Knowing how to specify a stability test chamber calls for a clear understanding of what stability test chambers do, how they relate to the various components or ingredients that go into the product you manufacture and where these products are used.
In this post we’ll provide some examples of things to consider when specifying a stability test chamber then share suggestions on what to look for in this critical equipment.
As a refresher or for readers new to the subject here is an answer to what constitutes a stability test chamber.
What is a Stability Test Chamber?
Most stability test chambers resemble a large scientific refrigerator. Only instead of keeping contents cool, their function is to replicate variations in temperature, humidity and light over long periods of time. This is critical when pharmaceutical companies, for example, wish to bring new products to market.
It has everything to do with the recommended shelf life of a pharmaceutical product. If you check your medicine cabinet, chances are you’ll find a “use by” date on prescriptions and headache remedies.
We’ll focus on pharmaceuticals here but the same can apply to many products whose performance and reliability must be maintained in the many climates found around the world.
Who Sets the Rules for Stability Testing?
These studies are required to be conducted in a planned way following the guidelines issued by The International Conference on Harmonization (ICH), the World Health Organization (WHO), the Food and Drug Administration (FDA) or other agencies.
The importance of various methods followed for stability testing of pharmaceutical products, guidelines issued for stability testing and other aspects related to stability of pharmaceutical products are available from several resources and some are presented in this post. (1)
Similar rules relate to veterinarian medicinal products as described in the Veterinary ICH publication “Stability Testing of New Veterinary Drug Substances and Medicinal Products (Revision)”
Stability Testing is not as Easy as it Sounds
One might think all one has to do is put the pill in the chamber and set the parameters to determine how long a drug maintains its potency.
Definitely not so.
Here are a few of the many stability tests that can apply to a new product:
- Quality, purity, potency, and identity which could be expected to change upon storage are chosen as stability tests
- Appearance, assay, degradation products, microbiological testing, dissolution, and moisture are standard tests performed on stability test samples
- Microbiological tests include sterility, preservative efficacy and microbial count as applicable e.g. for liquid injectable preparations.
- Other tests like enantiomeric purity, particle size and polymorphic form etc. have also been discussed in ICH guidance Q6A.
- Packaging integrity
- Resistance to light
In short, the pharmaceutical product may undergo a change in chemical stability as well as other characteristics in appearance, consistency, content uniformity, clarity (solution), moisture contents, particle size, as examples, over time. (2)
Stability Testing under Several Scenarios
Earlier we indicated that tests can relate to many products whose performance and reliability must be maintained in the many climates found around the world.
A drug manufactured in the USA may be shipped not only to US drug stores but to healthcare facilities elsewhere in the world where climates may be radically different.
Not only that – during the shipment to its final destination the drug may spend time in storage in a climate different from the origin and final destination.
To address this the ICH has divided the world into five climate zones to each of which has been assigned a testing temperature and relative humidity.
For example, if a drug is produced in the UK (Zone I) and shipped to Egypt (Zone IV) for distribution via Europe (Zones I and II), it would need to be tested under zones I, II and IV. Throughout the duration of the study, the stability of the drug is established through physical, chemical, biological and microbiological tests. Representative test parameters are shown in this table: (3)
|Zone I||21 °C (± 2 °C)||45% RH (± 5%)|
|Zone II||25 °C (± 2 °C)||60% RH (± 5%)|
|Zone III||30 °C (± 2 °C)||35% RH (± 5%)|
|Zone IV||30 °C (± 2 °C)||65% RH (± 5%)|
|Zone IVb||30 °C (± 2 °C)||75% RH (± 5%) ASEAN Nations|
|Refrigerated||5 °C (± 3 °C)||None|
|Frozen||-15 °C (± 5 °C)||None|
So, the takeaway is that if a pharmaceutical is intended for use in other countries it must be subjected to stability testing replicating the climates of its origin, destination and intermediate stops. (Think of it of getting vaccinations for all the stops on your proposed world tour.)
Now you can appreciate there is more to specifying a stability test chamber than simply putting a pill in it and setting some dials.
Selecting Stability Test Chambers in the U.S.
As noted earlier stability testing is a critical part of bringing new drugs to market, and stability test chambers play a vital role in this activity. Stability testing provides information on how the formulations react or respond to time (shelf life as an example) and environmental factors such as temperature and humidity.
FDA Documentation on Abbreviated New Drug Applications
A document published by the FDA’s Center for Drug Evaluation and Research (CDER) relates to stability testing for abbreviated new drug applications (ANDAs). The general recommendation is that ANDAs should be treated no differently than NDA stability recommendations provided by International Conference on Harmonization (ICH) stability guidelines. (4)
Pharmaceutical firms filing ANDAs and wishing to comply with these recommendations may consider purchasing a stability test chamber.
Getting to the Specifics on Specifying Stability Test Chambers.
We hope this rather long dissertation on what goes into a stability testing exercise has been helpful. It all boils down to having an appreciation of what these units do and their contribution to the development of safe, effective pharmaceuticals that retain their potency across the world’s many climates.
We’ll be brief in the following recommendations for your consideration and have summarized them as
The 3 Cs: Control, Conditioning and Construction
When specifying humidity and stability chambers satisfy yourself that the models you consider meet the critical 3 Cs. These are among the features found in the Nor-Lake Scientific NSRI series offered by Tovatech in 4 capacities from 24 to 80 cubic feet.
A fully programmable logic microprocessor puts you in control of the chamber. A single multifunction keypad is used for all set points: ramp soak; product and air temperature; alarm and temperature logging; heating/cooling mode; humidity, and alarming for temperature excursions, door ajar, power failure, and sensor failure; a real time clock, and service prompts plus the password entry system.
Chambers must have a uniform distribution of temperature and humidity throughout the interior. The NSRI series does this with a heavy-duty refrigeration system for rapid removal of heat caused by product load or door openings. The operating range is 4⁰ to 70⁰C or 5⁰ to 60⁰C with the humidity control. Cabinet warming is by electrically operated heaters factory set (but user programmable) with a cutout temperature to prevent the cabinet from exceeding its design limits.
Look for double wall construction with a enamel exterior finish (or stainless option), a stainless interior for easy cleaning, CFC-free foamed in place insulation for low heat transfer, self-closing key lock doors, and a thermostatically controlled anti-condensate heater wire for the door gasket.
In addition to the above selection criteria there are a number of other features that provide value to test chambers. Here is a sampling:
- Continuous product temperature display
- Remote alarm capability
- Condenser/compressor run time monitor
- Fan motor run time monitor
- 24-hour door opening counter
- Low battery test
- 18 month parts and labor, 5 year compressor warranty
- Measure first then buy. You new unit has to fit in the space. Allow room for air circulation.
- Check the power supply. Ideally you will have a dedicated circuit outlet with the required amp circuit breaker, and precaution notices against tripping the circuit or unplugging the unit.
- Provide access to a drain to accept condensate. Caution: Spilled samples may require special disposal procedures.
Tovatech offers several models of temperature/humidity test chambers available with glass or solid doors. They come with installation and operating instructions along with instructions on installing and maintaining the water recycling equipment essential to delivering the correct humidity.
When it comes to making a decision that best suits your requirements we invite you to contact our Ph.D. scientists for complete details on the Norlake Scientific test chambers and for recommendations on specifying the correct model to meet your needs.
(1) From “Stability Testing of Pharmaceutical Products” Journal of Applied Pharmaceutical Science
(3) From “The Importance of Stability Testing” SCIENTISTLIVE, June 23, 2016
(4) Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products