Working document QAS/19.793/Rev.

1
August 2019
Draft for comments

2 GOOD STORAGE AND DISTRIBUTION PRACTICES

3 FOR MEDICAL PRODUCTS
4 (August 2019)
5 DRAFT FOR COMMENTS

Please send any comments you may have to Dr Sabine Kopp, Group Lead, Medicines Quality Assurance,
Technologies Standards and Norms ([email protected]), with a copy to Ms Claire Vogel ([email protected]) by
20 September 2019.

Working documents are sent out electronically and they will also be placed on the WHO Medicines website
(http://www.who.int/medicines/areas/quality_safety/quality_assurance/guidelines/en/) for comments under
the “Current projects” link. If you wish to receive our draft guidelines, please send your email address to
[email protected] and your name will be added to our electronic mailing list.
6

7
8 © World Health Organization 2019
9
10 All rights reserved.
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12 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft
13 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any
14 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member
15 organizations) without the permission of the World Health Organization. The draft should not be displayed on any website.
16
17 Please send any request for permission to:
18
19 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential
20 Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland, email: [email protected].
21
22 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion
23 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or
24 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate
25 border lines for which there may not yet be full agreement.
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27 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or
28 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and
29 omissions excepted, the names of proprietary products are distinguished by initial capital letters.
30
31 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft.
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33 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility
34 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for
35 damages arising from its use.
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37 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.
38
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39 SCHEDULE FOR DRAFT WORKING DOCUMENT QAS/19.793:

40 GOOD STORAGE AND DISTRIBUTION PRACTICES
41 FOR MEDICAL PRODUCTS
42

Description of Activity Date

During the Fifty-third WHO Expert Committee on 22-26 October 2018

Specifications for Pharmaceutical Preparations (ECSPP), the
Expert Committee recommended the consolidation of good
storage practices and good distribution practices with
elements from the guidelines for inspection of drug
distribution channels, into one document.

Preparation of first draft working document. December 2018 - March

2019

Mailing of working document inviting comments, including April – June 2019

to the Expert Advisory Panel on the International
Pharmacopoeia and Pharmaceutical Preparations (EAP), and
posting of the working document on the WHO website for
public consultation.

Consolidation of comments received and review of End of June 2019

feedbacks. Preparation of working document for discussion.

Discussion of working document and feedbacks received 2-5 July 2019

during the public consultation in the informal Consultation on
Good Practices for Health Products Manufacture and
Inspection.

Revision of the working document based on comments End of July 2019

received during the informal Consultation on Good Practices
for Health Products Manufacture and Inspection.

Mailing of revised working document inviting comments, August – 20 September

including to the EAP, and posting the working document on 2019
the WHO website for the second round of public
consultation.

Consolidation of comments received and review of End of September 2019

feedbacks. Preparation of working document for discussion.

Presentation to the Fifty-fourth meeting of the ECSPP. 14 -18 October 2019

Any other follow-up action as required.

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43 GOOD STORAGE AND DISTRIBUTION PRACTICES FOR MEDICAL PRODUCTS

44
45 1. Introduction
46 2. Scope
47 3. Glossary
48 4. General principles
49 5. Quality management
50 6. Quality risk management
51 7. Management review
52 8. Complaints
53 9. Returned goods
54 10. Recalls
55 11. Self-inspection
56 12. Premises
57 13. Stock control and rotation
58 14. Equipment
59 15. Qualification and validation
60 16. Personnel
61 17. Documentation
62 18. Activities and operations
63 19. Outsourced activities
64 20. Substandard and falsified products
65 21. Inspection of storage and distribution facilities
66
67 References
68 Further reading
69 Annex 1: Recommended storage conditions
70
71
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72 GOOD STORAGE AND DISTRIBUTION PRACTICES FOR MEDICAL PRODUCTS

73
74 1. INTRODUCTION
75
76 1.1 Storage and distribution are important activities in the supply chain management of
77 medical products. Various people and entities may be responsible for the handling,
78 storage and distribution of medical products. Medical products may be subjected to
79 various risks at different stages in the supply chain, for example, purchasing, storage,
80 repackaging, relabelling, transportation and distribution.
81
82 1.2 Substandard and falsified products are a significant threat to public health and safety.
83 Consequently, it is essential to protect the supply chain against the penetration of such
84 products.
85
86 1.3 This document sets out steps to assist in fulfilling the responsibilities involved in the
87 different stages within the supply chain and to avoid the introduction of substandard and
88 falsified products into the market. The relevant sections should be considered as
89 particular roles that entities play in the storage and distribution of medical products.
90
91 1.4 This guideline is intended to be applicable to all entities involved in any aspect of the
92 storage and distribution of medical products, from the premises of the manufacturer of
93 the medical product to his or her agent, or the person dispensing or providing medical
94 products directly to a patient. This includes all entities involved in different stages of
95 the supply chain of medical products, manufacturers and wholesalers as well as brokers,
96 suppliers, distributors, logistics providers, traders, transport companies and forwarding
97 agents and their employees .
98
99 1.5 The relevant sections of this guideline should also be considered for implementation
100 by, amongst others, governments, regulatory bodies, international procurement
101 organizations, donor agencies and certifying bodies, as well as all health care workers.
102
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103 1.6 This guideline can be used as a tool in the prevention of the distribution of substandard
104 and falsified products. It should however be noted that these are general guidelines
105 which may be adapted to suit the prevailing situations and conditions in individual
106 countries. National or regional guidelines may be developed to meet specific needs and
107 situations in a particular region or country.
108
109 1.7 To maintain the quality of medical products, every party active in the supply chain has
110 to comply with the applicable legislation and regulations. Every activity in the storage
111 and distribution of medical products should be carried out according to the principles
112 of good manufacturing practices (GMP) (1), good storage practices (GSP) (2) and good
113 distribution practices (GDP) (3), as applicable.
114
115 1.8 This guideline does not deal with dispensing to patients as this is addressed in the World
116 Health Organization (WHO) Good Pharmacy Practice (GPP) (4).
117
118 1.9 This guideline should also be read in conjunction with other WHO guidelines.
119
120 2. SCOPE
121
122 2.1 This document lays down guidelines for the storage and distribution of medical
123 products. It is closely linked to other existing guidelines recommended by the
124 WHO Expert Committee on Specifications for Pharmaceutical Preparations,
125 such as referenced below.
126
127 2.2 Depending on the national and regional legislation, these guidelines may apply equally
128 to medical products for human and veterinary use.
129
130 2.3 The document does not specifically cover GMP aspects of finished products in bulk,
131 distribution of labels or packaging as these aspects are considered to be covered by
132 other guidelines. The principles for the distribution of starting materials (active
133 pharmaceutical ingredients (APIs) and excipients) are also not covered here. These are
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134 laid down in the WHO document Good Trade and Distribution Practices for
135 Pharmaceutical Starting Materials (5).
136
137 3. GLOSSARY
138
139 The definitions provided below apply to the words and phrases used in this guideline. Although
140 an effort has been made to use standard definitions as far as possible, they may have different
141 meanings in other contexts and documents.
142
143 active pharmaceutical ingredient (API).
144 Any substance or mixture of substances intended to be used in the manufacture of a
145 pharmaceutical dosage form and that, when used in the production of a drug, becomes
146 an active ingredient of that drug. Such substances are intended to furnish
147 pharmacological activity or other direct effect in the diagnosis, cure, mitigation,
148 treatment or prevention of disease, or to affect the structure and function of the body.
149
150 ALCOA.
151 A commonly used acronym for “attributable, legible, contemporaneous, original and accurate”.
152
153 auditing.
154 An independent and objective activity designed to add value and improve an organization’s
155 operations by helping the organization to accomplish its objectives by using a systematic,
156 disciplined approach to evaluate and improve the effectiveness of risk management, control
157 and governance processes.
158
159 batch.
160 A defined quantity of pharmaceutical products processed in a single process or series of
161 processes so that it is expected to be homogeneous.
162
163 batch number.
164 A distinctive combination of numbers and/or letters which uniquely identifies a batch, for
165 example, on the labels, its batch records and corresponding certificates of analysis.
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166 broker.
167 Arranges transactions in relation to the sale or purchase of medical products that consist of
168 negotiating, independently and on behalf of another legal or natural person, and that do not
169 include physical handling.
170
171 consignment.
172 The quantity of pharmaceutical products supplied at one time in response to a particular request
173 or order. A consignment may comprise of one or more packages or containers and may include
174 pharmaceutical products belonging to more than one batch.
175
176 container.
177 The material employed in the packaging of a pharmaceutical product. Containers include
178 primary, secondary and transportation containers. Containers are referred to as primary if they
179 are intended to be in direct contact with the product. Secondary containers are not intended to
180 be in direct contact with the product.
181
182 contamination.
183 The undesired introduction of impurities of a chemical or microbiological nature, or of foreign
184 matter, into or on to a starting material, intermediate or pharmaceutical product during handling,
185 production, sampling, packaging or repackaging, storage or transportation.
186
187 contract.
188 Business agreement for the supply of goods or performance of work at a specified price.
189
190 corrective and preventative actions (CAPA).
191 A system for implementing corrective and preventive actions resulting from an investigation
192 of complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory
193 inspections and findings and trends from process performance and product quality monitoring.
194
195 cross-contamination.
196 Contamination of a starting material, intermediate product or finished pharmaceutical product
197 with another starting material or product during production, storage and transportation.
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198 distribution.
199 The procuring, purchasing, holding, storing, selling, supplying, importing, exporting or
200 movement of pharmaceutical products, with the exception of the dispensing or providing
201 pharmaceutical products directly to a patient or his or her agent.
202
203 excipient.
204 A substance, other than the active ingredient, which has been appropriately evaluated
205 for safety and is included in a drug delivery system to aid in the processing of the drug
206 delivery system during its manufacture; protect, support or enhance stability,
207 bioavailability, or patient acceptability; assist in product identification; or enhance any
208 other attribute of the overall safety and effectiveness of the drug during storage or use.
209
210 expiry date.
211 The date given on the individual container (usually on the label) of a pharmaceutical product
212 up to and including the date on which the product is expected to remain within specifications, if
213 stored correctly. It is established for each batch by adding the shelf life to the date of
214 manufacture.
215
216 falsified product.
217 A product that has been deliberately and/or fraudulently misrepresented as to its identity, composition
218 or source. Such deliberate/fraudulent misrepresentation refers to any substitution, adulteration,
219 reproduction of an authorized product or the manufacture of a product that is not an authorized product.
220 “Identity” shall refer to the name, labelling or packaging or to documents that support the authenticity
221 of an authorized product. “Composition” shall refer to any ingredient or component of the product in
222 accordance with applicable specifications authorized/ recognized by the NRA. “Source” shall refer to
223 the identification, including name and address, of the marketing authorization holder, manufacturer,
224 importer, exporter, distributor or retailer, as applicable. (Reference: Member State mechanism on
225 substandard/spurious/falsely-labelled/falsified/counterfeit medical products. Report by the Director-
226 General; 2017, http://apps.who.int/gb/ebwha/pdf_files/WHA70/A70_23-en.pdf )
227
228 first expiry/first out (FEFO).
229 A distribution procedure that ensures that the stock with the earliest expiry date is distributed
230 and/or used before an identical stock item with a later expiry date is distributed and/or used.
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231 forwarding agent.

232 A person or entity engaged in providing, either directly or indirectly, any service concerned
233 with clearing and forwarding operations in any manner to any other person and includes a
234 consignment agent.
235
236 good distribution practices (GDP).
237 That part of quality assurance that ensures that the quality of a pharmaceutical product is
238 maintained by means of adequate control of the numerous activities which occur during the
239 distribution process, as well as providing a tool to secure the distribution system from falsified,
240 unapproved, illegally imported, stolen, substandard, adulterated and/or misbranded
241 pharmaceutical products.
242
243 good manufacturing practices (GMP).
244 That part of quality assurance which ensures that pharmaceutical products are consistently
245 produced and controlled to the quality standards appropriate to their intended use and as required
246 by the marketing authorization.
247
248 good pharmacy practice (GPP).
249 The practice of pharmacy aimed at providing and promoting the best use of medicines and
250 other health care services and products by patients and members of the public. It requires that
251 the welfare of the patient is the pharmacist’s prime concern at all times.
252
253
254 good practices (GXP).
255
256 Acronym for the group of good practice guides governing the preclinical, clinical, manufacturing,
257 testing, storage, distribution and post-market activities for regulated pharmaceuticals, biologicals
258 and medical devices, such as good laboratory practices (GLP), good clinical practices (GCP), good
259 manufacturing practices (GMP), good pharmacovigilance practices (GPP) and good distribution
260 practices (GDP).
261
262 good storage practices (GSP).
263 That part of quality assurance that ensures that the quality of pharmaceutical products is
264 maintained by means of adequate control throughout the storage thereof.
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265 good trade and distribution practices (GTDP).

266 That part of quality assurance that ensures that the quality of pharmaceutical products is
267 maintained by means of adequate control throughout the numerous activities which occur during
268 the trade and the distribution process.
269
270 heating, ventilation and air conditioning systems (HVAC).
271 Heating, ventilation and air-conditioning, also referred to as environmental control system
272 (ECS).
273
274 importation.
275 The act of bringing or causing any goods to be brought into a customs territory (national
276 territory, excluding any free zone).
277
278 intermediate product.
279 Partly processed product that must undergo further manufacturing steps before it becomes a
280 bulk finished product.
281
282 labelling.
283 Process of identifying a pharmaceutical product including the following information, as
284 appropriate: name of the product; active ingredient(s), type and amount; batch number; expiry
285 date; special storage conditions or handling precautions; directions for use, warnings and
286 precautions; names and addresses of the manufacturer and/or the supplier.
287
288 manufacture.
289 All operations of purchase of materials and products, production, packaging, labelling, quality
290 control, release, storage and distribution of pharmaceutical products and the related controls.
291
292 marketing authorization.
293 A legal document issued by the national regulatory authority for the purpose of marketing or
294 free distribution of a product after evaluation for safety, efficacy and quality. It must set out,
295 inter alia, the name of the product, the pharmaceutical dosage form, the quantitative formula
296 (including excipients) per unit dose (using International Nonproprietary Names (INNs) or
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297 national generic names where they exist), the shelf life and storage conditions, and packaging
298 characteristics, or other details as required by the product category. It specifies the information
299 on which authorization is based (e.g. “The product(s) must conform to all the details provided
300 in your application and as modified in subsequent correspondence”). It also contains the
301 product information approved for health professionals and the public, the sales category, the
302 name and address of the holder of the authorization and the period of validity of the
303 authorization. Once a product has been given marketing authorization, it is included on a list of
304 authorized products - the register - and is often said to be “registered” or to “have registration”.
305 Market authorization may occasionally also be referred to as a “licence” or “product licence”.
306
307 material.
308 A general term used to denote starting materials (APIs and excipients), reagents,
309 solvents, process aids, intermediates, packaging materials and labelling materials.
310
311 medical products.
312 Products including, but not limited to, finished pharmaceutical products, medical devices,
313 vaccines and in vitro diagnostics (IVDs).
314
315 packaging material.
316 Any material, including printed material, employed in the packaging of a
317 pharmaceutical product, but excluding any outer packaging used for transportation or
318 shipment. Packaging materials are referred to as primary or secondary according to
319 whether or not they are intended to be in direct contact with the product.
320
321 pedigree.
322 A complete record that traces the ownership of and transactions relating to a pharmaceutical
323 product as it is distributed through the supply chain.
324
325 pharmaceutical product.
326 Any product intended for human use, or veterinary product intended for administration to food-
327 producing animals, presented in its finished dosage form, which is subject to control by
328 pharmaceutical legislation in either the exporting or the importing state and includes products
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329 for which a prescription is required, products which may be sold to patients without a
330 prescription, biologicals and vaccines. It does not, however, include medical devices.
331
332 product recall.
333 A process for withdrawing or removing a pharmaceutical product from the pharmaceutical
334 distribution chain because of defects in the product, complaints of serious adverse reactions
335 to the product and/or concerns that the product is or may be falsified. The recall might be
336 initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency.
337
338 production.
339 All operations involved in the preparation of a pharmaceutical product, from receipt of
340 materials through processing, packaging and repackaging, labelling and relabelling, to
341 completion of the finished product.
342
343 quality assurance.
344 A wide-ranging concept covering all matters that individually or collectively influence the
345 quality of a product. It is the totality of the arrangements made with the object of ensuring that
346 pharmaceutical products are of the quality required for their intended use.
347
348 quality risk management.
349 A systematic process for the assessment, control, communication and review of risks to the
350 quality of pharmaceutical products across the product life cycle.
351
352 quality system.
353 An appropriate infrastructure, encompassing the organizational structure, procedures,
354 processes and resources and systematic actions necessary to ensure adequate confidence that a
355 product (or services) will satisfy given requirements for quality.
356
357 quarantine.
358 The status of pharmaceutical products isolated physically or by other effective means while a
359 decision is awaited on their release, rejection or reprocessing.
360
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361 retest date.

362 The date when a material should be re-examined to ensure that it is still suitable for
363 use.
364
365 sampling.
366 Operations designed to obtain a representative portion of a pharmaceutical product, based on
367 an appropriate statistical procedure, for a defined purpose, for example, acceptance of
368 consignments or batch release.
369
370 self-inspection.
371 Self-inspection is an internal procedure followed to evaluate the entity's compliance with GSDP and
372 GXP in all areas of activities, designed to detect any shortcomings and to recommend and implement
373 necessary corrective actions.
374
375 shelf life.
376 The period of time during which a pharmaceutical product, if stored correctly, is expected to
377 comply with the specification as determined by stability studies on a number of batches of the
378 product. The shelf life is used to establish the expiry date of each batch.
379
380 standard operating procedure (SOP).
381 An authorized written procedure giving instructions for performing operations not necessarily
382 specific to a given product but of a more general nature (e.g. equipment operation, maintenance
383 and cleaning, validation, cleaning of premises and environmental control, sampling and
384 inspection).
385
386 storage.
387 The storing of pharmaceutical products up to the point of use.
388
389 substandard products.
390 “Substandard” medical products (also called “out of specification”) are authorized by
391 national regulatory authorities but fail to meet either national or international quality
392 standards or specifications – or, in some cases, both.
393
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394 supplier.
395 A person or entity engaged in the activity of providing products and/or services.
396
397 transit.
398 The period during which pharmaceutical products are in the process of being carried, conveyed,
399 or transported across, over or through a passage or route to reach the destination.
400
401 vehicles.
402 Trucks, vans, buses, minibuses, cars, trailers, aircraft, railway carriages, boats and other means
403 which are used to convey pharmaceutical products
404
405 4. GENERAL PRINCIPLES
406
407 4.1 There should be collaboration between all entities, including governments, customs
408 agencies, law enforcement agencies, regulatory authorities, manufacturers, distributors
409 and entities responsible for the supply of medical products to patients to ensure the
410 quality and safety of medical products; to prevent the exposure of patients to
411 substandard and falsified products and to ensure that the integrity of the distribution
412 chain is maintained .
413
414 4.2 The principles of GSP and GDP should be included in national legislation and
415 guidelines for the storage and distribution of medical products in a country or region,
416 as applicable, as a means of establishing minimum standards. The principles of GSP
417 and GDP are applicable to:
418
419 • medical products moving forward in the distribution chain from the
420 manufacturer;
421 • medical products which are moving backwards in the chain, for example, as a
422 result of the return or recall thereof; and
423 • donations of medical products.
424
425
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426 5. QUALITY MANAGEMENT

427
428 Quality Systems
429
430 5.1 Entities involved in the storage and distribution of medical products should have a
431 comprehensively designed, documented and correctly implemented quality system that
432 incorporates good storage practices, good distribution practices, quality risk
433 management principles and management review .
434
435 5.2 Senior management has the ultimate responsibility to ensure that an effective quality
436 system is established, resourced, implemented and maintained.
437
438 5.3 The quality system should ensure that:
439
440 • GSP and GDP are adopted and implemented to ensure that the quality of
441 medical products is maintained throughout their shelf-life in the supply chain;
442 medical products are appropriately procured, stored, distributed and delivered
443 (in compliance with the legislation) to the appropriate recipients; (see 18.1)
444 • operations are clearly specified in written procedures;
445 • responsibilities are clearly specified in job descriptions;
446 • all risks are identified and necessary, effective controls are implemented;
447 • processes are in place to assure the management of outsourced activities;
448 • there is a procedure for self-inspection and quality audits;
449 • there is a system for quality risk management (QRM);
450 • there are systems for managing returns, complaints and recalls;
451 • there are systems to manage changes, deviations and corrective and preventive
452 actions (CAPAs).
453
454 5.4 There should be an authorized, written quality policy describing the overall intentions
455 and requirements regarding quality. This may be reflected in a quality manual.
456
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457 5.5 There should be an appropriate organizational structure. This should be presented in
458 an authorized organizational chart. The responsibility, authority and interrelationships
459 of personnel should be clearly indicated.
460
461 5.6 Roles and responsibilities should be clearly defined and understood by the individuals
462 concerned and recorded as written job descriptions.
463
464 5.7 The quality system should include appropriate procedures, processes and resources.
465
466 6. QUALITY RISK MANAGEMENT
467
468 6.1 There should be a system to assess, control, communicate and review risks identified
469 at all stages in the supply chain .
470
471 6.2 The evaluation of the risk should be based on scientific knowledge and experience and
472 ultimately be linked to the protection of the patient.
473
474 6.3 Appropriate controls should be developed and implemented to address all risks. The
475 effectiveness of the controls implemented should be evaluated at periodic intervals.
476
477 7. MANAGEMENT REVIEW
478
479 7.1 There should be a system for periodic management review. The review should include at
480 least:
481
482 • senior management;
483 • review of the quality system and its effectiveness by using quality metrics and key
484 performance indicators;
485 • identification of opportunities for continual improvement; and
486 • follow-up on recommendations from previous management review meetings.
487
488 7.2 Minutes and related documentation from management review meetings should be available.
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489 8. COMPLAINTS
490
491 8.1 There should be a written procedure for the handling of complaints. In the case of a
492 complaint about the quality of a medical product or its packaging, the original manufacturer
493 and/or marketing authorization holder should be informed as soon as possible.
494
495 8.2 All complaints should be recorded and appropriately investigated. The root cause
496 should be identified and the impact (e.g. on other batches or products) risk assessed.
497 Appropriate CAPAs should be taken.
498
499 8.3 Where required, the information should be shared with the national regulatory
500 authority and a recall initiated where appropriate.
501
502 8.4 A distinction should be made between complaints about a medical product or its
503 packaging and those relating to distribution.
504
505 8.5 The relevant information, such as the results of the investigation of the complaint,
506 should be shared with the relevant entities.
507
508 8.6 Medical product quality problems and suspected cases of substandard or falsified
509 products identified should be handled according to relevant authorized procedures. The
510 information should be shared with the manufacturer and appropriate national and/or
511 regional regulatory authorities without delay .
512
513 9. RETURNED GOODS
514
515 9.1 Returned medical products should be handled in accordance with authorized
516 procedures.
517
518 9.2 All returned medical products should be placed in quarantine upon receiving. The
519 status of the goods should be clear. Precautions should be taken to prevent access and
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520 distribution until a decision has been taken with regard to their disposition. The
521 particular storage conditions applicable to the medical products should be maintained.

522 9.3 Medical products returned should be destroyed unless it is certain that their quality is
523 satisfactory after they have been critically assessed in accordance with a written and
524 authorized procedure.

525 9.4 The nature of the medical product, any special storage conditions it requires, its
526 condition and history and the time lapse since it was issued, should all be taken into
527 account in this assessment. Where any doubt arises over the quality of the medical
528 product, it should not be considered suitable for reissue or reuse. Any action taken
529 should be appropriately recorded.

530 9.5 When handling returned goods, the following considerations at least
531 should be taken:
532
533 • A risk-based process should be followed when deciding on the fate of
534 the returned goods. This should include, but not be limited to, the
535 nature of the product, storage conditions, condition of the product
536 history, time-lapse since distribution and the manner and condition of
537 transport while being returned.
538 • The terms and conditions of the agreement between the parties.
539 • Examination of the returned goods, with decisions taken by suitably qualified,
540 experienced and authorized persons.
541
542 9.6 Where products are rejected, authorized procedures should be followed, including safe
543 transport.
544
545 9.7 Destruction of products should be done in accordance with international, national and
546 local requirements regarding disposal of such products and with due consideration to
547 the protection of the environment.
548
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549 9.8 Records of all returned, rejected and destroyed medical products should be kept for a
550 defined period in accordance with national requirements.
551
552 10. RECALLS
553
554 10.1 There should be a written procedure, in compliance with national or regional
555 requirements, to effectively and promptly recall medical products.
556
557 10.2 The effectiveness of the procedure should be checked annually and updated as
558 necessary.
559
560 10.3 The original manufacturer and/or marketing authorization holder, or other relevant contract
561 party, should be informed in the event of a recall.
562
563 10.4 Information on a recall should be shared with the appropriate national or regional
564 regulatory authority.
565
566 10.5 All recalled products should be secure, segregated, transported and stored under
567 appropriate conditions. These should be clearly labelled as recalled products. The
568 particular storage conditions applicable to the product should be maintained.
569
570 10.6 All customers and competent authorities of all countries to which a given medical
571 product may have been distributed should be informed promptly of the recall of the
572 product.
573
574 10.7 All records, including distribution records, should be readily accessible to the
575 designated person(s) responsible for recalls. These records should contain sufficient
576 information on products supplied to customers (e.g. name, address, contact detail, batch
577 numbers, quantities and safety features - including exported products).
578
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579 10.8 The progress of a recall process should be recorded and a final report issued which
580 includes a reconciliation between delivered and recovered quantities of medical
581 products.
582
583 11. SELF-INSPECTION
584
585 11.1 The quality system should include self-inspections. These should be conducted to
586 monitor the implementation, compliance with and effectiveness of SOPs as well as
587 compliance with regulations, GSP, GDP and other appropriate guidelines.
588
589 11.2 Self-inspections should be conducted periodically according to an annual schedule.
590
591 11.3 The team conducting the inspection should be free from bias and individual members should
592 have appropriate knowledge and experience
593
594 11.4 The results of all self-inspections should be recorded. Reports should contain all
595 observations made during the inspection and presented to the relevant personnel and
596 management.
597
598 11.5 Necessary CAPAs should be taken and the effectiveness of the CAPAs should be
599 reviewed.
600
601 12. PREMISES
602
603 General
604
605 12.1 Premises should be suitably located, designed, constructed and maintained to ensure
606 appropriate operations such as receiving, storage, picking, packing and dispatch of
607 medical products.
608
609 12.2 There should be sufficient space, lighting and ventilation to ensure required
610 segregation, appropriate storage conditions and cleanliness.
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611 12.3 Sufficient security should be provided and access should be controlled.
612
613 12.4 Appropriate controls and segregation should be provided for products requiring specific
614 handling or storage conditions such as radioactive materials, products containing
615 hazardous substances and products to be stored under controlled temperature and
616 relative humidity conditions.
617
618 12.5 Receiving and dispatch bays should be separate and should protect products from
619 weather conditions.
620
621 12.6 Activities relating to receiving and dispatch should be done in accordance with
622 authorized procedures. Areas should be suitably equipped for the operations.
623
624 12.7 Premises should be kept clean. Cleaning equipment and cleaning agents should not
625 become possible sources of contamination.
626
627 12.8 Premises should be protected from the entry of birds, rodents, insects and other animals.
628 A rodent and pest control programme should be in place.
629
630 12.9 Toilets, wash, rest and canteen facilities should be separate from other areas. Food,
631 eating, drinking and smoking should be prohibited in all areas where medical products
632 are stored or handled.
633
634 Receiving
635
636 12.10 Each incoming delivery should be checked against the relevant documentation
637 to ensure that the correct product is delivered from the correct supplier. This
638 may include, for example, the purchase order, containers, label description,
639 batch number, expiry date, product and quantity.
640
641 12.11 The consignment should be examined for uniformity of the containers and, if
642 necessary, should be subdivided according to the supplier’s batch number
 Working document QAS/19.793/Rev.1
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643 should the delivery comprise more than one batch. Each batch should be dealt
644 with separately.
645
646 12.12 Each container should be carefully checked for possible contamination, tampering
647 and damage. Any suspect containers or, if necessary, the entire delivery should
648 be quarantined for further investigation.
649
650 12.13 Receiving areas should be of sufficient size to allow the cleaning of incoming
651 medical products.
652
653 12.14 When required, samples of medical products should be taken by appropriately
654 trained and qualified personnel and in strict accordance with a written sampling
655 procedure and sampling plans. Containers from which samples have been taken
656 should be labelled accordingly.
657
658 12.15 Following sampling, the goods should be subject to quarantine. Batch
659 segregation should be maintained during quarantine and all subsequent storage.
660
661 12.16 Materials and products requiring storage under controlled conditions of
662 temperature and relative humidity, as applicable, should be handled as a
663 priority.
664
665 12.17 Medical products should not be transferred to saleable stock until an authorized
666 release is obtained.
667
668 12.18 Measures should be taken to ensure that rejected medical products cannot be
669 used. They should be segregated and securely stored while awaiting destruction
670 or return to the supplier.
671
672
673
674
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675 Storage areas

676
677 12.19 Precautions should be taken to prevent unauthorized persons from entering
678 storage areas.
679
680 12.20 Storage areas should be of sufficient capacity to allow the orderly storage of the
681 various categories of medical products.
682
683 12.21 Storage areas should be appropriately designed, constructed, maintained or
684 adapted. They should be kept clean and there should be sufficient space and
685 lighting.
686
687 12.22 Storage areas should be maintained within acceptable and specified temperature
688 limits. Where special storage conditions are required on the label (e.g.
689 temperature, relative humidity), these should be provided, controlled,
690 monitored and recorded.
691
692 12.23 Medical products should be stored off the floor and suitably spaced to permit
693 ventilation, cleaning and inspection. Suitable pallets should be used and kept
694 in a good state of cleanliness and repair.
695
696 12.24 A written sanitation programme should be available indicating the frequency of
697 cleaning and the methods to be used to clean the premises and storage areas.
698
699 12.25 There should be appropriate procedures for the clean-up of any spillage to
700 ensure complete removal of any risk of contamination.
701
702 12.26 Where the status is ensured by storage in separate areas, these areas should be
703 clearly marked and their access restricted to authorized personnel. Any system
704 replacing physical separation and labelling or demarcation should provide
705 equivalent security. For example, computerized systems can be used provided
706 that they are validated to demonstrate security of access (6).
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707 12.27 Sampling should be done under controlled conditions and conducted in such a
708 way that there is no risk of contamination or cross-contamination. Adequate
709 cleaning procedures should be followed after sampling.
710
711 12.28 Certain materials and products such as highly active and radioactive materials,
712 narcotics and other hazardous, sensitive and/or dangerous materials and
713 products, as well as substances presenting special risks of abuse, fire or
714 explosion (e.g. combustible liquids and solids and pressurized gases), should
715 be stored in a dedicated area that is subject to appropriate additional safety and
716 security measures; and in accordance with national legislation
717
718 12.29 Medical products should be handled and stored in such a manner as to prevent
719 contamination, mix-ups and cross-contamination.
720
721 12.30 Medical products should be stored in conditions which assure that their quality
722 is maintained. Stock should be appropriately rotated. The “first expired/first
723 out” (FEFO) principle should be followed.
724
725 12.31 Narcotic medical products should be stored in compliance with international
726 conventions, national laws and regulations on narcotics .
727
728 12.32 Broken or damaged items should be withdrawn from usable stock and
729 separated.
730
731 12.33 There should be appropriate procedures for the clean-up of any spillage to ensure
732 complete removal of any risk of contamination.
733
734 Storage conditions
735
736 12.34 The storage conditions for medical products should be in compliance with their
737 labelling.
738
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739 12.35 Heating, ventilation and air conditioning systems (HVAC) should be
740 appropriately designed, installed, qualified and maintained to ensure that the
741 required storage conditions are maintained (7).
742
743 12.36 Mapping studies for temperature and relative humidity, as appropriate, should
744 be done (8). This applies, for example, to areas, refrigerators and freezers.
745
746 12.37 Temperature and relative humidity, as appropriate, should be controlled and
747 monitored at regular intervals. Data should be recorded and the records should
748 be reviewed. The equipment used for monitoring should be calibrated and be
749 suitable for their intended use. All records pertaining to mapping and
750 monitoring should be kept for a suitable period of time and as required by
751 national legislation.
752
753 Note: See Annex 1 for recommended storage conditions.
754
755 13. STOCK CONTROL AND ROTATION
756
757 13.1 Periodic stock reconciliation should be performed at defined intervals by comparing
758 the actual and recorded stock.
759
760 13.2 The root cause for stock discrepancies should be identified and appropriate CAPAs
761 taken to prevent recurrence.
762
763 13.3 When damaged containers are received, this should be brought to the attention
764 of the person responsible for quality. Any action taken should be documented.
765 (These containers should not be issued unless the quality of the medical
766 products has been shown to be unaffected).
767
768 13.4 All stock should be checked regularly to identify obsolete, to be retested, and
769 expired stock.
770
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771 14. EQUIPMENT

772
773 14.1 Equipment, including computerized systems should be suitable for their intended use.
774 These should be appropriately designed, located, installed, qualified and maintained.
775
776 14.2 Computerized systems should be capable of achieving the desired output and results.
777
778 14.3 Where electronic commerce (e-commerce) is used, i.e. electronic means for any of the
779 steps, defined procedures and adequate systems should be in place to ensure
780 traceability and confidence in the supply chain and products concerned.
781
782 14.4 Electronic transactions (including those conducted via the Internet) relating to the
783 distribution of medical products should be performed only by authorized persons
784 according to defined and authorized access and privileges.
785
786 14.5 Where GXP systems are used, these should meet the requirements of WHO and other
787 guidelines on computerized systems (6,9).
788
789 15. QUALIFICATION AND VALIDATION
790
791 15.1 The scope and extent of qualification and validation should be determined
792 using documented risk management principles.
793
794 15.2 Premises, utilities, equipment and instruments, processes and procedures
795 should be considered. The scope and extent of qualification and validation in
796 case of any significant changes should be identified.
797 15.3 Qualification and validation should be done following procedures and
798 protocols. The results and outcome of the qualification and validation should
799 be recorded in reports. Deviations should be investigated and the completion
800 of the qualification and validation should be concluded and approved.
801
802
 Working document QAS/19.793/Rev.1
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803 16. PERSONNEL

804
805 16.1 There should be an adequate number of personnel.
806
807 16.2 Personnel should have appropriate educational qualification, experience and training
808 relative to the activities undertaken.
809
810 16.3 Personnel should have the authority and resources needed to carry out their duties and
811 to follow the quality systems, as well as to identify and correct deviations from the
812 established procedures.
813
814 16.4 There should be arrangements in place to ensure that management and personnel are
815 not subjected to commercial, political, financial and other pressures or conflict of
816 interest that may have an adverse effect on the quality of service provided or on the
817 integrity of medical products.
818
819 16.5 Safety procedures should be in place relating to all relevant personnel and property,
820 environmental protection and product integrity.
821
822 16.6 Personnel should receive initial and continued training in accordance with a written
823 training programme. The training should cover the requirements of GSP, GDP ( as
824 applicable), as well as on-the-job training. Other topics should be included, such as
825 product security, product identification and the detection of falsified products.
826
827 16.7 Personnel dealing with hazardous products (such as highly active materials, radioactive
828 materials, narcotics and other hazardous, environmentally sensitive and/or dangerous
829 pharmaceutical products, as well as products presenting special risks of abuse, fire or
830 explosion) should be given specific training.
831
832 16.8 Personnel should be trained in, and observe high levels of, personal hygiene and
833 sanitation.
834
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835 16.9 Records of all training, attendance and assessments should be kept.
836
837 16.10 Personnel handling products should wear garments suitable for the activities that they
838 perform. Personnel dealing with hazardous pharmaceutical products, including
839 products containing materials that are highly active, toxic, infectious or sensitizing,
840 should be provided with protective garments as necessary.
841
842 16.11 Appropriate procedures relating to personnel hygiene, relevant to the activities to be
843 carried out, should be established and observed. Such procedures should cover health,
844 hygiene and the clothing of personnel.
845
846 16.12 Procedures and conditions of employment for employees, including contract and
847 temporary staff, and other personnel having access to medical products, must be
848 designed and implemented to assist in minimizing the possibility of such products
849 coming into the possession of unauthorized persons or entities.
850
851 16.13 Codes of practice and punitive procedures should be in place to prevent and address
852 situations where persons involved in the storage and distribution of medical products
853 are suspected of, or found to be implicated in, any activities relating to the
854 misappropriation, tampering, diversion or falsifying of any product.
855
856 17. DOCUMENTATION
857
858 17.1 Documentation includes all procedures, records and data, whether in paper or electronic
859 form. Documents should be appropriately designed, completed, reviewed, authorized,
860 distributed and kept as required. Documents should be readily available.
861 17.2 Written procedures should be followed for the preparation, review, approval, use of and
862 control of all documents relating to the policies and activities for storage and
863 distribution of medical products process.
864
865 17.3 Documents should be laid out in an orderly fashion and be easy to complete, review and
866 check. The title, scope, objective and purpose of each document should be clear.
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867 17.4 The contents of documents should be accurate, legible, traceable, attributable and
868 unambiguous.
869
870 17.5 All documents should be completed, signed and dated as required by authorized
871 person(s) and should not be changed without the necessary authorization.
872
873 17.6 Documentation should be prepared and maintained in accordance with the national
874 legislation and principles of good documentation practices (9).
875
876 17.7 Data should meet ALCOA principles. Procedures should be followed and records
877 maintained for the back-up and restoration of data.
878
879 17.8 The distributor must establish and maintain procedures for the identification, collection,
880 indexing, retrieval, storage, maintenance, disposal of and access to all applicable
881 documentation.
882
883 17.9 Documents should be reviewed regularly and kept up-to-date. When a document has
884 been revised, a system should exist to prevent inadvertent use of the superseded version.
885
886 17.10 All records should be stored and retained using facilities that prevent unauthorized
887 access, modification, damage, deterioration and/or loss of documentation during the
888 entire life cycle of the record. Records must be readily retrievable.
889
890 17.11 Comprehensive records should be maintained for all receipts, storage, issues and
891 distribution. The records should include, for example:
892
893 • date (e.g. receipt or dispatch, as appropriate);
894 • name and description of the product;
895 • quantity received, or supplied;
896 • name and address of the supplier and customer.
897 • batch number(s);
898 • expiry date;
 Working document QAS/19.793/Rev.1
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899 • suitability of the supplier;

900 • qualification of suppliers; and
901 • customer qualification.
902
903 17.12 All containers should be clearly labelled with at least the name of the medical
904 product, batch number, expiry date or retest date, and the specified storage
905 conditions.
906
907 18. ACTIVITIES AND OPERATIONS
908
909 18.1 All activities and operations should be conducted in accordance with national
910 legislation, GSP, GDP and associated guidelines.
911
912 18.2 Storage and distribution of medical products should be done by persons so authorized,
913 in accordance with national legislation.
914
915 18.3 Activities and operations should be performed in accordance with documented
916 procedures.
917
918 18.4 Automated Storage and Retrieval Systems (AS/RS) and operations should comply
919 with current GSP, GDP and GXP guidelines, as well as the recommendations in this
920 guideline.
921
922 Receiving
923
924 18.5 Medical products should be procured from appropriately authorized suppliers.
925
926 18.6 Deliveries should be examined for damage, seal intactness, signs of tampering,
927 labelling, completeness of order and other related aspects, at the time of receiving.
928
 Working document QAS/19.793/Rev.1
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929 18.7 Containers and consignments not meeting acceptance criteria at the time of receipt
930 should be labelled, kept separate and investigated. This includes suspected falsified
931 products.
932
933 Storage
934
935 18.8 Medical products requiring specific storage conditions, or controlled access, (e.g.
936 narcotics) should be processed without delay and stored in accordance with their
937 requirements.
938
939 18.9 Appropriate controls should be implemented to prevent contamination and/or mix ups
940 during storage.
941
942 18.10 Controls and procedures should be in place to prevent and handle spillage and breakage.
943
944 Repackaging and relabelling
945
946 18.11 Repackaging and relabelling of materials and products are not recommended. Where
947 repackaging and relabelling occur, these activities should only be performed by entities
948 appropriately authorized to do so and in compliance with the applicable national,
949 regional and international requirements, and in accordance with GMP.
950
951 18.12 Procedures should be in place for the controlled disposal of original packaging to
952 prevent re-use thereof.
953
954 Distribution and transport
955
956 18.13 Medical products should be transported in accordance with the conditions stated on the
957 labels. There should be no risk to the quality of the medical product during transport
958 and distribution.
959
960 18.14 Product, batch and container identity should be maintained at all times.
 Working document QAS/19.793/Rev.1
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961 18.15 All labels should remain legible.

962
963 18.16 Distribution records should be sufficiently detailed to allow for a recall when required.
964
965 18.17 Drivers of vehicles should be identified and present appropriate documentation to
966 demonstrate that they are authorized to transport medical products.
967
968 18.18 Vehicles should be suitable for their purpose, with sufficient space and appropriately
969 equipped to protect medical products.
970
971 18.19 The design and use of vehicles and equipment must aim to minimize the risk of errors
972 and permit effective cleaning and/or maintenance to avoid contamination, build-up of
973 dust or dirt and/or any adverse effect on the quality of the products.
974
975 18.20 Where feasible, consideration should be given to adding technology, such as global
976 positioning system (GPS) electronic tracking devices and engine-kill buttons to
977 vehicles, which would enhance the security and traceability of vehicles with products.
978
979 18.21 Where possible, dedicated vehicles and equipment should be used for medical products.
980 Where non-dedicated vehicles and equipment are used, procedures should be in place
981 to ensure that the quality of the products will not be compromised. Defective vehicles
982 and equipment should not be used. These should either be labelled as such or removed
983 from service.
984
985 18.22 There should be procedures in place for the operation and maintenance of all vehicles
986 and equipment.
987
988 18.23 Equipment and materials used for the cleaning of vehicles should not become a source
989 of contamination or have an adverse effect on product quality.
990
991 18.24 Appropriate environmental conditions should be maintained, monitored and recorded.
992 All monitoring records should be kept for a defined period of time as required by
 Working document QAS/19.793/Rev.1
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993 national legislation. Records of monitoring data should be made available for
994 inspection by the regulatory or other oversight body.
995
996 18.25 Instruments used for monitoring conditions, for example, temperature and humidity,
997 within vehicles and containers should be calibrated at regular intervals.
998
999 18.26 Rejected, recalled and returned products, as well as those suspected as being falsified,
1000 should be securely packaged, clearly labelled and be accompanied by the appropriate
1001 supporting documentation.
1002
1003 18.27 Measures should be in place to prevent unauthorized persons from entering and/or
1004 tampering with vehicles and/or equipment, as well as to prevent the theft or
1005 misappropriation thereof.
1006
1007 18.28 Shipment containers should have no adverse effect on the quality of the medical
1008 products and should offer adequate protection to materials and these products.
1009 Containers should be labelled indicating, for example, handling and storage conditions,
1010 precautions, contents and source, and safety symbols, as appropriate.
1011
1012 18.29 Special care should be taken when using dry ice and liquid nitrogen in shipment
1013 containers due to safety issues and possible adverse effects on the quality of medical
1014 products.
1015
1016 18.30 Written procedures should be available for the handling of damaged and/or broken
1017 shipment containers. Particular attention should be paid to those containing potentially
1018 toxic and hazardous products.
1019
1020 Dispatch
1021
1022 18.31 There should be documented, detailed procedures for the dispatch of products.
1023
 Working document QAS/19.793/Rev.1
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1024 18.32 Medical products should only be sold and/or distributed to persons or entities that are
1025 authorized to acquire such products in accordance with the applicable national
1026 legislation. Written proof of such authorization must be obtained prior to the
1027 distribution of products to such persons or entities.
1028
1029 18.33 Dispatch and transportation should be undertaken only after the receipt of a valid order
1030 which should be documented.
1031
1032 18.34 Records for the dispatch of products should be prepared and should include information
1033 such as, but not limited to:
1034
1035 • date of dispatch;
1036 • complete business name and address (no acronyms), type of entity responsible
1037 for the transportation, telephone number, names of contact persons;
1038 • status of the addressee (e.g. retail pharmacy, hospital or community clinic);
1039 • a description of the products including, for example, name, dosage form and
1040 strength (if applicable);
1041 • quantity of the products, i.e. number of containers and quantity per container
1042 (if applicable);
1043 • applicable transport and storage conditions;
1044 • a unique number to allow identification of the delivery order; and
1045 • assigned batch number and expiry date (where not possible at dispatch, this
1046 information should at least be kept at receipt to facilitate traceability).
1047
1048 18.35 Records of dispatch should contain sufficient information to enable traceability of the
1049 product. Such records should facilitate the recall of a batch of a product, if necessary,
1050 as well as the investigation of falsified or potentially falsified products. In addition, the
1051 assigned batch number and expiry date of products should be recorded at the point of
1052 receipt to facilitate traceability.
1053
1054 18.36 Vehicles and containers should be loaded carefully and systematically on a last-in/first-
1055 out (LIFO) to save time when unloading, to prevent physical damage and to reduce
 Working document QAS/19.793/Rev.1
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1056 security risks. Extra care should be taken during loading and unloading of cartons to
1057 avoid damage.
1058
1059 18.37 Medical products should not be supplied or received after their expiry date, or so close
1060 to the expiry date that this date is likely to be reached before the products are used by
1061 the consumer (10).
1062
1063 18.38 Medical products and shipment containers should be secured in order to prevent or to
1064 provide evidence of unauthorized access. Vehicles and operators should be provided
1065 with additional security where necessary, to prevent theft and other misappropriation
1066 of products during transportation.
1067
1068 18.39 Medical Products should be stored and transported in accordance with procedures such
1069 that:
1070
1071 • the identity of the product is not lost;
1072 • the product does not contaminate and is not contaminated by other products;
1073 • adequate precautions are taken against spillage, breakage, misappropriation and
1074 theft; and
1075 • appropriate environmental conditions are maintained, for example, using cold
1076 chain for thermolabile products.
1077
1078 18.40 Written procedures should be in place for investigating and dealing with any failure to
1079 comply with storage requirements, for example, temperature deviations. If a deviation
1080 has been noticed during transportation by the person or entity responsible for
1081 transportation, this should be reported to the distributor and recipient. In cases where
1082 the recipient notices the deviation, it should be reported to the distributor.
1083
1084 18.41 Transportation of products containing hazardous substances or narcotics and other
1085 dependence-producing substances, should be transported in safe, suitably designed,
1086 secured containers and vehicles. In addition, the requirements of applicable
1087 international agreements and national legislation should be met.
 Working document QAS/19.793/Rev.1
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1088
1089 18.42 Spillages should be cleaned up as soon as possible in order to prevent possible
1090 contamination, cross-contamination and hazards. Written procedures should be in place
1091 for the handling of such occurrences.
1092
1093 18.43 Damage to containers and any other event or problem that occurs during transit must
1094 be recorded and reported to the relevant department, entity or authority and
1095 investigated.
1096
1097 18.44 Products in transit must be accompanied by the appropriate documentation.
1098
1099 19. OUTSOURCED ACTIVITIES
1100
1101 19.1 Any activity relating to the storage and distribution of a medical product which is
1102 delegated to another person or entity should be performed by the parties appropriately
1103 authorized in accordance with national legislation and the terms of a written contract.
1104
1105 19.2 There should be a written contract between the entities. The contract should define the
1106 responsibilities of each entity (contract giver and contract acceptor) and cover at least
1107 the following:
1108
1109 • compliance with this guideline and the principles of GSP and GDP;
1110 • responsibilities of all entities for measures to avoid the entry of substandard
1111 and falsified products into the distribution chain;
1112 • training of personnel;
1113 • conditions of subcontracting subject to the written approval of the contract
1114 giver; and
1115 • periodic audits.
1116
1117 19.3 The contract giver should assess the competence of the contract acceptor before
1118 entering into the contract.
1119
 Working document QAS/19.793/Rev.1
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1120 19.4 The contract giver should provide all relevant information relating to the material/
1121 products to the contract acceptor.
1122
1123 19.5 The contract acceptor should have adequate resources (e.g. premises, equipment,
1124 personnel, knowledge, experience and vehicles, as appropriate) to carry out the work.
1125
1126 19.6 The contract acceptor should refrain from performing any activity that may adversely
1127 affect the materials or products handled.
1128
1129 20. SUBSTANDARD AND FALSIFIED PRODUCTS
1130
1131 20.1 The quality system should include procedures to assist in identifying and handling medical
1132 products that are suspected to be substandard and/or falsified.
1133
1134 20.2 Where such medical products are identified, the holder of the marketing authorization, the
1135 manufacturer and the appropriate national, regional and international regulatory bodies
1136 (as appropriate), as well as other relevant competent authorities, should be informed.
1137
1138 20.3 Such products should be stored in a secure, segregated area and clearly identified to
1139 prevent further distribution or sale. Access should be controlled.
1140
1141 20.4 Records should be maintained reflecting the investigations and action taken, such as
1142 disposal of the product. Falsified products should not re-enter the market.
1143
1144 21. INSPECTION OF STORAGE AND DISTRIBUTION FACILITIES
1145
1146 21.1 Storage and distribution facilities should be inspected by inspectors so authorized by
1147 national legislation. This should be done at determined, periodic intervals.
1148
1149 21.2 Inspectors should have appropriate educational qualifications, knowledge and
1150 experience (11).
1151
 Working document QAS/19.793/Rev.1
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1152 21.3 An inspection should normally be conducted by a team of inspectors.

1153
1154 21.4 Inspectors should assess compliance with national legislation, GSP, GDP and related
1155 guidelines (GXP) as appropriate.
1156
1157 21.5 Inspections should cover the premises, equipment, personnel, activities, quality system,
1158 qualification and validation and other related aspects as contained in this guideline.
1159
1160 21.6 An inspection report should be prepared and provided to the inspected entity within a
1161 defined period of time from the last day of the inspection. Observations may be
1162 categorized based on risk assessment.
1163
1164 21.7 CAPA for observations listed as non-compliances in the inspection report, with the
1165 national legislation and guidelines, should be submitted for review by the inspectors
1166 within the defined period as stated by the inspectors.
1167
1168 21.8 Inspections should be closed with a conclusion after the review of the CAPAs.
1169

1170 References
1171
1172 1. WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles
1173 (WHO Technical Report Series, No. 986, 2014, Annex 2).
1174
1175 2. WHO Guide to Good Storage Practices for Pharmaceuticals (WHO Technical Report
1176 Series, No. 908, 2003, Annex 9). [under revision]
1177
1178 3. Good Distribution Practices for Pharmaceutical Products (WHO Technical Report
1179 Series, No. 957, 2010, Annex 5). [under revision]
1180
1181 4. Good Pharmacy Practice: Standards for Quality of Pharmacy Services (joint
1182 FIP/WHO) (WHO Technical Report Series, No. 961, 2011, Annex 8).
1183
 Working document QAS/19.793/Rev.1
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1184 5. Good Trade and Distribution Practices for Starting ;aterials (WHO Technical
1185 Report Series, No. 996, 2016, Annex 6).
1186
1187 6. Validation of Computerized Systems (WHO Technical Report Series, No. 1019, 2019,
1188 Annex 5).
1189
1190 7. Guidelines on Heating, Ventilation and Air-Conditioning Systems for Non-Sterile
1191 Pharmaceutical Products (WHO Technical Report Series, No. 1019, 2019, Annex 2).
1192
1193 8. Model Guidance for the Storage and Transport of Time- and Temperature-Sensitive
1194 Pharmaceutical Products (WHO Technical Report Series, No. 961, Annex 9).
1195
1196 9. Guidance on Good Data and Record Management Practices (WHO Technical Report
1197 Series, No. 996, 2016, Annex 5).
1198
1199 10. WHO Policy on Remaining Shelf Life of Medical Products (working document
1200 QAS/19.788).
1201
1202 11. Quality Systems Requirements for National Inspectorates (working document
1203 QAS/19.811/Rev.1).
1204

1205 Further reading

1206
1207 1. WHO Guidelines on Quality Risk Management (WHO Technical Report Series,
1208 No. 981, 2013, Annex 2).
1209
1210 2. Quality Risk Management, ICH Q9, 2015.
1211
1212 3. Risk Management – Guidelines. ISO 31000:2018.
1213
1214 4. Medical Devices – Application of Risk Management to Medical Devices. ISO
1215 14971:2018.
 Working document QAS/19.793/Rev.1
Page 40

1216 5. Medical Devices – Quality Management Systems – Requirements for Regulatory

1217 Purposes. ISO 13485:2016.
1218
1219 6. WHO Guidance on Testing of “Suspect” Falsified Medicines (WHO Technical
1220 Report Series, No. 1010, 2018, Annex 5).
1221
1222 7. Guidelines on Import Procedures for Pharmaceutical Products (WHO Technical
1223 Report Series, No. 1019, 2019, Annex 5).
1224
1225 8. Good Practices of National Regulatory Authorities in Implementing the
1226 Collaborative Registration Procedures for Medical Products (WHO Technical
1227 Report Series, No. 1019, 2019, Annex 6).
1228
1229 9. Guidelines for Medicine Donations, 3rd edition 2011. https://apps.who.int/iris/
1230 bitstream/handle/10665/44647/9789241501989_eng.pdf?sequence=1
1231
1232 10. Guidelines for Safe Disposal of Unwanted Pharmaceuticals in and after Emergencies:
1233 Interagency Guidelines. Geneva, World Health Organization, 1999
1234 (WHO/EDM/PAR/99.2).
1235
1236 11. Model quality assurance system for procurement agencies (WHO Technical Report
1237 Series, No 986, 2014, Annex 3).
1238
1239 12. Validation (WHO Technical Report Series, No 1019, 2019, Annex 3).
1240
1241
1242
1243
1244
1245
1246
 Working document QAS/19.793/Rev.1
Page 41

1247 ANNEX 1
1248 RECOMMENDED STORAGE CONDITIONS
1249
1250 Note: Appropriate conditions should be provided for medical products during storage and
1251 distribution. Conditions should be maintained as stated on their labels from the manufacturers
1252 and suppliers during storage and distribution. Statements such as “store at ambient
1253 conditions” should be avoided. Where possible, actual limits should be specified by the
1254 manufacturers, such as “store below 25oC”. See Table 1 below.
1255
1256 Table 1. Recommended limits for descriptive storage conditions1

Label description Recommended limits

Store at controlled room temperature 15 to 25 °C

Store in a cold or cool place 8 to 15 °C

Store in a refrigerator 5 + 3 °C

Store in a freezer -20 + 5 °C

Store in deep freezer Below -15 °C

or
-70 +10 °C

Store in a dry place No more than 60% relative humidity

Protect from moisture No more than 60% relative humidity

Store under ambient conditions Store in dry, well-ventilated premises at

temperatures of between 15 –30 °C.
Extraneous odours, other indications of
contamination and intense light must be
excluded.

Protect from light To be provided in light resistant containers.

Light level not exceeding 500 lux.

Chilled Refrigerated
1257
1
1258 These limits are recommended values and are based on pharmacopoeia limits and guidelines.
1259 ***