James Baker, President of Xtract Solutions, considers the effect of temperature on drug and vial storage.
In March of 2011, we at Xtract Solutions launched our first product, the Allergen Mixing Assistant or AMA. The goal of this product was to give immunotherapy providers and specifically allergists a tool that would allow them to continually refrigerate the extracts they purchase from any manufacturer, even while mixing. As you can imagine, the only way possible to refrigerate these drugs prior to our invention would be to have your mixing staff throw a winter coat on and mix in a walk-in refrigerator, but this is certainly not practical or comfortable.
The AMA has sold modestly in its five-year existence, but I always wondered why we haven’t sold more. What I have come to find over the years, is there is a general apathy and lack of knowledge among providers of immunotherapy about the importance of refrigerating extracts for allergy shots. So I thought I would bring together in one location as much information as I could find in order to spread awareness of the importance of keeping your extracts cold all the time.
For starters, the manufacturers themselves even recommend it! The quotation below was taken from ALK’s package insert for grass pollen extract. Note that they recommend storing at 2 to 8 degrees Celsius even during use! So I know people don’t want to take our word for it because we are the ones profiting from the sale of our device, but what about the manufacturers’ themselves who have no skin in the game?
STORAGE: To maintain stability of allergenic extracts, proper storage conditions are essential. Bulk concentrates and diluted extracts are to be stored at 2° to 8° C even during use. Bulk or diluted extracts are not to be frozen. Do not use after the expiration date shown on the vial label.
This is what Holister Stier says. They use even stronger language, at all times!
STORAGE: The expiration date is listed on the container label. To insure the maximum potency of Short Ragweed extract and its dilutions, it is recommended that the product be maintained at a temperature of 2° – 8°C at all times, even during use. Dilutions are less stable than the Concentrate. If loss of potency is suspected, the product should be checked by skin testing with equal units of a freshly prepared dilution on known ragweed pollen allergic individuals.
Here is what Greer has to say about storage of extracts:
16.1 Storage and Handling Store dust mite extract at 2°-8°C (36° to 46°F). Keep dust mite extract at 2°- 8°C (36° to 46°F) during office use.
In the same product insert Greer goes on to make this statement:
The previous extract has expired or is near expiry: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under ideal storage conditions (2° – 8°C) [see How Supplied/Storage and Handling (16)]. Some loss of potency occurs even when stored under ideal conditions, therefore extracts should not be stored beyond the expiration date. Instead, a new lot should be used (see “Changing to a different lot of extract”, above).
The question this causes me to ask is what if the extracts are not kept in ideal storage conditions? What do we know about how much they degrade when they are left out during the day like 99% of clinics do currently? Through a simple Google search you can find several articles that come to a variety of conclusions such as the many studies performed by Hal Nelson at National Jewish. He is a pioneer in extract research with a 1980 article, Effect of preservatives and conditions of storage on the potency of allergy extracts, which among many things determines that 50% glycerin is the best choice for extract preservation, but too high of a percentage for treatment because it stings when injected.
This 1996 study called, Effect of dilution, temperature, and preservatives on the long-term stability of standardized inhalant allergen extracts, looked at stability of four different extracts. Cat turned out to be very stable, but the other three tested antigens were found to be less stable over the time periods tested. So this introduces the notion that there is variability between extracts and the effect of temperature on them. This muddies the water a bit more since the treatment and testing boards vary from clinic to clinic and available data on most allergens resistance to temperature in unreleased or unstudied.
Greg Plunkett also authored the study for short term exposure to high temperature that you see when shipping extracts in the summer. My take away is you can certainly have short term high temperature exposure, but questions remain over long term exposure.
Here is an article from 2013 titled: The Effects of Storage Conditions on the Stability of House Dust Mite Extracts. Here is the conclusion: “This study confirms that storage in refrigerated conditions is the most important factor in maintaining the allergenicity of HDM extracts. Addition of HSA and glycerol may increase the shelf-life of the extracts at RT, though repeated warming for use a RT can result in significant degradation.”
So my final take away is this. You should keep your extracts continuously refrigerated. Why?
- Smarter people than me think so.
- Just because no one is auditing you, or fining you for not following instructions or recommendations, is not a reason to ignore them.
- It’s in the best interest of not only you, but of your patients! Would you want to be injected with a vaccine that had lost its potency due to poor storage conditions? Then when it came time for a shot out of a vial made with high potency fresh extract you had a reaction because you were getting basically water injected before? To make matters worse, you aren’t feeling the positive effects of your treatment because the doses are not as high as they should be which is the whole point of starting shots in the first place!
At Xtract Solutions, we aren’t trying to be whistle blowers to make you buy our products. Mix in a meat locker for all I care. I’m just a bit tired of seeing a specialty ignore the elephant in the room, and in this case it’s leaving a biological drug in a non-ideal storage condition when there is an alternative.
It would seem allergy could learn from the flu vaccine storage debacle in 2012 and get ahead of the curve as a specialty.
The flu shot story also pointed out the importance of monitoring the temperature of the drugs so you know the cold chain is intact. Xtract Solutions does provide a temperature monitoring service that will alert you if the Mixing Assistant is out of temperature range for a prolonged period of time via phone, email or text. We also can provide you with a graphical monthly report with the record of the temperature over that time period. JCAHO might want to look at that log if they ever get around to auditing allergy clinics, but that’s a discussion for another blog on another day.
Thanks for reading and I hope you continue to subscribe to our newsletter.
James M. Baker
President and CEO
Other valuable links to learn more about this topic:
- CHAPTER 9 – Practice Management Resource Guide, Allergen Immunotherapy Extract Preparation Manual
- Allergen immunotherapy: A practice parameter third update, AAAAI (PDF)
- Stability of unrefrigerated allergy extract, AAAAI
- Stability of allergen extracts used in skin testing and immunotherapy, Otolaryngology & Head & Neck Surgery
If you read this and know of an article on the subject that I missed please pass it on and I can add to this blog. You can email me at firstname.lastname@example.org.