Biologics Storage: Getting It Just Right


Is your patient’s refrigerator the problem with the inefficacy of biologic therapies?

Jack Cush, MD, discusses the ideal storage conditions

Biologics agents such as adalimumab (Humira), golimumab (Simponi), and ustekinumab (Stelara) should be stored at a temperature of 2-8°C (35.6-46.4°F). Several studies have identified a prevalent problem of unacceptable refrigeration storage of biologics used to treat immune-mediated inflammatory disorders (IMID), such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

 Dutch researchers studied 50 patients who received golimumab packaged with a temperature sensor that recorded sample temperature every 5 minutes. Patients were told to store their medication as usual. Temperature deviations were defined as any duration below 0°C and >30 minutes below 2°C or above 8°C.

After 3 months, data from 276 injectors and nearly 2.5 million temperature assessments showed that only one in eight (11.6%) were stored within the recommended temperature range. In addition, 11.2% were stored >30 minutes below 0°C and 33.2% were stored >1 week above 8°C. The authors suggested these findings may affect drug effectiveness in IMID-patients.

In 2016, another group from the Netherlands performed a similar observational study of patients given biologics with a temperature sensor. A majority (87.0%) of patients returned their temperature recordings to the pharmacy.

Only 6.7% stored their biologic within the recommended temperature range. Over 24% stored their drug for more than 2 hours below 0°C (median duration 3.7 hours) and 2% stored drug at temperatures above 25°C (median duration 11.8 hours).

An editorial in the Journal of Gastroenterology and Hepatology pointed out that none of these investigators studied the clinical impact of these missteps in drug storage. Thus it is unknown if the efficacy, viability, bioavailability or even the immunogenicity of these agents would be altered under these temperature variations. Changes in the complex protein structure of biologics may result from freeze-thawing or prolonged storage at elevated temperatures, and may lead to denaturation, irreversible formation of protein aggregates, and loss of biological activity.

Recommendations

  • Store biologics at 2-8°C; when taken out of the refrigerator, agents should be kept at room temperature less than 25°C
  • Studies have shown that etanercept (Enbrel) may be safely stored at room temperature conditions of 25°C ± 2°C (77°F) for up to 1 month
  • Discard drugs that have been frozen or improperly storage (call pharmacy or manufacturer for a replacement)
  • Pharmacists and nurses must counsel patients on the importance of storage conditions
  • There are companies developing apps to monitor drug temperature and usability
  • Manufacturers should develop and incorporate temperature-sensitive warning devices that can be incorporated into packaging.
  • Tell patients to avoid storing biologics in lower CRISPER Drawers, were the temperature is always lower (usually below 2°C or below 36°F). The lower temperature in the Crisper is optimal for storing produce and meats.

Finally, I advise patients who are traveling to either take their biologic a few days earlier or later to avoid traveling with drug, or if they travel with a biologic, keep it in a cool, dark, and dry place. Remove the agent from the refrigerator, wrap the injectable syringe in bubble wrap or light insulation (no need for an ice chest or dry ice), put it in a purse or briefcase, and bring the box label. The syringe is safe on planes and hotels as long as it’s at room temperature, away from sunlight or heat.

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