Main Chapters of Qualification of Shipping Containers
The major chapters of Annex 9 Supplement 13: Qualification of Shipping Containers include:
- Qualification Stages
- Design Qualification
- Operational Qualification
- Performance Qualification
- Materials and Test Equipment
- Qualification Protocol
- Qualification Report
The WHO have assembled their own GMP/GDP standard. It is a reflection of the current GMPs from PICS, USFDA and Europe. Attached to the standard are a number of appendix's which focus on specific knowledge areas.
Annex 9 is about Good Distribution Practices and is titled: "Model guidance for the storage and transportation of time and temperature sensitive pharmaceutical products".
Annex 9 itself is composed of 16 different sections called "supplements". This paper is reviewing the Supplement 13: Qualification of Shipping Containers.
Qualification of Shipping Containers must be performed.
Due the nature of the pharmaceutical product , any vessel that is used for the distribution of temperature sensitive goods needs to adhere to strict regulations & compliance codes. The containers need to be show they are able to do the task they are being used for; in other words, qualification of shipping containers needs to be completed.
The Qualification process covers various areas of use & performance for storage & transport of Time and Temperature Sensitive Pharmaceutical Product (TTSPP). The process is usually covered in a few main steps, each needs to be fulfilled successfully prior to the next one commencing. User Requirements for the container systems need to cover all areas of use, as stated by the pharmaceutical manufacturer. These qualifications must be documented in order to prove & demonstrate, to all concerned parties, that the packaging system can and will perform as it should.
The temperature stability of the product within the container is of paramount importance. As such the qualification package needs to be comprehensively outlined to demonstrate this.
Qualification of Shipping Containers differs from many Pharmaceutical Qualifications in that it usually only consists of three specific stages: – design, operational and performance qualification. Installational Qualification is typically not performed.
Prior to any qualification stage commencing, a full risk assessment of the life of the container must be completed. This includes the ambient environmental profile of the package as it travels from its origin to its intended destination. For each three stages of the qualification process, the packaging assembly must be fully defined, tested and documented. As part of the protocol, everything from the thermal conditioning process, (for packaging components), to the location of temperature monitors needs to be defined and documented.
It is also recommended that minimum and maximum payloads are tested and recorded to ensure all thermal load scenarios are covered.
Design Qualification (DQ)
Every new shipping container system must adhere to the expectations of the end customers User Requirement Specification. Product load specifications, ambient temperature profiles, shipping duration and allowable product temperature range should clearly be defined in the URS. Additional performance characteristics may also need to be considered for inclusion.
Approved DQ protocols are followed under laboratory conditions in order for testing to take place. Protocols outline the tests needed to assess the basic design requirements, constraints and suitability for use.
Any ‘Exception condition’ which is defined as a deviation from any given protocol must also be documented.
The packaging configurations that must be tested are: maximum & minimum loads for both a summer and winter ambient temperature challenge. The test loads should be chosen to represent the products that will be transported.
As part of the design qualification stage, simulated transport testing should also be included. This includes vibration and drop test protocols which must be satisfactorily completed prior to the Operational Qualification stage.
These tests must ensure that enough evidence is collected to prove that the container design is robust enough to withstand the environment it will be used in and to justify moving on to the OQ stage.
If a shipping system is already prequalified then this stage can be scaled back or even omitted. The only reason to complete the DQ stage is if the specifications of the system do not meet the URS.
Operational Qualification (OQ)
Systems that are Prequalified by the manufacturer may not require the OQ stage to be executed- or may be it can be scaled back.
However, if there are changes to the design of the packaging, such that the specifications of the URS are not met, then an OQ must be carried out. There may also be other reasons that justify an OQ.
OQ protocols must be carried out under "laboratory conditions" and should be clearly outline the pack out arrangements and the acceptance criteria for the shipping systems to be qualified.
As a basic overview, the OQ protocol should be guided by the test criteria developed from the initial risk assessment exercise. This will include:
- transport time periods,
- acceptable temperature ranges,
- payload details,
- ambient temperature profiles,
- location of temperature monitoring devices,
- location of refrigerant and refrigerant conditioning specifications.
- The additional criteria of vibration and drop testing may also be required.
The OQ as a whole must be approved by all stakeholders prior to qualification testing.
In order to demonstrate repeatability, the OQ tests must be conducted in triplicate. The results should successfully meet the acceptance criteria set out in the protocol.
Once the OQ is complete the results need to be documented. The report should show the test performance and compare the results with the acceptance criteria set out in the OQ protocol .
Performance Qualification (PQ)
The PQ stage is mandatory in almost all cases; except when every shipment on every route is monitored.
A PQ is conducted in the field: i.e. in the real operating environment. The PQ protocol that is developed should document the process and define the acceptance criteria. Criteria that is similar to as those defined in the DQ and OQ protocols.
The PQ protocol should be reflect:
- The current shipping operations
- the number of ship to,
- the number of ship from,
- the total number of shipments to be tested and
- the time of the year this will happen.
The PQ is important because it tests all elements of the process not just the packing system. These include:
- packing operators training and competence
- handling procedures (SOPs) and Work Instructions for packing shippers
- the fridges and freezers where the shipping systems' component are conditioned before packing
- The fringes and freezers where the medicines are stored
- The couriers handling of the parcel during transit
A final report will then compare the results with acceptance criteria.
The PQ must be repeated periodically, during different seasons, to ensure that nothing in the supply chain has changed and majorly impacted the process.
If the packaging systems are to be re-used , then they should be periodically re-qualified, to ensure that the thermal performance does not diminish with age. Some points to consider are Physical damage, material break-down or any other factors that would impact operational capacity.
The PQ Test Protocol
A completed protocol should contain the following key sections – Protocol title, Protocol approvals, Introduction, Purpose, Scope, Acceptance criteria and Responsibilities.
A step by step test procedure is then used to perform the PQ with the data generated to be defined as to how it will be interpreted in the protocol.
The PQ test should use an actual shipment to simulate payload performance within the thermal scenarios as stipulated by the URS.
The PQ Test Report
Once testing is completed, the PQ report should be written to summarise the data collected and provide conclusions based on this data. This will include any additional material to further display the data that has been generated.
Materials and Test Equipment
Operational qualification of shipping containers requires equipment situated in a controlled environment -usually a laboratory. Most importantly a thermal chamber is required where the shipping container can be placed inside and then various be exposed to various test (ambient) temperatures.
In order to complete any of the stages that are necessary to qualify storage containers for their specified purpose, a variety of equipment must be utilised.
These include – a thermal test chamber, multi-channel temperature loggers, weighing scales and packaging materials.
Wherever possible, the same equipment should be used for all stages of the qualification process.
The WHO's guide on Qualification of Shipping Containers (Passive Insulated Shippers) draws together much of the industry practise in a concise document which, oddly has not been written before. It does not go to far fetched extremes in terms of worst case testing
- WHO: Guide to Annex 9 Supplements.
- WHO Annex 9 Supplement# 8: Temperature mapping of storage areas.
- Temperature Qualification with ISTA standards.
CoolPac designs, manufactures and qualifies insulated shipping systems. Primarily they design and test their own packaging systems but also test other systems used by their pharmaceutical customers. Want more information on your cold chain? Contact [email protected]