Health Organization, CH-1211 34 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: [email protected]. 35 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 36 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 37 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 38 for which there may not yet be full agreement. 39 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended 40 by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions 41 excepted, the names of proprietary products are distinguished by initial capital letters. 42 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 43 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 44 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 45 damages arising from its use. 46 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 47 48 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 ([email protected]) with a copy to Ms Marie Gaspard ([email protected]) by 15 August 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 already receive our draft working documents please let us have your email address (to [email protected]) and we will add it to our electronic mailing list.
Transcript of GUIDELINES ON VALIDATION APPENDIX 6 VALIDATION ON ...
Working document QAS/16.673
June 2016
Draft document for comment
1
GUIDELINES ON VALIDATION – APPENDIX 6 2
VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES 3
AND EQUIPMENT 4
(June 2016) 5
DRAFT FOR COMMENTS 6
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
25
© World Health Organization 2016 26 All rights reserved. 27 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 28 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 29 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 30 organizations) without the permission of the World Health Organization. The draft should not be displayed on any website. 31 Please send any request for permission to: 32 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms, Regulation of Medicines and 33 other Health Technologies, Department of Essential Medicines and Health Products, World Health Organization, CH-1211 34 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: [email protected]. 35
The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 36 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 37 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 38 for which there may not yet be full agreement. 39 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended 40 by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions 41 excepted, the names of proprietary products are distinguished by initial capital letters. 42 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 43 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 44 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 45 damages arising from its use. 46 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 47 48
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 ([email protected]) with a copy to Ms Marie Gaspard
([email protected]) by 15 August 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 already receive our
draft working documents please let us have your email address (to
[email protected]) and we will add it to our electronic mailing list.
.
Working document QAS/16.673
page 2 49 50 51
SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/16.673: 52 GUIDELINES ON VALIDATION – APPENDIX 6 53
VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES AND EQUIPMENT 54
55
56 57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
Discussion of proposed need for revision in view of the
current trends in validation during informal consultation
on data management, bioequivalence, GMP and
medicines’ inspection
29 June–
1 July 2015
Preparation of draft proposal for revision of the main text
and several appendices by specialists in collaboration
with the Medicines Quality Assurance Group and
Prequalification Team (PQT)-Inspections, based on the
feedback received during the meeting and from PQT-
Inspections, draft proposals developed on the various
topics by specialists, as identified in the individual
working documents.
July 2015–
April 2016
Presentation of the progress made to the fiftieth meeting
of the WHO Expert Committee on Specifications for
Pharmaceutical Preparations
12–16 October 2015
Discussion at the informal consultation on good practices
for health products manufacture and inspection, Geneva
4–6 April 2016
Preparation of revised text by Dr A.J. van Zyl, participant
at the above-mentioned consultation, based on the
feedback received during and after the informal
consultation by the meeting participants and members of
PQT-Inspections
May 2016
Circulation of revised working document for public
consultation
June 2016
Consolidation of comments received and review of
feedback
August–September
2016
Presentation to the fifty-first meeting of the WHO Expert
Committee on Specifications for Pharmaceutical
Preparations
17–21 October 2016
Any other follow-up action as required …
Working document QAS/16.673
page 3
Background information 91 92
The need for revision of the published Supplementary guidelines on good manufacturing 93
practices: validation (World Health Organization (WHO) Technical Report Series, No. 937, 94
2006, Annex 4) was identified by the Prequalification of Medicines Programme and a draft 95
document was circulated for comment in early 2013. The focus of the revision was the Appendix 96
on non-sterile process validation (Appendix 7), which had been revised and was adopted by the 97
Committee at its forty-ninth meeting in October 2014. 98
99
The main text was sent out for consultation as Working document QAS/15.639 entitled 100 “Guidelines on Validation” which constitute the general principles of the new guidance on 101
validation. 102 103 The draft on the specific topics, the appendices to this main text, will follow. One of them, i.e. 104 the Validation on qualification of systems, utilities and equipment, constitutes this working 105
document. 106 107
The following is an overview on the appendices that are intended to complement the general text 108 on validation: 109 110
Appendix 1 111 Validation of heating, ventilation and air-conditioning systems 112
will be replaced by cross-reference to WHO Guidelines on GMP for HVAC systems 113 for considerations in qualification of HVAC systems 114
(update - working document QAS/15.639/Rev.1) 115 116
Appendix 2 117
Validation of water systems for pharmaceutical use 118 will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical 119
use for consideration in qualification of water purification systems 120 121
Appendix 3 122 Cleaning validation – consensus to retain 123
124 Appendix 4 125 Analytical method validation 126
will be replaced by update - working document QAS/16.671 127 128
Appendix 5 129 Validation of computerized systems 130
will be replaced by update - working document QAS/16.667 131
132
Appendix 6 133 Qualification of systems, utilities and equipment – updated text proposed in this 134 working document 135
Working document QAS/16.673
page 4
136 Appendix 7 137
Non-sterile process validation – update already published as Annex 3, WHO Technical 138
Report Series, No. 992, 2015 139
Working document QAS/16.673
page 5
GUIDELINES ON VALIDATION – APPENDIX 6 140
VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES AND 141
EQUIPMENT 142
143
1. Principle 144 2. Scope 145 3. Glossary 146
4. General 147 5. User requirement specifications 148
6. Factory acceptance test and site acceptance test 149 7. Design qualification 150 8. Installation qualification 151 9. Operational qualification 152 10. Performance qualification 153 11. Requalification 154 12. Qualification of “in use” systems and equipment 155
156 1. PRINCIPLE 157 158 1.1 Systems, utilities and equipment should be appropriately designed, located, installed, 159
operated, cleaned and maintained to suit their intended purpose. 160 161
1.2 Products should be manufactured on qualified equipment to ensure batch-to-batch 162 consistency 163 164
1.3 Procedures should be in place to ensure that systems, utilities and equipment remain in a 165 qualified state throughout the life of the system, utility and equipment. 166
167
2. SCOPE 168 169
2.1 These guidelines describe the general aspects of qualification for systems, utilities and 170
equipment. 171 172 2.2 The principles in this guideline may also be applied to the qualification of instruments 173
and testing devices, where appropriate. 174 175 2.3 Systems, utilities and equipment that may have an impact on the quality of products, 176 should be appropriately qualified. These may include, where appropriate: computerized systems; 177 water purification systems; heating, ventilation and air conditioning systems; compressed air 178
systems; steam systems; production and quality control of equipment and instruments. 179 180 2.4 Documented impact assessments should support decisions for the exclusion of systems, 181
utilities and equipment from qualification. 182 183
184
Working document QAS/16.673
page 6
3. GLOSSARY 185 186
design qualification. Documented evidence that the premises, supporting systems, 187 utilities, equipment and processes have been designed in accordance with the requirements of 188 good manufacturing practices. 189 190
factory acceptance test. A test conducted at the vendor’s premises to verify that the 191
system, equipment or utility, as assembled or partially assembled, meets expected specifications. 192 (new) 193 194
installation qualification. The performance of tests to ensure that the installations (such 195
as machines, measuring devices, utilities and manufacturing areas) used in a manufacturing 196 process are appropriately selected and correctly installed and operate in accordance with 197 established specifications. 198
199
operational qualification. Documented verification that the system or subsystem 200 performs as intended over all anticipated operating ranges. 201 202
performance qualification. Documented verification that the equipment or system 203 operates consistently and gives reproducibility within defined specifications and parameters for 204
prolonged periods. (In the context of systems, the term “process validation” may also be used.) 205
206
site acceptance test. A test conducted at the site of use to verify that the system, 207 equipment or utility, as assembled or partially assembled meets expected specifications. (new) 208 209
system. A regulated pattern of interacting activities and techniques that are united to form 210 an organized whole. 211
212 user requirement specifications. An authorized document that defines the requirements 213
for use of the system, equipment or utility in its intended production environment. (amended) 214
215 utility. A system consisting of one or more components to form a structure designed to 216
collectively operate, function or perform and provide a service such as electricity, water, 217 ventilation or other. (new) 218
219
4. GENERAL 220 221 4.1 The validation master plan, or other relevant document, should specify the policy, 222 organization, planning, scope and stages applied in qualification for systems, utilities and 223 equipment and should cover, e.g. production, quality control and engineering. 224 225 4.2 The scope and extent of qualification and requalification should be determined based on 226 the principles of impact assessment and risk assessment. Risk management principles should be 227
considered in all areas of the scope and stages of qualification. 228 229
Working document QAS/16.673
page 7
4.3 Where appropriate, new systems, utilities and equipment should pass through all stages of 230 qualification including the preparation of user requirement specifications (URS), design 231
qualification (DQ), installation qualification (IQ), operational qualification (OQ) and 232 performance qualification (PQ) (see Figure 1 as an example). 233 234
Figure 1. Examples of stages of qualification 235
Performance
Qualification
Operational
Qualification
Installation
Qualification
User Requirement
Specification
Functional Design
Specification
Detail Design and
Configuration
Specifications
Build & Project
Implementation
Desig
n
Qu
ali
ficati
on
V-Model for Direct Impact Systems
PQ Test Plan
(incl. UAT)
OQ Test Plan
(incl. FAT)
IQ Test Plan
(incl. PDI)
DQ Test Plan
236 (Note: For description of stages, see below) 237 238
4.4 Scientific justification should be provided where it is decided that not all stages of 239 qualification are required. 240 241
[Note from the Secretariat: The references below will be updated upon finalization of the related 242 texts.] 243 244 4.5 See WHO TRS XXX for aspects to be considered for inclusion in qualification of water 245
purification systems 246 247 4.6 See WHO TRS XXX for aspects to be considered for inclusion in qualification of 248 heating, ventilation and air-conditioning (HVAC) systems. 249 250
4.7 See WHO TRS XXX for aspects to be considered for inclusion in qualification and 251 validation of computerized systems. 252
253 254
Working document QAS/16.673
page 8
4.8 Qualification should be done in accordance with predetermined and approved 255 qualification protocols. 256
257 4.9 The results of the qualification should be recorded and reflected in qualification reports. 258 259 4.10 Rooms or areas, as appropriate, should be qualified prior to the qualification of utilities. 260 261
4.11 Utilities should be qualified prior to the qualification of equipment. 262 263 4.12 Equipment should qualified and brought into routine use only once there is documented 264 evidence that it is fit for its intended purpose. 265
266 4.13 Certain stages of the qualification may be done by the supplier or a third party, subject to 267 the conditions and responsibilities as defined in an agreement between the two parties. The 268
contract giver remains responsible to ensure that the qualification is done in accordance with 269
good manufacturing practices (GMP). 270 271 4.14 There should be a logical sequence in performing qualification. For example, operational 272
qualification should follow after the successful completion of installation qualification. 273 274
4.15 The relevant documentation associated with qualification including standard operating 275
procedures (SOPs), specifications and acceptance criteria, certificates and manuals should be 276
maintained and be traceable. 277 278 4.16 Systems, utilities and equipment should be maintained in a qualified state and undergo 279
periodic requalification where appropriate, as well as requalification after change when needed. 280 281
4.17 Processes should be validated on qualified equipment. 282 283
5. USER REQUIREMENT SPECIFICATIONS 284 285 5.1 URS should be prepared for systems, utilities and equipment, where appropriate 286
287 5.2 URS should be used to verify, at a later stage, that the purchased and supplied system, 288
utility or equipment is in accordance with the manufacturer’s needs as specified. 289 290
6. FACTORY ACCEPTANCE TEST AND SITE ACCEPTANCE TEST 291 292 6.1 Where a system, utility or equipment is assembled, or partially assembled at a site other 293 than that of the purchaser or end-user, testing and verification should be done to ensure that the 294 system, utility or equipment is appropriate and ready for dispatch. 295 296 6.2 The checks and tests during assembly or partial assemble, should be recorded. 297
298
Working document QAS/16.673
page 9
6.3 The acceptability of the assembly and overall status of the system, utility or equipment 299 should be described in a conclusion of the report for the factory acceptance test (FAT), prior to 300
shipment. 301 302 6.4 When the system, utility or equipment is received at the end user, tests should be 303 performed to verify the acceptability of the system, utility or equipment. 304 305
6.5 The results of the tests should be recorded and the outcome of the acceptability of the 306 system, utility or equipment recorded in the conclusion of the report for the site acceptance test 307 (SAT). 308 309
7. DESIGN QUALIFICATION 310 311 7.1 URS should be considered when deciding on the specific design of a system, utility or 312
equipment. 313
314 7.2 A suitable supplier should be selected for the appropriate system, utility or equipment. 315 316
7.3 The supplier should be approved prior to purchasing the system, utility or equipment 317 318
7.4 On delivery of the system, utility or equipment, the user should verify that it meets the 319
agreed design specifications and satisfies the URS 320
321 7.5 Once DQ is completed, IQ may commence. 322 323
8. INSTALLATION QUALIFICATION 324 325
8.1 Systems, utilities and equipment should be correctly installed, in an appropriate location 326 and in accordance with an installation plan 327 328
8.2 There should be documented evidence of the installation. This should be in accordance 329 with the IQ protocol which contains all the required detail. 330
331 8.3 IQ should include identification and verification of all system elements, parts, services, 332
controls, gauges and other components. 333 334 8.4 Measuring, control and indicating devices being installed should be calibrated. The 335 calibration should be traceable to relevant national or international standards. Certificates should 336 be available. 337 338 8.5 The execution of the protocol should be recorded in the IQ report. 339 340 8.6 The report should include at least the title, objective, site, details of the supplier and 341
manufacturer, system or equipment name and unique identification number, model and serial 342 number, date of installation, components and their identification numbers or codes, actual results 343
Working document QAS/16.673
page 10
of tests and measurements, spare parts list, relevant procedures followed for tests and certificates 344 as applicable. 345
346 8.7 All deviations and non-conformances from URS, DQ and acceptance criteria specified, 347 observed during installation, should be recorded and investigated. 348 349 8.8 The outcome of the IQ should be recorded in the conclusion of the report, before OQ is 350
started. 351 352 8.9 Requirements and procedures for calibration, maintenance and cleaning should be drawn 353 up during installation. 354
355
356
Figure 2. Example of an installation qualification protocol 357 358
Working document QAS/16.673
page 11
359
Working document QAS/16.673
page 12
360
Working document QAS/16.673
page 13
361
Working document QAS/16.673
page 14
362
Working document QAS/16.673
page 15
363 9. OPERATIONAL QUALIFICATION 364 365 9.1 Systems, utilities and equipment should operate correctly and their operation should be 366 verified in accordance with an OQ protocol. 367
368
9.2 Critical operating parameters should be identified. Studies on the critical variables should 369 include conditions encompassing normal, upper and lower operating limits and circumstances 370 (this includes “worst-case conditions”). 371
Working document QAS/16.673
page 16
372 9.3 OQ should include verification of operation of all system elements, parts, services, 373
controls, gauges and other components. 374 375 9.4 The results for the verification of operation should be documented in the OQ report to 376 indicate the satisfactory operation. 377 378
9.5 SOPs for the operation should be finalized and approved during this phase of 379 qualification. 380 381 9.6 Training of operators for the systems, utilities and equipment should be provided and 382
training records maintained. 383 384 9.7 Systems, utilities and equipment, as appropriate, should be released for PQ or routine use 385
after completion of OQ. 386
387 9.8 All calibration, cleaning, maintenance, training and related tests and results should be 388 verified to be acceptable. Any discrepancy or deviation should be recorded and investigated. 389
390 9.9 The outcome of the OQ should be recorded in the conclusion of the report, before PQ is 391
started. 392
393
394 Figure 3. Example of an operational qualification protocol 395 396
Working document QAS/16.673
page 17
397 398
Working document QAS/16.673
page 18
399
Working document QAS/16.673
page 19
400
Working document QAS/16.673
page 20
401
Working document QAS/16.673
page 21
402
Working document QAS/16.673
page 22
403
Working document QAS/16.673
page 23
404
Working document QAS/16.673
page 24
405
Working document QAS/16.673
page 25
406
Working document QAS/16.673
page 26
407
Working document QAS/16.673
page 27
10. PERFORMANCE QUALIFICATION 408 409
10.1 Systems, utilities and equipment should consistently perform in accordance with their 410
design specifications. The performance should be verified in accordance with a PQ protocol. 411 412 10.2 There should be records for the PQ (report) to indicate the satisfactory performance over 413 a period of time. Manufacturers should justify the selected period over which PQ is done. 414 415
10.3 PQ should be done once OQ is successfully completed. 416 417 10.4 Where two stages of qualification (e.g. OQ and PQ) are performed simultaneously, or 418
where PQ is executed at the same time as process validation, appropriate justification for such a 419 decision should be documented 420 421
422 Figure 4. Example of a performance qualification protocol 423 424
Working document QAS/16.673
page 28
425 426 427 428
429
Working document QAS/16.673
page 29
430
Working document QAS/16.673
page 30
431
Working document QAS/16.673
page 31
432
Working document QAS/16.673
page 32
433
Working document QAS/16.673
page 33
434
Working document QAS/16.673
page 34
435
Working document QAS/16.673
page 35
436
Working document QAS/16.673
page 36
11. REQUALIFICATION 437 438
11.1 Systems, utilities and equipment should be maintained in a qualified state through the life 439 of the system, utility or equipment. 440 441
11.2 Routine requalification of systems, utilities and equipment should be considered based 442 on the outcome of risk management principles which include factors such as calibration, 443 verification and maintenance data and information. 444
445 11.3 The qualification status and requalification due dates should be documented in a defined 446 schedule. 447
448 11.4 The scope and extent of qualification should be determined based on risk assessment 449 when changes to an existing system, utility or equipment are made. 450
451
12. QUALIFICATION OF “IN-USE” SYSTEMS, UTILITIES AND EQUIPMENT 452 453
12.1 There should be data to support and verify the suitable design, operation and performance 454 of systems, utilities and equipment that have been “in use” for a period of time and which have 455
not been subjected to IQ and or OQ. 456 457
12.2 In such cases, a qualification protocol and report should be prepared where elements of 458 design, operation and performance are verified for acceptability. These should include operating 459
parameters and limits for critical variables, calibration, maintenance and preventive maintenance, 460 SOPs and records. 461
462
*** 463
