There is an endless litany of logistics issues to consider when conducting a clinical trial – and plenty that can go wrong. Highly skilled and experienced clinical trials Program Managers within CROs are as coveted as a major league utility infielder with a .300 batting average. These program managers bear a great deal of responsibility and are counted on for their expertise in the coordination and oversight of the entire project from protocol execution and site selection, to resource allocation and results management. They are also required to possess considerable knowledge of supply chain management. They may not be self-proclaimed experts in this arena but the good ones know where, when and to whom to turn.

This jack-of-all-trades approach to clinical trial program management is necessary considering the nature of the clinical trials process, which generally operates in a chaotic series of fits-and-starts. As batch lots of the drug are manufactured, Clinical Trial Managers are hard at work aligning their research participants. The lot is distributed to the research facilities, the drugs administered to the subject patients, and the data are collected. Depending on the protocol and the dosage, months may go by as the results are collated and analyzed before the process begins again.

This first occurs during Phase II of the clinical trial process, the stage of drug development where all the toxicology testing has been successfully completed, and a small population of patients (up to several hundred) is selected to assess the drug’s short-term safety and determine its effectiveness. To use another baseball metaphor, it’s like spring training, although this can take anywhere from a few months to two years.

There is little difference between Phase II and Phase III Clinical Trials. Phase III represents a massive scale-up of what was analyzed and learned from Phase II and processes for commercializing the product are put into motion. This can include the installation and validation of new filling equipment, or other manufacturing processes, accelerated stability studies, cycling studies, drug presentation, marketing, and special packaging considerations.

Because of the magnitude of Phase III Clinical Trials, which can include thousands of subject patients, multiple countries and as much as four years of data collection, it is the most expensive part of the drug approval process. Producing good, “clean” data during Phase III trials is absolutely critical. To that end, every research center that participates in the trial uses exactly the same protocol to insure that the information collected can be accurately compared. Good clinical trial managers attempt to eliminate or at least minimize every possible variable that may adulterate the results, or otherwise cloud, muddy or add noise to the data. Failure to do so may be a costly mistake and can delay the drug’s approval.

Too often drug and performance variability is related to temperature exposure or temperature cycling during transport. Availability of stability data related to this process is usually limited during Phase II. It is widely accepted that the effects of temperature on a drug can have a significant impact on its quality, efficacy, purity, potency and safety. Without sufficient temperature stability data (or inconclusive stability or cycling data), temperature control of clinical trial materials during storage and transport is essential. It is also coming under greater scrutiny from regulatory authorities.

For these reasons, eliminating variability that can be the result of temperature exposure during transport can be achieved by using qualified packaging and incorporating data monitoring devices with the shipment of clinical trial drugs and patient samples. The correct packaging provides with a high degree of certainty, protection against possible temperature extremes within the distribution environment and temperature data loggers can provide documented evidence if environmental parameters have been maintained or if limits have been exceeded.

The hurry-up culture of the clinical trials market does not lend itself well to designing, developing, and implementing qualified distribution packaging. This process requires a considerable investment and can typically take several months to complete. Therefore, to meet the demand of this segment of the healthcare industry, a number of reputable packaging manufacturers have developed “off-the-shelf,” performance-driven insulated packaging systems. Often referred to as “pre-qualified containers,” these packaging systems are capable of protecting products contained within them from a wide range of temperature extremes and shipping locations. Some are more robust than others, some are reusable, and some come with a documented qualification report at additional cost which can be used as supporting documentation in regulatory submissions. They are massively over-engineered to meet a broad spectrum of customer needs, distribution environments and shipping durations. You can read between the lines here and conclude that they are not inexpensive. But they fill a critical need and the demand for such packaging is great as all of this comes at a time when the push for a drug to market is nearing critical mass. On average, the drug sponsor has six-and-a-half years invested at this point. They are in the home stretch, but a high percentage of the drugs that made it through Phase II will still fall out of the race during Phase III, never making it to the finish line. And making it to the finish line does not guarantee FDA approval. Patents by the innovator are filed when the drug is first discovered and is generally good for a period of 20 years. But it can take as many as 10 or 12 years after discovery to accumulate enough data to get a drug past the FDA. Once the patent expires, 80% or more of the brand name version’s revenues can vanish within a year as generic competitors invade the market. When you consider that each day that passes before the drug is approved is a day of lost revenue, mistakes and miscues can result in a much greater cost.

Consider the following fictitious example:

Lazarus Pharmaceuticals is in Phase III of a potential blockbuster drug called Heartsaphaylin. The first-year estimate of sales is a modest $400 million. Every day they don’t get the drug to market is a loss of $1,095,890.00 in just the first year. How reckless does one have to be to ignore those numbers? The expense of qualified packaging as part of an overall supply chain solution for clinical trial programs is pretty cheap insurance in the long run.

As a Phase III trial progresses, data supporting a broader range of storage temperatures or transport temperatures has likely been collected and justification for use can be submitted in the filing for final approval. Regulators often look for data to support their packaging solutions and logistics choices. This is an opportune time for companies to set their focus on product launch and begin to mine for a reduction in packaging costs. As a drug moves from clinical trial to the commercial side of manufacturing, there is sufficient time to develop and implement final, qualified, right-fit packaging so that they can hit the ground running with confidence on the day of final regulatory approval.

Kevin O’Donnell is director and chief technical advisor to industry at Tegrant Corp., ThermoSafe Brands. He can be reached at kevin.o’donnell@tegrant.com. His blog, Where Cooler Heads Prevail, can be found at www.coolerheadsblog.com/blog.