In an age of precision medicine and big data, we have more opportunities to see, identify and treat disease than ever before. New direct-to-consumer testing solutions, such as 23AndMe and Ancestory.com, have made us acutely aware of our susceptibility to disease and given us renewed vigor to tackle it through new techniques and treatment pathways. However, the ability for patients to benefit from these cutting-edge new treatments – be they drugs, medical devices or biological solutions such as vaccines or gene therapies – rests solely on the success of clinical trials.
Preclinical research provides a great deal of insight into a new treatment’s safety, but clinical studies are vital to determining how a drug will affect the human body, enabling researchers to gauge toxicity and overall efficacy of the treatment to achieve the desired patient outcome. While there is always risk associated with a clinical trial, there are elements that give the study its best possible chance of success. Paramount among these factors is the storage and handling of clinical compounds at each clinical trial site. Segregation and control of clinical compounds from approved drugs can be a heavy burden at the trial sites, especially considering the increasing volume of approved temperature-sensitive drugs.
Fighting an Uphill Battle
It is every pharmaceutical company’s greatest hope to move through the clinical trial phases smoothly and successfully, coming out the other side with an FDA-approved drug that will save lives. Sadly, this is not usually the case. The latest figures on clinical trial success, reported earlier this year by Andrew W. Lo, Ph.D. and his colleagues at MIT, conclude that only 14 percent of all drug development programs will lead to approval. While this is a notably higher approval rate than previous studies (including a 2016 Biotechnology Innovation Organization (BIO) report that put clinical trial success at 10 percent), it still signifies a difficult road for pharmaceutical companies investing billions of dollars in the hope of moving experimental treatments from concept to approval.
Despite the hurdles and uncertainties, clinical trials are an unavoidable reality of the life sciences and healthcare industries and, as such, are poised for expansive growth. Industry research firm Grand View Research, Inc. predicts the global clinical trial market will reach USD 65.2 billion by 2025, driven largely by advancements in personalized medicine, new product innovations aimed at enhancing disease assessment and drug discovery, and a growing contract research organization (CRO) market. This influx in investment, paired with the increasing pace of scientific development, has the potential to rapidly augment the number of clinical trials seeking FDA approval, which currently sits at approximately 289,000 trials, according to ClinicalTrials.gov, a U.S. National Library of Medicine resource that has been tracking clinical trial data since 2000.
Protecting Your Investment
Safeguarding the cold chain of a clinical drug in transit and at the point of care can be challenging, as it can be distributed to select groups throughout the various stages of the study. For example, a Phase I trial could have as few as 20 patients involved and a patient pool of this size can create greater hurdles when it comes to ensuring proper levels of care and attention are paid to the drug’s on-site storage conditions.
This is especially problematic for rare disease trials, where patients could be widely spread out across the world. In a situation like this, a pharmaceutical company may make 100 doses of a drug that is then dispersed to 10 different sites for administration to patients. In these cases, a drug can change hands several times before it reaches the patient, putting its integrity – and thus the trial itself – into question.
As we’ve seen for years with vaccinations, there are many points at which drugs can be put in jeopardy, from their transportation to endpoint storage and administration. A study from the U.S. Department of Health and Human Services found that of 45 vaccine providers monitored, none were meeting established cold chain requirements.
On top of this, 76 percent of the providers were exposing vaccinations to inappropriate temperatures at some point before they were administered. So, while clinical drugs and vaccine supplies have different supply chains, if approved drug products are being stored in conditions deemed uncontrolled, what is happening with the storage of experimental drugs in remote locations?
Unlike formulated vaccinations, experimental formulations are highly vulnerable in the early design phase and can be put at great risk by even the smallest external contamination, which can include variations in temperature. Therefore, evident and widespread challenges with vaccine storage should give pharmaceutical companies cause for concern and prompt them to assess their partners' cold chain management practices, especially when it comes to those established to safeguard sensitive clinical trial compounds.
Question Your Cold Chain
Within large clinical trial sites, experimental treatments are segregated and kept under lock and key to avoid any cross-contamination or administration mix ups. Smaller, remote sites may not have the cold storage infrastructure or the know-how to handle the new drugs requiring tight control.
This level of oversight is particularly important for the growing area of immuno-oncology, where many of the trial drugs being studied are considered hazardous. When it comes to these types of compounds, which include chemotherapy drugs, the addition of hazardous cold storage creates another layer of complexity. Many institutions prefer to isolate these unapproved, hazardous drugs in segregated refrigeration units. When this is not possible, as is the case for many traditional hospitals that lack the space for a dedicated clinical refrigerator, these drugs may be stored in a lock box within the pharmacy’s refrigeration unit.
The infrastructure for storing and handling clinical trial drugs oftentimes falls to the healthcare institution, CRO or pharmaceutical companies which must set mandates for compound care, supervision and administration. It is up to these groups to ensure their cold chain management procedures are up to the task - even for the most sensitive of compounds - and that they are equipped to provide these small batch formulations with the same care and attention as population-wide drugs and vaccines.
Ask yourself these questions:
- Do you have confidence in your cold chain control all the way to the patient?
- Are you confident your clinical trial participants are receiving the most effective product possible?
- If you faced a recent trial failure, could your cold chain have been a contributing factor?
Putting Protections into Practice
Fortunately, many of these cold chain challenges can be addressed through more diligent oversight and the use of new refrigeration technology that ensures tight temperature stability and automates many of the meticulous processes associated with cold chain management, such as temperature monitoring.
Upgrading Storage Solutions
As with vaccines, improper refrigeration can hinder or completely invalidate an experimental drug. According to CDC guidelines, placing drugs in the center of the middle shelf of a refrigerator and surrounding them with water bottles to help stabilize the unit’s internal temperature is a proper way to minimize temperature variability of the refrigerator. However, this method is not always practical, especially in situations where storage space is limited.
Facilities that lack floor space to expand cold storage capacity may find themselves storing clinical compounds in spaces that are more difficult for healthcare providers to access but where dorm-style or residential-style refrigerators will fit. Continuous temperature monitoring of these types of units demonstrates that temperature control is often inadequate, with temperatures fluctuating by 10°C or more. In the case of vaccinations, limited space can also force healthcare practitioners to overstock refrigerators, putting airflow at risk and creating out-of-spec temperature control. This can cause a drug to freeze, affecting its efficacy. These temperature variations can be even more devastating in a clinical trial setting, where a far more sensitive and expensive formulation could be put in peril.
Today, breakthroughs from advancements in solid-state refrigeration technology are upending traditional refrigeration practices, putting perfectly-controlled cold storage closer to the point of patient care without disrupting the work environment.
This shift is allowing healthcare facilities to eliminate dorm- or residential-style refrigerators, which offer the convenience of close storage due to their size but are not adequate for temperature sensitive clinical formulations. Rather, pharmaceutical-grade, solid state refrigerators ensure consistent temperature throughout the storage cabinet, regardless of how the unit is stocked or how often the door is opened or closed.
Taking the Work out of Tracking
Once again using vaccinations as a comparison, it’s clear that temperature monitoring provides a level of assurance in the stability – and thus viability – of clinical trial formulations. With the pace and complexity of clinical trials intensifying, manual logging at clinical sites is not a reliable means of documenting the temperature controls in place for experimental drugs. Refrigeration units equipped with automated alarms for temperature and system performance, coupled with continuous temperature monitoring, becomes an important component of the trial’s quality record keeping.
With these systems in place, pharmaceutical companies can be sure that their investment is being properly protected through a detailed tracking log and real-time notifications, should temperatures fluctuate or power at the facility go out. Through these by-the minute enhancements, those handling precious clinical therapies can respond quickly, minimizing lost costs and maximizing efficacy of the formulation throughout the duration of the trial.
Setting the Foundation for the Future
As personalized medicine continues to take hold, clinical trials are sure to face greater complexity. Already we are seeing clinical trials moving into homes, more studies tackling rare disease types and companies embarking on trials that could span decades to truly assess the long-term impacts of a treatment on patients.
Considering this, we’re poised to face significantly more cold chain demands. Beyond drug administration, clinical trials require an accurate and stable means to transport biological samples for testing. With these studies spanning cities, states and even countries, we face numerous challenges we face numerous challenges that can only be overcome if we have a strong cold chain foundation in place regard that will require a strong cold chain foundation to overcome them.
While the future is certainly bright for clinical research, assessing your cold chain management functions now will enable you to approach your next clinical venture with confidence, knowing you have the tools and procedures in place to safeguard your investment for years to come.