policy on remaining shelf life of medical products …...working document qas/19.788/rev.1 page 2 41...

Working document QAS/19.788/Rev.1

July 2019

Draft for comments

1

POLICY ON REMAINING SHELF LIFE OF MEDICAL 2

PRODUCTS UPON DELIVERY* 3

(July 2019) 4

DRAFT FOR COMMENTS 5

6 *Explanatory note : « delivery » could mean delivery at different stages of the supply chain 7

8

9 © World Health Organization 2019 10 11 All rights reserved. 12 13 This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 14 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 15 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 16 organizations) without the permission of the World Health Organization. The draft should not be displayed on any website. 17 18 Please send any request for permission to: 19 20 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential 21 Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland, email: [email protected]. 22 23 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 24 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or 25 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate 26 border lines for which there may not yet be full agreement. 27 28 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 29 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and 30 omissions excepted, the names of proprietary products are distinguished by initial capital letters. 31 32 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 33 34 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 35 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 36 damages arising from its use. 37 38 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 39

40

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 e-mail address to

[email protected] and your name will be added to our electronic mailing list.

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mailto:[email protected]



http://www.who.int/medicines/areas/quality_safety/quality_assurance/guidelines/en/



SCHEDULE FOR DRAFT WORKING DOCUMENT QAS/19.788: 41

42

POLICY ON REMAINING SHELF LIFE 43

OF MEDICAL PRODUCTS UPON DELIVERY 44

45

Description of Activity Date

Informal discussion at The Global Fund to Fight AIDS,

Tuberculosis and Malaria offices in Geneva, Switzerland.

February 2019

Preparation of the document. February 2019

Circulation of document, inviting comments. March and April 2019

Review of comments received. Preparation of discussion

document by a working group in close collaboration with the

IPC members.

May – June 2019

Discussion of working document and feedback received from

IPC members and during the public consultation in the

informal Consultation on Good Practices for Health Products

Manufacture and Inspection.

2-5 July 2019

Preparation of revised text. July 2019

Mailing of the revised working document for second round

inviting comments, including to the Expert Advisory Panel on

the International Pharmacopoeia and Pharmaceutical

Preparations (EAP), and posting the working document on the

WHO website for public consultation.

Mid July – September

2019

Consolidation of comments received and review of feedback. October 2019


46

Presentation to the Fifty-fourth meeting of the WHO Expert

Committee on Specifications for Pharmaceutical Preparations

in Geneva, Switzerland.

14-18 October 2019

Any other follow-up action as required.


POLICY ON REMAINING SHELF LIFE 47

OF MEDICAL PRODUCTS UPON DELIVERY 48

49

1. Introduction 50

2. Scope 51

3. Glossary 52

4. The need for policy 53

5. Policy on remaining shelf life 54

55

References 56

Further reading 57

Annexure – Recommended remaining shelf life of products; and examples of considerations 58

59

1. INTRODUCTION 60

61

Following discussions relating to establishing policy for remaining shelf life (RSL) of medical 62

products upon delivery, and considering the discussion between the Interagency 63

Pharmaceutical Coordination (IPC) group representatives, it was decided to initiate a project 64

to establish a policy on remaining shelf life for procurement and supply of medical products. 65

66

The concept and project to establish such a policy was also discussed during the meeting of the 67

Fifty-third Expert Committee on Specifications for Pharmaceutical Products (ECSPP) in 68

October 2018. It was noted that some guidance documents were available from different 69

procurement agencies. It was agreed that the World Health Organization (WHO) would initiate 70

the discussion and preparation of a policy whilst following the WHO process for the 71

establishment of such a policy paper. 72

73

Information and policy on remaining shelf life was collected from different agencies and 74

interested parties and a first draft document was prepared after an informal discussion meeting 75

in Geneva, Switzerland, in January 2019. 76

77


It was then agreed that the policy should not cover only finished pharmaceutical products but 78

should be extended to also cover other products including, but not limited to, medical 79

devices, vaccines and in vitro diagnostics (IVDs). (These products are collectively referred to 80

as “medical products” hereafter). 81

82

A draft document was prepared and circulated to IPC members, as well as other interested 83

parties, inviting comments. The comments received were reviewed during an informal 84

discussion meeting in June 2019 and the draft document was updated. 85

86

The aims of this policy document are: 87

88

• to ensure that there is a balance between enforcing the remaining shelf life policy and 89

ensuring availability of medical products; 90

• to facilitate the national authorization of importation of medical products where 91

applicable; 92

• to promote and support the efficient processing of medical products in the supply chain 93

at all levels and thus prevent wastage because of delays; 94

• to assist in ensuring that there is sufficient stock of medical products, with acceptable 95

remaining shelf life, in-country; 96

• to prevent dumping of medical products; 97

• to ensure that barriers to access and supply of medical products are addressed; 98

• to prevent stock-outs; 99

• to prevent receiving donations of medical products that are not in accordance with this 100

guideline; and 101

• to prevent having expired stock of medical products. 102

103

The policy contained in this document is intended to provide guidance on remaining shelf life 104

of medical products upon delivery and should be implemented by all stakeholders in the supply 105

chain of medical products. It is also recommended that the policy be considered in the national 106

policy of countries. 107

108

109


2. SCOPE 110

111

The principles contained in this document should be applied to medical products in the supply 112

chain. This includes donated products. (See WHO Guidelines on Donations). 113

114

This document presents policy on shelf life and does not address details contained in other 115

guidelines, guides and agreements between different parties in the supply chain. 116

117

As “kits” are made up of different products, and due to certain specifics related to the shelf life 118

of kits, these are not included in the scope of this guideline. The principles contained in this 119

guideline may however be used in considering the remaining shelf life of kits. 120

121

All stakeholders, including manufacturers, suppliers, donors and recipients should implement 122

the shelf life policy contained in this document. 123

124

3. GLOSSARY 125

126

(Note: the definitions below are taken from existing WHO guidelines where available, or 127

alternatively, from other recognised guidelines). 128

129

Batch 130

A defined quantity of starting material, packaging material, or product processed in a single process 131

or series of processes so that it is expected to be homogeneous. It may sometimes be necessary to 132

divide a batch into a number of sub-batches, which are later brought together to form a final 133

homogeneous batch. In the case of terminal sterilization, the batch size is determined by the 134

capacity of the autoclave. In continuous manufacture, the batch must correspond to a defined 135

fraction of the production, characterized by its intended homogeneity. The batch size can be defined 136

either as a fixed quantity or as the amount produced in a fixed time interval. 137

138

139

140

141


Consignment (or delivery) 142

The quantity of a pharmaceutical or pharmaceuticals, made by one manufacturer and supplied at 143

one time in response to a particular request or order. A consignment may comprise one or more 144

packages or containers and may include material belonging to more than one batch. 145

146

Expiry date (or expiration date) 147

The date placed on the container or labels of an API designating the time during which the API 148

is expected to remain within established shelf-life specifications if stored under defined 149

conditions and after which it should not be used. 150

151

Finished pharmaceutical product (FPP) 152

A product that has undergone all stages of production, including packaging in its final container 153

and labelling. An FPP may contain one or more APIs. 154

155

Install by date 156

The date by which an instrument, device or other has to be installed. 157

158

Manufacture 159

All operations of purchase of materials and products, production, quality control (QC), release, 160

storage and distribution of pharmaceutical products, and the related controls. 161

162

Manufacturer 163

A company that carries out operations such as production, packaging, repackaging, labelling and 164

relabelling of pharmaceuticals. 165

166

Marketing authorization (product licence, registration certificate) 167

A legal document issued by the competent medicines regulatory authority that establishes the 168

detailed composition and formulation of the product and the pharmacopoeial or other recognized 169

specifications of its ingredients and of the final product itself, and includes details of packaging, 170

labelling and shelf-life. 171

172

173


Manufacturer (IVD) 174

Means any natural or legal person with responsibility for design and/or manufacture of an IVD 175

with the intention of making the IVD available for use, under his or her name, whether or not 176

such an IVD is designed and/or manufactured by that person him- or herself or on his or her 177

behalf by (an)other person(s) 178

179

Manufacturing date 180

The date of production of a batch is defined as the date that the first step is performed involving 181

the combining of the active ingredient with other ingredients. Where there are no other 182

ingredients than an Active ingredient, the date of the start of the processing or filling operation 183

is considered as the date of production. (Adapted from EU.) 184

185

Medical product 186

Products including, but not limited to, finished pharmaceutical products, medical devices, 187

vaccines and in vitro diagnostics (IVDs). 188

189

Pharmaceutical product 190

Any material or product intended for human or veterinary use presented in its finished dosage form, 191

or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical 192

legislation in the exporting state and/or the importing state. 193

194

Production 195

All operations involved in the preparation of a pharmaceutical product, from receipt of materials, 196

through processing, packaging and repackaging, labelling and relabelling, to completion of the 197

finished product. 198

199

Remaining shelf life 200

Defined as the period remaining, from the date upon delivery, to the expiry date, retest date, 201

install by date or other use before date established by the supplier 202

203

Retest date 204

The date when a material should be re-examined to ensure that it is still suitable for use. 205


Shelf life 206

Shelf life is the period of time, from the date of manufacture, that a product is expected to 207

remain within its approved product specification while handled and stored under defined 208

conditions 209

210

Upon delivery 211

Means the date the medical product is delivered as specified, e.g. at the port; at the point in 212

country after customs clearance, or at the end-user – and as defined in the agreement between 213

relevant parties 214

215

4. THE NEED FOR POLICY 216

217

As there was no harmonized policy on remaining shelf life for medical products amongst 218

procurers, donors and recipient countries, it was agreed that it will be beneficial to have a 219

harmonized approach on policy for remaining shelf life. This will assist national regulatory 220

authorities (NRAs), suppliers, donors, procurers, importers and distributers to manage medical 221

products throughout the supply chain, thus ensuring the availability of quality medical products 222

within the remaining shelf life reaching the end-user. The authorization of importation of 223

medical products by NRAs sometimes delays access to medical products. A harmonized 224

approach among countries may facilitate authorization and release of medical products in the 225

supply chain in a timely manner. 226

227

This policy document is not a standalone document. It should be read with other documents, 228

guides and guidelines including, but not limited to, WHO guidelines such as Stability Testing, 229

Good Storage and Distribution Practices, Donations, Model Quality Assurance System for 230

Procurement Agencies (MQAS), Pharmacopoeia and International Council for Harmonisation 231

of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 232

guidelines. 233

234

235

236

237


5. POLICY ON REMAINING SHELF LIFE 238

239

Note: The manufacturing date of a medical product should be defined by the manufacturer 240

and be provided upon request, e.g. when this is not on the packaging. 241

242

Principles 243

244

Policy on remaining shelf life should be realistic. It should be defined for medical products 245

and be based on factors such as, but not limited to, the category and type of product, inventory 246

level, storage condition and resources in-country. 247

248

There should be agreements between suppliers, purchasers and recipients covering the relevant 249

responsibilities of each party, including remaining shelf life. 250

251

Products should be transported, received, stored and distributed in accordance with WHO Good 252

Storage and Distribution Practices (GSDP). Special attention should be given to temperature, 253

light and moisture sensitive products 254

255

Products supplied by the manufacturer or supplier should meet the policy of national 256

government and the recommendations in terms of remaining shelf life prescribed in this 257

guideline. Compliance with this requirement may be verified by an appropriate means, such 258

as a pre-shipment inspection or other. 259

260

Products should be appropriately labelled. The label should include the expiry, re-test or install 261

by date, as appropriate. Products with an “Install by” date should be installed prior to the date 262

specified by the supplier. 263

264

Products received should be scrutinised in an attempt to identify possible substandard and 265

falsified products. It should be ensured that, for example, the expiry date is not falsified. (See 266

Guidelines on Substandard and Falsified Products, WHO Guidance on Testing of “suspect” 267

falsified medicines.) 268

269


Where different periods for remaining shelf life have been defined for products, recipients 270

should ensure that the products meet the remaining shelf life requirement for the intended 271

destination, e.g. central warehouse, regional warehouse, testing site or user point. 272

273

National authorization for importation, where required, should be obtained based on the 274

available information, including the shelf life or expiry date of the product as well as the 275

remaining shelf life (where possible), to assist in expediting approval. 276

277

Where so justified, suppliers, recipients and national authorities may negotiate deviations from 278

the remaining shelf life policy provided that: 279

280

(a) the medical product quality will be assured; 281

(b) where the shelf life is shorter than stipulated in the policy, it is ensured that the stock 282

will be consumed prior to expiry; 283

(c) the medical product should reach end-users with adequate remaining shelf life to show 284

confidence on the quality of the medical product and time to consume it before expiry. 285

286

Risk assessment to ensure that the parameters are met should be done, taking into account at 287

least the following criteria: 288

289

• type of product: different criticality for the safety of the patient between pharmaceutical 290

products, vaccines, medical devices and IVDs; 291

• existing shelf-life: with this the remaining shelf-life at delivery time can be estimated; 292

• compliance with WHO GSDP guidelines; 293

• order frequency (based on consumption): recipients and end-user should regularly 294

verify that medical products in stock are rotated or used within their remaining shelf 295

life and adjust the quantities ordered to make sure that the medical products will be 296

used during their remaining shelf life; 297

• assessment of the real needs, to ensure that the medical products can be used within 298

their shelf-life; 299

• emergency: during an emergency situation, the remaining shelf-life policy should be 300

well balanced to ensure that patients will receive the medical products in time; 301


• the logistic set-up: the premises location, number of transportation means and its agility 302

will have an impact on the speed of the delivery and, hence, have the products being 303

used before their expiry date; 304

• the activity specificities: similarly, whether the medical products will be used by the 305

national programme, or at own driven activities managed directly by the importer, will 306

make a difference in terms of speed of delivery to the end-user; 307

• the point of delivery: national warehouses, importer or end-user facilities will also have 308

an impact on the speed of delivery. 309

310

Expiry date 311

Products, such as pharmaceutical products, should have an expiry date allocated by the 312

manufacturer. The expiry date should be established based on stability testing results 313

obtained in the relevant packaging (primary, and secondary packaging, where appropriate) 314

and required stability conditions. (See WHO Guideline: Stability Testing of Active 315

Pharmaceutical Ingredients and Finished Pharmaceutical Products. WHO Technical 316

Report Series, No. 1010, Annex 10, 2018.) 317

318

Retesting 319

Where a manufacturer or supplier has obtained approval from an NRA for a new or extended 320

shelf life, this may be applied. 321

322

Products with an expiry date should not be subjected to retesting by the purchaser or recipient 323

for the purpose of extension of shelf life. Only in exceptional cases, such as product shortages, 324

should a recipient consider to extend the expiry date of received batches subject to certain 325

conditions, such as availability of scientific data, the application of risk management principles 326

and NRA approval. The new expiry date should be reflected on the packaging. 327

328

Products with a retest date allocated by a manufacturer or supplier should have at least one year 329

of shelf life remaining (from the date of delivery to the end-user, to the labelled retest date). 330

Products with a retest date allocated by a manufacturer, e.g. chemicals and reagents, may be 331

retested and used if the quality parameters are met. 332

333


Examples of considerations and recommended remaining shelf life of products are given in the 334

Annexure. 335

336

References 337

338

[Note from the Secretariat: The references will be completed in the final text.] 339

340

Further Reading 341

342

1. WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles. WHO 343

Expert Committee on Specifications for Pharmaceutical Preparations. Forty-eight Report 344

Geneva, World Health Organization, 2014 (WHO Technical Report Series, No. 986), Annex 345

2. 346

Short name: WHO TRS No. 986, Annex 2 347

http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/trs_348

986/en/ 349

350

2. WHO Guidelines for Sampling of Pharmaceutical Products and Related Materials. WHO 351

Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-ninth Report. 352

Geneva, World Health Organization, 2005 (WHO Technical Report Series, No. 929), Annex 353

4. 354


http://whqlibdoc.who.int/trs/WHO_TRS_929_eng.pdf?ua=1 356

357

3. WHO Good Practices for Pharmaceutical Quality Control Laboratories. WHO Expert 358

Committee on Specifications for Pharmaceutical Preparations. Forty-fourth Report. Geneva, 359

World Health Organization, 2010 (WHO Technical Report Series, No. 957, Annex 1). 360

Short name: WHO TRS No. 961, 957), Annex 1 361

http://www.who.int/medicines/publications/44threport/en/ 362

363

4. Model Guidance for the Storage and Transport of Time-and Temperature-Sensitive 364

Pharmaceutical Products. WHO Expert Committee on Specifications for Pharmaceutical 365

Preparations. Forty-Fifth Report. Geneva, World Health Organization, 2011 (WHO 366

Technical Report Series, No. 961), Annex 9. 367

http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/trs_986/en/


http://whqlibdoc.who.int/trs/WHO_TRS_929_eng.pdf?ua=1

http://www.who.int/medicines/publications/44threport/en/



http://whqlibdoc.who.int/trs/WHO_TRS_961_eng.pdf?ua=1 369

370

5. WHO Guidelines on Quality Risk Management. WHO Expert Committee on Specifications 371

for Pharmaceutical Preparations. Forty-Seventh Report. Geneva, World Health 372

Organization, 2013 (WHO Technical Report Series, No. 981), Annex 2. 373


http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/trs_375

981/en/ 376

377

6. WHO Technical Supplements to Model Guidance for Storage and Transport of Time – and 378

Temperature–Sensitive Pharmaceutical Products. WHO Expert Committee on Specifications 379

for Pharmaceutical Preparations. Forty-Ninth Report. Geneva, World Health Organization, 380

2015 (WHO Technical Report Series, No. 992), Annex 5. 381


http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/WHO383

TRS_992_web.pdf 384

385

7. WHO Good Manufacturing Practices for Biological Products. WHO Expert Committee on 386

Specifications for Pharmaceutical Preparations. Fiftieth Report. Geneva, World Health 387

Organization, 2016 (WHO Technical Report Series, No. 996), Annex 3. 388


http://www.who.int/medicines/publications/pharmprep/WHO_TRS_996_annex03.pdf 390

391

8. WHO Guidance on Procurement of IVDs and Related Laboratory Items. 392

https://apps.who.int/iris/bitstream/handle/10665/255577/9789241512558-eng.pdf?sequence=1 393

394

9. WHO TGS-2 on Establishing Stability of In Vitro Diagnostic Medical Devices. 395

https://apps.who.int/iris/bitstream/handle/10665/259742/WHO-BS-2017.2304-eng.pdf?ua=1 396

397

10. Annex to TGS-2 Establishing Component Stability for In Vitro Diagnostic Dedical Devices. 398

https://apps.who.int/iris/bitstream/handle/10665/311345/WHO-MVP-EMP-RHT-PQT-399

2019.03-eng.pdf?ua=1 400

401

11. International Standards Organization. ISO 23640: 2011. In Vitro Diagnostic Medical Devices -402

Evaluation of Stability of In Vitro Diagnostic Reagents. 403

404

12. Clinical and Laboratory Standards Institute. CLSI EP25‑A Evaluation of Stability of In Vitro 405

Diagnostic Reagents; Approved Guideline, 2009. 406

http://whqlibdoc.who.int/trs/WHO_TRS_961_eng.pdf?ua=1



http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/WHOTRS_992_web.pdf

http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/WHOTRS_992_web.pdf

http://www.who.int/medicines/publications/pharmprep/WHO_TRS_996_annex03.pdf

https://apps.who.int/iris/bitstream/handle/10665/255577/9789241512558-eng.pdf?sequence=1

https://apps.who.int/iris/bitstream/handle/10665/259742/WHO-BS-2017.2304-eng.pdf?ua=1

https://apps.who.int/iris/bitstream/handle/10665/311345/WHO-MVP-EMP-RHT-PQT-2019.03-eng.pdf?ua=1

https://apps.who.int/iris/bitstream/handle/10665/311345/WHO-MVP-EMP-RHT-PQT-2019.03-eng.pdf?ua=1


13. Model Quality Assurance System for Procurement agencies. WHO Technical Report 937, 407

2006, Annex 6. 408

409

410

411


ANNEXURE 412

413

RECOMMENDED REMAINING SHELF LIFE OF PRODUCTS; 414

AND EXAMPLES OF CONSIDERATIONS 415

416

Note: The total shelf life of a product is based on results from testing during stability (and, 417

where relevant, sterility studies) under specified conditions. The storage and transport 418

conditions stipulated by the manufacturer should be followed to ensure the product quality is 419

maintained. 420

421

The recommended remaining shelf life of medical products at the time of dispatch and upon 422

delivery is presented in table 1 below. 423

424

Table 1. Recommended remaining shelf life upon delivery 425

426

Expiry date RSL at time of

dispatch from

Manufacturer’s

premises

RSL at time of

delivery at port of

entry of country

RSL at time of

delivery at point,

after customs

clearance

RSL at time of

delivery at

end-user level

48 months < RSL < 60 months 40 months 30 months 18 months 12 months



12 to 24 months 9 months 7 months 5 months 3 months

Less than 12 months Special arrangements and conditions apply

427

In cases where special arrangements and conditions apply, risk assessment should be done to 428

determine and justify the remaining shelf life upon delivery. Consideration should be given to 429

the following examples: 430

431

• type of product; 432

• shelf life determined through stability testing; 433

• required storage conditions; 434


• frequency of order; 435

• need and emergency; 436

• warehouse; 437

• supply chain and resources; 438

• order quantity (impact in cases where less than a full batch size is ordered); 439

• inventory management practices (e.g. inventory levels and inventory holding 440

timelines); 441

• time taken to ship product to port of entry in the country; 442

• time taken for special requirements (e.g. pre-delivery quality control testing, pre 443

delivery inspection, greenlight processes prior to delivery, customs clearance); 444

• length of in-country supply chain from port of entry to the end-user; 445

• compliance with WHO GSDP guidelines; 446

• assessment of the real needs, to ensure that the medical products can be used within 447

their shelf-life; 448

• emergency: during an emergency situation the remaining shelf-life policy should be 449

well balanced to be sure that patients will receive the medical products in time; 450

• the logistic set-up: the premises location, number of transportation means and its 451

agility will have an impact on the speed of the delivery and hence have the products 452

being used before their expiry date; 453

• the activity specificities: similarly, whether or not the medical products will be used 454

by the national programme, or at own driven activities managed directly by the 455

importer, will make a difference in terms of speed of delivery to the end-user; 456

• the point of delivery: national warehouses, importer or end-user facilities will also 457

have an impact on the speed of delivery. 458

459

*** 460

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