References

1. ICH Guideline Q1E Stability Data Evaluation

2. ASTM F1980 – 07: Standard Guide for Accelerated Aging Sterile Barrier Systems for
Medical Devices, Information for developing accelerated aging protocols to determine the aging
effects on sterile barrier system (packaging)
3. Medical Device Stability Storage
Due to the integration of active pharmaceutical ingredients (API) and antimicrobial agents, more
medical devices are being considered combination products than ever before.
While the stability of these ingredients is often known, it must be tested in conjunction with the
device and undergo a complete stability study according to the ICH guidelines.
We make the following stability conditions available for Medical Devices storage:

 25°C ± 2°C / 60% RH ± 5% RH

 30°C ± 2°C / 65% RH ± 5% RH
 40°C ± 2°C / 75% RH ± 5% RH
 5°C ± 3°C
 –20°C ± 5°C

4. Medical Device Stability Studies

The stability of medical devices is the extent to which a device holds-on, within specified limits,
and throughout its period of storage and use, the same properties, and characteristics that it
possessed at its time of manufacture.
Similar to pharmaceutical products, medical devices have a set of criteria to evaluate stability
such as:
 Chemical – Degradation, Interaction, Device packaging and interaction, Radioactive
decay, Manufacturing
 Physical – Physical characteristics, Manufacturing process, Storage conditions
 Microbiological – Sterility, Environmental control, Antimicrobial effectiveness
 Therapeutic
 Toxicological
 Biocompatibility
Stability and Shelf Life

This method is used for identifying weak links to a product. The impact of high and low
temperature and the vibration is determined to precipitate failure modes faster than normal
testing approaches.
It is not a pass/fail test and it requires root cause analysis and corrective action to achieve
optimum value from testing. It creates the ability to learn more about the design and material
limitations of the product and provides opportunities for continuous improvement of the design
before marketing the product.
 
A HALT testing program includes 5 individual tests such as High-temperature step stress, Low-
temperature step stress, Vibration step stress, Rapid thermal cycling, Combined Environment.
Type of Stability Studies in Medical Devices
Shelf life is estimated using two types of stability studies:
 Real-time stability studies
 Accelerated stability studies
A. Real-time stability studies
A real-time stability study is conducted to establish long term product stability. This is carried
out for a longer duration of the test period to allow greater degradation of the product under
specified storage conditions.
This type of study may assess the performance based on the physical characteristics and activity
of a product for the projected lifetime of the product. The product will be monitored until the
required dating period is achieved or it fails the specification. 
The test data will be collected at an acceptable frequency during this review, so that trend
analysis can differentiate uncertainty from day-to-day ambiguity. Real-time study measure points
a period of 6 months, 1 year or as many as 2-5 years. Product expiration can be determined from
this study.
B. Accelerated stability studies
Accelerated stability studies are used to predict a product’s expiration date or life period rapidly
when there is no real-time data available. 
It is a modified stability testing method. In this type of analysis, the product will be exposed to a
high level of stress (usually regulated changes in temperature or humidity), during which the
product will be placed in a condition that accelerates the degradation and this knowledge will be
used as an early indicator to predict the shelf life and thus shorten the development schedule. 
The test duration is the timeframe predicted or needed for the expiry of the product (1 year., 2yrs,
etc.). This test method is conducted to bring fresh or re-manufactured products into the market as
soon as possible. 
The concept of accelerated stability testing is based on the Arrhenius equation which describes
the relationship between storage temperatures and degradation rate:

 lnK= lnA + Δ𝐸/𝑅𝑇 

where K = degradation rate/s,

A = frequency factor/s, (Specifically relates to the molecular collision, deals with the frequency
of molecules that collide in the correct orientation and with enough energy to initiate a reaction.
It is a factor that is determined experimentally, as it varies with different reactions)
 ΔE = activation energy (kJ/mol),
 R = universal gas constant (0.00831kJ/mol),
 T=absolute temperature (K)
 The calculation can be interpreted with an example as below
Shelf Life Calculation
FACTOR (F):2 [TAA-TRT/10]
Where TAA = Accelerated aging temperature
TRT = Ambient temperature

 Shelf life = Study time period x Factor 

Example: For Monofilament Polydioxanone suture, if TAA = 550 C and the TRT = 300 C and
accelerated study is carried out for 12 months,

Shelf Life = 12 x (255-30/10)

= 12 x 22.5

= 12 x 5 = 60 months (5 years)

Shelf life vs. Lifetime
Shelf life

 Duration during which the product remains sterile and usable to attain the intended use

 Can be determined by real-time stability study and accelerated stability study

Lifetime

 The maximum time period specified by the manufacturer during which the devices are
expected to maintain safe and effective use

 Can be determined by reliability studies, HALT, HASS, and Accelerated Weathering