Biorad Medisys Pvt. Ltd.

Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

1. PURPOSE : The Accelerated Aging test simulates real-time aging using elevated temperatures to
artificially speed up the aging process. It is used to help determine the long-term effects of expected
levels of stress and environmental conditions within a shorter period on a product and its packaging.

It is a testing procedure that is used to help with the assessment of the sterile integrity of a package
and product designed for medical use. In order to validate a product and package’s Sterile Barrier
System (SBS) over the intended storage shelf life, accelerated aging is conducted to evaluate a
package and product's long-term usability and efficacy.

The real - time aging studies are performed to confirm the accelerated aging test results using
same methods of evaluation. This testing is conducted at ambient conditions in actual real time in
order to analyze the conditions of packages and/or products and the effects that time has on them.

2. SCOPE : This protocol is limited to carrying out stability study of the products manufactured at Biorad
Medisys Pvt Ltd.

3. DESCRIPTION OF AGING STUDY

In accelerated aging tests for medical devices, a material or Sterile Barrier System (SBS) is exposed to
elevated temperatures for a condensed amount of time. By exposing the testing materials to more
extreme conditions during a shorter time frame, we can evaluate how a product will age under
normal conditions without waiting for the entire desired duration. With this knowledge, we can
determine shelf life, storage, in-use, and transportation parameters more accurately for the product.
Accelerated aging is a standard practice in the medical device industry for determining shelf-life
parameters by accelerating the effects of time on a Sterile Barrier System (SBS). The accelerated
aging process is based on the relationship between temperature and reaction rate, in which the
reaction rate increases as the temperature rises. The Arrhenius Equation is the basic formula used for
an accelerated aging test for medical devices is:

Accelerated Aging Time (AAT) = Desired Real Time (RT)/Q10^[(TAA−TRT)/10]

The Arrhenius equation indicates that a +10°C increase in temperature doubles the rate (known as an
Q10 factor of 2) of chemical reaction. This is the most popular and conservative method of
calculating Accelerated Aging. It's used to test shelf-life claims and document expiration dates by
simulating real-world shelf-life aging.

4. TERMINOLGY

4.1. ACCELERATED AGING (AA): Storage of sample at an elevated temperature. (TAA) to simulate real
time aging in reduced amount of time.

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

4.2. ACCELERATED AGING FACTOR (AAF): An estimated or calculated ratio of the time to achieve the
same level of physical property change as a sterile barrier system stored at real time (RT)
conditions.

4.3. ACCELERATED AGING TEMPERATURE (TAA): The elevated temp. at which the aging study is
conducted, and it may be based on the estimated storage temperature, estimated usages
temperature or both.

4.4. ACCELERATED AGING TIME (AAT): The length of time the accelerated aging is conducted.

4.5. AMBIENT TEMPERATURE (TRT): Storage temperature for real time aging (RT) samples that is
typical for storage conditions. Also, the temperature used to calculate the accelerated aging
duration.

4.6. REAL TIME EQUIVALENT (RTE): Amount of real time aging to which given accelerated aging
conditions are estimated to be equivalent.

4.7. REAL TIME AGING (RT): Storage time of samples at ambient conditions.

4.8. Q10: An aging factor for 10°C increase or decrease in temperature.

5. PROCEDURE

5.1. EQUIPPMENTS/MATERIALS

Stability Chamber - Labtop

Equipment Name Part Description Range

Stability Chamber_ Temperature Controller 20.0 – 70.0 °C

LABTOP Humidity Controller 40 – 95%

5.2. AGING CONDITIONS:

Accelerated aging temperature (TAA) : 60°C ± 2°C

Accelerated aging ambient temperature (TRT) : 30°C

(Storage temperature range is 15°C to 30°C, therefore the upper limit of the range is selected as it will
yield a longer, more conservative accelerated aging duration and can be useful for creating
accelerated aging data that verifies compatibility with a range of storage temperature conditions).

Accelerated aging humidity conditions (RH) : 45％ ± 5％

Q10: 2

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

5.3. STERILIZATION CYCLE:

The sterile barrier system is sterilize using a validated sterilization process. The sterilization process
may affect the stability of the materials or sterile barrier system, therefore 3X sterilization is done to
simulate worst -case conditions prior to aging.

5.4. ACCELERATED AGED TIME POINTS:

As per standard ASTM F1980, the number of accelerated aged time points, minimally is one i.e the
time equivalent to the desired shelf life, however using only one accelerated time point leaves the risk
of failure without warning from an earlier accelerated aged time point. Therefore at least 3 points are
to be considered.

If the Desired shelf life is 3 years,

Accelerated aged time points - 0th day, 1st year, 2nd year, 3rd year.

6. ACCELERATED AGING PLAN

6.1. Plan the quantity of the products for testing.

6.2. Accordingly prepare Accelerated Aging study plan.

6.3. Select the Q10 value.

6.4. Define the desired shelf life of the sterile barrier system.

6.5. Define aging test time intervals, including time zero.

6.6. Define test conditions, room temperature (TRT) and accelerated aging temperature (TAA).

6.7. Decide humidity conditions (RH).

6.8. Calculate the accelerated aging duration using Q10, TRT & TAA.

6.9. Define sterile barrier system or material properties or both, to be evaluated (such as, seal
strength and integrity test) sample sizes and acceptance criteria.

6.10.Age samples at TAA. In parallel, age samples at real-life aging conditions (TRT).

Using the Arrhenius equation with Q 10 equal to 2 is a common and conservative means of calculating an
aging factor.
An accelerated aging factor (AAF) estimate is calculated by the following equation.
Accelerated Aging Factor (AAF) = Q10^[(TAA-TRT)/10] ------------------------------- Equation 1

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

where, TAA = Accelerated aging temperature (°C )

TRT = Ambient temperature (°C )
Accelerated aging time (AAT) = Desired real time (RT) / AAF ------------------------- Equation 2
If our desired shelf life is 3 years, the accelerated aged time points are 0th day, 1st year, 2nd year, 3rd year as
mentioned in 6.5
Initiate real time and accelerated aging. Use the defined accelerated aging temperature for the
appropriate period of time. The time duration for sample to be placed in elevated temperature oven can
be calculated from equation 1 and equation 2.

Calculations:

For 1st year stability study

Q10 - 2

Accelerated aging temperature (TAA) - 60°C ± 2°C

Ambient temperature (TRT) - 30°C

Humidity (RH) - 45％ ± 5％

Accelerated Aging Factor (AAF) = Q10^[(TAA-TRT)/10]

= 2 ^ [ ( 60 - 30 ) / 10 ]

=2^[3]=8

Accelerated aging time (AAT) = Desired real time (RT) / AAF

= 365 days / 8
= 45. 625 ≈ 46 days at accelerated aging conditions or a shelf-life test of 12months (real
time equivalent)

For 2nd year stability study

Q10 - 2

Accelerated aging temperature (TAA) - 60°C ± 2°C

Ambient temperature (TRT) - 30°C

Humidity (RH) - 45％ ± 5％

Accelerated Aging Factor (AAF) = Q10^[(TAA-TRT)/10]

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

= 2 ^ [ ( 60 - 30 ) / 10 ]

=2^[3]=8

Accelerated aging time (AAT) = Desired real time (RT) / AAF

= 730 days / 8
= 91.25 ≈ 92 days at accelerated aging conditions or a shelf life test of 24months (real
time equivalent)

For 3rd year stability study

Q10 - 2

Accelerated aging temperature (TAA) - 60°C ± 2°C

Ambient temperature (TRT) - 30°C

Humidity (RH) - 45％ ± 5％

Accelerated Aging Factor (AAF) = Q10^[(TAA-TRT)/10]

= 2 ^ [ (60 - 30 ) / 10 ]

=2^[3]=8

Accelerated aging time (AAT) = Desired real time (RT) / AAF

= 1095 days / 8
= 136.875 ≈ 137 days at accelerated aging conditions or a shelf-life test of 36 months
(real time equivalent)

Similarly, If the desired shelf life is 5 years, corresponding accelerated aged time points to be considered
and accelerated Aging Factor (AAF) and accelerated aging time (AAT) to be calculated for the respective
time points.

6.11.Evaluate the sterile barrier system after accelerated aging to the predetermined sterile barrier
system specification requirements such as, package seal strength and package integrity.

6.12.Evaluate the sterile barrier system after real time aging against the predetermined sterile barrier
system to confirm the accelerated aging test results using same methods of evaluation.

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

7. POST AGING TESTS

List of tests to be executed after each accelerated aged time points:

Sr.No Test Acceptance Criteria

* PRODUCT WITH PACKAGING TEST
1 Package Integrity No peel off in package & Label
2 Label Content Should be Legible
3 Deformation in Package No Deformation
4 Color of ETO Indicator No fading of color (Visual)
5 Color of the product No fading of color (Visual)
6 Deformation in Product No Deformation
7 Dye Penetration Test No leakage
8 Seal Strength Test Minimum 2.5 N/15mm width
*PRODUCT TESTING
9 Surface Finish As per specification
10 Product Length As per specification
11 Diameter of Product As per specification
12 Kinking of Product As per specification
13 Product Specific test, if any As per specification
*PRODUCT FUNCTIONAL TESTING
14 Tensile Strength As per specification
15 Product Specific test, if any As per specification
*MICROBIAL TESTING
16 Sterility Test No Microbial Growth
17 Bacterial Endotoxin test Less than 20 EU/Device

8. CONCLUSION:

8.1. If all the tests pass with the given parameters and time frame the product shall pass the
Accelerated Aging test for shelf life study.

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

8.2. If all the tests pass with the same method of evaluation as accelerated aging and with the given
parameters and time frame the product shall pass the Real - Time Aging test and confirms the
accelerated aging conclusions.

9. REPORTS:

The results of accelerated aging and Real time aging shall be documented in the respective reports
numbered as :

XXX - YYY - ZZZ - NN

Where, XXX - Project code
YYY - Type of File, suffix if required added.
ZZZ - Product Identification (short name) suffix if required added.
NN - Revision No

For Eg : Gastro Stone Basket Numbering will be as follows:

Accelerated aging Study: 504-AAS-GSB-00

Real Time Aging : 504-RTA-GSB-00

Refer Annexure for summary report

Accelerated aging Study: 504-AASSR-GSB-00

Real Time Aging : 504-RTSR-GSB-00

10. REFERENCES :

10.1. ASTM F1980-16: Standard Guide for Accelerated Aging of Sterile Barrier Systems and Medical
Devices.

10.2. ISO 11607-1:2006 Packaging for terminally sterilized medical devices.

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 Biorad Medisys Pvt. Ltd.
Survey No. 48/3 & 48/7, Pashan-Sus Road, Sus Village, Tal.
Mulshi,Pune-411021 Maharashtra, India

SHELF LIFE STUDY PROTOCOL

Doc No. BRP-SLS-P-00 Revision No 00 Effective Date 06-07-2022

11. REVISION HISTORY

Revision
Rev No Effective Date
Section No Description of change
00 06-07-2022 ALL First Issue

Approvals
Khushboo V&V Engineer -
Prepared By
Warhade R&D
Reviewed By Dinesh Diwakar HOD - Operations

Approved By Debasish Pradhan HOD - R&D

“END OF DOCUMENT”

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