Non-sterile (P)
Rate

Non-sterile (P)
Rate

Units
Tested (N)

Percent chance to fail sterility test (F)

1:10,000

0.0001

1

0.01

1:1000

0.001

1

0.1

1:100

0.01

1

1.0

1:10

0.1

1

11.1

1:10,000

0.0001

5

0.05

1:1000

0.001

5

0.5

1:100

0.01

5

5.3

1:10

0.1

5

82.4

1:10,000

0.0001

10

0.10

1:1000

0.001

10

1.0

1:100

0.01

10

11.1

1:10

0.1

10

271.8

The above probability of a false negative sterility test F is calculated without respect to the sample volume tested. It is based on the number of units tested and the contamination rate P. Obviously, if a preparation has a contamination rate of P and N units are tested for sterility then the percent chance of correctly identifying a true sterility failure F is directly proportional to the volume of medium tested.

In this example I have highlighted the case where 1 in 1000 units are expected to be non-sterile. Ideally, a sterility test will correctly identify this level of contamination. However, the USP <71> test does not accomplish this. The chance of correctly identifying this level of contamination is 1, 0.5 and 0.1% when 10, 5 or 1 units are tested. Thus, even when 10 units are tested the USP sterility test will miss the contamination event 99% of the time.

Non-sterile (P)
Rate

Non-sterile (P)
Rate

Units
Tested (N)

Percent chance to fail sterility test (F)

1:1000

0.001

1

0.1

1:1000

0.001

2

0.2

1:1000

0.001

3

0.3

1:1000

0.001

4

0.4

1:1000

0.001

5

0.5

1:1000

0.001

6

0.6

1:1000

0.001

7

0.7

1:1000

0.001

8

0.8

1:1000

0.001

9

0.9

1:1000

0.001

10

1.0

1:1000

0.001

20

2.0

1:1000

0.001

40

4.2

In this table it is shown that the chances of correctly identifying a contaminated lot when the contamination rate is 1 in 1000 as a function of sample size. When only a single unit is tested then the there is a 0.1% chance of an accurate result or a 99.9% chance of a False negative result. By expanding the test to include 40 units as the sample size the chance of correctly identifying the non-sterile lot slightly increases to about 4.2%.

Accordingly, any rational to justify a reduced number of units tested should take into account the limits of the statistical meaning of the USP sterility test.

Respectfully Submitted,

By: Daniel Prince

 

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