Determination of the Efficacy of Sterile Barrier Systems

Hartmut Dunkelberg

University Medical Center, Goettingen

STUDIEDAG VSZ

October 4, 2012 Lamot Mechelen

Maintenance of sterility: packaging is a sterile barrier system

• sterilization container, • wrapped baskets, • paper/film

constructions, • paper sheets, • non-woven sheets, • paper sterilization bag.

Gaseous sterilization agents

• steam • ethylene oxide • formaldehyde steam • hydrogen peroxide

gas plasma

Theoretical probability of a non-sterile product ≤ 1 :1,000,000 = Sterility Assurance Level (SAL) of 10-6 *

*CDC: Guideline for disinfection and sterilization in healtcare facilities, 2008; Pharmaceutical inspection cooperation scheme, 2002.

Sterile: state of being free from all living micro-organisms

Initial sterility provided by the sterilization process

0,0000010,000010,00010,0010,010,1

110

1001000

10000100000

1000000

0 2 4 6 8 10 12 14 16 18 20

Exposure time (min)

Num

ber o

f col

ony

form

ing

units

(cfu

)D121°C-value*

SAL ≤ 10-6

*D-value= decimal reduction time

Event-related factors limit shelf life

Impacts causing visible changes to the packaging

- cuts or breaks on gaskets;

- punctures, tears; - wetness, water stains; - loosened locks; - settled dust following

storage on open shelving;

airborne microbial concentration; weather-influenced atmospheric pressure changes; transport to different heights above sea level; temperature variations.

Demonstration of gas permeability: enter of gaseous bromine into the packaging

Impacts by air flow into the packaging during transport and storage challenge the filter efficiency

0.0000010.00001

0.00010.001

0.010.1

110

99.99

999

99.99

990

99.99

900

99.99

000

99.90

000

99.00

000

90.00

000

0.000

00

Required filtration efficiency (%)

Mic

robi

al c

halle

nge

(CFU

)

Relationship between the required filtration efficiency and the microbial challenge of the

packaging

Assessment of the product’s sterility according to the SAL of 10-6 at the point of use

• whole package microbial challenge test (laboratory method);

• on-site application in hospitals;

• assessment of sterility at the point of use

Nebulizer

Impinger

Time control module

Vacuum pump

Exposure chamber method

paper/film pouch

basket

Atmospheric Pressure Changes

-20

0

20

40

60

80

09:4

2:21

09:5

3:54

10:0

5:27

10:1

7:00

10:2

8:33

10:4

0:06

10:5

1:39

11:0

3:12

11:1

4:45

11:2

6:18

11:3

7:51

11:4

9:24

12:0

0:57

12:1

2:30

12:2

4:03

12:3

5:36

12:4

7:09

12:5

8:42

13:1

0:15

13:2

1:48

13:3

3:21

13:4

4:54

13:5

6:27

14:0

8:00

14:1

9:33

14:3

1:06

Time

hPa

Humidity

020406080

09:3

6:40

09:4

8:20

10:0

0:00

10:1

1:40

10:2

3:20

10:3

5:00

10:4

6:40

10:5

8:20

11:1

0:00

11:2

1:40

11:3

3:20

11:4

5:00

11:5

6:40

12:0

8:20

12:2

0:00

12:3

1:40

12:4

3:20

12:5

5:00

13:0

6:40

13:1

8:20

13:3

0:00

13:4

1:40

13:5

3:20

14:0

5:00

14:1

6:40

14:2

8:20

Time

%

Calculation of the microbial barrier efficiency of the packaging against airborne microbial challenge

N0 = Number of bacteria in the air volume passing the packaging material (= microbial challenge)

N1 = Number of bacteria registered on the plates in the packaging

LRV = Log N0 – Log N1

Microbial barrier effectiveness in terms of the Logarithmic Reduction Value (LRV.):

N0 LRV = Log ----

N1

N1 Filtration efficiency (%) = [1 – ---- ] x 100

N0

Microbial barrier efficiency of double wrapped baskets

835

80

0

50

100

150

2,600 cm³ 5,300 cm³ 7,900 cm³

Packaging volume

num

ber o

f m

icro

orga

nism

s (C

FU) p

er

pack

age ± Standard error

Filtration efficiency and logarithmic reduction value (LRV) of double wrapped baskets

4.81 4.53 4.27

0123456

2,600 cm³ 5,300 cm³ 7,900 cm³Packaging volume

LRV

± Standard error

Filtration efficiency: 99.998 %

99.997 % 99.995 %

1. sterility assurance level ≤ 10-6

2. N0 = Microbial challenge 3. LRV or penetration rate

Assessment of sterility in the post-sterilization period

Assessment of sterility: N0 • penetration rate ≤ 10-6

or Log N0 – LRV ≤ - 6

Example for assessment of continued sterility

microbial challenge: N0 = 0.038 CFU Log 0.038 = - 1.42

Sterility is confirmed. 0.038 * 0.00002=0.76 * 10-6

or

- 1.42 - 4.81 = - 6.23

filtration efficiency: 99.998 % penetration rate: 0.00002 LRV: 4.81

Logarithmic reduction value (LRV) of double wrapped baskets

4,81 4,53 4,27

0123456

2,600 cm³ 5,300 cm³ 7,900 cm³Packaging volume

LRV

± Standard error

2,600 cm³-basket, cooling from 60 to 20 °C, air flow : 381 cm³ 100 CFU/m³

… … …

Airborne microbial barrier efficiency: LRV: … or Filtration efficiency: …

Assessment of maintenance of sterility in the hospital routine

Assessment of maintenance of sterility in the

hospital routine

Filtration efficiency in %

www.microbial-evaluation-of-sterile-barrier-systems.com/

On-site application of the mobile exposure chamber for determining the filtration efficiency of sterile barrier

systems used on-site

Filtration efficiency (%) of paper/film pouches after on-site testing

Test conditions: 457 periodic air pressure changes of 200 hPa; airborne microbial concentration: 210 CFU/m³; 41 paper/film pouches; volume: 6900 cm³

3

38

0

20

40

%

7.3% non sterile packages sterile packages

Conclusion

• The continued sterility can be assessed at the point of use if data on the microbial filtration efficiency and information about the microbial challenge during the post-sterilization period are available.

• This assessment ensures the safety and high quality of sterile supplies.

• The described concept of stability testing opens possibilities to optimize the barrier properties by the modification of the design, the volume, and the method of packaging.

Thank you for your attention!