Drugs shipped by truck, train, ship, or aircraft can be subjected to temperatures ranging from far below zero to well above
100 °F, sometimes during the same trip. Exposure to these extremes can be disastrous for temperature-sensitive products. In
less severe cases, shelf life can be shortened. In worst-case scenarios, product can be ruined, resulting in losses that can
add up to hundreds of thousands of dollars.
To help pharmaceutical manufacturers protect temperature-sensitive products during shipment, the Parenteral Drug Association (Bethesda, MD,
http://www.pda.org/) has published a guidance document drafted by its Cold Chain Management Task Force and reviewed by technical experts from
the industry. Several years in the making, "Technical Report No. 39: Cold Chain Guidance for Medicinal Products: Maintaining
the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment" discusses how to develop protective
packages and systems to provide "thermally controlled transportation" (1). The guidance also aligns with the Center for Drug Evaluation and Research's (Bethesda, MD,
http://www.fda.gov/) "General Principles of Process Validation: Component Qualification (CQ), Operating Qualification (OQ), and Performance Qualification
Stability studies. Determining how to protect products depends heavily on stability studies. Actual studies are needed because "Long-term storage
or label storage temperatures may be different from short-term shipping/distribution temperatures" (1). Three types of studies
should be undertaken to address temperature control issues: long-term, accelerated, and temperature excursion. Temperature
excursion studies are particularly important because it's not uncommon for shipments to be exposed to conditions outside anticipated
extremes because of weather, delays, equipment malfunctions, mishandling, or other causes.
Multiple layers of CrioMED Plus insulated bag protect product inside from temperature extremes.
All levels of packaging from primary container–closures to distribution packaging affect the product's thermal stability and
should be included in the testing program. In fact, "The more empty space within the secondary package not utilized by the
thermal mass of the product, the more difficult it is to control the system thermally" (1).
Developing a protective system. The development of a thermally protective system begins with the creation of a functional requirements document and the specification
of components such as insulated containers and refrigerants. The functional requirements document includes the critical parameters related to the packaging and transport systems such as the types of vehicle, routes, trip
duration, product stability, likely temperature range of exposure, and packaging. The component specification is a detailed description of requirements for features such as material composition, mechanical characteristics, dimensions,
printing, storage, sampling, weight, insulation, calibration limits, fragility limits, and shock and vibration limits.
Design testing is the next step. "The outcome of design testing assures a high confidence for successful operational qualification
of a specific package or system," the report explains (1).
Then, qualification testing is "performed using the designated configuration to provide assurance that product quality
is maintained during transport." Both design and qualification testing results should be documented in a formal report (1).