Guidelines on the International Packaging and Shipping of Vaccines

1 2 3 4 DIP 818 5 6 7 8 9

10 Guidelines on

11 the international packaging

12 and shipping of vaccines 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 The Department of Essential Medicines and Products 36 thanks the donors whose unspecified financial support 37 has made the production of this publication possible. 38 39 This publication was produced by the 40 Vaccines Assessment Team 41 of the Department of Essential Medicines and Products

Page 1 42 43 44 Ordering code: WHOEMP- Revision history: This 45 Printed: 2019 document, Guidelines on the46 international packaging and47 This publication is available on the Internet at: shipping of vaccines, was first48 www.who.int/vaccines-documents/ published in 1990. Since then it has gone through four revisions:49 in 1995, 1998, 2001 50 Copies may be requested from: (WHO/V&B/01.05), 2005 and51 World Health Organization 2017. This revision, produced52 in Department of Immunization, Vaccines and Biologicals xxx 2019, replaces all previous53 CH-1211 Geneva 27, Switzerland versions. 54 • Fax: + 41 22 791 4227 • Email: [email protected] • 55

56 57 58 © World Health Organization 2019 59 60 61 All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World 62 Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: 63 [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for 64 noncommercial distribution – should be addressed to Marketing and Dissemination, at the above address (fax: +41 22 791 4806; 65 email: [email protected]). 66 The designations employed and the presentation of the material in this publication do not imply the expression of any opinion 67 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 68 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 69 for which there may not yet be full agreement. 70 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended 71 by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions 72 excepted, the names of proprietary products are distinguished by initial capital letters. 73 All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the 74 published material is being distributed without warranty of any kind, either express or implied. The responsibility for the 75 interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages 76 arising from its use. 77 Printed by the WHO Document Production Services, Geneva, Switzerland 78

Page 2 79 Contents 80 81 Abbreviations 82 83 Glossary 84 85 Preface 86 87 1. Insulated Packaging Standards 88 1.1 Introduction 89 1.2 Temperature Criteria 90 1.2.1 Class A packaging 91 1.2.2 Class B packaging 92 1.2.3 Class C packaging 93 1.3 General Packaging Criteria 94 1.3.1 Insulated Cartons 95 1.3.2 Pallet Shipper & other shipping units 96 97 2. Temperature monitoring devices 98 2.1 Introduction 99 2.2 Electronic Device specifications 100 2.3 Electronic Device instruction card 101 102 103 3. Labelling for International Shipments 104 3.1. Labelling for secondary packages 105 3.2. Labelling for tertiary packages (Insulated packages) 106 107 4. International Shipping Procedures 108 4.1. Temperature control during international transport 109 4.2 Route and arrival dates 110 4.3. Advance shipment arrival notification 111 4.3. Documents that accompany shipments 112 113 5. Vaccine Arrival Report 114 115 Annex 1: Guidelines to confirm that packaging complies with WHO recommendations 116 Annex 2: Shake test protocol 117 Annex 3: List of contact points for NRAs 118 Annex 4: Bulking factors for insulated packaging 119 Annex 5: UNICEF Vaccine Arrival Report 120 Annex 6: PAHO Form 183: Confirmation of Arrival of Shipments 121 Annex 7: Complete list of WHO prequalified vaccines, their recommended class of shipping boxes 122 and their recommended types of electronic temperature monitors to be used 123 Annex 8: List of changes to the current edition

Page 3 124 Abbreviations 125 ° C degree Celsius 126 ° F degree Fahrenheit 127 AWB airway bill 128 BCG Bacille Calmette–Guérin (tuberculosis vaccine) 129 CCM (vaccine) cold chain monitor 3 130 cm cubic centimetres 131 DT Diphtheria–Tetanus vaccine 132 DTP Diphtheria–Tetanus –pertussis vaccine 133 DTP-HepB-Hib Diphtheria–Tetanus –Pertussis, Hepatitis B, Haemophilus influenzae type B 134 ETA Estimated Time of Arrival 135 136 HepB Hepatitis B (vaccine) 137 Hib Haemophilus influenzae type B (vaccine) 138 HPV Human Papillomavirus Vaccine 139 IPV Inactivated Polio Vaccine 140 IATA International Air Transportation Association 141 IVB (Department of) Immunization, Vaccines and Biologicals (WHO) 142 JE Japanese Encephalitis (vaccine) 143 kg kilogram 144 LCD liquid crystal display 145 LRC lot release certificate 146 LSP Logistics Service Provider 147 MMR Mumps–Measles–Rubella (vaccine) 148 MR Measles–Rubella (vaccine) 149 NRA national regulatory authority 150 OCV Oral Cholera Vaccine 151 OPV Oral Polio Vaccine 152 PAHO Pan American Health Organization 153 PCV Pneumococcal Conjugate Vaccine 154 PQS performance, quality and safety 155 PQT Pre-Qualification Team (WHO) 156 RV Rotavirus Vaccine 157 SD Supply Division (UNICEF) 158 SLP summary lot protocols 159 Td Tetanus Toxoid and Diphtheria (reduced component) vaccine 160 TT Tetanus Toxoid (vaccine) 161 UN United Nations 162 UNICEF United Nations Children’s Fund 163 VAR Vaccine Arrival Report 164 VVM Vaccine Vial Monitor 165 WHO World Health Organization 166 YF Yellow Fever (vaccine) 167 168

Page 4 169 Glossary

Definition The first level of container for the vaccine: the vaccine primary Primary packaging container – vial, ampoule, pouch or other. The second level of packaging comprises the intermediate Secondary packaging packaging that contains the primary packages: the vaccine carton box with the vials/ampoules/leaflet. The grouping case is a box in which there are multiple units of Grouping case secondary packaging. The third level of packaging is the shipping unit. The shipping unit is the outer insulated box (protected by a cardboard or plastic Tertiary packaging external layer) that contains the secondary packages or grouping cases. Tertiary packaging shall be the outer shipping unit. Electronic Temperature Electronic device pre-qualified by WHO as a shipping indicator for Monitoring Device use in international shipments of vaccines The logistics provider responsible for the planning and Logistics Service Provider coordination of the international shipment of vaccines

170

Page 5 171 Preface 172 173 174

Page 6 175 1. Insulated Packaging Standards 176

This chapter describes requirements by manufacturers to ensure vaccine packaging is of sufficient quality and performance to: - maintain the integrity of the packaging during international transportation - prevent vaccine loss or damage due to exposure to heat or freezing or physical damage during international transportation

177 1.1 Introduction 178 To protect the vaccines from exposure to both extreme temperatures and physical damage during 179 international transportation, WHO requires manufacturers to pack and dispatch vaccines in an 180 insulated box (shipping unit). The vaccine is kept cool during transport with the use of coolant 181 packs and packed inside the shipping unit 182 183 In addition to the insulation, the design of the shipping unit must be able to withstand the physical 184 conditions encountered during international transportation by air.

185 1.2 Temperature Criteria 186 On the basis of their thermo-stability and presentation, vaccines are classified into three 187 categories (see Table 1) for packaging for international shipments. WHO specifies the minimum 188 and maximum acceptable temperatures to which vaccines in each category can be exposed during 189 international transport. 190 191 As part of the WHO prequalification scheme, vaccine manufacturers are required to ensure that 192 their packaging complies with the appropriate temperature criteria specified below. Qualification 193 data should be produced in three consecutive successful runs. If any changes are introduced in 194 the packaging after qualification, the solution must be re-qualified. 195 196 The temperature criteria listed in Table 1 have been defined to represent temperature exposure 197 situations unlikely to occur outside a temperature-controlled supply chain. These situations may 198 include exposure to ambient temperature extremes during airport tarmac transfer, logistics 199 delays, cold chain equipment breakdown or handling errors, which can be outside the limits 200 described by the manufacturer or as labelled on the outer packaging, but within the limits the 201 temperature excursion allowances as defined by thermo-stability data of the vaccine. 202 203 All vaccine manufacturers are encouraged to validate their Class A and B packaging with frozen 204 icepacks in order to phase out the use of dry ice. 205 206 The validation test protocol is provided in Annex 1.

Page 7 207 1.2.1 Class A packaging - Highly heat sensitive and not freeze sensitive 208 Prior to and at the time of packing, the vaccines must be kept within the storage temperature 209 limits recommended by the manufacturer. 210 The vaccine must be packed to ensure that the warmest temperature inside the insulated package 211 does not rise above +8°C in continuous outside ambient temperatures of +43°C for a period of at 212 least 48 hours.

213 1.2.2 Class B packaging –Heat sensitive and not freeze sensitive 214 Prior to - and at the time of packing, - the vaccines must be kept within the storage temperature 215 limits recommended by the manufacturer. 216 217 The vaccine must be packed to ensure that the warmest temperature inside the insulated package 218 does not rise above +30°C in continuous outside ambient temperatures of +43°C for a period of at 219 least 48 hours. 220 221 Diluents for lyophilized vaccines must always be included with the vaccine shipment in a quantity 222 that matches the quantity of vaccine; diluents however, do not require temperature-controlled 223 packaging unless specifically requested by the manufacturer. Refer Chapter 4 for diluent labelling 224 requirements. 225 226 For lyophilized vaccines bundled in the same packaging as diluents, freezing can only be allowed if 227 supportive data is available to demonstrate that freezing has no impact on the diluent’s safety, 228 quality, potency and presents no risk for the diluent ampoule/vial glass damage.

229 1.2.3 Class C packaging –Heat sensitive and freeze sensitive 230 Prior to and at the time of packing, the vaccines must be kept within the storage temperature 231 limits recommended by the manufacturer. 232 233 The vaccines must be packed to ensure that: 234 235 ▪ the warmest temperature inside the insulated package does not rise above +30°C in 236 continuous outside ambient temperatures of +43°C for a period of 48 and 237 ▪ The coolest storage temperature of the vaccine does not fall below +2°C in continuous 238 external temperatures of -5°C for a period of 48 hours. 239 240 Table 1. WHO classification and temperature criteria for international shipment of vaccines (For a complete 241 classification of vaccines according to their Class of shipping box, please go to Annex XX Type of vaccine (see Minimum Maximum Ambient Class annex 7 for complete temperature temperature Time Criteria temperature list) allowed allowed A OPV +43oC no limit +8oC 48 hours BCG Hib (freeze-dried) B +43oC no limit +30oC 48 hours Measles MR

Page 8 MMR Meningococcal A&C Yellow Fever DT DTP DTP–HepB DTP–Hib (liquid) DTP-HepB-Hib IPV +43oC not applicable +30oC 48 hours JE C HepB Hib (liquid) HPV Td TT 48 hours OCV -5oC +2oC not applicable PCV RV 242 243 1.3 General Packaging Criteria 244 245 Shipping units are defined as an outer insulated box designed to package and transport vaccines 246 during international shipment by air. This can either be an individual insulated shipping carton or a 247 pallet shipper. 248 249 Shipping units must be of sufficient durability to protect vaccines against mechanical manipulation, 250 repeated manual handling and environmental conditions whilst keeping the physical integrity and 251 properties intact, and ensuring carton quality is maintained throughout shipment. 252 253 Ice packs packed inside shipping units must be of satisfactory durability to ensure they do not leak 254 or crack during repetitive or poor handling. 255 256 1.3.1 Insulated shipping cartons 257 258 WHO recommends that each international insulated carton should weigh less than 50kg to ensure 259 ease of handling during transport as they are frequently loaded and offloaded manually at airports 260 and intermediate vaccine stores. 261 262 263 1.3.2 Insulated Pallet Shippers 264 265 Pallet shippers are defined as an outer shipping unit containing secondary packaging or grouping 266 cases designed to package and transport vaccines during export and the international shipment by 267 air. 268

Page 9 269 Pallet shippers have a built in wooden or plastic pallet platform to enable handling and transport 270 by forklift or pallet handling equipment. Pallet shippers will generally accommodate higher 271 volumes of vaccines per unit, and normally with a reduction ratio of coolants to vials. 272 273 It is recommended that external dimensions of pallet shippers for vaccines procured through 274 UNICEF or other UN agencies should not exceed standard ISO pallet sizes: 275 ⋅ US Pallet 1200mm x 1000mm, or 276 ⋅ Euro Pallet 1200mm x 800mm 277 278 Pallet shipper height should not exceed 1600mm.

279 280 It is recommended that pallet shippers are NOT qualified using dry ice as coolant. 281 282 NB: Where manufacturers wish to introduce use of pallet shippers for packaging vaccines for 283 international shipments, the UN procuring agencies must be consulted and the agency will agree 284 to a transition plan upon with respective countries prior to introduction. 285 286 Due to infrastructure and logistics constraints in some receiving countries, manufacturers must 287 ensure smaller pallet shippers or individual insulated cartons can still be supplied as and when 288 required. 289 290 Active packaging systems with a mechanical refrigeration are not to be used for the international 291 shipment of vaccines unless specifically requested by the UN agency. 292

293 294 295 296 297 298 299 300 301

Page 10 302 2. Temperature Monitoring Devices 303 304 This chapter describes the requirements for temperature monitoring devices and required manufacturer practices for using these devices in international shipments to ensure the internal and ambient temperatures of the vaccine packaging are monitored from the manufacturer site until vaccine arrival in the recipient country.

305 2.1 Introduction 306 International shipments of vaccines must be in accordance with the recommendations established 307 by vaccine manufacturer and agreed to by the Logistics Service provider in order to keep the 308 product temperature within the defined range as described by the manufacturer or on the outer 309 packaging. The acceptance of shipments with temperature excursion outside the defined storage 310 temperature limits are addressed by the temperature alarm settings recommended by WHO in 311 this chapter. 312 Temperature monitoring devices should be included in all vaccine shipments to document 313 whether temperature allowance limits have been exceeded. These devices should: 314 1) serve as a quick reference to help recipient countries determine whether the shipment – or 315 parts of the shipment – have been exposed to temperatures at which vaccines could have 316 been damaged; and 317 2) help the procurement agency determine when, where, and to what extent temperature 318 allowance limits have been exceeded. 319 Electronic temperature monitoring devices provide the most reliable and accurate record of the 320 above information. 321 In addition to the temperature monitoring devices placed inside each shipping box mentioned 322 above, WHO now recommends one external data logger to be placed on the “index shipping box”. 323 This data logger ensures that unusual shipping conditions e.g. exposure to ambient conditions on 324 airport tarmac can be easily identified during the investigation of shipment complaint. This data 325 logger must be robustly fixed to the index box in such a way as to prevent any detachment during 326 the shipment. 327 Before accepting a shipment, the recipient should make sure that alarms have not been triggered 328 on the monitoring devices. If there is an alarm in one or more of the temperature monitoring 329 devices, the recipient should contact the procurement agency for action and ensure affected 330 vaccines are stored under the appropriate conditions and segregated under quarantine until 331 further assessment of the impact on the vaccine. 332 The point in time when a temperature excursion has occurred is important for the purchasing 333 agency and the manufacturer so they can identify the cause of the excursion, take corrective 334 measures, avoid similar situations in future shipments, and for insurance purposes.

335 2.2 Electronic Device - General information

Page 11 336 WHO recommends that at least one electronic temperature monitoring device is included in each 337 and every insulated vaccine shipping unit. For shipping units exceeding 800mm in height, it is 338 recommended that two devices should be used and positioned according to the cold and hot spots 339 identified by thermal mapping. 340 Devices must NOT be started more than 72 hours prior to the shipping boxes being sealed 341 dispatch from manufacturer. 342 Diluents that are packaged separately are not required to have a temperature monitoring device 343 except in the case where diluent is freeze sensitive, then each diluent shipping carton requires use 344 of a device that can indicate exposure to freeze conditions. 345 WHO no longer recommends the use of the vaccine cold chain monitor (CCM). ) card. However 346 when batteries for electronic devices do not perform under extremely cold temperatures such as 347 when vaccines are being transported with dry ice, CCM cards may be used. 348 Shipments Use of lithium battery should be avoided (2017 Lithium Battery Guidance Document 349 IATA) as this would require shipments to be labelled as Dangerous Goods.).). 350 351 Table 2. Specifications of the electronic devices for international shipmentsa Storage temperature Range: -25oC to +70oC Operating temperature Range: -25oC to +55oC Display visibility range Range: -10oC to +55oC Temperature measuring accuracy +/- 0.5oC or better Time measuring accuracy +/- 10 seconds per day, or better Logging Interval 10 minutes or less Initial delay (see point 2 below) 1 hour Recording period 40 days Storage before START minimum of 18 months Data retention after STOP minimum of 6 months Battery specification & Labelling Compliant with IATA regulations a For specific devices with these features, refer to the WHO website: http://www.who.int/vaccines-access/pqs.htm

352 353 2.3 Electronic Device Specifications 354 The electronic devices should, at a minimum, meet the specifications outlined in Table 2 (above) 355 and have the functions outlined below. 356 1) A "start" function to activate the device at the time the carton is being loaded with vaccine1. . 357 2) A “stop” function to allow the recipient to stop the recording when the vaccine arrives at its 358 destination. 359 3) A one hour "initial delay" function so the device can acclimatize to the temperature inside the 360 shipping carton before it starts recording.

Page 12 361 4) A "history" function to provide details of violations of the temperature limits in terms of time, 362 range and duration displayed on the LCD screen. This function is primarily to provide 363 information for the use of the procurement agency. 364 5) A USB interface to download a time-temperature graph in PDF format obtained by plug-in and 365 without the need for user to download special software. 366 6) A liquid crystal display (LCD) screen to provide a visual display of the information and also to 367 show the symbol that indicates whether the device is functional or not. This symbol, and also 368 the alarm indicator, should be static (i.e. should not flash or blink) so as to be visible when the 369 screen is scanned or photocopied for documentation purposes. 370 7) An alarm set according to WHO recommended settings (see Tables 3, 4, 5 and 6 below). For a 371 complete classification of vaccines according to type of shipping indicator used, please kindly 372 go to Annex 7. 373 Table 3 (Type 1) WHO-recommended alarm settings for international shipments of DTP, DT, DTP-HepB-Hib, IPV, HPV, JE, 374 TT, Td, OCV, PCV, HepB, RV (Rotarix), liquid Hib and combination vaccines Period for triggering Temperature Alarm type the alarm

High threshold >= 45°C single event 1 hour

Medium threshold >= 30°C cumulative 10 hours exposure

Low threshold <= -0.5°C single event 1 hour

375 376 Table 4. (Type 2) WHO-recommended alarm settings for international shipments of BCG, measles, MR, MMR, 377 meningococcal meningitis, lyophilized Hib, yellow fever and OPV Period for triggering Temperature Alarm type the alarm High threshold >= 45°C single event 1 hour

Medium threshold >= 30°C cumulative 10 hours exposure

Low threshold >= 10°C cumulative 20 hours exposure

378 379 Table 5. (Type Rotateq) WHO-recommended alarm settings for international shipments of Rotateq Period for triggering Temperature Alarm type the alarm High threshold >= 27°C single event 1 minute

Medium threshold >= 17°C cumulative 2 hours exposure Low threshold <= -25°C 1 single 1 minute event

Page 13 380 381 Table 6. (Type Prevnar) WHO-recommended alarm settings for international shipments of Prevnar 382 Period for triggering Temperature Alarm type the alarm High threshold >= 40°C single event 1 hour

Medium threshold >= 30°C cumulative 10 hours exposure Low threshold <= -0.5°C single event 1 hour

383 384 2.3 Electronic Device Instruction Card 385 386 Each electronic device should be attached to a backing card that includes the information outlined 387 below, in the appropriate language. 388 1. The type of device: (see annex 7 for a complete list of vaccines) 389 Type 1: for DTP, DT, DTP-HepB-Hib, IPV, HPV, JE, PCV, Rotarix, TT, Td, HepB, liquid 390 Hib and combination vaccines 391 Type 2: for OPV and freeze-dried BCG, measles, MR, MMR, lyophilized Hib, yellow 392 fever and meningococcal vaccines 393 Type Rotateq: for Rotateq vaccine 394 Type Prevnar: For Prevnar vaccine 395 2. For the person packing/sending the shipment: 396 a. instructions on how to activate the device; 397 b. a reminder that one device must be placed in each shipping carton; 398 c. devices should be numbered to clearly identify corresponding shipping carton for 399 use by recipient 400 d. space for the following information to be entered: 401 ▪ the supplier’s name; 402 ▪ place, date and time of the packing; 403 ▪ vaccine purchase order number; 404 ▪ Number of boxes 405 ▪ vaccine type; 406 3. For the person receiving the shipment: 407 a. instructions on how to stop the device; 408 b. illustrations to show information on the LCD screen – how it will indicate 409 problems/no problems and the alarm-status display; 410 c. Tables 5 and 6 (below) showing what to do.

Page 14 411 Table 57. Information to be displayed on the backing card of electronic device – Type 1 (for DTP, DT, DTP-HepB-Hib, IPV, 412 JE, HPV, OCV, PCV, Rotarix, TT, Td, HepB, IPV, liquid Hib and combination vaccines) 413 Alarm What to do with vaccines temperature >=45oC Contact procurement agency >=30oC Contact procurement agency Conduct shake testa. USE vaccine if passes. <=-0.5oC Inform procurement agency of alarm and of test result. a Shake test guidelines are given in Annex 2.

414 Table 6. Information to be displayed on the backing card of electronic device – Type 2 (for OPV and freeze-dried BCG, 415 measles, MR, MMR, lyophilized Hib, yellow fever and meningitis vaccines) 416

Alarm What to do with vaccines temperature OPV Other vaccines >=45oC Contact procurement agency Contact procurement agency >=30oC Contact procurement agency Contact procurement agency >=10oC Contact procurement agency Accept 417 418 Table 7. Information to be displayed on the backing card of electronic device – Type Rotateq Alarm What to do with vaccines temperature >=27oC Contact procurement agency >=17oC Contact procurement agency <=-25oC Contact procurement agency 419 420 Table 8. Information to be displayed on the backing card of electronic device – Type Prevnar 421 Alarm What to do with vaccines temperature >=45oC Contact procurement agency >=30oC Contact procurement agency <=-5oC Contact procurement agency 422 423 424 Note on decimal rounding: During storage and distribution of vaccines, in different temperature 425 scale with 0, 1 or 2 decimal places, it is recommended to apply rounding rules to evaluate 426 reported temperature data expressed in whole numbers to be aligned with controlled cold 427 temperature limits reported without decimals as mentioned in international pharmacopeias and 428 guidelines. 429 430 When rounding is required, consider only one digit in the decimal place to the right of the last 431 place in the limit expression. If this digit is smaller than 5, it is eliminated and the preceding digit is

Page 15 432 unchanged. If this digit is equal to or greater than 5, it is eliminated and the preceding digit is 433 increased by 1". In any case, numbers should not be rounded until the final calculations for 434 reportable value 435

436 3. Labelling for International

437 Shipments 438

This chapter describes labels that must be attached by the vaccine manufacturer to different packaging levels for international shipments.

439 440 3.1 Labelling for Secondary packaging 441 A label must be affixed either to the top and/or front surface of the secondary package. It should 442 indicate the type of vaccine, the name of the manufacturer, presentation, batch number, date of 443 manufacture, date of expiry, quantity and storage conditions. Labels for secondary packaging of 444 both diluents and OPV droppers must also indicate above details 445 446 3.2 Labelling for Grouping case 447 A label must be affixed either to the top and/or front surface of the grouping case. It should 448 indicate the type of vaccine, the name of the manufacturer, presentation, batch number, date of 449 manufacture, date of expiry, and storage conditions. 450 451 3.3 Labelling for Shipping unit 452 The external surface of insulated shipping units should be either white or in the natural colour of 453 corrugated carton or plastic. Dark colours must be avoided. 454 A label must be affixed to the front surface of each package indicating type of vaccine, name of 455 manufacturer, presentation, batch number, date of manufacture, date of expiry, quantity, and 456 storage conditions. The manufacture date and expiry date on all labels should be written in full, 457 not in a coded form (i.e. June 2017, not 06.17). 458 Required temperature conditions for transportation must be clearly visible on the outer carton, 459 indicating clearly where recommended transportation temperatures differ from recommended 460 storage temperatures. 461 In addition to above the following labelling requirements must be met: 462 i. “Vaccine Rush” Label 463 A label must be affixed to each face of the vaccine package in a language appropriate to 464 the country of destination (e.g., in English: “Vaccine Urgent”; in French: “Vaccin Urgent”; in 465 Spanish: “Vacuna Urgente”; in Portuguese “Vacinas – Urgente”etc.). 466 ii. “Do Not Freeze” Label

Page 16 467 A label must be affixed to each face of the vaccine package in a language appropriate to 468 the country of destination as follows: 469 a) Shipping units containing freeze-sensitive vaccines (DTP,DT,DTP-HepB-Hib, IPV, 470 PCV, HPV, RV, OCV, Td, TT, IPV liquid Hib and hepatitis B vaccines, or combinations 471 containing any of these), 472 b) Shipping units containing freeze-sensitive diluents, and 473 c) Shipping units containing OPV droppers where droppers are at risk of being 474 damaged by freezing. 475 iii. IATA Time and Temperature Sensitive Label 476 The IATA Time and Temperature Sensitive Label is a shipment label specific to the 477 healthcare industry that must be affixed to all shipping units booked as time and 478 temperature sensitive cargo. It is the responsibility of the manufacturer to ensure the label 479 is applied properly to each shipping unit indicating approved transportation temperatures, 480 and in accordance with IATA Guidelines. 481 iv. Shipping documents should be included in the box labelled Number 1, and this box 482 should be clearly labelled with the words "Containing vaccine shipping documents". 483 All insulated shipping units should be numbered consecutively and box numbers shall not be 484 repeated for shipments containing boxes of droppers or diluents shipped in the same 485 consignment as vaccines. There shall be only one box Number 1 per shipment. 486 Manufacturers should indicate on the outer carton where boxes are not stackable or maximum 487 stacking height, where applicable. 488 Where dry ice is used as a coolant, labelling and marking should be in accordance with IATA 489 Dangerous Goods Regulations. 490 Note: Where diluents are required to be stored at ambient temperature, they can be booked at 491 +2°C to +8°C for the practical reason that they are shipped with the vaccine on the same Airway Bill. 492 (AWB). IATA regulations do not allow two or more different temperatures on the same AWB. 493 494 3.4 Bar-coding 495 496 WHO does not currently require bar codes on the shipping units but vaccine manufacturers should 497 comply with GS1 standards and associated specifications if used. Bar code data should include: 498 Purchase order number, Purchase order item, Material Number, quantity, Batch Number, Batch 499 manufacturing date and Batch expiry date. 500 501 502 503 504 505

Page 17 506 507 508 509

510 4. International Shipping Procedures

511 The arrival of a vaccine shipment in a country, its subsequent clearance through customs and 512 transportation to the central vaccine store are the most critical stages in the shipping process. These 513 are frequently the times when mistakes and delays occur, resulting in damage to the vaccines. The 514 smooth arrival and handling of vaccine shipments depends on the manner in which each step in the 515 delivery process is performed. Because numerous parties are involved (UNICEF Supply Division, 516 other UN agencies, the manufacturer, the forwarder, the airline, the UN country office, customs 517 authorities, clearing agents, or the national immunization service, etc.), and because of the need to 518 communicate accurate, time-sensitive information, it is essential to have strict guidelines to 519 determine and assign responsibilities at every step of the process. These are described in the 520 general terms and conditions of the tender documents and are further detailed in individual 521 contracts. The specific conditions depend on the country of destination.

522 5.1 Temperature Control during international Transportation

523 Vaccines must be kept in temperature-controlled environments at all times throughout the 524 shipment process including in transit storage points/warehousing. Carriers selected for vaccine and 525 temperature controlled shipments must be able to provide a reliable temperature control service. 526 All vaccines must be booked and shipped at +2°C to +8°C ambient temperature, or otherwise as 527 specified by manufacturer or indicated on shipping unit labels.

528 It is prohibited to send vaccines or diluents by general cargo. Shipment of droppers as general cargo 529 must be agreed in advance with the UN agency and manufacturer. 530 Vaccines should not be transported with radioactive products, fish or meat. 531 Re-icing of shipments must be performed in accordance with the written instructions of the 532 manufacturer of each shipment whenever deemed necessary. 533 5.2 Route and arrival dates 534 Vaccines should travel by the fastest and most direct route wherever possible. Where trans- 535 shipment is unavoidable, the journey should be planned through airports that have adequate cold 536 storage facilities. 537 If the route deviates significantly from the standard routing, or delays are expected, the Logistics 538 Service Provider shall contact the UN agency in advance. 539 Shipments should be scheduled to arrive outside weekends and/or public holidays in the recipient 540 country and airline bookings should be made well ahead of the date of departure and as specified 541 by the UN procurement agency. Any additional requirements regarding arrival times must be

Page 18 542 stated in the contract between UNICEF and/or the other UN agencies or manufacturers and the 543 designated freight forwarder. 544 Consolidation or splitting of consignments is not permitted unless approved in advance by the UN 545 agency. 546 5.3 Advance shipment arrival notification 547 It is the obligation of the Logistics Service Provider to inform the consignee and all requested 548 “notify parties” of all shipment details in advance of the shipment, in a format pre-defined by the 549 UN agency. Required documentation for the shipment must be sent at least seven days2 in 550 advance of arrival of the shipment, or as otherwise specified by the UN agency. 551 The documentation must include the following: 552 ▪ Pre-advice cover page defined by UNICEF, PAHO and/or the other UN agencies; 553 ▪ Airway Bill (AWB); 554 ▪ Supplier’s Invoice; 555 ▪ Packing List; Packing slip correlating information of electronic shipping devices with the 556 insulated shipping unit (PAHO). 557 ▪ Lot Release Certificate (LRC) issued by the national regulatory authority (NRA) of the 558 country of manufacture for each lot of vaccine supplied; and 559 ▪ Certificate of Pharmaceutical Product 560 ▪ Summary protocol of production and quality control 561 ▪ any other document, certificate or instruction specified in the purchase order. 562 The documents should be sent by e-mail by the Logistics Service Provider to the consignee, the 563 UNICEF or UN agency country office in the receiving country, Vaccine Centre, UNICEF Supply 564 Division for UNICEF shipments and any other parties specified in the individual contract. 565 The pre-advice must contain the following information: 566 ▪ Purchase Order reference; 567 ▪ consignee requisition reference; 568 ▪ number of packages, gross weight (in kilograms) and volume (in cubic metres); 569 ▪ type of vaccine, total number of primary containers and number of doses per primary 570 container; 571 ▪ value of shipment (in US$); 572 ▪ AWB and flight number(s); 573 ▪ date and time for place of departure, transit (if applicable), and arrival; 574 ▪ instructions for collection; 575 ▪ any other information specified in the purchase order must also be included for the 576 consignee.

2 This period must include at least five working days.

Page 19 577 The following information shall be stated on the AWB: 578 ▪ consignee’s name, address and telephone number; 579 ▪ Purchase Order reference; 580 ▪ consignee’s requisition reference; 581 ▪ type of vaccine and quantity; 582 ▪ Handling information: “Vaccine – For human use – Highly perishable – Not to be delayed”. 583 For all vaccines the following instruction should be stated in the AWB: “Throughout shipment, 584 pending reshipment and prior to collection by the consignee, the vaccine must be transported at 585 +2°C to +8°C”. 586 House Airway Bills (HAWB) are not permitted unless approved in writing in advance by UNICEF, 587 PAHO and/or other UN agencies. 588 Vaccines are not to be advance shipped or arrive earlier than notified ETA. 589 Insulated shipping units are not to be opened in transit by the Logistics Service Provider, with the 590 exception of the requirement for re-icing as agreed with manufacturer. Electronic devices are not 591 to be stopped by the LSP until receipt by consignee in recipient country, unless otherwise agreed 592 by , PAHOUN agency. 593 If any shipment incurs loss or damage during transit, the Logistics service provider, manufacturer, 594 freight forwarder or consignee shall inform UNICEF, PAHO or UN agency immediately to provide 595 the shipment details and the estimation of the loss and damage to initiate the insurance claims 596 process. 597 5.4 Documents that accompany shipment 598 The following original documents must accompany the consignment when it is shipped. One set of 599 the following original documents must also be placed inside the shipping unit numbered “1”: 600 ▪ Signed and/or stamped supplier’s invoice; 601 ▪ Packing List; 602 ▪ Lot Release Certificate and lot summary protocol issued by the national regulatory 603 authority of the country of manufacture for each lot of vaccine supplied; (signed and/or 604 stamped) 605 ▪ Vaccine Arrival Report (VAR) for UNICEF shipments 606 ▪ any other documents, certificates or instructions specified in the purchase order. 607 The shipping unit containing the documents should be clearly labelled with the words "Containing 608 vaccine shipping documentation". 609 The lot release certificate/s from the national regulatory authority (or from the national control 610 laboratory) of the producing country should be included for each lot contained in the shipment. 611 The lot release certificates are considered to be the only evidence that the lots received have 612 been released by the regulatory authority of the producing country. Vaccines delivered without a 613 lot release certificate cannot be accepted and must be kept on hold under appropriate storage 614 conditions. In such cases, the lot release certificate/s should be requested and provided 615 immediately by the manufacturer.

Page 20 616 5. Vaccine Arrival Report

617 Vaccine Arrival Report (VAR) is a means of monitoring international shipments of vaccines in order 618 to ensure that shipping guidelines are followed and that vaccine quality is maintained. The VAR 619 provides a means of indicating any inadequacies in the shipping process and problems relating to 620 the condition of vaccines at the time of delivery (see Annex 5). UNICEF and/or WHO officers 621 should support with recipient governments to ensure that the VAR is duly completed by 622 authorized staff, checked and verified by the immunization program manager, and forwarded to 623 UNICEF within three working days of the arrival of the vaccine. In the case of combined shipments, 624 a separate report should be filled in for each vaccine in the shipment.

625 For countries receiving vaccines through UN agencies, all complaints should be sent immediately 626 to the local country office of the procurement agency for them to follow up with their 627 procurement organization. Depending on the nature of the complaint, the procurement agency 628 may handle the issue itself or may request assistance from WHO. For countries procuring vaccine 629 directly, all complaints should be handled directly with the vaccine manufacturer; WHO assistance 630 can, however, be sought if required, for WHO prequalified vaccines (?).

631 Table 9 sets out the vaccine arrival and complaints procedures for vaccines procured by UNICEF. 632 These procedures may be adapted for other procurement routes. 633 634 Table 9. Procedure for reporting UNICEF vaccine arrivals 635 Arrival of vaccines and customs clearance ↓ Inspection at Central cold stores. VAR completed and signed. ↓ Copy of VAR sent to UNICEF country office or Supply Division (SD), Copenhagen. ↓ INDICATOR OK DEFECTIVE Advance notification Recorded UNICEF to follow up with Freight Forwarder Vaccine type/expiry Recorded UNICEF to follow-up with manufacturer Eventual report to WHO Pre-Qualification Team Biologicals (PQT) for further investigation if necessary. Documents accompanying the Recorded UNICEF to follow-up with Freight Forwarder or manufacturer. shipment Eventual report of problems related to lot release certificate to WHO PQT. Quantities received Recorded UNICEF to follow-up with Freight Forwarder/manufacturer Status of temperature Recorded UNICEF to report to WHO PQT; investigation to be carried out. UNICEF indicators to initiate claims process. Temperature monitors to be retained by consignee.

636 Any defect in the process can lead to a complaint, claim and/or rejection of a shipment. Each 637 individual situation will be investigated and dealt with by all involved parties. 638 If the quantity of damaged vaccine is substantial it could affect immunization delivery. In such 639 cases, emergency measures will have to be taken to obtain sufficient vaccine to maintain the 640 program’s scheduled activities.

Page 21 641 Annex 1:

642 Guidelines to confirm that packaging 643 complies with WHO recommendations 644 645 646 1. Introduction

This procedure referred to as “qualification” is the measurement and/or confirmation that temperatures inside the shipping containers of every vaccine shipment remain within the defined temperature range (for the specific vaccine/s being transported) for a period of 48 hours according to the packaging class A,B or C

647 648 As part of the WHO vaccine prequalification process, vaccine manufacturers must document the 649 qualification of their packaging. 650 Qualification data should be produced for three successful consecutive tests at the defined 651 ambient temperatures for the period of time mentioned in the Table 10. If changes are introduced 652 either in the packaging or the shipment procedures, the shipment must be validated again and 653 submitted to WHO PQT (for review/file/information). 654 Table 10: Test temperature and established criteria for class A, B and C vaccines for validation of the packaging Type of vaccine (see Class annex 7 for Ambient temperature Minimum Maximum Time Criteria complete list) A OPV +43oC no limit +8oC >=48 hours BCG Hib (freeze-dried) measles MR B +43oC no limit +30oC >=48 hours MMR meningococcal A&C yellow fever DTP DTP–HepB +43oC n/a +30oC >=48 hours DTP–Hib (liquid) DTP-HepB-Hib DT IPV C HPV OCV JE -5oC +2oC n/a hours PCV RV HepB Hib (liquid)

Page 22 Td TT As above 655 Temperatures within the container should be continuously monitored within an accuracy of ± 656 0.5ºC; the sensors used for this purpose must not be allowed to influence the test in any way. A 657 minimum of 8 simultaneous temperature measurements are required for an insulated box (see 658 figure below). The ambient temperatures at which the insulated box is tested must remain within 659 a tolerance of ± 1ºC. 660 Locations of temperature sensors for insulated containers 661 a) Insulated container: top view

x 1, 2 3, 4 x

x 6, 7 8, 9 x

662 663 b) Insulated container: side view 664

Lid

x 1, 6 3, 8 x

x 5

x 2, 7 4, 9 x

Page 23

665 2. Loading 666 The qualification must be done with a minimum vaccine thermal mass representative of a full 667 transportation load configuration. Coolant packs and product temperature must be conditioned as 668 per normal use. Water-based placebo can be used to mimic the vaccine thermal mass. 669 In the case of a vaccine manufacturer having more than one type of vaccine in one category, 670 testing with any of the listed vaccine is acceptable. The validation does not need to be repeated 671 with other presentations. 672 Insulated boxes should be fully loaded with vaccine vials conditioned at +5ºC ±3ºC. Loads can be 673 pre-fitted with thermocouples. Loading should be carried out as quickly as possible and the time 674 taken for loading should be recorded and reported for each container. 675 3. Temperature recording 676 The internal temperature of an insulated container is recorded at specified points within the load 677 during the validation tests. The figure above shows the position of these points, each of which is 678 2.5/3.0 cm from the nearest icepack surface, with the exception of the central points. 679 Thermocouples should be attached to the outside of the vials and should not be inserted into the 680 vials. Thermocouple leads can be introduced into the secondary packaging container either: 681 ▪ through the seal – taking care not to affect the quality of the seal; or 682 ▪ through a hole in the geometric centre of the lid or of one of the sides of the container – 683 taking care to adequately seal the outer and inner openings. 684 4. Reporting 685 An initial validation report should be sent to WHO along with the dossier submitted for 686 prequalification or in case of changes for reassessment or as part of a variation submission 687 relating to a change in packaging configuration. It should include: 688 ▪ standard operating procedure (or test protocol) used for the validation; 689 ▪ start date, end date and time of the three consecutive validation runs; 690 ▪ conditioning temperature of the product and gel packs used in the test 691 ▪ detailed information on external and internal dimensions of insulated container, type of 692 material it is made of, weight empty and weight fully loaded (total weight); information on 693 the probes distance from the nearest icepack surface should also be provided 694 ▪ detailed temperature history for all tests in tabular format (for all internal and external 695 ambient channels). 696

Page 24 697 Annex 2: 698 Shake test protocol 699 700 Purpose 701 The shake test is designed to determine whether some adsorbed vaccines with aluminum 702 phosphate/hydroxide formulations have been affected by freezing. After freezing, the lattice 703 (bond between adsorbent and antigen) gets broken. Separated adsorbent tends to form granules 704 that get bigger in particle size and weight then gradually settle to the bottom after the vial has 705 been shaken. The size of the granules seems to increase after repeated freezing and thawing 706 cycles. Sedimentation occurs faster in a vaccine vial that has been frozen than in a vaccine vial 707 (from the same manufacturer) that has never been frozen. 708 Individual batches of vaccine may behave differently from one another. The test procedure 709 described below should, therefore, be repeated with all suspect batches. In the case of 710 international arrivals, whenever there is an indication that temperatures have dropped below 711 zero, the shake test should be conducted on a random sample of vaccines. However, if there is 712 more than one lot of vaccine in the shipment, the random sample must include a vial taken from 713 each and every lot. 714 Test procedure

715 1. Take a vial of vaccine of the same type and batch number as the vaccine you want to test, and 716 made by the same manufacturer. This is your control vial. 717 2. Clearly mark the control vial: “FROZEN.” 718 3. Freeze the control vial at -20oC overnight, until the contents are completely solid. 719 4. Let the control vial thaw. Do not actively heat it! 720 5. Take a “test” vial from the batch that you suspect has been frozen. 721 6. Hold the control (“frozen”) vial and the “test” vial together in one hand. 722 7. Shake both vials vigorously for 10–15 seconds. 723 8. Place both vials on a flat surface side-by-side and start continuous observation of the vials until 724 the test is finished. (If the vials have large labels that conceal their contents, turn both vials 725 upside down and observe sedimentation in the neck of each vial.) Observation period must be 726 a minimum period of 24 hours. 727 9. Use an adequate source of light to compare the sedimentation rates between vials. 728 Conclusion 729 If sedimentation is slower in the “test” vial than in the control (“frozen”) vial, the vaccine has not 730 been damaged. Use the vaccine. 731 If sedimentation is similar in both vials, or if sedimentation in the “test” vial is faster than in the 732 control (“frozen”) vial, the vaccine has been damaged. Do NOT use the vaccine. Notify your 733 supervisor.

Page 25 734 735 The figure below shows the difference between a control (“frozen”) vial and a (non-frozen) test 736 vial. 737 738 Seeing the difference in sedimentation rates during a shake test 739 740 741 742 10:25 am 1

743 744

745 Test vial 746 747

748 10:28 am 2 749 Frozen control vial 4 minutes after placing 750 the vials on the table

751 752 753 754 10:31 am 755 3 756 757 758 759 760 761 10:33 am 762 4

763 764

765 Sedimentation in test vial is slower than in the frozen control 766 vial. Test vial has not been damaged and can be used. 767 768 769

Page 26 770 Annex 3:

771 List of contact points for national regulatory authorities in 772 countries producing vaccines prequalified for purchase by 773 United Nations agencies 774 775 American Region 776 777 Argentina 778 Administración Nacional de Medicamentos, 779 Alimentos y Tecnología Médica (ANMAT) 780 Ministerio de Salud y Acción Social 781 Avenida de Mayo 869 (C1084AAD) 782 Ciudad Autónoma de Buenos Aires 783 T: 54 11-4340-0800 / 5252-8200 784 F: 54 1 342 1997 785 Website: http://www.anmat.gov.ar/ 786 787 Canada 788 Bureau of Biologics and Radiopharmaceuticals (BBR) 789 Health Protection Branch (HPB) 790 Health Canada 791 L.C.D.C Building # 6 (0603 C) 792 Tunney’s Pasture 0603C 793 Ottawa, Ontario K1A OL2 794 795 United States of America 796 Food and Drug Administration 797 Center for Biologics Evaluation and Research 798 1401 Rockville Pike, Suite 2000 799 Rockville, MD 20852 800 801 Brazil 802 Agencia Nacional da Vigilancia Sanitaria (ANVISA) 803 Esplanada dos Ministerios, Bloco G, 9o andar, sala 900 804 cep: 70058-900 Brasilia DF 805 T: 882 5328 F: 801 5330 806 E-mail: [email protected] 807 Website: http://www.anvisa.gov.br 808 809 Cuba 810 Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED) 811 Calle 5ta A #6020 e/ 60 y 62. Miramar, Playa. Código postal: 11300 812 La Habana

Page 27 813 T: (+53) 7 216 4100 814 E-mail: [email protected] 815 Website: http://www.cecmed.cu/ 816 817 818 819 Europe 820 821 Belgium 822 General Pharmaceutical Inspectorate 823 Ministry of Social Affairs, Public Health and Environment 824 Bd Bishoffsheim 33 825 1000 Brussels 826 827 Bulgaria 828 Bulgarian Drug Agency 829 26 Yanko Sakazov Blvd 830 1504 Sofia 831 832 Denmark 833 Danish Medecines Agency 834 Axel heides Gade 1 835 2300 Kobenhavn 5 836 837 France 838 Agence française de Sécurité Sanitaire des Produits de Santé 839 Direction de l'Inspection et des Etablissements 840 143-147 Boulevard Anatole France 841 93285 Saint Denis Cedex 842 843 Hungary 844 Italy 845 Ministero della Salute 846 Lungo Tevere Ripa 1 847 00153 Roma 848 849 Germany 850 Paul-Ehrlich-Institut 851 Paul Ehrlich Strasse 51–59 852 Postfach 1740 853 D-63225 Langen 854 855 Switzerland 856 857 United Kingdom 858 Medicines and Healthcare Products Regulatory Agency (MHRA) 859 Department of Health

Page 28 860 Market Towers 861 1 Nine Elms Lane 862 London SW8 5NQ 863 864 Oceania 865 866 Australia 867 Therapeutic Goods Laboratories (TGAL) 868 Therapeutic Goods Administration 869 P.O. Box 100, 870 Woden ACT 2606 871 872 873

Page 29 874 Asia 875 876 India 877 Drugs Controller General of India, DCG(I) 878 Directorate General of Health Services 879 Ministry of Health and Family Welfare 880 Nirman Bhawan, New Delhi 110 011 881 Government of India 882 883 Indonesia 884 Directorate General of Drug and Food Control 885 Ministry of Health 886 Jalan Percetakan Negara 23 887 Jakarta Pusat 10560 888 889 Japan 890 Pharmaceutical and Medical Safety Bureau 891 Ministry of Health, Labour and Welfare 892 1-2-2 Chome, Kasumigaseki 893 Chiyoda-ku 894 Tokyo 100–8916 895 896 Republic of Korea 897 The Korea Food and Drug Administration (KFDA) 898 5 Nokbun-Dong Eunpyung-Ku 899 Seoul 900 901 China 902 China Food and Drug Administration (CFDA) 903 Building 2 904 26 Xuanwumen Xidajie 905 Beijing 100053 906 People's Republic of China 907 Website: http://www.sfda.gov.cn/eng/ 908 909 Africa 910 911 Senegal 912 Direction de la Pharmacie et du Medicament (DPM) 913 Ministere de la Sante Publique 914 153 rue Mousse Diop 915 B.P 6150, Dakar 916 Tel: +2218224470 917 Fax: +2218210910 918 919 920

Page 30 921

922 Annex 5: 923 Vaccine Arrival Report (VAR) 924 This report is to be filled in by authorized staff, ratified by the Store Manager or the EPI Manager, and forwarded to the UNICEF within 925 three working days of vaccine arrival. Use one report for each vaccine in the shipment. 926 COUNTRY REPORT No. Date of report 927 Place, date and time of inspection Name of cold store, date and time vaccines entered into cold store

928 929 PART I — ADVANCE NOTICE 930 Date received Copy airway bill Copy of packing Copy of release MAIN DOCUMENTS Copy of invoice by consignee (AWB) list certificate Pre-advice shipment notification Yes No Yes No Yes No Yes No 931 List other documents (if requested) 932 933 PART II — FLIGHT ARRIVAL DETAILS 934 Airport of ETA as per notification Actual time of arrival AWB Number Flight No destination Date Time Date Time

935 936 NAME OF CLEARING AGENT: ______ON BEHALF OF: ______937 938 PART III — DETAILS OF VACCINE SHIPMENT 939 Purchase Order Vaccine description Consignee Manufacturer Country No. (Type and doses/vial)

940 Vaccine Diluent/droppers Number of Number of Number of Number of Lot Number Expiry date Lot Number Expiry date boxes vials boxes units

941 (Continue on separate sheet if necessary) 942 Yes No Comments Was quantity received as per shipping notification?

If not, were details of short-shipment provided prior to

vaccine arrival?

943 944 1 Adopted from the Standard UNICEF Vaccine Arrival Report from WHO Guidelines on the international packaging and shipping of 945 vaccines (WHO/IVB/05.23) 946 No. = Number 947 WHO recommends all UN agencies, countries and non-governmental organizations procuring vaccines adopt this report.

Page 31 Report No. 948 949 PART IV — DOCUMENTS ACCOMPANYING THE SHIPMENT 950 Invoice Packing list Release certificate Vaccine Arrival Report Other Yes No Yes No Yes No Yes No

Comments 951 952 PART V — STATUS OF SHIPPING INDICATORS 953 Total number of boxes

inspected:

Coolant type: Dry ice Icepacks No coolant Temperature monitors VVM Cold-chain card Electronic device Type: ______present: 954 955 956 PROVIDE BELOW DETAILS OF STATUS ONLY WHEN PROBLEMS ARE OBSERVED 957 (in addition fill in ALARM REPORTING FORM if there are any ALARMS in electronic devices): 958 Box Alarm in electronic device Cold-chain monitor LOT NO Date/time of inspection Number >=450C >=300C >=100C <=-0.50C A B C D

959 (Continue on separate sheet if necessary) 960 Note: For shipments of certain types of PCV and Rotavirus, alarm settings on the temperature monitor device may be different than those listed above. If different alarms are 961 recorded, please provide comments in General Conditions of Shipment section. 962 963 PART VI — GENERAL CONDITIONS OF SHIPMENT 964

What was the condition of boxes on arrival?

Were necessary labels attached to shipping boxes? Other comments including description of alarms in electronic devices:

(continue on separate sheet if necessary)

965 966 PART VII — NAME AND SIGNATURE 967 968 969 Authorized Inspection Supervisor DATE Central store or EPI Manager DATE 970 For UNICEF Country Office use only

Date received by Country Office: ______Contact Person:______

Page 32 971 Guidelines for completing the Vaccine Arrival Report 972 973 The Vaccine Arrival Report (VAR) is a comprehensive record of cold-chain conditions during transport and of required compliance 974 with shipping instructions. Recipient governments and procurement agencies (UNICEF country offices, UNICEF Supply Division, 975 PAHO Revolving Fund), are responsible for the report, and for taking appropriate action if problems are reported (e.g. follow-up 976 with the manufacturer, forwarding agent, WHO, etc.). 977 Use one report form for each shipment and for each vaccine in the shipment. In the case of short-shipments (where parts of the 978 original quantities are not delivered), complete a separate report for each part delivered. 979 Complete the form as described below. In the header boxes at the top of the form, enter the name of the recipient country, the 980 report number, and details of place and date of inspection and storage. The report number is an internal number for organizing 981 records; compile it as follows: country code; year; number for each report (e.g. BUR–2005–001 for one vaccine; BUR–2005–002 for 982 a second vaccine, etc.). In the case of a short-shipment, the numbers for the separate deliveries would be, for example, BUR– 983 2005–003.1, BUR-2005-003.2, etc. 984 Part I — Advance notice Inspect the temperature monitors in all boxes I.1 Enter dates and details of documents received before putting vaccines into cold storage. For very in advance of the vaccine shipment. large shipments, or when immediate storage in the Part II — Flight arrival details shipping boxes is required, check a representative II.1 Fill in details of expected and actual arrival number of boxes before placing the shipment in the times for the shipment. cold store. Complete inspection of all boxes the next II.2 Fill in the name a) of the clearing agent and b) day, or as soon as possible thereafter; under for whom the agent acts (e.g. the Ministry of Comments, note the date and time when the Health, UNICEF or WHO). complete inspection took place. Part III — Details of vaccine shipment Note: In this report, enter the information below III.1 Fill in details of the order (purchase order (V.1) only for boxes in which the temperature number, consignee, vaccine description etc.). monitor shows a change that indicates potential III.2 For each batch of vaccine included in the damage to vaccines (alarm indication in the shipment, record: electronic device, or cold-chain monitor card as per a) the number of shipping boxes; vaccine/threshold table in card). b) the number of vials; V.1 Enter: c) the expiry date. a) the number of boxes inspected (this The number of boxes you enter should always should equal the total number in the match the number of boxes shown in the packing shipment); list. If it does not, note under Comments if advance b) the type of coolant used; notice of a change in the quantity was provided. It is c) details of any temperature exposure not necessary to count the number of individual detected. vaccine packs in each shipping box for this report. V.2 Photocopy or scan LCD screens in electronic III.3 For the diluents and droppers (if included) in devices that show alarm status and attach to the shipment, record: the report. a) the number of shipping boxes; V.3 Clearly identify vaccines in boxes in which the b) the number of vials; indicator shows exposure to temperatures c) the expiry date. that risk damage and keep them in the cold The information for III.2 and III.3 is also in the room for further assessment of their packing list. condition. Do not discard vaccines until Note: Diluents for freeze-dried vaccine and assessment is completed. droppers for oral polio vaccine (OPV) are integral PART VI — General conditions of shipment parts of the vaccine, so always include them on the VI.1 Indicate if the shipping boxes were received in same form. If diluent/droppers are delivered good condition and if all necessary labels on separately, consider it a short-shipment. the outside of the shipping boxes were Part IV — Documents accompanying shipment present; add any comments. The packing list should indicate which box contains PART VII — Name and signature the shipping documents (usually Box 1). VII.1 The authorized person responsible for the IV.1 If this information is not included in the inspection and the Central Store Manager or packing list or in documents sent separately the EPI Manager should sign this report. by courier, pouch or other means, note this VII.2 Send the form, completed and signed, to the under Comments. UNICEF within three days of arrival of the IV.2 Verify that all necessary documents are vaccine. present and complete the form accordingly. Note: If the lot release certificate is missing, do not use the vaccines; keep them on hold in cold storage until the relevant document has been obtained from the vaccine manufacturer. PART V — Status of shipping indicators

Page 33

Electronic Alarm Report Form

Reporting alarm details in UNICEF international vaccine shipments

A special form has been designed for the purpose of reporting alarm details displayed in electronic devices. This form should ONLY be filled in if any alarms have occurred, and should be attached to the Vaccine Arrival Report (VAR). A clear photocopy and/or printed copy of the scanned image of the electronic devices displaying alarm status should be attached to this form.

Country: Date of Report: Vaccine: Compiled by:

Type of device Q-Tag2Plus ☐ Q-Tag Clm ☐ VaxAlert ☐ TIC20 Other ☐ ☐ Elapsed Box Time >=450C >=300C >=100C <=-0.50C Serial No transit Other No stopped 1 hour 10 hrs 20 hrs 1 hr time Time oC Time oC Time oC Time oC Time oC

Note: For shipments of certain types of PCV and Rotavirus, alarm settings may be set at different thresholds than those listed on the VAR and alarm reporting form. In the case of these alarms, please comment in “Other” column. Use additional pages if necessary.

Guidelines for completing the Electronic Device Alarm Report Form

Country Enter name of the country Date of report Enter date of report Type of device Mark the type of device by ticking the appropriate box Type of vaccine Enter the type of vaccine, e.g. BCG, OPV, HepB, etc. Box number Write the number of the box (carton) that the electronic device was taken out of, e.g. 001, 002…099.

Serial number Write down the serial number of the electronic device from the bar code/serial number, e.g. 10000001 Time stopped Enter the local time you stopped this particular device in 00hrs:00min format Elapsed transit time Enter elapsed transit time Time Enter time displayed in HISTORY mode for each alarm. oC Enter minimum or maximum temperatures displayed for each alarm, e.g. 34.7oC, 13.5oC, or -0.5oC If any of the alarms are repeated in the same electronic device, enter this information in a new row.

Annex 6: PAHO Form 183 - Confirmation of Arrival of Shipments

Acknowledgement of Shipment Arrival. Within 24 hours of the shipment’s arrival at the destination airport, the consignee must acknowledge via email the arrival of goods to PAHO’s Country Office. Acknowledgement does not imply acceptance of the goods; it simply indicates arrival of the goods. Therefore, acknowledgement should not be delayed pending final determination of acceptance. If subsequently the goods are found to be damaged or incomplete, the prior acknowledgment of arrival will not interfere with the claim process, provided the claim is reported within 72 hours of the delivery of the shipment.

Confirmation of Arrival. The consignee will confirm arrival of shipment by filling electronically or by hand PAHO Form 183 (the last page of the purchase order) or a statement written on the consignee’s letterhead. The consignee will email this form to the PAHO Country Office Procurement Focal Point. This acknowledgement will reference the purchase order (PO) number, awb information, date of arrival and any remarks about the shipment conditions on the bottom of the form. The clearance and claim of vaccines from customs facilities must be immediate.

Delayed Arrival. Consignees shall acknowledge vaccines’ arrival as described above. For shipments that have not arrived within 24 hours after the date indicated in the shipping details, the consignee will initiate tracing of shipments locally with the responsible airline or freight agent. The consignee immediately will notify the PAHO Country Office, via email.

Verification of Shipment. Complete verification of vaccines shipments will take place within 72 hours of delivery. Verification means the act of opening boxes and confirming that the contents are in good order. The consignee also will inform the PAHO Country Office of any alarm being displayed on temperature monitors or if monitors are not included in shipment as required.

Cold Chain Rupture of Vaccines. The consignee should take the following actions: 1. Verify the condition of the shipment and stop the electronic temperature monitors in each box within 24 hours of arrival of the shipment. 2. Retain temperature devices. 3. If the electronic temperature monitors have set off an alarm, send the readings to the PAHO Country Office Procurement Focal Point. 4. Separate the insulated shipping units with temperature deviation from the ones in good conditions. 5. Keep all shipment under the manufacturer’s recommended temperature range. 6. Review insurance policy clauses and follow the insurance claim instructions. 7. Report the situation to the carrier. 8. PAHO will advise the member state of the technical concept for the use of the concerned shipment.

PAHO 183 (1-02) PAGE/PAGINA:

PAN AMERICAN HEALTH ORGANIZATION Regional Office of the PURCHASE ORDER World Health Organization Procurement Services (PRO) 525 Twenty-third Street, N.W., Washington, D.C. 20037 Telephone (202) 974-3433 No: APO Fax: (202) 974-3615 Date: E-Mail: [email protected]

Confirmation of Arrival of Shipment Confirmación de la Llegada del Embarque

Dear Sir/Madam, Estimados Señores,

We hereby confirm the arrival of Por la presente confirmamos la llegada the following shipment: del siguiente embarque:

Order Number AWB Pieces Weight Date of arrival Complete shipment Orden Número Guía aérea Bultos Peso Fecha de llegada Embarque completo

The shipment was received at: / El embarque fue recibido en: Airport / Aeropuerto

Port / Puerto

Customs Warehouse / Bodega de la aduana

Consignee's facility / Bodega del consignatario

Name/Signature/Title/Date Nombre/Firma/titulo/Fecha

Please mark the last column if the shipment Sírvase marcar la última columna si el was received complete. embarque llego completo.

Please send this confirmation to your Agradecemos enviar esta confirmación a su counterpart at PAHO/WHO Representative contraparte en la representación de la Office. OPS/OMS.

Annex 7: Complete list of WHO prequalified vaccines, their recommended class of shipping boxes and their recommended types of electronic temperature monitors to be used (as of May 2019)

Prequalified Type Commercial Name Pharmaceutical Form Presentation No. of Manufacturer WHO Class Electronic Doses of shipping device Type 1 01/01/1987 Hepatitis B Engerix Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Class C Type 1

2 01/01/1987 Hepatitis B Engerix Liquid: ready to use Vial 10 GlaxoSmithKline Biologicals SA Class C Type 1

3 01/01/1987 Hepatitis B Engerix Liquid: ready to use Vial 20 GlaxoSmithKline Biologicals SA Class C Type 1

4 01/01/1987 BCG BCG Freeze Dried Lyophilised active component to be Ampoule 20 Japan BCG Laboratory Class B Type 2 Glutamate reconstituted with excipient diluent vaccine before use 5 01/01/1987 Yellow Fever STAMARIL Lyophilised active component to be Vial 10 Sanofi Pasteur SA Class B Type 2 reconstituted with excipient diluent before use 6 01/01/1987 BCG BCG Freezed Lyophilised active component to be Ampoule 10 Japan BCG Laboratory Class B Type 2 Dried Glutamate reconstituted with excipient diluent vaccine before use 7 01/02/1991 BCG BCG Vaccine Lyophilised active component to be Ampoule 10 BB- NCIPD Ltd. (Bul Bio-National Class B Type 2 reconstituted with excipient diluent Center of Infectious and Parasitic before use Diseases Ltd.) 8 01/02/1991 BCG BCG Vaccine Lyophilised active component to be Ampoule 20 BB- NCIPD Ltd. (Bul Bio-National Class B Type 2 reconstituted with excipient diluent Center of Infectious and Parasitic before use Diseases Ltd.) 9 01/04/1998 Haemophilus Act-HIB Lyophilised active component to be Vial 1 Sanofi Pasteur SA Class B Type 2 influenzae type b reconstituted with excipient diluent before use 10 01/06/2011 Typhoid Typhim-Vi Liquid: ready to use Vial 20 Sanofi Pasteur SA (Polysaccharide) 11 01/09/2006 Rubella Rubella Vaccine, Lyophilised active component to be Vial 1 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 12 01/09/2006 Rubella Rubella Vaccine, Lyophilised active component to be Vial 2 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 13 01/09/2006 Rubella Rubella Vaccine, Lyophilised active component to be Vial 5 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 14 01/09/2006 Rubella Rubella Vaccine, Lyophilised active component to be Vial 10 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 15 01/09/2011 Diphtheria- None used on Lyophilised active component to be Two vial set 1 Biological E. Limited Tetanus-Pertussis labelling for reconstituted with liquid active (active + active) (whole cell)- supply through component before use Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Reconstituted). 16 01/09/2011 Diphtheria- None used on Lyophilised active component to be Two vial set 10 Biological E. Limited Tetanus-Pertussis labelling for reconstituted with liquid active (active + active) (whole cell)- supply through component before use Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Reconstituted). 17 01/10/2018 Polio Vaccine - ShanIPV Liquid: ready to use Vial 5 Shantha Biotechnics Private Limited Class C Type 1 Inactivated (IPV) (A Sanofi Company) 18 01/12/2009 Influenza, Panvax Liquid: ready to use Vial 10 Seqirus Limited Class C Type 1 pandemic H1N1 19 02/02/2006 Polio Vaccine - Polioviral vaccine Liquid: ready to use Vial 20 Haffkine Bio Pharmaceutical Oral (OPV) Corporation Ltd Trivalent 20 02/08/2011 Polio Vaccine - none Liquid: ready to use Vial 20 Sanofi Pasteur SA Oral (OPV) Bivalent Types 1 and 3 21 02/10/2013 Diphtheria- Easyfive-TT Liquid: ready to use Vial 10 Panacea Biotec Ltd. Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 22 02/10/2013 Diphtheria- Easyfive-TT Liquid: ready to use Vial 1 Panacea Biotec Ltd. Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B-

Haemophilus influenzae type b 23 02/10/2018 Japanese JEEV® (6µg) Liquid: ready to use Vial 5 Biological E. Limited Encephalitis Vaccine (Inactivated) 6µg 24 02/10/2018 Japanese JEEV® (3µg) Liquid: ready to use Vial 5 Biological E. Limited Encephalitis Vaccine (Inactivated) (3µg Pediatric) 25 03/04/2017 Influenza, GCFLU Liquid: ready to use Vial 10 Green Cross Corporation seasonal Quadrivalent Quadrivalent Multi inj. 26 03/08/2016 Japanese JEEV® (3µg) Liquid: ready to use Vial 1 Biological E. Limited Encephalitis Vaccine (Inactivated) (3µg Pediatric) 27 03/11/2009 Polio Vaccine - Monovalent type Liquid: ready to use Vial 20 Haffkine Bio Pharmaceutical Oral (OPV) 1 Oral Corporation Ltd Monovalent Type Poliomyelitis 1 vaccine, IP (mOPV1) 28 03/11/2009 Polio Vaccine - Monovalent Oral Liquid: ready to use Vial 20 PT Bio Farma (Persero) Oral (OPV) Poliomyelitis Monovalent Type Vaccine Type 1 1 (mOPV1) 29 04/02/2013 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Oral (OPV) Vaccine (Oral), Bivalent Types 1 Bivalent types 1 and 3 and 3 30 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Ampoule 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus Tetanus Vaccine Adsorbed (Paediatric) 31 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus Tetanus Vaccine Adsorbed (Pediatric) 32 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus Tetanus Vaccine Adsorbed (Pediatric) 33 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Ampoule 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus (reduced Tetanus Vaccine antigen content) Adsorbed for Adults and Adolescents 34 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus (reduced Tetanus Vaccine antigen content) Adsorbed for Adults and Adolescents 35 04/04/1995 Diphtheria- Diphtheria and Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus (reduced Tetanus Vaccine antigen content) Adsorbed for Adults and Adolescents 36 04/04/1995 Diphtheria- Diphtheria- Liquid: ready to use Ampoule 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis Tetanus-Pertussis (whole cell) Vaccine Adsorbed 37 04/04/1995 Diphtheria- Diphtheria- Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis Tetanus-Pertussis (whole cell) Vaccine Adsorbed 38 04/04/1995 Diphtheria- Diphtheria- Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis Tetanus-Pertussis (whole cell) Vaccine Adsorbed 39 04/04/1995 Tetanus Toxoid Tetanus Toxoid Liquid: ready to use Ampoule 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine Adsorbed 40 04/04/1995 Tetanus Toxoid Tetanus Toxoid Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine Adsorbed 41 04/04/1995 Tetanus Toxoid Tetanus Toxoid Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine Adsorbed 42 04/09/2006 Measles Measles vaccine Lyophilised active component to be Vial 20 PT Bio Farma (Persero) Class B Type 2 reconstituted with excipient diluent before use 43 04/11/2015 Influenza, Fluzone Liquid: ready to use Vial 1 Sanofi Pasteur-USA seasonal Quadrivalent Quadrivalent 44 04/11/2015 Influenza, Fluzone Liquid: ready to use Vial 10 Sanofi Pasteur-USA seasonal Quadrivalent Quadrivalent 45 05/01/2018 Rotavirus (live, Rotavac Liquid: ready to use Vial 5 Bharat Biotech International Limited attenuated) 46 05/01/2018 Rotavirus (live, Rotavac Liquid: ready to use Vial 10 Bharat Biotech International Limited attenuated) 47 05/03/2019 Influenza, Afluria® Liquid: ready to use Vial 10 Seqirus Limited Class C Type 1 seasonal Quadrivalent Quadrivalent

48 05/08/2010 Polio Vaccine - Poliorix Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Inactivated (IPV) 49 05/08/2010 Polio Vaccine - Poliorix Liquid: ready to use Vial 2 GlaxoSmithKline Biologicals SA Inactivated (IPV) 50 05/10/2010 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 10 GlaxoSmithKline Biologicals SA Oral (OPV) Three (oral) Monovalent Type 3 51 05/10/2010 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 20 GlaxoSmithKline Biologicals SA Oral (OPV) Three (oral) Monovalent Type 3 52 05/11/2015 Polio Vaccine - Bivalent Oral Liquid: ready to use Vial 10 PT Bio Farma (Persero) Oral (OPV) Poliomyelitis Bivalent Types 1 Vaccine Type 1&3 and 3 (bOPV 1&3) 53 06/01/2009 Measles, Mumps rHA M-M-R II Lyophilised active component to be Vial 1 Merck Vaccines Class B Type 2 and Rubella reconstituted with excipient diluent before use 54 06/02/2019 Rabies VaxiRab N Lyophilised active component to be Vial 1 Cadila Health Care Ltd Class B Type 2 reconstituted with excipient diluent before use 55 06/04/2001 Diphtheria- DTP Vaccine Liquid: ready to use Vial 10 PT Bio Farma (Persero) Class C Type 1 Tetanus-Pertussis (whole cell) 56 06/07/2011 Diphtheria- none Liquid: ready to use Vial 10 PT Bio Farma (Persero) Class C Type 1 Tetanus (reduced antigen content) 57 06/11/2015 BCG BCG vaccine Lyophilised active component to be Vial + Ampoule 20 GreenSignal Bio Pharma Limited (Freeze Dried) - reconstituted with excipient diluent Intradermal before use 58 06/12/2010 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 1 Bilthoven Biologicals B.V. Inactivated (IPV) vaccine 59 07/10/2008 Rotavirus Rotateq Liquid: ready to use Plastic Tube 1 Merck Vaccines Class C Type Rotateq 60 07/11/2012 Influenza, GC FLU Multi inj. Liquid: ready to use Vial 10 Green Cross Corporation Class C Type 1 seasonal 61 07/12/2018 Polio Vaccine - Bivalent OPV Type Liquid: ready to use Vial 20 Panacea Biotec Ltd. Oral (OPV) 1 and 3 Bivalent Types 1 Poliomyelitis and 3 Vaccine, Live (Oral) 62 08/04/2019 Influenza, SKYCellflu Multi Liquid: ready to use Vial 10 SK Bioscience Co., Ltd. Class C Type 1 seasonal inj 63 08/05/2008 Polio Vaccine - ORAL Liquid: ready to use Vial 20 Sanofi Pasteur SA Oral MONOVALENT (OPV)Monovalent TYPE 1 Type 1 POLIOMYELITIS VACCINE 64 08/05/2017 Diphtheria- Adacel Liquid: ready to use Vial 1 Sanofi Pasteur Limited Class C Type 1 Tetanus-Pertussis (acellular) 65 08/07/2009 Human Cervarix Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Class C Type 1 Papillomavirus (Bivalent) 66 08/07/2009 Human Cervarix Liquid: ready to use Vial 2 GlaxoSmithKline Biologicals SA Class C Type 1 Papillomavirus (Bivalent) 67 08/08/2003 Measles, Mumps Measles, Mumps Lyophilised active component to be Vial 1 Serum Institute of India Pvt. Ltd. Class B Type 2 and Rubella and Rubella reconstituted with excipient diluent Vaccine, Live, before use Attenuated 68 08/08/2003 Measles, Mumps Measles, Mumps Lyophilised active component to be Vial 2 Serum Institute of India Pvt. Ltd. Class B Type 2 and Rubella and Rubella reconstituted with excipient diluent Vaccine, Live, before use Attenuated 69 08/08/2003 Measles, Mumps Measles, Mumps Lyophilised active component to be Vial 5 Serum Institute of India Pvt. Ltd. Class B Type 2 and Rubella and Rubella reconstituted with excipient diluent Vaccine, Live, before use Attenuated 70 08/08/2003 Measles, Mumps Measles, Mumps Lyophilised active component to be Vial 10 Serum Institute of India Pvt. Ltd. Class B Type 2 and Rubella and Rubella reconstituted with excipient diluent Vaccine, Live, before use Attenuated 71 08/10/2013 Japanese Japanese Lyophilised active component to be Two vial set 1 Chengdu Institute of Biological Encephalitis Encephalitis reconstituted with excipient diluent (active + Products Co.,Ltd Vaccine (live, Vaccine Live before use excipient) attenuated) (SA14-14-2) 72 08/10/2013 Japanese Japanese Lyophilised active component to be Two vial set 5 Chengdu Institute of Biological Encephalitis Encephalitis reconstituted with excipient diluent (active + Products Co.,Ltd Vaccine (live, Vaccine Live before use excipient) attenuated) (SA14-14-2) 73 09/02/2018 Human Gardasil 9 Liquid: ready to use Vial 1 Merck Vaccines Papillomavirus (Ninevalent) 74 09/02/2018 Varicella Varivax Lyophilised active component to be Two vial set 1 Merck Vaccines Class B Type 2 reconstituted with excipient diluent (active + before use excipient) 75 09/03/2001 Measles, Mumps Priorix Lyophilised active component to be Vial 1 GlaxoSmithKline Biologicals SA Class B Type 2 and Rubella reconstituted with excipient diluent before use 6

76 09/04/1997 Polio Vaccine - Oral polio Liquid: ready to use Vial 10 PT Bio Farma (Persero) Oral (OPV) Trivalent 77 09/04/1997 Polio Vaccine - Oral polio Liquid: ready to use Vial 20 PT Bio Farma (Persero) Oral (OPV) Trivalent 78 09/04/1997 Measles Measles vaccine Lyophilised active component to be Vial + Ampoule 10 PT Bio Farma (Persero) Class B Type 2 reconstituted with excipient diluent before use 79 09/05/2006 Tetanus Toxoid Tetatox Liquid: ready to use Vial 10 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Center of Infectious and Parasitic Diseases Ltd.) 80 09/05/2006 Tetanus Toxoid Tetatox Liquid: ready to use Vial 20 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Center of Infectious and Parasitic Diseases Ltd.) 90 09/05/2006 Diphtheria- Diftet Liquid: ready to use Vial 10 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Tetanus Center of Infectious and Parasitic Diseases Ltd.) 91 09/05/2006 Diphtheria- Diftet Liquid: ready to use Vial 20 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Tetanus Center of Infectious and Parasitic Diseases Ltd.) 92 09/05/2006 Diphtheria- Tetadif Liquid: ready to use Vial 10 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Tetanus (reduced Center of Infectious and Parasitic antigen content) Diseases Ltd.) 93 09/05/2006 Diphtheria- Tetadif Liquid: ready to use Vial 20 BB- NCIPD Ltd. (Bul Bio-National Class C Type 1 Tetanus (reduced Center of Infectious and Parasitic antigen content) Diseases Ltd.) 94 09/06/2015 Influenza, Influenza Vaccine Liquid: ready to use Vial 1 Hualan Biological Bacterin Co., Ltd Class C Type 1 seasonal (Split virion, inactivated) 95 09/07/2013 Diphtheria- Boostrix Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Class C Type 1 Tetanus-Pertussis (acellular) 96 09/12/2005 Polio Vaccine - IMOVAX POLIO Liquid: ready to use Vial 10 Sanofi Pasteur SA Inactivated (IPV) 97 09/12/2009 Influenza, Fluvirin Liquid: ready to use Vial 10 Seqirus Vaccines Limited Class C Type 1 seasonal 98 09/12/2009 Influenza, Fluvirin-H1N1 Liquid: ready to use Vial 10 Seqirus Vaccines Limited Class C Type 1 pandemic H1N1 99 10/02/2016 Diphtheria- Eupenta Liquid: ready to use Vial 1 LG Chem Ltd Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 100 10/02/2016 Diphtheria- Eupenta Liquid: ready to use Vial 10 LG Chem Ltd Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 101 10/04/2018 Rabies Rabipur Lyophilised active component to be Vial 1 Chiron Behring Vaccines Private Ltd. Class B Type 2 reconstituted with excipient diluent before use 102 10/12/2007 Yellow Fever Yellow Fever Lyophilised active component to be Two vial set 10 Bio-Manguinhos/Fiocruz Class B Type 2 reconstituted with excipient diluent (active + before use excipient) 102 11/03/1999 Diphtheria- Adsorbed DT Liquid: ready to use Vial 10 PT Bio Farma (Persero) Class C Type 1 Tetanus Vaccine 104 11/03/1999 Tetanus Toxoid TT vaccine Liquid: ready to use Vial 10 PT Bio Farma (Persero) Class C Type 1

105 11/03/1999 Tetanus Toxoid TT vaccine Liquid: ready to use Vial 20 PT Bio Farma (Persero) Class C Type 1

106 11/05/2010 Influenza, Green Flu-S Liquid: ready to use Vial 1 Green Cross Corporation Class C Type 1 pandemic H1N1 107 11/05/2011 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 20 GlaxoSmithKline Biologicals SA Oral (OPV) Two (oral) Monovalent Type 2 108 11/05/2011 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 10 GlaxoSmithKline Biologicals SA Oral (OPV) Two (oral) Monovalent Type 2 109 11/08/2017 cholera: Euvichol-Plus Liquid: ready to use Plastic Tube 1 EuBiologics Co., Ltd. inactivated oral 110 11/12/2001 Hepatitis B Heberbiovac HB Liquid: ready to use Vial 1 Centro de Ingenieria Genetica y Class C Type 1 Biotecnologia 111 11/12/2001 Hepatitis B Heberbiovac HB Liquid: ready to use Vial 10 Centro de Ingenieria Genetica y Class C Type 1 Biotecnologia 112 12/03/2009 Rotavirus Rotarix Liquid: ready to use Plastic Tube 1 GlaxoSmithKline Biologicals SA

113 12/03/2009 Rotavirus Rotarix Liquid: ready to use Applicator 1 GlaxoSmithKline Biologicals SA

114 12/04/2011 Influenza, GC FLU inj Liquid: ready to use Vial 1 Green Cross Corporation Class C Type 1 seasonal 115 12/07/2012 Tetanus Toxoid None used on Liquid: ready to use Vial 1 Biological E. Limited labelling for supply through 7

UN agencies. Also marketed with labelled commercial name BEtt. 116 12/07/2012 Tetanus Toxoid None used on Liquid: ready to use Vial 10 Biological E. Limited labelling for supply through UN agencies. Also marketed with labelled commercial name BEtt. 117 12/07/2013 Japanese JEEV® (6µg) Liquid: ready to use Vial 1 Biological E. Limited Encephalitis Vaccine (Inactivated) 6µg 118 12/11/2004 Hepatitis B Hepatitis B Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine (rDNA) (Adult) 119 12/11/2004 Hepatitis B Hepatitis B Liquid: ready to use Ampoule or Vial 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine (rDNA) (Adult) 120 12/11/2004 Hepatitis B Hepatitis B Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine (rDNA) (Paediatric) 121 12/11/2004 Hepatitis B Hepatitis B Liquid: ready to use Ampoule or Vial 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Vaccine (rDNA) (Paedriatic) 122 13/05/2004 Hepatitis B Hepatitis B Liquid: ready to use Uniject 1 PT Bio Farma (Persero) Class C Type 1 Vaccine Recombinant 123 14/01/2016 Polio Vaccine - ORAL Liquid: ready to use Vial 20 Sanofi Pasteur SA Oral (OPV) MONOVALENT Monovalent Type TYPE 2 2 POLIOMYELITIS VACCINE (mOPV2) 124 14/02/2019 Rotavirus Rotarix Liquid: ready to use Plastic Tube 5 GlaxoSmithKline Biologicals SA

125 14/07/2016 Pneumococcal Prevenar 13 Liquid: ready to use Vial 4 Pfizer Class C Type Prevnar (conjugate) Multidose Vial 126 15/02/1993 Measles Measles Vaccine, Lyophilised active component to be Vial 1 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 127 15/02/1993 Measles Measles Vaccine, Lyophilised active component to be Vial 2 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 128 15/02/1993 Measles Measles Vaccine, Lyophilised active component to be Vial 5 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 129 15/02/1993 Measles Measles Vaccine, Lyophilised active component to be Vial 10 Serum Institute of India Pvt. Ltd. Class B Type 2 Live, Attenuated reconstituted with excipient diluent before use 120 16/06/2002 Polio Vaccine - OPVERO Liquid: ready to use Vial 10 Sanofi Pasteur SA Oral (OPV) Trivalent 131 16/06/2002 Polio Vaccine - OPVERO Liquid: ready to use Vial 10 Sanofi Pasteur SA Oral (OPV) Trivalent 132 16/06/2002 Polio Vaccine - OPVERO Liquid: ready to use Vial 20 Sanofi Pasteur SA Oral (OPV) Trivalent 133 16/10/2017 Pneumococcal Synflorix Liquid: ready to use Vial 4 GlaxoSmithKline Biologicals SA (conjugate) 134 16/12/2009 Influenza, Focetria Liquid: ready to use Vial 10 Seqirus Vaccines Limited pandemic H1N1 135 17/09/2014 Diphtheria- None used on Liquid: ready to use Vial 1 Biological E. Limited Tetanus (reduced labelling for antigen content) supply through UN agencies. Also marketed with labelled commercial name BE Td 136 17/09/2014 Diphtheria- None used on Liquid: ready to use Vial 10 Biological E. Limited Tetanus (reduced labelling for antigen content) supply through UN agencies. Also marketed with labelled commercial name BE Td 137 17/10/2001 Yellow Fever Yellow Fever Lyophilised active component to be Two vial set 5 Bio-Manguinhos/Fiocruz Class B Type 2 reconstituted with excipient diluent (active + before use excipient) 138 17/10/2001 Yellow Fever Yellow Fever Lyophilised active component to be Two vial set 50 Bio-Manguinhos/Fiocruz Class B Type 2 reconstituted with excipient diluent (active + before use excipient) 139 17/11/2008 Haemophilus Haemophilus Lyophilised active component to be Vial 1 Serum Institute of India Pvt. Ltd. Class B Type 2 influenzae type b influenzae type b reconstituted with excipient diluent before use 8

Conjugate Vaccine 140 17/12/2009 Influenza, Celtura Liquid: ready to use Vial 17 Seqirus GmbH Class C Type 1 pandemic H1N1 141 18/05/2012 Diphtheria- None used on Liquid: ready to use Vial 1 Biological E. Limited Class C Type 1 Tetanus-Pertussis labelling for (whole cell)- supply through Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Liquid). 142 18/05/2012 Diphtheria- None used on Liquid: ready to use Vial 10 Biological E. Limited Class C Type 1 Tetanus-Pertussis labelling for (whole cell)- supply through Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Liquid). 143 18/07/2000 Measles and Measles and Lyophilised active component to be Vial 1 Serum Institute of India Pvt. Ltd. Class B Type 2 Rubella Rubella Vaccine, reconstituted with excipient diluent Live, Attenuated before use 144 18/07/2000 Measles and Measles and Lyophilised active component to be Vial 2 Serum Institute of India Pvt. Ltd. Class B Type 2 Rubella Rubella Vaccine, reconstituted with excipient diluent Live, Attenuated before use 145 18/07/2000 Measles and Measles and Lyophilised active component to be Vial 5 Serum Institute of India Pvt. Ltd. Class B Type 2 Rubella Rubella Vaccine, reconstituted with excipient diluent Live, Attenuated before use 146 18/07/2000 Measles and Measles and Lyophilised active component to be Vial 10 Serum Institute of India Pvt. Ltd. Class B Type 2 Rubella Rubella Vaccine, reconstituted with excipient diluent Live, Attenuated before use 147 18/08/1997 Haemophilus Vaxem HIB Liquid: ready to use Vial 1 Novartis Vaccines and Diagnostics influenzae type b S.r.l 148 18/09/2014 Japanese IMOJEV MD Lyophilised active component to be Two vial set 4 GPO-MBP Co., Ltd. Class B Type 2 Encephalitis reconstituted with excipient diluent (active + Vaccine (live, before use excipient) attenuated) 149 19/03/2010 Pneumococcal Synflorix Liquid: ready to use Vial 2 GlaxoSmithKline Biologicals SA Class C Type 1 (conjugate) 150 19/03/2010 Polio Vaccine - Bivalent type 1&3 Liquid: ready to use Vial 20 Haffkine Bio Pharmaceutical Oral (OPV) Oral Poliomyelitis Corporation Ltd Bivalent Types 1 vaccine, IP and 3 (bOPV1&3) 151 19/07/2013 Hepatitis A Havrix 1440 Adult Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Class C Type 1 (Human Diploid Cell), Inactivated (Adult) 152 19/07/2013 Hepatitis A Havrix 720 Junior Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA Class C Type 1 (Human Diploid Cell), Inactivated (Paediatric) 153 19/12/2014 Diphtheria- Hexaxim Liquid: ready to use Vial 1 Sanofi Pasteur SA Class C Type 1 Tetanus-Pertussis (acellular)- Hepatitis B- Haemophilus influenzae type b-Polio (Inactivated) 154 19/12/2014 Diphtheria- Pentabio Liquid: ready to use Vial 5 PT Bio Farma (Persero) Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 155 19/12/2014 Diphtheria- Pentabio Liquid: ready to use Vial 10 PT Bio Farma (Persero) Class C Type 1 Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 156 20/03/2001 Yellow Fever Stabilized Yellow Lyophilised active component to be Vial 5 Institut Pasteur de Dakar Class B Type 2 Fever Vaccine reconstituted with excipient diluent before use 157 20/03/2001 Yellow Fever Stabilized Yellow Lyophilised active component to be Vial 20 Institut Pasteur de Dakar Class B Type 2 Fever Vaccine reconstituted with excipient diluent before use 158 20/03/2001 Yellow Fever Stabilized Yellow Lyophilised active component to be Vial 10 Institut Pasteur de Dakar Class B Type 2 Fever Vaccine reconstituted with excipient diluent before use 159 20/03/2015 Polio Vaccine - BIOPOLIO B1/3 Liquid: ready to use Vial 20 Bharat Biotech International Limited Oral (OPV) Bivalent Types 1 and 3 160 20/03/2015 Polio Vaccine - BIOPOLIO Liquid: ready to use Vial 20 Bharat Biotech International Limited Oral (OPV) Trivalent

161 20/03/2015 Polio Vaccine - BIOPOLIO Liquid: ready to use Vial 10 Bharat Biotech International Limited Oral (OPV) Trivalent 162 20/05/2009 Human Gardasil Liquid: ready to use Vial 1 Merck Vaccines Papillomavirus (Quadrivalent) 163 20/08/2010 Pneumococcal Prevenar 13 Liquid: ready to use Vial 1 Pfizer (conjugate) 164 20/12/2018 Rabies Rabies Vaccine Lyophilised active component to be Vial + Ampoule 1 Serum Institute of India Pvt. Ltd. Class B Type 2 (Inactivated) Inactivated reconstituted with excipient diluent (Freeze Dried) before use 165 21/01/2010 Influenza, Fluzone Liquid: ready to use Vial 1 Sanofi Pasteur-USA Class C Type 1 seasonal 166 21/01/2010 Influenza, Fluzone Liquid: ready to use Vial 10 Sanofi Pasteur-USA Class C Type 1 seasonal 167 21/03/2014 Meningococcal Menactra Liquid: ready to use Vial 1 Sanofi Pasteur-USA Class C Type 1 ACYW-135 (conjugate vaccine) 168 21/07/2006 Diphtheria- Diphtheria Liquid: ready to use Ampoule 1 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis ,Tetanus, (whole cell)- Pertussis and Hepatitis B Hepatitis B Vaccine Adsorbed 169 21/07/2006 Diphtheria- Diphtheria Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis ,Tetanus, (whole cell)- Pertussis and Hepatitis B Hepatitis B Vaccine Adsorbed 170 21/07/2006 Diphtheria- Diphtheria Liquid: ready to use Vial 20 Serum Institute of India Pvt. Ltd. Class C Type 1 Tetanus-Pertussis ,Tetanus, (whole cell)- Pertussis and Hepatitis B Hepatitis B Vaccine Adsorbed 171 21/09/2018 Rotavirus (live, ROTASIIL Lyophilised active component to be Two vial set 1 Serum Institute of India Pvt. Ltd. Class B Type 2 attenuated) reconstituted with excipient diluent (active + before use excipient) 172 21/09/2018 Rotavirus (live, ROTASIIL Lyophilised active component to be Two vial set 2 Serum Institute of India Pvt. Ltd. Class B Type 2 attenuated) reconstituted with excipient diluent (active + before use excipient) 173 21/12/2009 Tetanus Toxoid None used on Liquid: ready to use Vial 20 Biological E. Limited Class C Type 1 labelling for supply through UN agencies. Also marketed with labelled commercial name BEtt. 174 21/12/2011 Measles, Mumps Priorix Lyophilised active component to be Vial 2 GlaxoSmithKline Biologicals SA Class B Type 2 and Rubella reconstituted with excipient diluent before use 175 21/12/2016 Influenza, GCFLU Liquid: ready to use Vial 1 Green Cross Corporation seasonal Quadrivalent inj. Quadrivalent 176 21/12/2017 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 20 Beijing Institute of Biological Oral (OPV) Vaccine (live, oral Products Co.,Ltd Bivalent Types 1 attenuated, and 3 human Diploid Cell), type 1 and 3 177 22/01/2010 Influenza, Panenza Liquid: ready to use Vial 10 Sanofi Pasteur SA Class C Type 1 pandemic H1N1 178 22/06/2005 Rabies VERORAB Lyophilised active component to be Vial 1 Sanofi Pasteur SA Class B Type 2 reconstituted with excipient diluent before use 179 22/07/1997 Diphtheria- IMOVAX dT adult Liquid: ready to use Vial 10 Sanofi Pasteur SA Tetanus (reduced antigen content) 180 22/07/1997 Tetanus Toxoid TETAVAX Liquid: ready to use Vial 10 Sanofi Pasteur SA

181 22/07/1997 Tetanus Toxoid TETAVAX Liquid: ready to use Vial 20 Sanofi Pasteur SA

182 22/07/1997 Meningococcal POLYSACCHARIDE Lyophilised active component to be Two vial set 10 Sanofi Pasteur SA Class B Type 2 A+C MENINGOCOCCAL reconstituted with excipient diluent (active + A+C VACCINE before use excipient) 183 22/09/2010 Diphtheria- Diphtheria, Liquid: ready to use Vial 1 Serum Institute of India Pvt. Ltd. Tetanus-Pertussis Tetanus, (whole cell)- Pertussis, Hepatitis B- Hepatitis B and Haemophilus Haemophilus influenzae type b influenzae type b Conjugate Vaccine Adsorbed 184 22/09/2010 Diphtheria- Diphtheria, Liquid: ready to use Vial 2 Serum Institute of India Pvt. Ltd. Tetanus-Pertussis Tetanus, (whole cell)- Pertussis, Hepatitis B- Hepatitis B and Haemophilus Haemophilus influenzae type b influenzae type b Conjugate Vaccine Adsorbed

185 22/09/2010 Diphtheria- Diphtheria, Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Tetanus-Pertussis Tetanus, (whole cell)- Pertussis, Hepatitis B- Hepatitis B and Haemophilus Haemophilus influenzae type b influenzae type b Conjugate Vaccine Adsorbed 186 22/10/2014 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 10 Serum Institute of India Pvt. Ltd. Oral (OPV) Vaccine (Oral), Bivalent Types 1 Bivalent types 1 and 3 and 3 187 22/11/1996 Hepatitis B Euvax B Liquid: ready to use Vial 1 LG Chem Ltd

188 22/11/1996 Hepatitis B Euvax B Liquid: ready to use Vial 10 LG Chem Ltd

189 22/12/2017 Typhoid Typbar-TCV Liquid: ready to use Vial 1 Bharat Biotech International Limited (Conjugate) 190 22/12/2017 Hepatitis A HEALIVE Liquid: ready to use Vial 1 Sinovac Biotech Co. Ltd (Human Diploid Cell), Inactivated (Adult) 191 22/12/2017 Hepatitis A HEALIVE Liquid: ready to use Vial 1 Sinovac Biotech Co. Ltd (Human Diploid Cell), Inactivated (Paediatric) 192 22/12/2017 Typhoid Typbar-TCV Liquid: ready to use Vial 5 Bharat Biotech International Limited (Conjugate) 193 23/06/2010 Meningococcal A Meningococcal A Lyophilised active component to be Vial + Ampoule 10 Serum Institute of India Pvt. Ltd. Class B Type 2 Conjugate 10 µg Conjugate reconstituted with excipient diluent MenAfriVac before use 194 23/06/2010 Diphtheria- Diphtheria, Lyophilised active component to be Vial + Ampoule 1 Serum Institute of India Pvt. Ltd. Class B Type 2 Tetanus-Pertussis Tetanus, Pertussis reconstituted with liquid active (whole cell)- and Haemophilus component before use Haemophilus influenzae type b influenzae type b Conjugate Vaccine 195 23/12/2010 Polio Vaccine - IPV Vaccine SSI Liquid: ready to use Vial 1 AJ Vaccines A/S Inactivated (IPV) 196 23/12/2015 cholera: Euvichol Liquid: ready to use Vial 1 EuBiologics Co., Ltd. inactivated oral 197 23/12/2016 Influenza, AGRIFLU Liquid: ready to use Vial 10 Seqirus Vaccines Limited seasonal 198 25/01/2016 Polio Vaccine - ORAL Liquid: ready to use Vial 20 Sanofi Pasteur SA Oral (OPV) MONOVALENT Monovalent Type TYPE 3 3 POLIOMYELITIS VACCINE 199 25/02/2010 Influenza, Influenza A Liquid: ready to use Sprayer 1 MedImmune pandemic H1N1 (H1N1) 2009 monovalent vaccine 200 25/05/2018 Influenza, IL-YANG FLU Liquid: ready to use Vial 1 IL-YANG PHARMACEUTICAL CO., seasonal Vaccine INJ. LTD. 201 25/05/2018 Influenza, Serinflu Liquid: ready to use Vial 1 Abbott Biologicals BV seasonal 202 25/08/2017 Polio Vaccine - BIOPOLIO B1/3 Liquid: ready to use Vial 10 Bharat Biotech International Limited Oral (OPV) Bivalent Types 1 and 3 203 25/10/2001 cholera: Dukoral Liquid: ready to use Vial + Buffer 1 Valneva Sweden AB inactivated oral Sachet 204 26/04/2010 Haemophilus Quimi-Hib Liquid: ready to use Vial 1 Centro de Ingenieria Genetica y influenzae type b Biotecnologia 205 26/05/2010 Diphtheria- Diphtheria, Lyophilised active component to be Vial + Ampoule 1 Serum Institute of India Pvt. Ltd. Class B Type 2 Tetanus-Pertussis Tetanus, reconstituted with liquid active (whole cell)- Pertussis, component before use Hepatitis B- Hepatitis B and Haemophilus Haemophilus influenzae type b influenzae type b Conjugate Vaccine 206 26/05/2010 Polio Vaccine - Bivalent Oral Liquid: ready to use Vial 20 PT Bio Farma (Persero) Oral (OPV) Poliomyelitis Bivalent Types 1 Vaccine Type 1&3 and 3 (bOPV 1&3) 207 26/05/2010 Diphtheria- Diphtheria, Lyophilised active component to be Vial + Ampoule 2 Serum Institute of India Pvt. Ltd. Tetanus-Pertussis Tetanus, reconstituted with liquid active (whole cell)- Pertussis, component before use Hepatitis B- Hepatitis B and Haemophilus Haemophilus influenzae type b influenzae type b Conjugate Vaccine 208 26/05/2010 Diphtheria- Diphtheria, Lyophilised active component to be Vial + Ampoule 10 Serum Institute of India Pvt. Ltd. Tetanus-Pertussis Tetanus, reconstituted with liquid active (whole cell)- Pertussis, component before use Hepatitis B- Hepatitis B and Haemophilus 11

Haemophilus influenzae type b influenzae type b Conjugate Vaccine 209 26/09/2006 Diphtheria- Quinvaxem Liquid: ready to use Vial 1 Janssen Vaccines Corp. Tetanus-Pertussis (whole cell)- Hepatitis B- Haemophilus influenzae type b 210 26/11/2012 Influenza, NASOVAC Lyophilised active component to be Vial + Ampoule 1 Serum Institute of India Pvt. Ltd. Class B Type 2 pandemic H1N1 Influenza Vaccine, reconstituted with excipient diluent Live Attenuated before use (Human) Freeze- Dried 211 26/11/2012 Influenza, NASOVAC Lyophilised active component to be Vial + Ampoule 5 Serum Institute of India Pvt. Ltd. Class B Type 2 pandemic H1N1 Influenza Vaccine, reconstituted with excipient diluent Live Attenuated before use (Human) Freeze- Dried 212 27/09/1994 BCG BCG Vaccine SSI Lyophilised active component to be Two vial set 10 AJ Vaccines A/S Class B Type 2 reconstituted with excipient diluent (active + before use excipient) 213 27/11/2014 Diphtheria- None used on Liquid: ready to use Vial 5 Biological E. Limited Tetanus-Pertussis labelling for (whole cell)- supply through Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Liquid). 214 27/11/2014 Diphtheria- None used on Liquid: ready to use Vial 2 Biological E. Limited Tetanus-Pertussis labelling for (whole cell)- supply through Hepatitis B- UN agencies. Haemophilus Also marketed influenzae type b with labelled commercial name ComBE Five (Liquid). 215 28/01/2010 Influenza, Influenza A Liquid: ready to use Vial 1 Sanofi Pasteur-USA pandemic H1N1 (H1N1) 2009 monovalent vaccine 216 28/01/2010 Influenza, Influenza A Liquid: ready to use Vial 10 Sanofi Pasteur-USA pandemic H1N1 (H1N1) 2009 monovalent vaccine 217 28/10/2016 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 5 Serum Institute of India Pvt. Ltd. Inactivated (IPV) Vaccine (Inactivated) 218 28/10/2016 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 2 Serum Institute of India Pvt. Ltd. Inactivated (IPV) Vaccine (Inactivated) 219 28/10/2016 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 1 Serum Institute of India Pvt. Ltd. Inactivated (IPV) Vaccine (Inactivated) 220 28/11/2014 Polio Vaccine - Poliomyelitis Liquid: ready to use Vial 5 Bilthoven Biologicals B.V. Inactivated (IPV) vaccine multidose, suspension for injection 2.5 mL 221 29/04/2014 Diphtheria- Shan-5 Liquid: ready to use Vial 1 Shantha Biotechnics Private Limited Tetanus-Pertussis (A Sanofi Company) (whole cell)- Hepatitis B- Haemophilus influenzae type b 222 29/04/2014 Diphtheria- Shan-5 Liquid: ready to use Vial 10 Shantha Biotechnics Private Limited Tetanus-Pertussis (A Sanofi Company) (whole cell)- Hepatitis B- Haemophilus influenzae type b 223 29/05/2003 BCG BCG Vaccine Lyophilised active component to be Vial 20 Serum Institute of India Pvt. Ltd. Class B Type 2 reconstituted with excipient diluent before use 224 29/09/2011 cholera: Shanchol Liquid: ready to use Vial 1 Shantha Biotechnics Private Limited inactivated oral (A Sanofi Company) 225 29/10/2003 Tetanus Toxoid TT vaccine Liquid: ready to use Uniject 1 PT Bio Farma (Persero)

226 29/10/2009 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 10 GlaxoSmithKline Biologicals SA Oral (OPV) T1 Monovalent Type 1 227 29/10/2009 Polio Vaccine - Polio Sabin Mono Liquid: ready to use Vial 20 GlaxoSmithKline Biologicals SA Oral (OPV) T1 Monovalent Type 1 228 29/10/2009 Polio Vaccine - Polio Sabin One Liquid: ready to use Vial 10 GlaxoSmithKline Biologicals SA Oral (OPV) and Three Bivalent Types 1 and 3 12

229 29/10/2009 Polio Vaccine - Polio Sabin One Liquid: ready to use Vial 20 GlaxoSmithKline Biologicals SA Oral (OPV) and Three Bivalent Types 1 and 3 230 30/06/2011 Influenza, Vaxigrip Liquid: ready to use Vial 10 Sanofi Pasteur SA seasonal 231 30/08/2007 Tetanus Toxoid ShanTT Liquid: ready to use Vial 10 Shantha Biotechnics Private Limited (A Sanofi Company) 232 30/08/2007 Tetanus Toxoid ShanTT Liquid: ready to use Vial 20 Shantha Biotechnics Private Limited (A Sanofi Company) 233 30/09/2015 Influenza, Nasovac-S Lyophilised active component to be Vial + Ampoule 1 Serum Institute of India Pvt. Ltd. Class B Type 2 seasonal Influenza Vaccine, reconstituted with excipient diluent Live, Attenuated before use (Human) 234 30/10/2009 Pneumococcal Synflorix Liquid: ready to use Vial 1 GlaxoSmithKline Biologicals SA (conjugate) 235 30/12/2014 Meningococcal A Meningococcal A Lyophilised active component to be Vial + Ampoule 10 Serum Institute of India Pvt. Ltd. Class B Type 2 Conjugate 5 µg Conjugate 5 reconstituted with excipient diluent micrograms before use MenAfriVac 5µg 236 31/07/2013 Meningococcal Menveo Lyophilised active component to be Two vial set 1 GlaxoSmithKline Vaccines S.r.l. Class B Type 2 ACYW-135 reconstituted with liquid active (active + active) (conjugate component before use vaccine) 237 31/07/2014 Diphtheria- None used on Liquid: ready to use Vial 1 Biological E. Limited Tetanus-Pertussis labelling for (whole cell) supply through UN agencies. Also marketed with labelled commercial name TRIPVAC 238 31/07/2014 Diphtheria- None used on Liquid: ready to use Vial 10 Biological E. Limited Tetanus-Pertussis labelling for (whole cell) supply through UN agencies. Also marketed with labelled commercial name TRIPVAC 239 31/08/2016 Meningococcal Nimenrix Lyophilised active component to be Vial + Ampoule 1 Pfizer Class B Type 2 ACYW-135 reconstituted with excipient diluent (conjugate before use vaccine)