Stability
How stable are drugs, how are
shelf lives/expiry dates of food (milk, cake, etc), drugs, and medical devices,
such as a rapid diagnostic device (pregnancy device, rapid drug test device,
etc) are determined?
The
Food and Drug Administration (FDA)
has strict rules on what is written on the packages of food, drugs, and medical
devices. Before expiry date of a product is determined, pilot lots of the
product must be manufactured following the exact manufacturing procedures.
The performance data of these pilot lots are tested for collecting the product's
performance data. Stability or shelf life under certain storage conditions of
these products are collected. There are two ways to conduct a stability study.
One is accelerated stability study and another is real time stability study. The
acceleration is usually achieved by increased temperature condition, therefore,
such studies are called temperature accelerated stability study and real
time/real temperature stability study.
Real Time - Real Temperature
Stability Study
Because most FDA regulated
products have confined storage temperature, the real time/real temperature
stability study may be confined to the proposed storage temperature. The FDA
requires that real time/real temperature stability study be made for all
products that has an expiration date on the label. To do so, the manufacturer or
a contractor testing lab obtain three pilot lots of the product and place them
at the recommended storage temperature condition and monitor how the products
degrades. The time for the first lot of product that falls out of the
specification is established as the shelf-life of the product.
Temperature Accelerated Stability
Study
How is temperature accelerated
stability study designed and how are the data analyzed
FDA
Guideline
Arrhenius
Treatment
|
The
stability
data
from
the
accelerated
stability
studies
can
be
treated
according
to
the
Arrhenius
equation.
STABILITY
SYSTEM
computes
the
activation
energy
and
the
pre-exponential
factor
as
well
as
the
rate
constants
and
the
expiry
dating
periods
for
several
temperature
ranges
of
interest
to
the
pharmaceutical
system. |
ScienTek Software, Inc. STABILITY SYSTEM JAN-03-2000 page 1
ARRHENIUS TREATMENT
Summary of kinetic treatment for all temperatures:
Test: CPD456 Kinetic order: 0
Rate
File Temp(C) Constant R square (R)
==========================================================================================
X2000.RT 30 0.5433333333 0.871829368334774 (-0.933718034705753)
X2000.40 40 3.3521978021 0.95616327672629 (-0.97783601729855)
X2000.50 50 4.5870967741 0.995050053071919 (-0.997521956185386)
Arrhenius treatment result:
Activation energy = 20891.3247211976 cal/mole
Pre-exponential coefficient = 804753537220173
R square (R) = 0.870185483272351 (-0.932837329480521)
The following speicifications are used to calculate
the expiry dating periods shown on the next page:
Theory = 100
Lower spec = 90
Upper spec = 110
ScienTek Software, Inc. STABILITY SYSTEM JAN-03-2000 page 2
ARRHENIUS TREATMENT
Summary of predicted rate constants and expiry dating periods at several temperatures:
Test: CPD456 Kinetic order: 0
Rate Expiry
Temp (C) Constant Dating (months)
============================================================
0 0.0151269724 661.07081
5 0.0302396974 330.69113
10 0.0589893405 169.52215
15 0.1124328325 88.94199
20 0.2096297716 47.70314
25 0.3827652016 26.12567
30 0.6851448304 14.59545
35 1.2034381612 8.30952
40 2.0761031601 4.81671
45 3.5206815816 2.84035
50 5.8735782295 1.70253
55 9.647222153 1.03656
60 15.6109514737 0.64057
65 24.9042355783 0.40153
70 39.1924832571 0.25515
75 60.8799502177 0.16425
80 93.3957136489 0.10707
85 141.5755519656 0.07063
90 212.1641181024 0.04713
95 314.4720759962 0.03179
100 461.2220728806 0.02168
***** 'REFRIGERATED TEMPERATURES' *****
2 0.0200168141 499.57999
3 0.0229908565 434.95552
4 0.0263804125 379.06912
5 0.0302396974 330.69113
6 0.0346297298 288.76921
7 0.039618658 252.40632
8 0.0452829517 220.83366
***** 'ROOM TEMPERATURES' *****
15 0.1124328325 88.94199
16 0.1275714723 78.38743
17 0.144622734 69.14542
18 0.1638114583 61.04579
19 0.1853881674 53.94087
20 0.2096297716 47.70314
21 0.2368428701 42.22208
22 0.2673673221 37.40172
23 0.3015783659 33.15887
24 0.3398922037 29.42109
25 0.3827652016 26.12567
26 0.4307043256 23.21778
27 0.4842656742 20.64982
28 0.5440654184 18.38014
29 0.6107769015 16.37259
30 0.6851448304 14.59545
ScienTek Software, Inc. STABILITY SYSTEM JAN-03-2000 page 3
ARRHENIUS TREATMENT
Summary of predicted rate constants and expiry dating periods at several temperatures:
Test: CPD456 Kinetic order: 0
Rate Expiry
Temp (C) Constant Dating (months)
============================================================
***** 'FREEZING TEMPERATURES' *****
0 0.015126972442334 661.07081
-5 0.007373979123876 1356.11992
-10 0.003497727960802 2858.99878
-15 0.001611816037681 6204.18197
-20 0.000720352339248 13882.09554
-25 0.000311654148066 32086.85031
-30 0.000130264293955 76767.00726
-35 0.000052487795498 190520.48014
-40 0.000020340008056 491641.88983
-45 0.000007561105973 1322557.84206
-50 0.000002688727778 3719231.10965
-55 0.000000911828359 10966976.29104
-60 0.000000293918958 34022983.92968
-65 0.000000089723072 111454052.64574
-70 0.000000025834318 387082006.00206
-75 0.000000006985215 1431595003.63076
-80 0.00000000176495 5665879697.55248
-85 0.000000000414482 24126485272.0797
-90 0.000000000089928 111200056808.577
-95 0.000000000017906 558468051786.956
Reference
Sites
http://www.stabilitysystem.com/arrhenius.htm
|
