Working document QAS/20.

869
December 2020

1
2

3 DRAFT WORKING DOCUMENT FOR COMMENTS:

4

5 WHO guidelines on the transfer of technology

6 in pharmaceutical manufacturing
7
8
Please send your comments to Dr Sabine Kopp, Team Lead, Norms and Standards for Pharmaceuticals,
Technical Standards and Specifications (kopps@who.int), with a copy to Ms Claire Vogel
(vogelc@who.int) before 20 February 2021. Please use the attached “Table of Comments” document for
this purpose.
Our working documents are sent out electronically and they will also be placed on the WHO Medicines
website (https://www.who.int/teams/health-product-and-policy-standards/standards-and-
specifications/pharmaceuticals/current-projects) for comments under the “Working documents in public
consultation” link. If you wish to receive all our draft guidelines, please send your email address to
jonessi@who.int and your name will be added to our electronic mailing list.
9
10
11
12 © World Health Organization 2020
13
14 All rights reserved.
15
16 This is a draft. The content of this document is not final, and the text may be subject to revisions before publication. The
17 document may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or
18 in whole, in any form or by any means without the permission of the World Health Organization.
19
20 Please send any request for permission to: Dr Sabine Kopp, Team Lead, Norms and Standards for Pharmaceuticals, Technical
21 Standards and Specifications, Department of Health Products Policy and Standards, World Health Organization, CH-1211
22 Geneva 27, Switzerland, email: kopps@who.int.
23
24 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion
25 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or
26 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate
27 border lines for which there may not yet be full agreement.
28
29 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or
30 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors
31 and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
32
33 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft.
34
35 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility
36 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable
37 for damages arising from its use.
38
39 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.
40
 Working document QAS/20.869
Page 2

41 SCHEDULE FOR DRAFT WORKING DOCUMENT QAS/20.869:

42 WHO guidelines on the transfer of technology

43 in pharmaceutical manufacturing
44

Description of Activity Date

Following a recommendation by the WHO Local Production & October 2020

Assistance Unit, the Fifty-fifth Expert Committee on Specifications
for Pharmaceutical Preparations (ECSPP) recommended that the
WHO Secretariat enquire if the WHO guidelines on the transfer of
technology in pharmaceutical manufacturing should be updated in
order to support inspections for COVID-19 therapeutics.

Preparation of first draft working document. November 2020

Mailing of working document to the Expert Advisory Panel on the December 2020
International Pharmacopoeia and Pharmaceutical Preparations
(EAP) inviting comments and posting of the working document on
the WHO website for public consultation

Consolidation of comments received and review of feedback. February 2021

Preparation of working document for discussion.

Discussion of the feedback received on the working document in a February-March 2021

virtual meeting with an expert working group

Preparation of working document for next round of public April 2021

consultation.

Mailing of revised working document inviting comments, including

to the EAP, and posting of the working document on the WHO
April 2021
website for a second round of public consultation.

Consolidation of comments received and review of feedback. June – July 2021

Preparation of working document for discussion.

Discussion of the feedback received on the working document in a August 2021

virtual meeting with an expert working group

Presentation to the Fifty-sixth meeting of the ECSPP. October 2021

Any other follow-up action as required.

45
 Working document QAS/20.869
Page 3

46 WHO guidelines
47 on the transfer of
48 technology in
49 pharmaceutical
50 manufacturing
51
52

53 Background
54
55 During the Fifty-fifth World Health Organization (WHO) Expert Committee on Specifications for
56 Pharmaceutical Preparations (ECSPP) meeting, Expert Committee members were updated on the
57 annual consultation of Good Practices for Health Products and Inspection which took place in July 2020
58 in a series of virtual meetings due to the COVID-19 pandemic. During these virtual meetings, a group
59 of experts made a series of proposals for future activities, one of which was how to determine whether
60 or not the WHO guidelines on the transfer of technology in pharmaceutical manufacturing (1) should
61 also be updated. This document was published in 2011 and it was considered that it should require
62 updating, not least to support the inspections for COVID-19 therapeutics.
63
64 The Expert Committee asked the WHO Secretariat to explore this proposal.
65
66 Background
67 1. Introduction
68 2. Scope
69 3. Glossary
70 4. Due diligence and gap assessments
71 5. Organization and management
72 6. Quality management and quality risk management
73 7. Documentation
74 8. Premises
75 9. Equipment and instruments
76 10. Qualification and validation
77 11. Product life cycle and project management principles
78 12. Phases of a technology transfer project
79 Phase I: Project initiation
 Working document QAS/20.869
Page 4

80 Phase II: Project proposal

81 o Establishing a team
82 o Risk assessment
83 o Project plan
84 o Control strategy
85 Phase III: Project transfer
86 Production: transfer (processing, packaging)
87 Starting materials
88 Active pharmaceutical ingredients
89 Excipients
90 Information on process and finished pharmaceutical products information
91 Packaging
92 Quality control: analytical method transfer
93 Cleaning
94 Phase IV: Project review
95
96 References
97 Further reading
98 Abbreviations
99 Appendix 1. Example of documentation commonly required for the transfer of technology
100 Appendix 2. Example of possible experimental designs and acceptance criteria for analytical testing
101
 Working document QAS/20.869
Page 5

102 1. Introduction
103
104 1.1. Production and control procedures, validation and other related activities may be transferred
105 from one site to another site prior to obtaining a marketing authorization. In some cases, this
106 transfer takes place after the approval of, for example, a product, by a regulatory authority.
107 This transfer can be, for example, from drug discovery to product development; to clinical trials;
108 or to full-scale commercialization and commercial batch manufacturing; cleaning and
109 validation.
110
111 1.2. A technology transfer, particularly one between different companies, has legal and economic
112 implications. If such issues, which may include intellectual property rights, royalties, pricing,
113 conflicts of interest and confidentiality agreements, are expected to impact on the open
114 communication of technical matters in any way, they should therefore be addressed before
115 and during the planning and execution of the transfer.
116
117 1.3. A technology transfer requires a planned approach by trained, knowledgeable personnel
118 working within a quality system, with documentation, data and information covering all aspects
119 of development, production and quality control (QC), as applicable.
120
121 1.4. A technology transfer takes place between a sending unit (SU) and a receiving unit (RU). In
122 some cases, there may be a separate unit managing the project.
123
124 1.5. The technology transfer project should fulfil the following general principles and requirements.
125 There should be:
126 • a documented project plan covering the relevant aspects of the project;
127 • a detailed risk management plan;
128 • a comprehensive technical gap analysis, including due diligence performed covering
129 technical and regulatory aspects;
130 • similar capabilities between the SU and RU, including but not limited to, facilities and
131 equipment;
132 • an adequate number of adequately trained personnel with suitable qualifications and
133 experience; and
 Working document QAS/20.869
Page 6

134 • effective process and product knowledge management.

135
136 1.6. A technology transfer should include relevant documentation, data, information and
137 knowledge from the SU in order to enable the RU to effectively perform the specified process
138 or procedure in, for example, production and QC. A successful transfer of technology should
139 result in proof that the RU can routinely reproduce the transferred product, process or
140 procedure against a predefined set of specifications as agreed between the SU and RU.
141
142 1.7. This document should be read in conjunction with other WHO guidelines as referenced below
143 (2-14), as well as other regulatory guidelines which include The International Council for
144 Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q7, Q8,
145 Q9, Q10 and Q11. This guideline does not intend to replace any of these guidelines.
146
147 1.8. This version of the guideline provides updated requirements and expectations reflecting
148 current good practices (GxP) in the transfer of technology and replaces the previous version
149 published (1).
150

151 2. Scope
152
153 2.1. This document provides guiding principles on technology transfer.
154
155 2.2. This guideline should be applied when transferring the technology of processes and procedures
156 relating to active pharmaceutical ingredients (APIs), in-process bulk materials, finished
157 pharmaceutical products (FPPs), process validation, cleaning procedure development and
158 validation and analytical procedures.
159
160 2.3. The guideline applies to all pharmaceutical dosage forms and may be adapted on a case-by-
161 case basis by using risk management principles. Particular attention should be given to certain
162 complex formulations such as, for example, sterile products and metered dose aerosols.
163
 Working document QAS/20.869
Page 7

164 2.4. Although this document focuses on pharmaceutical products, the principles can also be applied
165 to the transfer of production, related processes and controls for other products such as
166 biopharmaceutical products, vaccines, medical devices and vector control products.
167
168 2.5. Because each transfer project is unique, the provision of a comprehensive set of guidelines
169 specific to a product or process is beyond the scope of this document.
170
171 2.6. This document does not provide guidance on any legal, financial or commercial considerations
172 associated with technology transfer projects.
173
174 2.7. This document addresses the following principal areas:
175 • organization and management of the transfer;
176 • transfer of development information in production, including but not limited to
177 processing and packaging;
178 • transfer of development information and analytical procedures;
179 • documentation, premises, equipment;
180 • personnel qualification and training;
181 • quality management and risk management;
182 • life cycle approach;
183 • control strategy; and
184 • qualification and validation.
185

186 3. Glossary
187
188 The definitions given below apply to the terms used in these guidelines. They have been aligned as far
189 as possible with the terminology in related WHO guidelines and Good Practices and included in the
190 WHO Quality Assurance of Medicines Terminology Database - List of Terms and related guideline
191 https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/mqa-
192 terminology-sept-2020.pdf?sfvrsn=48461cfc_5 ), but may have different meanings in other contexts.
193
194 acceptance criteria. Measurable terms under which a test result will be considered acceptable.
195
 Working document QAS/20.869
Page 8

196 active pharmaceutical ingredient (API). Any substance or mixture of substances intended to be used in
197 the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active
198 ingredient of that pharmaceutical dosage form. Such substances are intended to furnish
199 pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or
200 prevention of disease, or to affect the structure and function of the body.
201
202 ALCOA+. A commonly used acronym for “attributable, legible, contemporaneous, original and accurate
203 that puts additional emphasis on the attributes of being complete, consistent, enduring and available
204 – implicit basic ALCOA principles.
205
206 bracketing. An experimental design to test the extremes of, for example, dosage strength. The design
207 assumes that the extremes will be representative of all the samples between the extremes.
208
209 change control. A formal system by which qualified representatives of appropriate disciplines review
210 proposed or actual changes that might affect a validated status. The intent is to determine the need
211 for action that would ensure that the system is maintained in a validated state.
212
213 control strategy. A planned set of controls, derived from current product and process understanding
214 that assures process performance and product quality. The controls can include parameters and
215 attributes related to API and finished pharmaceutical product materials and components, facility and
216 equipment operating conditions, in-process controls, finished product specifications and the associated
217 methods and frequency of monitoring and control.
218
219 corrective action. Any action to be taken when the results of monitoring at a critical control point
220 indicate a loss of control.
221
222 critical. Having the potential to impact on product quality or performance in a significant way.
223
224 critical control point. A step at which control can be applied and is essential to prevent or eliminate a
225 pharmaceutical quality hazard or to reduce it to an acceptable level.
226
 Working document QAS/20.869
Page 9

227 design qualification. Documented evidence that, for example, the premises, supporting systems,
228 utilities, equipment and processes have been designed in accordance with the requirements of good
229 manufacturing practices (GMP).
230
231 design space. The multidimensional combination and interaction of input variables (e.g. material
232 attributes) and process parameters that have been demonstrated to provide assurance of quality.
233
234 drug master file. Detailed information concerning a specific facility, process or product submitted to
235 the medicines regulatory authority, intended for incorporation into the application for marketing
236 authorization.
237
238 finished pharmaceutical product (FPP). A product that has undergone all stages of production, including
239 packaging in its final container and labelling. An FPP may contain one or more active pharmaceutical
240 ingredients (APIs).
241
242 gap analysis. The identification of the critical elements of a process which are available at the sending
243 unit (SU) but are missing from the receiving unit (RU).
244
245 good manufacturing practices (GMP). That part of quality assurance which ensures that pharmaceutical
246 products are consistently produced and controlled to the quality standards appropriate to their
247 intended use and as required by the marketing authorization.
248
249 in-process control (IPC). Checks performed during production in order to monitor and, if necessary, to
250 adjust the process to ensure that the product conforms to its specifications. The control of the
251 environment or equipment may also be regarded as a part of in-process control.
252
253 installation qualification (IQ).
254 Documented verification that the installations (such as machines equipment and instruments,
255 computer system components, measuring devices, utilities and manufacturing) used in a processor
256 system are appropriately selected and correctly installed, in accordance with established specifications.
257
258 intercompany transfer. A transfer of technology between the sites of different companies.
259
 Working document QAS/20.869
Page 10

260 intracompany transfer. A transfer of technology between sites of the same group of companies.
261
262 operational qualification (OQ). Documented verification that the system or subsystem performs as
263 intended over all anticipated operating ranges.
264
265 performance qualification (PQ). Documented verification that the equipment or system performs
266 consistently and reproducibly within defined specifications and parameters in its normal operating
267 environment (i.e. in the production environment).
268
269 process validation. The collection and evaluation of data, from the process design stage through to
270 commercial production, which establishes scientific evidence that a process is capable of continuously
271 delivering the finished pharmaceutical product meeting its predetermined specifications and quality
272 attributes.
273
274 qualification. Documented evidence that premises, systems or equipment are able to achieve the
275 predetermined specifications when properly installed, and/or work correctly and lead to the expected
276 results.
277
278 qualification batches. Those batches produced by the receiving unit (RU) to demonstrate its ability to
279 reproduce the product .
280
281 quality assurance (QA). “Quality assurance” is a wide-ranging concept covering all matters that
282 individually or collectively influence the quality of a product. It is the totality of the arrangements made
283 with the objective of ensuring that pharmaceutical products are of the quality required for their
284 intended use.
285
286 quality control (QC). All measures taken, including the setting of specifications, sampling, testing and
287 analytical clearance, to ensure that starting materials, intermediates, packaging materials and finished
288 pharmaceutical products (FPP) conform with established specifications for identity, strength, purity and
289 other characteristics.
290
291 quality planning. Part of quality management, focused on setting quality objectives and specifying
292 necessary operational processes and related resources to fulfil the quality objectives.
 Working document QAS/20.869
Page 11

293 quality policy. A brief statement that describes the organization’s purpose, overall intentions and
294 strategic direction; provides a framework for quality objectives; and includes a commitment to meet
295 applicable requirements.
296
297 quality risk management (QRM). A systematic process for the assessment, control, communication and
298 review of risks to the quality of the pharmaceutical product throughout the product’s life cycle.
299
300 receiving unit (RU). The involved disciplines at an organization where a designated product, process or
301 method is expected to be transferred.
302
303 sending unit (SU). The involved disciplines at an organization from where a designated product, process
304 or method is expected to be transferred.
305
306 standard operating procedure (SOP). An authorized written procedure giving instructions for
307 performing operations, not necessarily specific to a given product or material , but of a more general
308 nature (for example, operation of equipment, maintenance and cleaning, validation, cleaning of
309 premises and environmental control, sampling and inspection). Certain standard operating procedures
310 may be used to supplement product-specific master and batch production documentation.
311
312 transfer of technology. A logical procedure that controls the transfer of any process, together with its
313 documentation and professional expertise between development and manufacture or between
314 manufacture sites. It is a systematic procedure that is followed in order to pass the documented
315 knowledge and experience gained during development and/or commercialization to an appropriate,
316 responsible and authorized party.
317
318 technology transfer report. A documented summary of a specific technology transfer project listing
319 procedures, acceptance criteria, results achieved and conclusions.
320
321 validation. Action of proving and documenting that any process, procedure or method actually and
322 consistently leads to the expected results.
323
324 validation master plan (VMP). A high-level document that summarizes the manufacturer’s overall
325 philosophy and approach, to be used for establishing performance adequacy. It provides information
 Working document QAS/20.869
Page 12

326 on the manufacturer’s qualification and validation work programme and defines details of and timelines
327 for the work to be performed, including a statement of the responsibilities of those implementing the
328 plan.
329
330 validation protocol (VP). A document describing the activities to be performed during validation,
331 including the acceptance criteria.
332
333 validation report (VR). A document in which the records, results and evaluation of validation are
334 documented and summarized. It should also contain a conclusion of the outcome of the validation.
335

336 4. Due diligence and gap assessments

337
338 4.1. A process of due diligence, gap assessment or audits of the SU and RU should be one of the
339 first steps when considering a technology transfer project.
340
341 4.2. The suitability and degree of preparedness of the RU should be assessed prior to the start of
342 the transfer. The procedure to be followed should be documented.
343
344 4.3. The assessment should be done by a team of appropriately qualified persons with knowledge
345 and experience in the field of GxP and the activity to be transferred.
346
347 4.4. The assessment should further cover resources including personnel, premises, equipment and
348 instruments, utilities, QC, documentation, computerized systems, qualification and validation
349 and waste management.
350
351 4.5. The assessment to determine feasibility and readiness for technology transfer may include
352 technical, business, regulatory and legal aspects.
353

354 5. Organization and management

355
356 5.1. All technology transfer activities should be organized and planned.
357
 Working document QAS/20.869
Page 13

358 5.2. There should be a formal agreement between the parties which specifies the responsibilities
359 of each party before, during and after transfer. The agreement should cover, for example, data
360 management, data integrity, documentation and validation.
361
362 5.3. All the necessary activities to be executed during the technology transfer project should be
363 identified, organized and documented at the start of the project. Responsibilities should be
364 defined.
365
366 5.4. The SU should provide the necessary documentation relating to the process, product or
367 procedure to be transferred.
368
369 5.5. The SU should provide criteria and information on inherent risks, hazards and critical steps
370 associated with the process, product or procedure to be transferred. This may serve as a basis
371 for the risk assessment exercise.
372
373 5.6. The technology transfer should be managed by responsible persons from the SU and RU. A
374 technology transfer team may be appointed with identified and documented responsibilities.
375
376 5.7. The team members should have the necessary qualifications and experience to manage the
377 particular aspects of the transfer.
378
379 5.8. The SU should make all the necessary information and knowledge with regard to the product,
380 process or procedure available in relevant documents in order to ensure a successful transfer.
381
382 5.9. A training programme should be implemented specific to the process, product or procedure to
383 be transferred.
384
385 5.10. Any changes and adaptations made during the course of the project should be fully
386 documented and agreed to by both parties.
387
388 5.11. The execution of the technology transfer project should be documented in a report which is
389 supported by the relevant data.
390
 Working document QAS/20.869
Page 14

391 5.12. Data should meet ALCOA+ principles.

392

393 6. Quality management and quality risk management

394
395 6.1. The SU and RU should each have an appropriately designed, clearly defined and documented
396 quality system.
397
398 6.2. The quality system should be adequately resourced, implemented and maintained.
399
400 6.3. The quality system should incorporate GxP which should be applied to the life cycle stages of
401 the products and processes, including the technology transfer.
402
403 6.4. The quality system should ensure that:
404 • responsibilities are clearly specified in writing;
405 • operations are clearly defined in writing;
406 • there is a system for quality risk management; and
407 • arrangements are made for the documented technology transfer.
408
409 6.5. Quality risk management should be implemented as a systematic process for the assessment,
410 control, communication and review of risks.
411
412 6.6. The system for quality risk management should be described in writing and cover appropriate
413 areas such as, but not limited to, premises, equipment, materials, products, production,
414 processes, QC, qualification, validation and the process of technology transfer.
415
416 6.7. The evaluation of the risk should be based on scientific knowledge and experience including
417 that of the process and product.
418
419 6.8. The level of effort, formality and documentation of the quality risk management process should
420 be commensurate with the level of risk.
421
422 6.9. The procedures and records for quality risk management should retained.
 Working document QAS/20.869
Page 15

423 7. Documentation
424
425 Note: A list with examples of documents commonly required in technology transfer is presented in
426 Appendix 1.
427
428 7.1. An authorized technology transfer document should list the intended sequential phases and
429 activities of the transfer. The document should include, for example, the following:
430 • title;
431 • objective;
432 • scope;
433 • name and addresses of the SU and RU;
434 • names of key personnel and their responsibilities;
435 • phases of the project and actions;
436 • a parallel comparison of premises, equipment, instruments, materials, procedures, and
437 methods;
438 • experimental design, quality attributes, process parameters and acceptance criteria;
439 • information on trial production batches, qualification batches and process validation;
440 • change and deviation management;
441 • arrangements for keeping retention samples of active ingredients, intermediates and
442 finished products, and information on reference substances where applicable; and
443 • review of the transfer, outcome, signature(s) and date of conclusion of the transfer.
444
445 7.2. Standard operating procedures (SOPs) should be followed, describing actions to be taken
446 during the technology transfer process.
447
448 7.3. Records should be maintained for the activities performed during the technology transfer
449 process (e.g. a technology transfer report). The report content should reflect the protocol and
450 SOPs that were followed. The report should summarize the scope of the transfer, the critical
451 parameters as obtained in the SU and RU, and the final conclusions of the transfer. The
452 discrepancies and appropriate actions taken to resolve them should be recorded. Supportive
453 documents with data, results and other relevant information should be referenced in the report
454 and be readily available.
 Working document QAS/20.869
Page 16

455 8. Premises
456
457 8.1. The RU should have appropriate premises with the layout, construction and finishing to suit the
458 intended operations. Utilities such as heating, ventilation and air conditioning, as well as gas
459 and water systems, should be appropriate for the intended process, product or procedure to
460 be transferred.
461
462 8.2. The SU should provide the RU with information on relevant health, safety and environmental
463 issues, including:
464 • inherent risks of the manufacturing processes (e.g. reactive chemical hazards,
465 exposure limits, fire and explosion risks);
466 • health and safety requirements to minimize operator exposure (e.g. atmospheric
467 containment of pharmaceutical dust);
468 • emergency planning considerations (e.g. in case of gas or dust release, spillage, fire and
469 firewater run-off); and
470 • identification of waste streams and provisions for re-use, recycling and/or disposal.
471

472 9. Equipment and instruments

473
474 9.1. The SU should provide a list of equipment and instruments involved in the production, filling,
475 packing and QC testing. The list should include the makes and models of the relevant
476 equipment and instruments.
477
478 9.2. Other relevant documentation may include, on a case-by-case basis as required, drawings;
479 manuals; maintenance procedures and records; calibration procedures and records; as well as
480 procedures such as equipment set-up, operation and cleaning.
481
482 9.3. A review and a side-by-side comparison of equipment and instruments of the SU and RU should
483 be carried out in terms of their working principle, make and models.
484
485 9.4. Where the review and comparison identify any gaps or differences, appropriate action should
486 be taken. This may include the adaptation of existing equipment or acquisition of new
 Working document QAS/20.869
Page 17

487 equipment. Such action should be taken by following a change management procedure which
488 should be documented.
489
490 9.5. Production volumes and batch sizes at the SU and RU should be compared. Where batch sizes
491 are different, the impact should be assessed and the appropriate action planned and taken.
492 Other factors relating to equipment to be reviewed may include:
493 • minimum and maximum capacity;
494 • material of construction of contact surfaces;
495 • critical operating parameters;
496 • components (e.g. filters, screens, and temperature/pressure sensors); and
497 • range of intended use.
498
499 9.6. The impact of the potential product to be transferred, on existing products manufactured on
500 site, should be assessed.
501

502 10. Qualification and validation

503
504 10.1. The extent of qualification and validation to be performed should be determined on the basis
505 of risk management principles.
506
507 10.2. The qualification of premises, utilities and equipment should be done in accordance with a
508 qualification master plan and protocols.
509
510 10.3. Validation, such as process validation, should be done in accordance with a validation master
511 plan and protocols.
512
513 10.4. Where technology is transferred to commercial sites, the qualification of equipment and
514 instruments should be completed prior to the actual technology transfer.
515
516 10.5. Process validation usually starts in research and development facilities either as prospective
517 validation (traditional approach) or as stage I process validation (see references regarding the
518 new approaches in process validation; and the life cycle approach). Note: Process validation
 Working document QAS/20.869
Page 18

519 should be done according to current guidelines as published in current WHO Technical Report
520 Series (3).
521
522 10.6. Procedures including processing and analytical procedures, should be appropriately validated
523 at the SU and transferred to the RU following documented procedures. Verification and
524 validation, as appropriate, should be continued at the RU as identified and documented in the
525 technology transfer protocol.
526
527 10.7. For cleaning procedures, development and validation should be done in accordance with the
528 guidelines as published in current WHO Technical Report Series (6). Points to consider when
529 using HBEL in cleaning validation (14) should be taken into account in establishing cleaning
530 procedures, cleanability studies and setting acceptance limits.
531
532 10.8. Analytical procedures should be validated according to the guidelines as published in current
533 WHO Technical Report Series (7).
534
535 10.9. Qualification and validation procedures, protocols, data and results should be appropriately
536 recorded. The documents should be retained as defined in procedures.
537

538 11. Product life cycle and project management

539 principles
540
541 11.1. The relevant stage of the life cycle of the facility, equipment, instrument, utility, product,
542 process or procedure to be transferred should be taken into consideration when the transfer
543 is planned and executed.
544

545 12. Phases of a technology transfer project

546
547 12.1. The technology transfer project plan may be divided into different phases. These may include,
548 for example:
549 • Phase I: Project initiation;
 Working document QAS/20.869
Page 19

550 • Phase II: Project proposal;

551 ▪ establishing a team;
552 ▪ risk assessment;
553 ▪ project plan;
554 ▪ control strategy;
555 • Phase III: Project transfer; and
556 • Phase IV: Project review.
557
558 Phase I: Project initiation
559
560 12.2. During the initiation phase of the project, a unit should normally identify the need for the
561 technology transfer. This may be because of lack of capacity, transfer from development to
562 commercial site or transfer from one company to another.
563
564 12.3. The units should establish initial discussion and identify whether or not there is any interest for
565 such a project. (See also section on due diligence above).
566
567 12.4. The RU should be able to accommodate the intended activity.
568
569 12.5. The RU should have the necessary technical expertise, technology and capability.
570
571 12.6. A sufficient level and depth of detail to support the activity, and any further development and
572 optimization at the RU, should be transferred.
573
574 Phase II: Project proposal
575
576 12.7. The SU and RU should jointly establish a team that will coordinate activities and execute the
577 technology transfer exercise.
578
579 12.8. The team should perform a risk assessment based on the available data, information and
580 knowledge of the premises, materials, products, procedures and other related information.
581
582 12.9. The team should prepare the technology transfer document.
 Working document QAS/20.869
Page 20

583 12.10. The team should develop a control strategy which includes, for example:
584 • risks;
585 • material attributes;
586 • processing steps and stages in production;
587 • testing steps in QC;
588 • equipment working principles and their impact on the process;
589 • critical quality attributes (CQAs), critical process parameters (CPPs) and in-process
590 controls;
591 • QC instruments;
592 • acceptance criteria and limits;
593 • alarms and trends;
594 • personnel requirements, such as qualification and training; and
595 • qualification and validation.
596
597 Phase III: Project transfer
598
599 12.11. The team should execute the project in accordance with the procedures and agreed plan.
600
601 Production:
602
603 Starting materials
604
605 12.12. The specifications and relevant functional characteristics of the starting materials (APIs and
606 excipients) to be used at the RU should be consistent with those materials used at the SU. Any
607 properties which are likely to influence the process or product should be identified and/or
608 characterized.
609
610 Active pharmaceutical ingredients
611
612 12.13. The SU should provide the RU with the open part of the Drug Master File (API master file), or
613 equivalent information, as well as any relevant additional information on the API of importance
614 for the manufacture of the pharmaceutical product. The following are examples of the
 Working document QAS/20.869
Page 21

615 information which may typically be provided; however the information needed in each specific
616 case should be assessed using the principles of QRM:
617 • manufacturer and associated supply chain;
618 • step of the API to be transferred;
619 • flow chart of synthesis pathway outlining the process, including entry points for raw
620 materials, critical steps, process controls and intermediates;
621 • where relevant, definitive physical form of the API (including photomicrographs and
622 other relevant data) and any polymorphic and solvate forms;
623 • solubility profile;
624 • if relevant, pH in solution;
625 • partition coefficient, including the method of determination;
626 • intrinsic dissolution rate, including the method of determination;
627 • particle size and distribution, including the method of determination;
628 • bulk physical properties, including data on bulk and tap density, surface area and
629 porosity as appropriate;
630 • water content and determination of hygroscopicity, including water activity data and
631 special handling requirements;
632 • microbiological considerations (including sterility, bacterial endotoxins and bioburden
633 levels where the API supports microbiological growth) in accordance with national,
634 regional or international pharmacopoeia requirements;
635 • specifications and justification for release and end-of-life limits;
636 • summary of stability studies conducted in conformity with current guidelines, including
637 conclusions and recommendations on retest date;
638 • list of potential and observed synthetic impurities, with data to support proposed
639 specifications and typically observed levels;
640 • information on degradants, with a list of potential and observed degradation products
641 and data to support proposed specifications and typically observed levels;
642 • potency factor, indicating observed purity and justification for any recommended
643 adjustment to the input quantity of API for product manufacturing, providing example
644 calculations; and
645 • special considerations with implications for storage and or handling, including but not
646 limited to, safety and environmental factors (e.g. as specified in material safety data
647 sheets) and sensitivity to heat, light or moisture.
 Working document QAS/20.869
Page 22

648 Excipients
649
650 12.14. The specifications and relevant functional characteristics of excipients should be made
651 available by the SU for transfer to the RU site. The following are examples of the information
652 which may typically be provided; however, the information needed in each specific case should
653 be assessed using the principles of QRM:
654 • manufacturer and associated supply chain;
655 • description of functionality, with justification for inclusion of any antioxidant,
656 preservative or any excipient;
657 • definitive form (particularly for solid and inhaled dosage forms);
658 • solubility profile (particularly for inhaled and transdermal dosage forms);
659 • partition coefficient, including the method of determination (for transdermal dosage
660 forms);
661 • intrinsic dissolution rate, including the method of determination (for transdermal
662 dosage forms);
663 • particle size and distribution, including the method of determination (for solid, inhaled
664 and transdermal dosage forms);
665 • bulk physical properties, including data on bulk and tap density, surface area and
666 porosity as appropriate (for solid and inhaled dosage forms);
667 • compaction properties (for solid dosage forms);
668 • melting point range (for semi-solid or topical dosage forms);
669 • pH range (for parenteral, semi-solid or topical, liquid and transdermal dosage forms);
670 • ionic strength (for parenteral dosage forms);
671 • specific density or gravity (for parenteral, semi-solid or topical, liquid and transdermal
672 dosage forms);
673 • viscosity and or viscoelasticity (for parenteral, semi-solid or topical, liquid and
674 transdermal dosage forms);
675 • osmolarity (for parenteral dosage forms);
676 • water content and determination of hygroscopicity, including water activity data and
677 special handling requirements (for solid and inhaled dosage forms);
678 • moisture content range (for parenteral, semisolid or topical, liquid and transdermal
679 dosage forms);
 Working document QAS/20.869
Page 23

680 • microbiological considerations (including sterility, bacterial endotoxins and bioburden

681 levels where the excipient supports microbiological growth) in accordance with
682 national, regional or international pharmacopoeia requirements, as applicable (for
683 general and specific monographs);
684 • specifications and justification for release and end-of-life limits;
685 • information on adhesives supporting compliance with peel, sheer and adhesion design
686 criteria (for transdermal dosage forms);
687 • special considerations with implications for storage and or handling, including but not
688 limited to, safety and environmental factors (e.g. as specified in material safety data
689 sheets {MSDS}) and sensitivity to heat, light or moisture; and
690 • regulatory considerations (e.g. documentation to support compliance with
691 transmissible animal spongiform encephalopathy certification requirements, where
692 applicable).
693
694 Information on process and finished pharmaceutical product information
695
696 Processing, packaging
697
698 12.15. Product, process and procedure knowledge should be an essential part of the transfer process
699 from SU to RU.
700
701 12.16. The quality target product profile, critical quality attributes, critical process parameters,
702 material attributes, control strategy and any other impacting elements on the quality of the
703 product should be available. (See also ICH guidelines.)
704
705 12.17. The SU should provide the total product quality profile with its qualitative and quantitative
706 composition, physical description, method of manufacture, in-process controls, control
707 method and specifications, packaging components and configurations, and any safety and
708 handling considerations to the RU.
709
710 12.18. The SU should provide any information on the history of process development which may be
711 required to enable the RU to perform any further development and or process optimization
712 after successful transfer.
 Working document QAS/20.869
Page 24

713 12.19. Such information may include the following:

714 • information on clinical development (e.g. information on the rationale for the
715 synthesis, route and form selection, technology selection, equipment, clinical tests,
716 and product composition);
717 • information on scale-up activities: process optimization, statistical optimization of
718 critical process parameters, critical quality attributes, pilot report and/or information
719 on pilot-scale development activities indicating the number and disposition of batches
720 manufactured;
721 • information or report on full-scale development activities, indicating the number and
722 disposition of batches manufactured, and deviation and change control (sometimes
723 referred to as change management) reports which led to the current manufacturing
724 process;
725 • the change history and reasons (e.g. a change control log, indicating any changes to
726 the process or primary packaging or analytical methods as a part of process
727 optimization or improvement); and
728 • information on investigations of problems and the outcomes of the investigations.
729
730 12.20. The SU should provide to the RU information on any health, safety and environmental issues
731 associated with the manufacturing processes to be transferred, and the implications thereof
732 (e.g. need for gowning or protective clothing).
733
734 12.21. The SU should provide to the RU information on current processing and testing, including but
735 not limited to:
736 • a detailed description of facility requirements and equipment;
737 • information on starting materials, applicable MSDS and storage requirements for raw
738 materials and finished products;
739 • description of manufacturing steps (narrative and process maps or flow charts, and/or
740 master batch records), including qualification of in-processing hold times and
741 conditions, order and method of raw material addition and bulk transfers between
742 processing steps;
743 • description of analytical methods;
744 • identification and justification of control strategy (e.g. identification of critical
745 performance aspects for specific dosage forms, identification of process control points,
 Working document QAS/20.869
Page 25

746 product quality attributes and qualification of critical processing parameter ranges,
747 statistical process control {SPC} charts);
748 • design space, in cases where this has been defined;
749 • validation information (e.g. validation plans and reports);
750 • annual product quality reviews;
751 • stability information;
752 • an authorized set of protocols and work instructions for manufacturing; and
753 • environmental conditions or any special requirement needed for the facility or
754 equipment depending on the nature of the product to be transferred.
755
756 12.22. During the transfer process, the RU should identify any differences in facilities, systems and
757 capabilities and discuss these with the SU. The potential impact should be understood and
758 satisfactorily addressed in order to assure equivalent product quality. Based on the information
759 received from the SU, the RU should consider its own capability to manufacture and pack the
760 product to the required standards and should develop the relevant site operating procedures
761 and documentation before the start of routine production.
762
763 12.23. Process development at the RU should address the following tasks:
764 • comparison and assessment of suitability and qualification of facility and equipment;
765 • description of manufacturing process and flow of personnel and of materials at the RU
766 (narrative and or process maps or flow charts);
767 • determination of critical steps in manufacture, including hold times, endpoints,
768 sampling points and sampling techniques;
769 • writing and approval of SOPs for all production operations (e.g. dispensing, granulation
770 or blending or solution preparation, tablet compression, tablet coating, encapsulation,
771 liquid filling, primary and secondary packaging and in-process QC), packaging, cleaning,
772 testing and storage;
773 • evaluation of stability information, with generation of site-specific stability data if
774 required; and
775 • compliance with regulatory requirements for any changes made (e.g. in terms of batch
776 size).
777
778
 Working document QAS/20.869
Page 26

779 Packaging
780
781 12.24. The transfer of packaging operations should follow the same procedural principles as those of
782 the product processing.
783
784 12.25. Information on packaging to be transferred from the SU to the RU should include specifications
785 for a suitable container and closure system, as well as any relevant additional information on
786 design, packing, processing or labelling requirements and tamper-evident and anti-
787 counterfeiting measures.
788
789 12.26. For QC testing of packaging components, specifications should be provided including drawings,
790 artwork and material.
791
792 12.27. Based on the information provided, the RU should perform a suitability study for the initial
793 qualification of the packaging components.
794
795 12.28. Packaging is considered suitable if it provides adequate protection (preventing degradation of
796 the medicine due to environmental influences), safety (absence of undesirable substances
797 released into the product), compatibility (absence of interaction possibly affecting medicine
798 quality) and performance (functionality in terms of drug delivery).
799
800 Quality control: analytical method transfer
801
802 12.29. Analytical methods used to test pharmaceutical products, starting materials, packaging
803 components and cleaning (residue) samples, if applicable, should be implemented at the
804 testing laboratory before the testing of samples for process validation studies is performed by
805 the RU.
806
807 12.30. A protocol defining the steps should be prepared for transfer of analytical methods. The
808 analytical methods transfer protocol should include:
809 • a description of the objective, scope and responsibilities of the SU and the RU;
810 • a specification of materials and methods;
811 • the experimental design and acceptance criteria;
 Working document QAS/20.869
Page 27

812 • documentation (including information to be supplied with the results, and report forms
813 to be used, if any);
814 • procedure for the handling of deviations; and
815 • details of reference samples (starting materials, intermediates and finished products).
816
817 12.31. The SU’s responsibilities for the transfer of analytical procedures are to:
818 • provide method-specific training for analysts and other QC staff, if required;
819 • assist in analysis of QC testing results;
820 • define all methods to be transferred for testing a given product, starting material or
821 cleaning sample;
822 • define experimental design, sampling methods and acceptance criteria;
823 • provide any validation reports for methods under transfer and demonstrate their
824 robustness;
825 • provide details of the equipment used, as necessary (part of validation report, if
826 available) and any standard reference samples;
827 • provide approved procedures used in testing; and
828 • review and approve transfer reports.
829
830 12.32. The RU should exercise its responsibility to:
831 • review analytical methods provided by the SU, and formally agree on acceptance
832 criteria before execution of the transfer protocol;
833 • ensure that the necessary equipment for QC is available and qualified at the RU site.
834 The equipment used by the RU during the analytical transfer should meet the
835 appropriate specifications in order to ensure the requirements of the method or
836 specification are met;
837 • ensure that adequately trained and experienced personnel are in place for analytical
838 testing;
839 • provide a documentation system capable of recording receipt and testing of samples
840 to the required specification using approved test methods, and of reporting, recording
841 and collating data and designation of status (approved, rejected, quarantine);
842 • execute the transfer protocol;
843 • perform the appropriate level of validation to support the implementation of the
844 methods; and
 Working document QAS/20.869
Page 28

845 • generate and obtain approval of transfer reports.

846
847 12.33. The appropriate training should be provided and all training activities and outcomes should be
848 documented.
849
850 12.34. Reference should be made to compendial monographs such as The International
851 Pharmacopoeia, European Pharmacopoeia, British Pharmacopoeia and United States
852 Pharmacopeia), where these are available.
853
854 12.35. An experimental design should be prepared which includes acceptance criteria for the main
855 analytical testing procedures. (See Appendix 2.)
856
857 12.36. Where products are transferred from one unit to another, the applicable analytical procedures
858 should also be transferred.
859
860 12.37. All relevant analytical procedure development and validation documentation should be made
861 available by the SU to the RU.
862
863 12.38. The appropriate transfer protocols and procedures should be followed when analytical
864 procedures are transferred.
865
866 12.39. The number of analysts involved in the transfer, from both SU and RU, should be defined and
867 justified.
868
869 12.40. The parameters of the analytical procedure to be included in the validation should be defined
870 and justified.
871
872 12.41. Acceptance criteria should be set to determine the success of the transfer. Statistical trending
873 of results should be considered in order to show capability of the procedure.
874
875
876
877
 Working document QAS/20.869
Page 29

878 Cleaning
879
880 12.42. To minimize the risk of contamination and cross-contamination, adequate cleaning procedures
881 should be followed.
882
883 12.43. Cleaning procedures and their validation should normally be site-specific. In order for the RU
884 to define its cleaning strategy, the SU should provide information on cleaning at the SU to
885 minimize cross-contamination due to residues from previous manufacturing steps, operator
886 exposure and environmental impact, including:
887 • information on solubility of active ingredients, excipients and vehicles;
888 • minimum therapeutic doses of active ingredients;
889 • therapeutic category and toxicological assessment; and
890 • existing cleaning procedures.
891
892 12.44. Additional applicable information should be provided, such as:
893 • cleaning validation reports (chemical and microbiological);
894 • information on cleaning agents used (efficacy, evidence that they do not interfere with
895 analytical testing for residues of APIs, removal of residual cleaning agents); and
896 • recovery studies to validate the sampling methodology.
897
898 12.45. Before the transfer, the SU should provide information on limits for product residues and the
899 rationale for limit selection.
900
901 12.46. Based on the information provided by the SU, cleaning procedures should be designed at the
902 RU, taking into account relevant characteristics of the starting materials (e.g. potency, toxicity,
903 solubility, corrosiveness and temperature sensitivity), manufacturing equipment design and
904 configuration, cleaning agent and product residue.
905
906 Phase IV: Project review
907
908 12.47. The progress and success of the transfer of technology should be monitored and reviewed
909 during and after completion of the project.
910
 Working document QAS/20.869
Page 30

911 12.48. Compliance with the procedures and protocols should be verified. Deviations and changes
912 should be documented and investigated where appropriate.
913
914 12.49. Where possible, data and results should be subjected to appropriate statistical calculation and
915 evaluation to determine trends, compliance with control limits and capability studies.
916
917 12.50. A technology transfer report should be prepared, based on the data and information obtained
918 during the project. The supportive data should be kept and be accessible.
919
920 12.51. The report, which should include a conclusion, should be authorized by the persons responsible
921 to do so.
922
 Working document QAS/20.869
Page 31

923 References
924
925 1. WHO guidelines on the transfer of technology in pharmaceutical manufacturing. In: WHO
926 Expert Committee on Specifications for Pharmaceutical Preparations: forty-fifth report.
927 Geneva: World Health Organization; 2011: Annex 7 (WHO Technical Report Series, No. 961;
928 https://www.who.int/docs/default-source/medicines/norms-and-
929 standards/guidelines/production/trs961-annex7-transfer-technology-pharmaceutical-
930 manufacturing.pdf?sfvrsn=2e302838_0, accessed 30 November 2020).
931 2. WHO guidelines on good manufacturing practices for pharmaceutical products: main
932 principle. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations:
933 forty-eighth report. Geneva: World Health Organization; 2014: Annex 2 (WHO Technical
934 Report Series, No. 986;
935 https://www.who.int/medicines/areas/quality_safety/quality_assurance/TRS986annex2.pdf?
936 ua=1, accessed 30 November 2020).
937 3. WHO good manufacturing practices: guidelines on validation. In: WHO Expert Committee on
938 Specifications for Pharmaceutical Preparations: fifty-third report. Geneva: World Health
939 Organization; 2019: Annex 3 (WHO Technical Report Series, No. 1019;
940 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
941 nex3.pdf?ua=1, accessed 30 November 2020).
942 4. WHO guidelines on heating ventilation and air-conditioning systems for non-sterile
943 pharmaceutical products and Part 2: interpretation of guidelines on heating ventilation and
944 air-conditioning systems for non-sterile pharmaceutical products. In: WHO Expert Committee
945 on Specifications for Pharmaceutical Preparations: fifty-third report. Geneva: World Health
946 Organization; 2019: Annex 2 (WHO Technical Report Series, No. 1019;
947 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
948 nex3.pdf?ua=1, accessed 20 November 2020).
949 5. WHO good manufacturing practices: guidelines on validation. Appendix 4. Validation of
950 water systems for pharmaceutical use. In: WHO Expert Committee on Specifications for
951 Pharmaceutical Preparations: fortieth report. Geneva: World Health Organization; 2006:
952 Annex 3 (WHO Technical Report Series, No. 937;
953 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
954 nex3.pdf?ua=1, accessed 30 November 2020).
 Working document QAS/20.869
Page 32

955 6. WHO good manufacturing practices: guidelines on validation. Appendix 3. Cleaning

956 validation. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations:
957 fifty-third report. Geneva: World Health Organization; 2019: Annex 3 (WHO Technical Report
958 Series, No. 1019;
959 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
960 nex3.pdf?ua=1, accessed 30 November 2020).
961 7. WHO good manufacturing practices: guidelines on validation. Appendix 4. Analytical
962 procedure validation. In: WHO Expert Committee on Specifications for Pharmaceutical
963 Preparations: fifty- third report. Geneva: World Health Organization; 2019: Annex 3 (WHO
964 Technical Report Series, No. 1019;
965 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
966 nex3.pdf?ua=1, accessed 30 November 2020).
967 8. WHO good manufacturing practices: guidelines on validation. Appendix 5. Validation of
968 computerized systems. In: WHO Expert Committee on Specifications for Pharmaceutical
969 Preparations: fifty-third report. Geneva: World Health Organization; 2019: Annex 3 (WHO
970 Technical Report Series, No. 1019;
971 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
972 nex3.pdf?ua=1, accessed 30 November 2020).
973 9. WHO good manufacturing practices: guidelines on validation. Appendix 6. Guidelines on
974 qualification. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations:
975 fifty-third report. Geneva: World Health Organization; 2019: Annex 3 (WHO Technical Report
976 Series, No. 1019;
977 https://www.who.int/medicines/areas/quality_safety/quality_assurance/WHO_TRS_1019_An
978 nex3.pdf?ua=1, accessed 30 November 2020).
979 10. WHO guidelines on good manufacturing practices: validation. Appendix 7. Non-sterile
980 process validation. In: WHO Expert Committee on Specifications for Pharmaceutical
981 Preparations: forty-ninth report. Geneva: World Health Organization; 2015: Annex 3 (WHO
982 Technical Report Series, No. 992;
983 https://www.who.int/medicines/areas/quality_safety/quality_assurance/Annex3-TRS992.pdf,
984 accessed 30 November 2020).
985 11. WHO guidelines on quality risk management. In: WHO Expert Committee on Specifications
986 for Pharmaceutical Preparations: forty-seventh report. Geneva: World Health Organization;
987 2013: Annex 2 (WHO Technical Report Series, No. 981;
 Working document QAS/20.869
Page 33

988 http://digicollection.org/whoqapharm/documents/s20093en/s20093en.pdf, accessed 30

989 November 2020).
990 12. WHO guidance on good data and record management practices. In: WHO Expert Committee
991 on Specifications for Pharmaceutical Preparations: fiftieth report. Geneva: World Health
992 Organization; 2016: Annex 5 (WHO Technical Report Series, No. 996;
993 https://www.who.int/medicines/publications/pharmprep/WHO_TRS_996_annex05.pdf,
994 accessed 30 November 2020).
995 13. WHO guideline on data integrity. Draft for comments. Geneva: World Health Organization;
996 2019 (working document QAS/19.819;
997 https://www.who.int/medicines/areas/quality_safety/quality_assurance/QAS19_819_rev1_g
998 uideline_on_data_integrity.pdf?ua=1, accessed 30 November 2020).
999 14. WHO points to consider when including Health Based Exposure Limits in cleaning validation.
1000 In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-fifth
1001 report. Geneva: World Health Organization; 2021: Annex 2, (WHO Technical Report Series,
1002 No. xxx, 2021).
1003

1004 Further reading

1005
1006 15. Guideline on setting health-based exposure limits for use in risk identification in the
1007 manufacture of different medicinal products in shared facilities. EMA, 2014 (EMA/CHMP/
1008 CVMP/ SWP/169430/2012).
1009 16. ISPE Baseline, Good Practice Guide. Technology Transfer. Third edition, 2018.
1010 17. Guideline on setting health-based exposure limits for use in risk identification in the
1011 manufacture of different medicinal products in shared facilities and Questions and answers
1012 on implementation of risk-based prevention of cross-contamination in production. European
1013 Medicines Agency, 2018.
1014 18. International conference on harmonisation of technical requirements for registration of
1015 pharmaceuticals for human use. ICH harmonised tripartite guideline. Pharmaceutical
1016 development q8(r2). Current step 4 version. August 2009.
1017 19. International conference on harmonisation of technical requirements for registration of
1018 pharmaceuticals for human use. ICH harmonised tripartite guideline. Quality risk
1019 management. Q9. Current step 4 version. 9 November 2005.
 Working document QAS/20.869
Page 34

1020 20. International conference on harmonisation of technical requirements for registration of

1021 pharmaceuticals for human use. ICH harmonised tripartite guideline. Development and
1022 manufacture of drug substances (chemical entities and biotechnological/biological entities).
1023 Q11. Current step 4 version. 1 May 2012.
1024 21. International conference on harmonisation of technical requirements for registration of
1025 pharmaceuticals for human use. ICH harmonised tripartite guideline. Technical and
1026 regulatory considerations for pharmaceutical product life cycle management. Q12. Final
1027 version. 20 November 2019.
1028
1029
1030
1031
 Working document QAS/20.869
Page 35

1032 Abbreviations
1033
1034 ALCOA+ “attributable, legible, contemporaneous, original and accurate”.
1035 API active pharmaceutical ingredient
1036 FPP finished pharmaceutical product
1037 GMP good manufacturing practices
1038 GxP good practices
1039 ICH The International Council for Harmonisation of Technical
1040 Requirements for Pharmaceuticals for Human use
1041 IPC in-process control
1042 IQ installation qualification
1043 OQ operational qualification
1044 PQ performance qualification
1045 QA quality assurance
1046 QC quality control
1047 QRM quality risk management
1048 RU receiving unit
1049 SOP standard operating procedure
1050 SU sending unit
1051 TRS Technical Report Series
1052 VMP validation master plan
1053 VP validation protocol
1054 VR validation report
1055
 Working document QAS/20.869
Page 36

1056 Appendix 1
1057 Example of documentation commonly required for the
1058 transfer of technology*
1059
1060 The table below provides an example of documentation commonly required for the transfer of
1061 technology.
1062
Aspect Related documentation

Starting materials (API and excipients) Material Safety Data Sheets

Product development report
Storage conditions
Stability data
Forced stability data
Specifications
Supplier qualification
References
Formulation Formulation development reports
Master formula
Material compatibility/interaction studies
Batch manufacturing Batch manufacturing document
Scale up information
Risk assessment
Critical process parameters In-process control
specification
Scale up protocol and report
Process validation
Batch packaging Packaging material specification
Batch packaging document
Validation
Finished product Specification

Analytical procedures Analytical test procedures

Analytical method development
Analytical procedure validation
Standard test procedures
Instrument specifications
Quality control Sampling procedures (e.g. in-process control)
Stability testing protocol and procedures
Equipment and instruments List of equipment and instruments
Calibration information
Preventive maintenance information
Overview of qualification
 Working document QAS/20.869
Page 37

Cleaning Overview of cleaning approach

Cleaning procedure development and
cleanability
Cleaning procedures
Health Based Exposure Level (Permitted daily
exposure) information reports
Analytical procedures validation for cleaning
validation sample analysis
Other documents Rejected batch information
Bio-batch information
Pilot batch information
History of changes and change management
Hold time protocols and reports
1063
1064 *Note: These are examples. All the required documents should be identified for the different tasks.
1065
1066
 Working document QAS/20.869
Page 38

1067 Appendix 2
1068 Example of possible experimental designs and
1069 acceptance criteria for analytical testing
1070
1071 The table below provides an example of possible experimental designs and acceptance criteria for
1072 analytical testing. The numbers in the table are given as examples only and should not be considered
1073 as recommendations. Method transfers should account for the variability and sensitivity of the method
1074 and the specifications for the quality parameter. Alternative procedures and acceptance criteria may
1075 be applied based on science and the characteristics of the analytical method and the analyte.
1076
Test Considerations Replication Set-up Acceptance
for transfer of tests criteria Statistically
Direct derived

Assay for Specific At each site: Different sets Comparison Two one-
potency methods 2 analysts of instruments of mean and sided
where possible × 3 lots, in and columns variability t-tests
should be used triplicate with inter-site
(= 18 per site) Independent differences
A bracketing solution ≤2% , 95%
approach may preparation confidence
be used for
multiple
strengths
Content If method is At each site: Different sets Mean at RU Two one-
uniformity equivalent to 2 analysts, of instruments within ± 3% sided
assay method, × 1 lot and columns of mean at t-tests
separate (= 2 per site) SU; with inter-site
transfer Independent comparison differences
is not usually solution of relative ≤ 3% , 95%
required preparation standard confidence
deviation
Dissolution Bracketing 6 units Mean at RU Compare
may (12, if not within ± 5% profile
be appropriate routine at RU, of mean (e.g. F2), or
for multiple and for at SU compare
strengths extended data at Q
release time points,
products) as for assay
1077
1078 ***