Guidelines on

the international packaging

and shipping of vaccines
WHO/IVB/05.23
ORIGINAL: ENGLISH
Immunization, Vaccines and Biologicals
I
V
II
B
VV
Guidelines on
the international packaging
and shipping of vaccines
Immunization, Vaccines and Biologicals
WHO/IVB/05.23
ORIGINAL: ENGLISH
i i
The Department of Immunization, Vaccines and Biologicals
thanks the donors whose unspecified financial support
has made the production of this document possible.
This document was produced by the
Access to Technologies team
of the Department of Immunization, Vaccines and Biologicals
Ordering code: WHO/IVB/05.23
Printed: December 2005
Revision history: This document, Guidelines on the international packaging and shipping of vaccines, was
first published in 1990. Since then it has gone through four revisions: in 1995, 1998, 2001 (WHO/V&B/01.05),
and 2005. This revision, produced in December 2005, replaces all previous versions.
This publication is available on the Internet at:
www.who.int/vaccines-documents/
Copies may be requested from:
World Health Organization
Department of Immunization, Vaccines and Biologicals
CH-1211 Geneva 27, Switzerland
Fax: + 41 22 791 4227 Email: [email protected]
World Health Organization 2005
All rights reserved. Publications of the World Health Organization can be obtained from
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Printed by the WHO Document Production Services, Geneva, Switzerland
i i i
Contents
Acronyms ........................................................................................................................... v
Preface ............................................................................................................................. vii
1. Insulated packaging standards .............................................................................. 1
1.1. Class A packaging ............................................................................................ 1
1.2. Class B packaging ............................................................................................ 1
1.3. Class C packaging ............................................................................................ 1
2. Temperature monitoring devices to be included in international
shipments ................................................................................................................... 3
3. Storage volume standards ...................................................................................... 7
4. Labelling and packaging ...................................................................................... 10
4.1. Labelling for secondary packaging .............................................................. 10
4.2. Labelling for tertiary packaging (insulated packaging) ............................. 10
4.3. Numbering of tertiary packaging ................................................................. 11
5. Standard shipping and arrival procedures ........................................................ 12
5.1. Route and arrival dates .................................................................................. 12
5.2. Advance notice of arrival and advance shipping documentation............. 13
5.3. Documents that accompany shipments ........................................................ 14
5.4. Vaccine arrival report .................................................................................... 15
Annex 1: Guidelines to confirm that packaging complies
with WHO recommendations ............................................................... 17
Annex 2: Shake test protocol .................................................................................. 20
Annex 3: List of contact points for national regulatory authorities in
countries producing vaccines prequalified for purchase by
United Nations agencies ......................................................................... 22
Annex 4: Bulking factors for insulated packaging.............................................. 25
Annex 5: Vaccine Arrival Report .......................................................................... 27
i v
v
Acronyms
The following acronyms are used in this document.
C degree Celsius
F degree Fahrenheit
AWB airway bill
BCG bacille CalmetteGurin (tuberculosis vaccine)
CCM (vaccine) cold chain monitor
cm
3
cubic centimetres
DT diphtheriatetanus vaccine
DTP diphtheriatetanus pertussis vaccine
ETA estimated time of arrival
HepB hepatitis B (vaccine)
Hib Haemophilus influenzae type b (vaccine)
IPV inactivated polio vaccine
IVB (Department of) Immunization, Vaccines and Biologicals (WHO)
kg kilogram
LCD liquid crystal display
LRC lot release certificate
MMR mumpsmeaslesrubella (vaccine)
MR measlesrubella (vaccine)
NRA national regulatory authority
OPV oral polio vaccine
PAHO Pan American Health Organization
PQS performance, quality and safety
SD Supply Division (UNICEF)
SLP summary lot protocols
Td tetanus toxoid and diphtheria (reduced component) vaccine
TT tetanus toxoid (vaccine)
UN United Nations
UNICEF United Nations Childrens Fund
VAR vaccine arrival report
VVM vaccine vial monitor
WHO World Health Organization
YF yellow fever (vaccine)
v i
vi i
Preface
The World Health Organization (WHO) document, Guidelines on the international
packaging and shipping of vaccines, has been one of the most widely used manuals in
the field of immunization. It is referenced by UNICEF and PAHO in all their
invitations to bid for vaccine supplies and also by countries that directly procure
their vaccines.
This 2005 edition
*
takes into account new developments in the field of vaccine
stability, temperature monitoring and information on recently prequalified vaccines.
In addition to the updated volume per dose of vaccine, it provides data on the packed
volume of diluents and droppers and includes transport-box bulking factors for
countries where insulated packages are used for the storage of vaccines. A special
section on temperature monitoring has been added to describe the temperature limits
for international shipments.
WHO recommends that all United Nations (UN) procurement agencies include the
Guidelines on the international packaging and shipping of vaccines as part of the
technical specifications and requirements in invitations to bid.
This document has been reviewed and commented upon by personnel in the vaccine
industry.
*
Printed in November 2005, this document revises and replaces all previous versions, including the
2001 version (WHO/V&B/01.05).
viii
1 WHO/IVB/05.23
1. Insulated packaging
standards
On the basis of their thermostability and presentation, vaccines are classified into
three categories (see Table 1) for packaging of international shipments. WHO specifies
the minimum and maximum acceptable temperatures to which vaccines in
each category can be exposed during international transport, for a period of at least
48 hours.
As part of the WHO prequalification scheme, vaccine manufacturers are
expected to ensure that their packaging complies with the criteria specified below.
Validation data should be produced in three consecutively successful runs.
Any changes introduced in the packaging must be validated again. The validation
test protocol is provided in Annex 1.
1.1. Class A packaging
Prior to and at the time of packing the vaccines must be kept within the storage
temperature limits recommended by the manufacturer.
The vaccine must be packed to ensure that the warmest temperature inside the
insulated package does not rise above +8C in continuous outside ambient
temperatures of +43C for a period of at least 48 hours.
1.2. Class B packaging
Prior to and at the time of packing the vaccines must be kept within the storage
temperature limits recommended by the manufacturer.
The vaccines must be packed to ensure that the warmest temperature inside the
insulated package does not rise above +30C in continuous outside ambient
temperatures of +43C for a period of at least 48 hours.
Diluents for freeze-dried vaccines must always be included with the vaccine shipment
in a quantity that matches the quantity of vaccine; diluents, however, do not require
temperature-controlled packaging.
1.3. Class C packaging
Prior to and at the time of packing the vaccines must be kept within the storage
temperature limits recommended by the manufacturer.
Guidelines on the international packaging and shipping of vaccines 2
The vaccines must be packed to ensure that:
the warmest temperature inside the insulated package does not rise above +30C
in continuous outside ambient temperatures of +43C for a period of at least
48 hours; and
the coolest storage temperature of the vaccine does not fall below +2C in
continuous external temperatures of -5C for a period of at least 48 hours.
Table 1: WHO classification and temperature criteria for international
shipment of vaccines (for at least 48 hours)
Class Type of vaccine Ambient Minimum Maximum
temperature temperature temperature
allowed allowed
A OPV +43
o
C no limit +8
o
C
BCG
Hib (freeze-dried)
measles
B MR +43
o
C no limit +30
o
C
MMR
meningococcal A&C
yellow fever
DTP
DTPHepB
DTPHib (liquid) +43
o
C +2
o
C +30
o
C
C DT
IPV
HepB
Hib (liquid) -5
o
C +2
o
C +30
o
C
Td
TT
3 WHO/IVB/05.23
Temperature monitoring devices should be included in all vaccine shipments to
document whether temperature limits have been exceeded. These devices should:
1) serve as a quick reference to help recipient countries determine whether the
shipment or parts of the shipment have been exposed to temperatures at
which vaccines could have been damaged; and
2) help the procurement agency determine when, where, and to what extent
temperature limits have been exceeded.
Before accepting a shipment, the recipient should make sure that temperature limits
have not been exceeded.
The point in time when a temperature change has occurred is not of immediate concern
to the recipient. This information is important a) for the purchasing agency and the
manufacturer so they can identify the cause of the change, take corrective measures,
and avoid similar situations in future shipments; and b) for insurance purposes.
Electronic temperature devices provide the most reliable and accurate record of the
above information. WHO recommends that one electronic temperature device is
included in each and every international vaccine shipping carton. Furthermore,
WHO no longer recommends the use of the vaccine cold chain monitor card (CCM)
1
and/or freeze indicators in international shipments.
2. Temperature monitoring
devices to be included in
international shipments
1
Except under exceptional circumstances where dry ice continues to be used.
Guidelines on the international packaging and shipping of vaccines 4
Table 2: Specifications of the electronic devices for international shipments
a
Storage temperature Range: -20
o
C to +70
o
C
Operating temperature Range: -20
o
C to +55
o
C
Display visibility range Range: -10
o
C to +55
o
C
Temperature measuring accuracy 0.5
o
C or better
Time measuring accuracy 10 seconds per day, or better
Initial delay (see point 2 below) 1 hour
Recording period 10 days
Storage before START minimum of 18 months
Data retention after STOP minimum of 6 months
a
For specific devices with these features, refer to the WHO web site:
http://www.who.int/vaccines-access/vacman/pis/pqs.htm
The electronic devices should, at a minimum, meet the specifications outlined in
Table 2 (above) and have the functions outlined below.
1) A start function to activate the device at the time the carton is being loaded
with vaccine.
2) A stop function to allow the recipient to stop the recording when the vaccine
arrives at its destination.
3) A one hour initial delay function so the device can acclimatize to the
temperature inside the shipping carton before it starts recording.
4) A history function to provide details of violations of the temperature
limit in terms of time, range and duration. This function is primarily to provide
information for the use of the procurement agency.
5) A liquid crystal display (LCD) screen
2
to provide a visual display of the
information and also to show the symbol that indicates whether the device is
functional or not. This symbol, and also the alarm indicator, should be static
(i.e. should not flash or blink) so as to be visible when the screen is scanned or
photocopied for documentation purposes.
6) An alarm set according to WHOs recommended settings (see Tables 3 and
4 below).
Table 3: WHO-recommended alarm settings for international shipments of
DTP, DT, TT, Td, HepB, IPV, liquid Hib and combination vaccines
Temperature Alarm type Period for triggering
the alarm
45
o
C single event 1 hour
30
o
C cumulative 10 hours
-0.5
o
C single event 1 hour
2
In addition to the LCD screen feature on which all history can be read, the data can be
downloaded. However, devices with a download option but without an LCD screen are not
recommended.
5 WHO/IVB/05.23
Table 4: WHO-recommended alarm settings for international shipments of
OPV and freeze-dried BCG, measles, MR, MMR, lyophilized Hib,
yellow fever and meningitis vaccines
Temperature Alarm type Period for triggering
the alarm
45
o
C single event 1 hour
30
o
C cumulative 10 hours
10
o
C cumulative 20 hours
Vaccine manufacturers are required to validate their packaging twice for a period of
48 hours: i) at ambient temperatures under +43
o
C and ii) at ambient temperatures
under -5
o
C. This validation is critical to ensure that the packaging complies with the
above requirements and will not set off an alarm.
Batteries for electronic devices do not perform under extremely cold temperatures,
such as when vaccines are being transported with dry ice. All vaccine manufacturers
are encouraged to validate their Class A and B packaging with frozen icepacks in
order to phase out the use of dry ice. In exceptional cases where dry ice continues
to be used WHO recommends the inclusion of one cold chain monitor card per
shipping carton instead of an electronic device.
Each electronic device should be attached to a backing card that includes the
information outlined below, in the appropriate language.
1. The type of device:
Type 1: for DTP, DT, TT, Td, HepB, IPV, liquid Hib and combination vaccines
Type 2: for OPV and freeze-dried BCG, measles, MR, MMR, lyophilized
Hib, yellow fever and meningitis vaccines
2. For the person packing/sending the shipment:
a) instructions on how to activate the device;
b) a reminder that one device must be placed in each shipping carton;
c) space for the following information to be entered:
the suppliers name;
date and time of the packing;
vaccine purchase order number;
vaccine type.
3. For the person receiving the shipment:
a) instructions on how to stop the device;
b) illustrations to show information on the LCD screen how it will indicate
problems/no problems and the alarm-status display;
c) Tables 5 and 6 (below) showing what to do.
Guidelines on the international packaging and shipping of vaccines 6
Table 5: Information to be displayed on the backing card
of electronic device Type 1 (for DTP, DT, TT, Td, HepB,
IPV, liquid Hib and combination vaccines)
Alarm temperature What to do with vaccines
45
o
C Contact UNICEF
30
o
C Contact UNICEF
-0.5
o
C Conduct shake test
a
.
USE vaccine if passes.
Inform UNICEF of test result.
a
Shake test guidelines are given in Annex 2.
Table 6: Information to be displayed on the backing card
of electronic device Type 2 (for OPV and freeze-dried BCG, measles,
MR, MMR, lyophilized Hib, yellow fever and meningitis vaccines)
What to do with
OPV Other vaccines
45
o
C Contact UNICEF Contact UNICEF
30
o
C Contact UNICEF Contact UNICEF
10
o
C Contact UNICEF Accept
Alarm temperature
7 WHO/IVB/05.23
The storage volume per dose of vaccine varies according to the type of vaccine,
the number of doses per vial or ampoule, the dimensions of a) the vial or ampoule
and b) the secondary packaging
3
. Countries that receive their vaccines through
UN agencies and do not know in advance which vaccines they will receive,
should estimate their cold-chain requirements on the basis of the figures for maximum
volume per dose provided in Table 7 below.
Vaccine manufacturers should ensure that the storage volume per dose of the vaccines
they supply to UN agencies remains below the maximum figures listed in Table 7.
If, however, this proves impossible, WHO should be notified.
3. Storage volume
standards
3
Secondary packaging includes the primary packaging (i.e. the vaccine vial), the packet containing the
vaccine vial and any intermediate packaging.
Guidelines on the international packaging and shipping of vaccines 8
Table 7: Maximum recommended packed volume per vaccine dose
a
Vaccine type Dose per vial cm
3
per dose
BCG (freeze-dried) 20 1.2
10 3.0
20 2.0
2 6.0
10 3.0
DTPHib 10 2.5
1 45.0
10 12.0
1 22.0
2 11.0
1 18.0
1 in UNIJECT 30.0
HepB 2 13.0
6 4.5
10 4.0
20 3.0
1 15.0
10 2.5
1 13.0
Hib (freeze-dried) 2 6.0
10 2.5
Measles (freeze-dried) 10 3.5
1 16.0
10 3.0
MR (freeze-dried) 10 2.5
20 2.5
50 1.5
10 2.0
20 1.0
TT in UNIJECT 1 25.0
5 6.5
Yellow fever 10 2.5
20 1.0
a
The packed volume includes the vaccine vial, the packet
containing the vaccine vial and any intermediate packaging
(secondary packaging).
DTP + Hib (freeze-dried)
DTP-HepB + Hib (freeze dried)
Hib (liquid)
MMR (freeze-dried)
Meningitis A&C
OPV
DTP, DT, Td, TT
DTPHepB
9 WHO/IVB/05.23
Table 8: Maximum recommended packed volume for diluents and droppers
Vaccine type Dose per vial cm
3
per dose
Diluent for BCG 20 0.70
1 35.0
10 3.0
1 20.0
10 4.0
20 2.5
50 1.5
5 7.0
Diluent for yellow fever 10 6.0
20 3.0
OPV droppers n/a 17.0 (per unit)
Countries should use packed volume-per-dose to calculate cold-chain requirements
if vaccines are to be kept in the cold chain in their secondary packaging.
Storing vaccines in the shipping containers greatly increases the volume of cold storage
needed, hence involves extra cost. However, this extra cost may be justifiable at
higher-level stores where vaccine is kept alongside other refrigerated pharmaceuticals.
In very large cold stores, where goods are stored and moved on pallets,
vaccine should be stocked in their insulated shipping containers
4
. Bulking factors
for insulated shipping containers for estimation of volume requirements are given in
Annex 4.
WHO recommends that each international shipping carton should weigh less than
50 kg. It is important that individual boxes are not too heavy during transport as
they are frequently loaded and offloaded manually at airports and intermediate stores.
Diluent for Hib
Diluent for measles, MR, MMR
Diluent for meningitis A&C
4
Shipping containers function as tertiary packaging.
Guidelines on the international packaging and shipping of vaccines 1 0
Primary packaging constitutes the first level of container for the vaccine: the vaccine vial or
ampoule itself.
Secondary packaging, the second level of packaging, comprises the intermediate
packaging that contains the primary packages (the vials/ampoules of vaccines).
It must be cl earl y l abel l ed for the reci pi ent, gi vi ng i nformati on on i ts contents
(see below).
Tertiary packaging, the third level of packaging, is the outer box, the shipping container that
contains the secondary packages. It must be clearly labelled for international transport with
the final address and other details (see below).
All labelling and packaging requirements listed in section 4 apply to both vaccine
and diluent.
4.1. Labelling for secondary packaging
A label must be affixed either to the top and/or front surface of the secondary
packages. It should indicate the type of vaccine, the name of the manufacturer,
presentation, batch number, date of manufacture, date of expiry, quantity and storage
conditions.
4.2. Labelling for tertiary packaging (insulated packaging)
The external surface of insulated packages should be either white or in the natural
colour of corrugated carton. Dark colours must be avoided.
All labels on tertiary packaging must be attached to all four sides.
Vaccine Rush: A label must be affixed to all four sides of the vaccine package in a
language appropriate to the country of destination (e.g., in English: Vaccine Rush;
in French: Vaccin Urgent; in Spanish: Vacuna Urgente; etc.).
4. Labelling and packaging
5
5
Labelling and packaging in this section refers to secondary and tertiary packaging.
1 1 WHO/IVB/05.23
Do not freeze: For shipments of freeze-sensitive vaccines (DTP/DT/Td/TT,
liquid Hib and hepatitis B vaccines, or combinations containing any of these) a
Do not freeze sticker (again, in the appropriate language) should be attached to
all four sides of the vaccine package.
Contents: A label with information on the contents of the box (name of
manufacturer, type of vaccine, presentation, batch number, date of expiry,
quantity, and storage conditions) should be affixed to all four sides of each box.
The manufacture and expiry date on all labels should be written in full, not in a
coded form (i.e. June 2005, not 06.05).
4.3. Numbering of tertiary packaging
All boxes should be numbered consecutively. Shipping documents should be included
in the box labelled number 1, and this box should be clearly labelled with the words
Containing vaccine shipping documents.
Guidelines on the international packaging and shipping of vaccines 1 2
The arrival of a vaccine shipment in a country, its subsequent clearance through
customs and transportation to the central vaccine store are the most critical stages in
the shipping procedure. These are frequently the times when mistakes and delays
occur, resulting in damage to the shipments. The smooth arrival and handling of
vaccine shipments depends on the manner in which each step in the delivery process
is performed. Because numerous parties are involved (UNICEF Supply Division,
other UN agencies, the manufacturer, the forwarder, the airline, the UN field office,
customs authorities, clearing agents, or the national immunization service, etc.),
and because of the need to communicate accurate, time-sensitive information,
it is essential to have strict guidelines to determine and assign responsibilities at
every step of the process. These are described in the general terms and conditions of
the tender documents and are further detailed in individual contracts. The specific
conditions depend on the country of destination.
The essential elements of the process are outlined below.
5.1. Route and arrival dates
Vaccines should travel by a direct route wherever possible. Where trans-shipment is
unavoidable, the journey should be planned through airports that: a) have cold storage
facilities, and b) are located in countries with a temperate climate. The maximum
transit time from the manufacturer to arrival at the airport of final destination must
not exceed 48 hours, unless this is unavoidable and has been specifically agreed to in
writing in advance by UNICEF and/or the other UN agencies involved.
Shipments should be scheduled to arrive outside weekends and/or public holidays in
the recipient country and airline bookings should be made well ahead of the date of
departure. Any additional requirements regarding arrival times must be stated in the
contract between UNICEF and/or the other UN agencies or manufacturers and the
designated freight forwarder.
In addition to the above routing and booking procedures, the following general
principles should be observed:
Vaccines must not be transported with radioactive products, fish or meat;
correct cold-chain procedures must be observed during transit, warehousing
and shipping (i.e., all vaccines must be kept in temperature-controlled
environments at all times throughout the shipment process);
re-icing of shipments must be performed in accordance with the instructions
of the supplier of each shipment whenever deemed necessary;
5. Standard shipping and
arrival procedures
1 3 WHO/IVB/05.23
consolidation or split consignments are not permitted unless approved in writing
in advance by UNICEF and/or the other UN agencies;
shipments must be dispatched as booked unless approved in writing in advance
by UNICEF and/or other UN agencies;
house airway bills are not permitted unless approved in writing in advance
by UNICEF and/or other UN agencies.
5.2. Advance notice of arrival and advance shipping documentation
Copies of the documentation for the goods to be shipped must be sent at least seven
days
6
in advance of arrival of the shipment. In the case of an individual contract for
a specific destination that requires a longer period of advance notice, a longer period
should apply.
The documentation must include the following:
pre-advice defined by UNICEF and/or the other UN agencies;
airway bill (AWB);
suppliers invoice;
packing list;
lot release certificate (LRC) issued by the national regulatory authority (NRA)
of the country of manufacture for each lot of vaccine supplied; and
any other document, certificate or instruction specified in the individual order.
The documents should be sent by e-mail and fax by the freight forwarder or the
manufacturer to the consignee, the UNICEF country office in the receiving country,
the Immunization Team at the UNICEF Supply Division and any other parties
specified in the individual contract.
The pre-advice must contain the following information:
purchase order reference;
consignee requisition reference;
number of packages, gross weight (in kilograms) and volume (in cubic metres);
type of vaccine, total number of vials and number of doses per vial/ampoule/
tube;
value of shipment (in US$);
AWB and flight number(s);
date and time for place of departure, transit (if applicable), and arrival;
instructions for collection;
any other information specified in the individual contract must also be included
for the consignee.
6
This period must include at least five working days.
Guidelines on the international packaging and shipping of vaccines 1 4
The following information shall be stated on the airway bill:
consignees name, address and telephone number;
purchase order reference;
consignees requisition reference;
type of vaccine and quantity;
instructions to: Telephone consignee upon arrival (repeat telephone
number);
handling information: Medicines Vaccine For human use Highly
perishable Not to be delayed.
For all vaccines other than oral polio vaccine (OPV), the following instruction should
be stated in the AWB: Throughout shipment, pending reshipment and prior to
collection by the consignee, the vaccine must be stored at +2
o
C to +8
o
C (i.e., +35
o
F
to +50
o
F).
For OPV, the following instruction should be stated in the AWB: Throughout
shipment, pending reshipment and prior to collection by the consignee, the vaccine
must be stored at -15
o
C to -25
o
C (i.e., +5
o
F to -13
o
F).
5.3. Documents that accompany shipments
The following original documents must accompany the consignment when it is
shipped, and a copy of these must also be placed in the box numbered one:
airway bill;
suppliers invoice;
packing list;
lot release certificate issued by the national regulatory authority of the country
of manufacture for each lot of vaccine supplied;
any other documents, certificates or instructions specified in the individual
contract.
The shipping carton containing the documents should be clearly labelled with the
words Containing vaccine shipping documentation.
The lot release certificate/s from the national regulatory authority (or from the national
control laboratory) of the producing country should be included for each lot contained
in the shipment. The lot release certificates are considered to be the only evidence
that the lots received have been released by the regulatory authority of the producing
country. Vaccines delivered without a lot release certificate cannot be accepted and
must be kept on hold under appropriate storage conditions. In such cases, the lot
release certificate/s should be requested and provided immediately by the
manufacturer.
1 5 WHO/IVB/05.23
Inclusion of the lot release certificate is one of the most critical conditions for
acceptance of the vaccine by the consignee and for its distribution in country
7
.
Manufacturers internal release documents and any other papers that may accompany
a shipment do not replace and are not a substitute for the official lot release
certificates issued by the national regulatory authority of the producing country.
5.4. Vaccine arrival report
The vaccine arrival report (VAR) provides a means of indicating inadequacies in the
shipping process and problems relating to the condition of vaccines at the time of
delivery (see Annex 5). The VAR is a means of monitoring international shipments
of vaccines in order to ensure that shipping guidelines are followed and that vaccine
quality is maintained. Indeed, it encourages increased involvement in the procurement
process by all the parties implicated. UNICEF and/or WHO officers should
collaborate with recipient governments to ensure that the VAR is duly completed by
authorized staff, checked and verified by the immunization programme manager,
and forwarded to the UNICEF country office within three days of the arrival of the
vaccine. In the case of combined shipments, a separate report should be filled in for
each vaccine in the shipment.
For countries receiving vaccines from UN agencies, all complaints should be sent
immediately to the local country office of the procurement agency for them to follow
up with their procurement organization. Depending on the nature of the complaint,
the procurement agency may handle the issue itself or may request assistance from
WHO. For countries procuring vaccine directly, all complaints should be handled
directly with the vaccine manufacturer; WHO assistance can, however, be sought if
required.
Table 9 sets out the vaccine arrival and complaints procedures for vaccines procured
by UNICEF. These procedures may be adapted for other procurement routes.
7
For the use of the recipient, Annex 3 lists the contact points for national regulatory authorities and
national control laboratories in all vaccine-producing countries that supply UN agencies.
Guidelines on the international packaging and shipping of vaccines 1 6
Table 9: Procedure for reporting vaccine arrivals
Arrival of vaccines and customs clearance.

Inspection at airport or central cold stores. Vaccine Arrival Report (VAR) filled in and signed.

Copy of VAR sent to UNICEF Country Office.

Copy of VAR sent to UNICEF Supply Division, Copenhagen (SD)

INDICATOR OK DEFECTIVE
Advance notification Recorded SD to follow-up with forwarder
Vaccine type/expiry Recorded SD to follow-up with manufacturer
Eventual report to WHO/V&B for further
investigation if necessary
Shipping documents Recorded SD to follow-up with forwarder or manufacturer
Eventual report to WHO/V&B of problems
related to release certificate
Quantities received Recorded SD to follow-up with forwarder/manufacturer
Status of temperature indicators Recorded SD to report to WHO/V&B,
investigation to be carried out
Any defect in the process can lead to compensation claims and/or rejection of a
shipment. Each individual situation will be investigated and dealt with by all involved
parties.
If the quantity of damaged vaccine is substantial it could affect immunization delivery.
In such cases, emergency measures will have to be taken to obtain sufficient vaccine
to maintain the programmes scheduled activities.
1 7 WHO/IVB/05.23
1. Introduction
This procedure referred to as validation is the measurement and/or confirmation that
temperatures inside the shipping containers of every vaccine shipment remains within the defined
temperature range (for the specific vaccine/s being transported) for a period of 48 hours.
As part of the WHO vaccine prequalification process, vaccine manufacturers must
document the validation of their packaging.
Validation data should be produced for three successful consecutive tests at the defined
ambient temperatures for at least 48 hours. If changes are introduced either in the
packaging or the shipment procedures, the shipment must be validated again.
Test temperature and established criteria for class A, B and C vaccines
for the validation of the packaging (for minimum of 48 hours)
Class Type of vaccine Ambient Minimum Maximum
temperature temperature temperature
allowed allowed
A OPV +43
o
C no limit +8
o
C
BCG
Hib (freeze-dried)
measles
B MR +43
o
C no limit +30
o
C
MMR
meningococcal A&C
yellow fever
DTP
DTPHepB
DTPHib (liquid) +43
o
C +2
o
C +30
o
C
C DT
IPV
HepB
Hib (liquid) -5
o
C +2
o
C +30
o
C
Td
TT
Annex 1:
Guidelines to confirm that packaging complies
with WHO recommendations
Guidelines on the international packaging and shipping of vaccines 1 8
x 1, 2 3, 4 x
x 6, 7 8, 9 x
X 5
Temperatures within the container should be continuously monitored within an
accuracy of 0.5C; the sensors used for this purpose must not be allowed to influence
the test in any way. A minimum of 8 simultaneous temperature measurements are
required for an insulated box (see figure below). The ambient temperatures at which
the insulated box is tested must remain within a tolerance of 1C.
Locations of temperature sensors for insulated containers
a) Insulated container: top view
b) Insulated container: side view
x 1,6 3, 8 x
x 2, 7 4, 9 x
X 5
Lid
1 9 WHO/IVB/05.23
2. Loading
Insulated boxes should be fully loaded with vaccine vials conditioned at +5C 3C.
Loads can be pre-fitted with thermocouples. Loading should be carried out as quickly
as possible and the time taken for loading should be recorded for each container.
In the case of a vaccine manufacturer having more than one type of vaccine in one
category, testing with any of the listed vaccine is acceptable. The validation does not
need to be repeated with other presentations.
3. Temperature recording
The internal temperature of an insulated container is recorded at specified points
within the load during the validation tests. The figure above shows the position of
these points, each of which is 2.5/3.0 cm from the nearest icepack surface, with the
exception of the central points.
Thermocouples should be attached to the outside of the vials and should not be
inserted into the vials. Thermocouple leads can be introduced into the container
either:
through the seal taking care not to affect the quality of the seal; or
through a hole in the geometric centre of the lid or of one of the sides of the
container taking care to adequately seal the outer and inner openings.
4. Reporting
An initial validation report should be sent to WHO along with the dossier submitted
for prequalification or reassessment. It should include:
standard operating procedure (or test protocol) used for the validation;
start date, end date and time of the three consecutive validation runs;
detailed information on external and internal dimensions of insulated
container, type of material it is made of, weight empty and weight fully loaded
(total weight);
detailed temperature history for all tests in tabular format (for all internal and
external ambient channels).
Guidelines on the international packaging and shipping of vaccines 2 0
Annex 2:
Shake test protocol
Purpose
The shake test is designed to determine whether adsorbed vaccines (DPT, DT, Td,
TT, hepatitis B, Hib liquid, and/or combinations of these) have been affected by
freezing. After freezing, the lattice (bond between adsorbent and antigen) gets broken.
Separated adsorbent tends to form granules that get bigger in particle size and weight
then gradually settle to the bottom after the vial has been shaken. The size of the
granules seems to increase after repeated freezing and thawing cycles. Sedimentation
occurs faster in a vaccine vial that has been frozen than in a vaccine vial (from the
same manufacturer) that has never been frozen.
Individual batches of vaccine may behave differently from one another. The test
procedure described below should, therefore, be repeated with all suspect batches.
In the case of international arrivals, whenever there is an indication that temperatures
have dropped below zero, the shake test should be conducted on a random sample of
vaccines. However, if there is more than one lot of vaccine in the shipment,
the random sample must include a vial taken from each and every lot.
Test procedure
1) Take a vial of vaccine of the same type and batch number as the vaccine you
want to test, and made by the same manufacturer. This is your control vial.
2) Clearly mark the control vial: FROZEN.
3) Freeze the control vial at -20
o
C overnight, until the contents are completely
solid.
4) Let the control vial thaw. Do not heat it!
5) Take a test vial from the batch that you suspect has been frozen.
6) Hold the control (frozen) vial and the test vial together in one hand.
7) Shake both vials vigorously for 1015 seconds.
8) Place both vials on a flat surface side-by-side and start continuous observation
of the vials until the test is finished. (If the vials have large labels that conceal
their contents, turn both vials upside down and observe sedimentation in the
neck of each vial.)
9) Use an adequate source of light to compare the sedimentation rates between
vials.
2 1 WHO/IVB/05.23
Conclusion
If sedimentation is slower in the test vial than in the control (frozen) vial,
the vaccine has not been damaged. Use the vaccine.
If sedimentation is similar in both vials, or if sedimentation in the test
vial is faster than in the control (frozen) vial, the vaccine has been damaged.
Do NOT use the vaccine. Notify your supervisor.
The figure below shows the difference between a control (frozen) vial and a
(non-frozen) test vial.
Seeing the difference in sedimentation rates during a shake test
Photo: U. Kartoglu (WHO)
4 minutes after placing
the vials on the table
10:25 am
Frozen control vial
Test vial
Sedimentation in test
vial is slower than
the frozen control
vial. Test vial has not
been damaged and
can be used.
10:28 am
10:31 am
10:33 am
1
2
3
4
Guidelines on the international packaging and shipping of vaccines 2 2
Annex 3:
List of contact points for national regulatory
authorities in countries producing vaccines
prequalified for purchase by
United Nations agencies
Americas
Agencia Nacional da Vigilancia Sanitaria (ANVISA)
Esplanada dos Ministerios, Bloco G,
9o andar, sala 900
cep: 70058-900 Brasilia DF
Brazil
Bureau of Biologics and Radiopharmaceuticals (BBR)
Health Protection Branch (HPB)
Health Canada
L.C.D.C Building # 6 (0603 C)
Tunneys Pasture 0603C
Ottawa, Ontario K1A OL2
Canada
Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED)
National Regulatory Authority of Cuba
Centro para el Control Estatal de la Calidad de los Medicamentos CECMED
Ave. 19, No 21002 entre 210 y 214
Atabey Playa
Ciudad Habana
Cuba
Food and Drug Administration
Center for Biologics Evaluation and Research
1401 Rockville Pike, Suite 2000
Rockville, MD 20852
USA
Europe
General Pharmaceutical Inspectorate
Ministry of Social Affairs, Public Health and Environment
Bd Bishoffsheim 33
1000 Brussels
Belgium
2 3 WHO/IVB/05.23
Bulgarian Drug Agency
26 Yanko Sakazov Blvd
1504 Sofia
Bulgaria
Danish Medecines Agency
Axel heides Gade 1
2300 Kobenhavn 5
Denmark
Agence franaise de Scurit Sanitaire des Produits de Sant
Direction de lInspection et des Etablissements
143-147 boulevard Anatole France
93285 Saint Denis Cedex
France
National Institute of Pharmacy
Zrinyi utca 3, Budapest
H - 1051
Hungary
Ministero della Salute
Lungo Tevere Ripa 1
00153 Roma
Italy
Paul-Ehrlich-Institut
Paul Ehrlich Strasse 51-59
Postfach 1740
D-63225 Langen
Germany
Medecines Evaluation Board (MEB)
PO Box 16229
2500 BE The Hague
T: 31-70 356 74 00
F: 31-70 356 75 15
Visitors address: Kalvermarkt-53
2511 CB The Hague
The Netherlands
Swissmedic
Swiss Agency for Therapeutic Products
Hallerstrasse 7
CH-3000 Bern 9
Switzerland
Guidelines on the international packaging and shipping of vaccines 2 4
Medicines and Healthcare Products Regulatory Agency (MHRA)
Department of Health
Market Towers
1 Nine Elms Lane
London SW8 5NQ
United Kingdom
South-East Asia
Drugs Controller General of India, DCG(I)
Directorate General of Health Services
Ministry of Health and Family Welfare
Nirman Bhawan, New Delhi 110 011
Government of India
India
Directorate General of Drug and Food Control
Ministry of Health
Jalan Percetakan Negara 23
Jakarta Pusat 10560
Indonesia
Western Pacific
Therapeutic Goods Laboratories (TGAL)
Therapeutic Goods Administration
P.O. Box 100, Woden
ACT 2606
Australia
Pharmaceutical and Medical Safety Bureau
Ministry of Health, Labour and Welfare
1-2-2 Chome, Kasumigaseki
Chiyoda-ku, Tokyo 100-8916
Japan
The Korea Food and Drug Administration (KFDA)
5 Nokbun-Dong Eunpyung-Ku
Seoul, South Korea
Republic of Korea
2 5 WHO/IVB/05.23
Insulated packaging occupies up to 8.5 times the volume of the vaccine that it contains.
If insulated boxes are to be re-used for further vaccine distributions in the country,
they cannot be nested. If they are to be kept, provide sufficient storage space so
that they can be stacked. Bulking factors for insulated packaging based on the
prequalified vaccines list (as of 1 April 2005) are given in the table below.
Bulking factors for insulated packaging
Vaccine type Dose per vial Bulking factor
BCG (freeze-dried) 10 or 20 5.5
DTP, DT, Td,TT 10 4.5
DTP, DT, Td,TT 20 5.5
2 3.0
10 5.0
1 4.0
10 3.5
DTP-HepB+Hib 1 or 2 3.5
1 4.0
HepB 1 in UNIJECT 5.5
2, 6, or 20 5.0
10 7.5
Hib (liquid) 1 or 10 4.5
1 3.5
10 4.0
Measles (freeze-dried) 10 5.0
1 4.0
10 6.0
MR (freeze-dried) 10 5.0
Meningitis A&C 20 or 50 4.0
OPV 10 or 20 6.0
TT in UNIJECT 1 5.5
5 6.5
Yellow fever 10 4.0
20 5.0
Diluents and droppers n/a 1.5
Annex 4:
Bulking factors for insulated packaging
MMR (freeze-dried)
DTPHepB
DTPHib
Hib (freeze-dried)
Guidelines on the international packaging and shipping of vaccines 2 6
If the packaging volume is critical, countries should obtain accurate dimensions from
the procurement agency or, in case of direct procurement, directly from the vaccine
manufacturer.
2 7 WHO/IVB/05.23
This report is to be filled in by authorized staff, ratified by the Store Manager or
the EPI Manager, and forwarded to UNICEF within 3 days of vaccine arrival.
Use one report for each vaccine in the shipment.
1
Annex 5:
Vaccine Arrival Report
Guidelines on the international packaging and shipping of vaccines 2 8
No. = number
1
WHO recommends that all UN agencies, countries and non-governmental organizations procuring vaccines
adopt this report.
COUNTRY
REPORT No.
Place, Date and Time of Inspection Name of cold store, date and time vaccines entered into cold store
PART I-ADVANCE NOTICE
MAIN DOCUMENTS Date received by Copy airway bill Copy of packing list Copy of invoice Copy of lot release
consignee (AWB) certificate
Pre-advice
Shipping notification Yes No Yes No Yes No Yes No
List other documents (if requested)
PART II- FLIGHT ARRIVAL DETAILS
AWB number Airport of Flight No ETA as per notification Actual time of arrival
destination Date Time Date Time
NAME OF CLEARING AGENT: ___________________________ ON BEHALF OF: ______________________________________
PART III- DETAILS OF VACCINE SHIPMENT
Purchase order No. Consignee Vaccine description Manufacturer Country
(Type and doses/vial)
Vaccine Diluent/droppers
Lot number Number Number Expiry Lot number Number Number Expiry
of boxes of vials date of boxes of units date
(Continue on separate sheet if necessary)
Yes No Comments
Was quantity received as per shipping notification?
If not, were details of short-shipment provided prior to
vaccine arrival?
Date of report
Vaccine arrival report
2 9 WHO/IVB/05.23
Report No.
PART IV-DOCUMENTS ACCOMPANYING THE SHIPMENT
Invoice Packing list Lot release certificate Vaccine arrival report Other
Yes No Yes No Yes No Yes No
Comments
PART V- STATUS OF SHIPPING INDICATORS
Total number of boxes inspected
Coolant type: Dry ice Icepacks No coolant
Temperature monitors present: VVM Cold chain card Electronic device
PROVIDE BELOW DETAILS OF STATUS ONLY WHEN PROBLEMS ARE OBSERVED:
Box Lot Alarm in Vaccine vial monitor Cold Chain Monitor Date/time of inspection
number number electronic device
Yes No 1 2 3 4 A B C D
(Continue on separate sheet if necessary)
PART VI- GENERAL CONDITIONS OF SHIPMENT
What was the condition of boxes on arrival?
Were necessary labels attached to shipping boxes?
Other comments:
(continued in separate sheet if necessary)
PART VII- NAME AND SIGNATURE
___________________________________ ___________ ______________________________________ ____________
Authorized Inspection Supervisor DATE Central Store or EPI Manager DATE
For UNICEF Country Office use only
Date received by Country Office: _______________________ Contact Person: ________________________________________
Guidelines on the international packaging and shipping of vaccines 3 0
Guidelines for completing the Vaccine Arrival Report
The Vaccine Arrival Report (VAR) is a comprehensive record of cold-chain conditions during transport and of compliance
with shipping instructions. Recipient governments, UNICEF country offices and the UNICEF Supply Division are
responsible for the report and for taking appropriate action if problems are reported (e.g., follow-up with the
manufacturer, forwarding agent, WHO, etc.).
Use one report form for each shipment and for each vaccine in the shipment. In shipments containing
diphtheriatetanuspertussis (DTP)Hepatitis B (HepB) and Haemophilus influenzae type b (Hib) vaccines,
use one form for DTPHepB and a separate form for Hib. In the case of short-shipments (where parts of the original
quantities are not delivered), complete a separate report for each part delivered.
Complete the form as described below. In the header boxes at the top of the form, enter the name of
recipient country, report number and details of place and date of inspection and storage. The report number is
an internal number for organizing records; compile it as follows: country codeyearnumber for each report
(e.g., BUR2005001 for one vaccine; BUR2005002 for a second vaccine etc.). In the case of a short-shipment,
the numbers for the separate deliveries would be, for example, BUR2005003.1, BUR-2005-003.2 etc.
Part I Advance notice
I.1 Enter dates and details of documents received in
advance of the vaccine shipment.
Part II Flight arrival details
II.1 Fill in details of expected and actual arrival times
for the shipment.
II.2 Fill in the name a) of the clearing agent and b) for
whom the agent acts (e.g. the ministry of health or
UNICEF).
Part III Details of vaccine shipment
III.1 Fill in details of the order (purchase order number,
consignee, vaccine description etc.).
III.2 For each batch of vaccine included in the shipment,
record:
a) the number of shipping boxes,
b) the number of vials, and
c) the expiry date.
The number of boxes you enter should always match the
number of boxes shown in the packing list. If it does not,
note (under Comments) if advance notice of a change in
the quantity was provided. It is not necessary to count the
number of individual vaccine packs in each shipping box
for this report.
III.3 For the diluents and droppers (if included) with
each batch of vaccine in the shipment, record:
a) The number of shipping boxes,
b) the number of vials, and
c) the expiry date.
The information for III.2 and 3 is also in the packing list.
Note: Diluents for freeze-dried vaccine and droppers for
oral polio vaccine (OPV) are integral parts of the vaccine,
so al ways i ncl ude them on the same form.
If diluent/droppers are delivered separately, consider it a
short-shipment.
Part IV Documents accompanying shipment
The packing list should indicate which box contains the
shipping documents (usually Box 1).
IV.1 If this information is not included in the packing list
or in documents sent separately by courier, pouch
or other means, note this under Comments.
IV.2 Verify that all necessary documents are 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
Inspect the temperature monitors in all boxes before
putting vaccines into cold storage. For very large
shipments, or when immediate storage in the shipping
boxes is required, check a representative number of
boxes before placing the shipment in the cold store.
Complete inspection of all boxes the next day, or as soon
as possible thereafter; under comments, note the date
and time when the complete inspection took place.
Note: In this report, enter the information below (V.1) only
for boxes in which the temperature monitor shows a
change that indicates potential damage to vaccines
(vaccine vial monitor = stage 3 and 4, cold chain monitor
card as per vaccine/threshold table in card, or alarm
indication in the electronic device).
V.1 Enter:
a) the number of boxes inspected (this should
equal the total number in the shipment),
b) the type of coolant used, and
c) details of any temperature exposure,
if detected.
V.2 Photocopy or scan LCD screens in electronic
devices that show alarm status and attach to report.
V.3 Clearly identify vaccines in boxes in which the
indicator shows exposure to temperatures that risk
damage and keep them in the cold room for further
assessment of their condition. Do not discard
vaccines until assessment is completed.
PART VI General conditions of shipment
VI.1 Indicate if the shipping boxes were received in good
condition and if all necessary labels on the outside
of the shipping boxes were present; add any
comments.
PART VII Name and signature
VII.1 The authori zed person responsi bl e for the
inspection and the Central Store Manager or the
EPI Manager should sign this report.
VII.2 Send the form, completed and signed, to the
UNICEF Country Office within three days of
arrival of the vaccine; they will forward it to the
UNICEF Supply Division (Immunization Team
Fax: +45 35269421).
Department of Immunization,
Vaccines and Biologicals
Family and Community Health
World Health Organization
CH-1211 Geneva 27
Switzerland
Fax: +41 22 791 4227
Email: [email protected]
or visit our web site at: http://www.who.int/vaccines-documents
The World Health Organization has managed
cooperation with its Member States and
provided technical support in the feld of
vaccine-preventable diseases since 1975.
ln 2003, the offce carrying out this function
was renamed the WHO Department of
Immunization, Vaccines and Biologicals.
The Departments goal is the achievement
of a world in which all people at risk are
protected against vaccine-preventable
diseases. Work towards this goal can be
visualized as occurring along a continuum.
The range of activities spans from research,
development and evaluation of vaccines
to implementation and evaluation of
immunization programmes in countries.
WHO facilitates and coordinates research
and development on new vaccines and
immunization-related technologies for viral,
bacterial and parasitic diseases. Existing
life-saving vaccines are further improved and
new vaccines targeted at public health crises,
such as HIV/AIDS and SARS, are discovered
and tested (Initiative for Vaccine Research).
The quality and safety of vaccines and other
biological medicines is ensured through the
development and establishment of global
norms and standards (Quality Assurance and
Safety of Biologicals).
The evaluation of the impact of vaccine-
preventable diseases informs decisions to
introduce new vaccines. Optimal strategies
and activities for reducing morbidity and
mortality through the use of vaccines are
implemented (Vaccine Assessment and
Monitoring).
Efforts are directed towards reducing fnancial
and technical barriers to the introduction
of new and established vaccines and
immunization-related technologies (Access to
Technologies).
Under the guidance of its Member States,
WHO, in conjunction with outside world
experts, develops and promotes policies and
strategies to maximize the use and delivery
of vaccines of public health importance.
Countries are supported so that they
acquire the technical and managerial skills,
competence and infrastructure needed to
achieve disease control and/or elimination
and eradication objectives (Expanded
Programme on Immunization).