Tuesday, 16 Oct 2018

You are here

Problems with Biologic Drug Storage

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

Biologics agents as adalimumab, golimumab and ustekinumab should be stored at a temperature of 2–8°C.  Several studies have identified a prevalent problem of unacceptable refrigeration storage of biologics used to treat immune mediated inflammatory disorders such as rheumatoid arthritis, psoriasis and inflammatory bowel disease.

de Jong and colleagues from the Netherlands studied 50 patients receiving 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 Vlieland et al performed a similar observational study of Dutch 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% were guilty of storing their drug for more than 2 hours below 0°C  (median duration 3.7 h) and 2% stored drug at temperatures above 25°C (median duration 11.8 h).  (Citation source: https://buff.ly/2DoDQ34)

An editorial by Rentsch et al in the Journal of Gasteroenterology and Hepatology points out that none of these investigators studied the clinical impact of these missteps in drug storage. (Citation source https://buff.ly/2rsxkGU)

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 ºC;  when taken out of the refrigerator should be kept at room temperature less than 25ºC
  • Studies have shown that etanercept may be safely stored at room temperature conditions of 25°C±2°C (77°F) for up to 1 month https://t.co/HMf7pcVudE
  • I advise patients who are traveling to either: A) take their biologic a few days earlier or later to avoid traveling with drug; or B) if they travel with a biologic they keep it cool, dark and dry. Remove 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 & hotels as long as they are at room temperature, away from sunlight or heat.  http://rheumnow.com/blog/tips-arthritis-travelers-best-2015-3
  • 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. https://buff.ly/2rsHJ5v
  • 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. 

 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

New BSR Guidelines on Biologic Safe Use with Inflammatory Arthritis

The British Society of Rheumatology has produced a set of NICE accredited guidelines for the use of biologic therapies in patients with inflammatory arthritis.

It addresses safety recommendations for all biologic therapies approved by the National Institute for Health and Care Excellence (NICE) up to June 2016, for use in all inflammatory arthritides [RA, PsA and axial SpA (SpA) including AS].

The Safety of Paternal Exposure to DMARDs and Biologics

Pregnancy and drug safety is a complex issue, often with limited informatoin about maternal drug exposure on the offspring. Greater uncertainty exists when considering whether paternal exposure may also influence fetal outcomes.

A systematic review examined the effect of disease modifying anti-rheumatic drugs (DMARDs) on male fertility and if peri-conception (within 3 months) paternal exposure was detrimental to fetal outcomes.

2018-2019 ACIP Recommendations for Seasonal Influenza Vaccination

The current issue of the CDC's MMWR reviews the new seasonal recommendations for vaccination against influenza. This is an update to the previous recommendations of the Advisory Committee on Immunization Practices (ACIP). 

Health Secretary Azar Eyes Rebate Reform

Reuters reports that the U.S. Health and Human Services Secretary Alex Azar had declared his agency has the authority to eliminate rebates on prescription drug purchases, a key element in the administration’s plan to lower prescription medicine costs.

Azar has said rebates created a perverse incentive to continuously raise drug prices.

Hydroxychloroquine Being Over-Dosed with New Guidelines?

Hydroxychloroquine retinopathy prevention guidelines have revised from ideal body weight-based dosing to actual body weight-based dosing; the question remains whether these have been adopted in clinical practice. A database of nearly 21,000 new HCQ users from a UK general population database studied HCQ dosing and use between 2007 and 2016. Specifically they examined whether users were subjected to excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW).