Introduction
International shipping of vaccines is the first leg of the complex journey that vaccines undertake to reach the end users in a country. Particular challenges include the size and weight of packages, implementation of quality control checks at reception, ensuring environmental sustainability, and maintaining required temperatures during the journey. Air freight currently remains the most widely used means of transport for vaccines. Manufacturing Vaccines is one challenge and reaching the manufactured vaccines to end user is another challenge!
In order to protect the vaccines from exposure to both extreme temperatures and physical damage during international air transportation, WHO requires manufacturers to pack and ship vaccines in insulated shipping containers. The vaccine should be kept at recommended temperature range during transport with the help of coolants packed inside the shipping containers.
Classification of vaccines for packaging
Vaccines are classified into three categories for their packaging for international air shipments on the basis of their thermostability and presentation.
Use of coolants in international air shipments
WHO recommends use of water-based packs (frozen or chilled depending on the class of packaging) or packs with phase change materials (PCM). All vaccine manufacturers are encouraged to qualify their class A and class B packaging with frozen packs or appropriate phase change materials
Diluents in international air shipment
Diluents for lyophilized 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 unless specifically requested by the manufacturer. However, it should be noted that two different temperature regimes cannot be marked for the shipment that is on the same airway bill (AWB) according to IATA rules. If freezing temperatures are requested to be maintained throughout the air shipment, the manufacturer must submit supportive data to demonstrate that freezing has no impact on the diluent and no impact on the physical integrity of the ampoule/vial/tube as it relates to the quality, safety and potency of the vaccine. The same requirement is in place for the lyophilized vaccines that are bundled in one secondary package with their diluents. In the absence of such supporting data, for lyophilized vaccines bundled in the same packaging with their diluents, Class C packaging would apply.
General packaging criteria
WHO requires manufacturers to qualify their shipping containers in refer to technical supplements to WHO Technical Report Series, No. 961, 2011 – Annex 9: Model guidance for the storage and transport of time-and temperature-sensitive pharmaceutical products
Weight and size of insulated shipping cartons
Insulated containers (cartons) used for shipping vaccines should not weigh more than 50 kg each at full weight. Any voids in the container should be filled with dunnage. Cargo covers may be used as an additional risk mitigation approach. The use of stretch wrap or other plastic films applied over cargo covers should be avoided where possible; it can create greenhouse effect if exposed to strong sunlight which can significantly reduce the effectiveness of the insulation materials below.
Active vs. passive air shipment systems
Active air shipping system is a dedicated portable container, which may be one of two types: systems with cooling only and systems with both heating and cooling.
WHO recommends use of passive container systems for international air transport of vaccines, unless use of an active system is specifically requested by the UN procuring agency. Passive systems maintain a temperature-controlled environment inside an insulated enclosure.
Transport route profiling qualification
The initial route profiling exercise should be carried out before actual products are distributed. Historical route profile data used for the shipment of other vaccines can be used to qualify packaging for new vaccines. The fundamental purpose of a transport route profiling study is to collect temperature data that accurately represent real distribution practice. Once a representative ambient profile has been derived it can be used to qualify a shipping system.
Qualification of shipping containers
Every shipping container system must be fully qualified to show that it is “fit for purpose” and capable of maintaining a vaccine within the temperature range needed to meet the product manufacturer’s stability profile, under the anticipated transport conditions.
Method A (operational qualification) uses the collected route profile data to create a statistically robust test profile; this can then be used as a basis for testing proposed packaging solutions under laboratory conditions in a temperature- controlled test chamber.
Method B is an empirical rule-of-thumb approach, for use where the performance of the proposed passive container is already known, because it is based on a simple empirical calculation, it is strongly recommended that this method should only be used for in-country transport operations
WHO does not recommend use of Method B for qualification of international shipping containers since real life temperatures may fluctuate above and below 0.0°C.
The PQ stage is mandatory in all cases, except where every shipment on every route is monitored. PQ is conducted as a field test in the real operating environment. As with the OQ, PQ tests must be performed three times.
Manufacturers are requested to file the following reports in support of qualification of their shipping containers:
transport route profiling study results,
operational qualification (OQ) of the shipping container, and
performance qualification of the shipping container.
Electronic data integrators for international shipments
WHO recommends that one electronic data integrator is included in each and every shipping container. For shipping containers exceeding 800 mm in height, it is recommended that two devices should be used and positioned according to the cold and hot spots identified by thermal mapping
EDIs must be started when vaccine is packed in tertiary package and must be capable of recording data for the planned duration until receipt. Diluents that are packaged separately are not required to have a temperature monitoring device except in the case where diluent is freeze sensitive. Use of temperature monitoring devices powered by lithium batteries should be avoided.
Primary container- A first level package presentation that is in direct contact with the product itself.
Secondary pack-The package presentation intended for the end-user (e.g., bottle + cap liner + dose cap + leaflets + carton).
Tertiary pack- The pack or carton that contains a number of secondary cartons or grouping cases.
Specifications of the electronic shipping indicators
Type 1 and Type 2 devices are now renamed ‘A’, ‘B’, or ‘C’, in line with the packaging type.
Type A/B – previously called Type 2: WHO-recommended alarm settings for international shipments
Type C – previously called Type 1:
Shipment information card
Each electronic device should be mounted on a moisture resistant backing card, using moisture resistant adhesive. The card material must accept indelible markings in ball point pen. The width of the card must be at least the same as the length of the device, subject to a minimum width of 7.5cm. The length of the card must not exceed 14cm. The card design must follow the generic format (yellow for Type C and blue for Type A/B). User instructions must be available either in English, French or Spanish language, as requested by the customer. Text must be in a high legibility font – minimum 8 point, colour black.
The below tables provide instructions for the receiver about the actions to take in the case of alarm. Information to be displayed on the backing card of electronic device – [Type A/B previously called Type 2]
Information to be displayed on the backing card of electronic device -(Type C previously called Type 1)
Impact of packaging type on temperature excursions
A/B type packaging uses frozen icepacks, because this category packaging includes OPV and only other vaccines that are not affected by freezing. In principle, the temperature in the vaccine load section of the container is always at negative degree Celsius in the beginning of the shipment. As a result, there is a very low probability of a high temperature alarm with this category packaging.
The vaccine load of the shipping container is at 2-8°C in the beginning of the shipment of C type packaging. High temperature alarms are therefore more likely compared to class A/B type packaging.
Volume per dose for calculating necessary storage
For primary containers (vials)
Vaccines in presentations from one to five 0.5-ml doses are recommended should be filled in a “2R” vial conforming to ISO (International Organization for Standardization) 8362 dimensions.
Vaccines in presentations of six to ten 0.5-ml doses should be filled in a “4R” vial conforming to ISO 8362 dimensions.
Vaccines in presentations of twenty 0.5-ml doses should be filled in a “10R” vial conforming to ISO 8362 dimensions.
For vaccines with a dose size less than 0.5ml the most compact of these three vial sizes should be used, depending on the number of doses in the presentation.
It is recommended that for vaccines with a dose size greater than 0.5ml, the most compact of these three vial sizes be used, depending on the number of doses in the presentation.
For secondary packages
It is recommended that secondary cartons should contain vials in one or more of the following formats:
10 vials in an array of 5×2 vials,
25 vials in an array of 5×5 vials,
50 vials in an array of 5×10 vials,
100 vials in an array of 10×10 vials.
Note-The images given for representation in this blog are taken from Google Images. Many thanks for Google.
Value added information
Thank you Srikanth