Sterilies

Question 1

What are the CQAs of a sterile product?

Answer 1

Absence of micro-organisms, absence of endotoxins, absence of particles, isotonic, labelled correctly, container closure integrity.

Question 2

What standards are applied for HEPA filter testing, Air velocities and room air change rates?

Answer 2

HEPA filters- 99.97% DOP at 0.3u
Air velocities - 0.45m/s -+ 20%
Air change rates- 20 per hour minimum, more in grade A/B.

Question 3

Annex 1 viable limits per grade

Answer 3

A- <1 for all samples
B- 10 for AAS, 5 for all other samples
C- 100 for AAS, 50 for SP, 25 for CP
D- 200 for AAS, 100 for SP, 50 for CP

Question 4

Tell me about Gamma radiation

Answer 4

25Kgray of Cobalt 50
1-3 hours exposure time
Perspex dosimeter (red dot)
Bi- Bacillus Pumilis

Question 5

What controls are present for freeze drier cycle?

Answer 5

Drop temp, drop pressure, raise temp under pressure = sublimation.

1 and 2 drying phases

Leak rate 0.02 mbar/l/s
Chamber sterilisation per batch

Question 6

What are the specifications for purified water?

Answer 6

<100cfu/ml
<500PPB TOC
<0.2ppm Nitrates
<5.3ms Conductivity

Question 7

What are the specifications for WFI?

Answer 7

<10cfu/100ml- 200ml min sample volume
<500PPB TOC
<0.2ppm Nitrates
<1.3ms Conductivity
<0.1ppb heavy metals

Question 7

What are the steam quality standards?

Answer 7

EN285
>95% dryness fraction for porus loads
3.5% Non condensable gasses

Question 8

What do you understand by D value, Z value and F0?

Answer 8

D value is the time taken at 121 degrees to reduce bacterial count by factor of 10

Z value is the change in temperature required to adjust the D value by a factor of 10 at the same time value

F0 is the total lethality time over a sterilisation cycle- taking into account heat up and cool down. Minimum EU F0 is 8. F0 at 121, Fh at 170

Question 9

What would you expect to see in autoclave validation?

Answer 9

Assume aseptic
IQ/OQ/PQ
Calibration of thermocouples
Fertility test for BIs + Spore count
Geobacillus stereothermophillus
Empty chamber temperature mapping
Worst case load temperature mapping- TCs and BI in hard to reach areas
Include coldest areas (drain)
Review TC data for cycles performed
Watch for slow temp increase- could be conduction rather than latent heat
Combination of TC data and BI kill data
Post fertility test for BI media and BI batch control sample.
Review Leak rate data (1.3mbar)
Review steam penetration in comply packs colour change.

Question 10

Tell me about ETO sterilisation

Answer 10

Ethylene oxide- chemical sterilisation
Entry of ETO into area/ isolater
Exhaust system in place
Need to ensure no occluded surfaces
Need to control temp + humidity within environment

Question 11

How do you validate sterile filters?

Answer 11

HMA/ASTM bacterial challenge test
Product surrogate flow and Brevindimonus dimintua 10 to 7 contamination
Worst case filter conditions- Temp, humidity, flow, pressure, time.
Analytical filter post test filter to incubate and identify any organisms.

Question 12

What are standards for HVAC qualification?

Answer 12

ISO 14644
At rest and in operation
Particle counts
3520 0.5u and 29u for grade A

Question 13

What standards are there for dry heat serilisation?

Answer 13

160degrees - 2 hours (EP)
250 degrees- 30min depyrogenation, 3 log endotoxin reduction
BI bacillus atropheus.

Question 14

Pipework requirements

Answer 14

2% orientation
No deadlegs 3x diameter of pipe
Turbulent flow in pipe
1-3m/s movement