For several years, the pharmaceutical industry has been moving away from primarily chemical and synthesized based drugs toward biologics. And while research and development is complex for all types of drug therapies, biologics have special challenges since they are made of up living microorganisms and cells. This is especially true where logistics is concerned – whether related to R&D, clinical trials or, ultimately, getting a drug to market.
To start biologics must be handled within a strict temperature range, usually between 2° and 8° Celsius with little or no room for error. Chemical and synthesized drugs are often less temperature and time sensitive. The cost of biologics is a factor as well. While some classical, chemically based drugs are still expensive to produce, they are easier to replace should something go wrong during transport. A similar error can be financially devastating when it comes to biologics,
especially for today’s small and mid-sized biotech firms.
The commodities that present the most significant challenges include:
In addition to a lengthy and costly production process, vaccines are highly temperature sensitive with a very small TOR (time out refrigerated) – sometimes even a TOR of 0. That means a vaccine is compromised if the temperature fluctuates outside the range needed for it to remain stable, again typically between 2 and 8 degrees Celsius. Since vaccines are a liquid form, it’s particularly dangerous for the temperature to drop too low because once it solidifies and thaws it can no longer be injected into a patient.
The key is to determine the right type of packaging, which depends mainly on the size of the shipment:
For smaller shipments, one-time use or reusable thermal packaging using phase changing material (PCM) and Vacuum Insulated Panels, may be appropriate
Larger shipments, such as pallets, or even very expensive or sensitive vaccines may require a more sophisticated solution such as an Envirotainer, which allows for temperatures ranging from refrigerated to controlled ambient to be set and maintained electronically
Time is also an issue when moving vaccines, especially when shipping into countries with very strict regulations. In some cases, customs can take days and less expensive systems are not an option since they only provide a maximum of 72 hours validation, even when placed in a cold room. The best course of action is to use PCM with vacuum insulated panels. These have a validation that can last up to 168 hours and sometimes even several additional days when place in a cold room.
You can learn more about managing temperature controlled shipments in our white paper: "Best Practices in Cold Chain Logistics Planning"
2. Peripheral Blood Mononucleated Cells (PBMCs)
In the human body, PMBCs are an important part of the immune system. For the purposes of developing new biologics and vaccines, they are extracted from whole blood that is drawn from patients as a part of a clinical study. As a result, they are not replaceable – making any mishap during shipment unacceptable.
PBMCs are highly temperature sensitive. Once separated from whole blood they need to be contained in liquid nitrogen and kept at -196° Celsius, never going above -150°. To achieve this, PBMCs should be transported in a dry shipper. The dry shipper is filled with liquid nitrogen, which absorbs any humidity in the air and holds the necessary temperature. Dry shippers are then moved from one area to another in a larger box, and are usually able to maintain the necessary temperature for 8 to 10 days.
This type of packaging is not rechargeable, so PBMC shipments are time sensitive and must be monitored closely, especially in those countries where customs can be complicated.
Considered the new era of personalized medicine, the research and development associated with biologics such as monoclonal antibodies is extremely costly. For example, the average manufacturing cost for monoclonal antibodies is estimated to be between $650 million and $750 million over the course of 8 or 9 years.
The living systems used to produce biologics can be sensitive to very minor changes in the manufacturing and the distribution process. Small process differences can significantly affect the nature of the finished biologic and, most importantly, the way it functions in the body.
This is exacerbated by the fact that many of the firms doing work in this area are small and medium sized biotech companies (although big pharma is also now very involved). However, unless the smaller players have the backing of a large biotech or big pharma, they have only state subsidies, bank loans or an IPO to fall back on for funding their product development. If the product is compromised during transport, the associated clinical trials are likely to feel an impact if the product cannot be replaced on time due to both the lengthy process as well as insufficient budgets.
As a result, biologics often have a TOR of 0. The majority (80%) must be stored or shipped at between 2 and 8 degrees Celsius.
4. Whole Blood
Whole blood has a very short life span and begins to degrade and lose its properties with each passing hour. Since it must be as fresh as possible for clinical trials, the primary challenge when transporting whole blood is time sensitivity. When extracting PBMCs or platelets, for example, the blood must arrive at its destination within two hours of being drawn. The maximum amount of time that whole blood can remain viable, however, is 22 hours depending on the study requirements.
As a result, dedicated drive or charter flights are usually the only option for moving whole blood. In some cases it may be possible to use a regular carrier as long as there are back up flights available. Temperature can also be a factor, especially where platelets are concerned. While some labs might accept ambient room temperature, more and more are asking for a controlled ambient temperature of 15 to 25 degrees Celsius.
During a clinical trial biotech/pharma firms need to compare their drug against the industry leader. These samples must be purchased, and obviously a competitor is not going to give researchers specific logistics instructions. In this case, the shipment should be considered to have a TOR of 0, removing any room for error. Taking this approach protects the drug and the company from potentially having to repurchase comparators in the event they are compromised during transport.
In addition, the manufacturer of the first molecule is unlikely to provide any kind of data such as to the stability of the drug, especially when dealing with first-in-class products and blockbusters. Therefore, it is important to keep the product within the defined range of temperature during transport since deviation could make justification difficult in the absence of product stability data.
All of the commodities listed are highly temperature sensitive. To learn more about managing temperature controlled shipments, download our white paper: "Best Practices in Cold Chain Logistics Planning"