August 12, 2021: Pharmaceutical Interview Questions and Answers

#Sterilization #Sterility #AsepticProcessing #OverkillSterilization #F0AndFhValues

1. What is sterilization:

A suitably designed, validated and controlled process that inactivates or removes viable microorganisms in a product until sterility is obtained.

2. What is Sterility:

Sterility is the absence of viable microorganisms, as defined by a sterility assurance level equal to or less than 10−6. The inactivation of microorganisms by physical or chemical means follows an exponential law; thus there is always a finite statistical probability that a micro-organism may survive the sterilizing process. For a given process, the probability of survival is determined by the number, types and resistance of the microorganisms present and by the environment in which the organisms exist during treatment.

3. What is Aseptic processing?

A process performed maintaining the sterility of a product that is assembled from components, each of which has been sterilised by steam, dry heat, ionizing radiation, gas or sterile filtration. This is achieved by using conditions and facilities designed to prevent microbiological contaminants.

4. Bioburden:

The total number of micro-organisms associated with a specific item prior to any sterilisation or bioburden reduction step.

5. Biological indicator:

Biological indicators are test systems containing viable microorganisms (usually spores of bacteria) that provide a defined challenge to verify the required effectiveness of a specified sterilisation process.

6. Colony Forming Unit (CFU):

A microbiological term that describes the formation of a single macroscopic colony after the introduction of one or more micro-organisms to microbiological growth media. One colony forming unit is expressed as 1 CFU.

7. Depyrogenation

A process used to destroy or remove pyrogens (e.g. endotoxins).

8. D-value (decimal reduction value)

The value of a parameter of sterilisation (duration or absorbed dose) required to reduce the number of viable organisms to 10 per cent of the original number. It is only of significance under precisely defined experimental conditions. D121 is the D-value of the relevant spores at 121° C.

9. F0 value

The F0 value of a saturated steam sterilization process is the lethality expressed in terms of the equivalent time in minutes at a temperature of 121 °C delivered by the process to the load in its container with reference to micro-organisms possessing a theoretical Z-value of 10.

10. Holding time

The time between two process steps.

11. Lethal (process)

A process that kills the microorganisms exponentially.

12. Overkill sterilization

A process with a lethality of F0BIO > 12 minutes. For example a process that provides at least a 12 log reduction of biological indicator microorganisms having a minimum D value of 1 minute.

13. Ph. Eur. sterilization reference conditions

The reference conditions for sterilisation specified in Ph. Eur. 5.1.1, i.e. terminal steam sterilization at ≥121 °C for 15 min, terminal dry heat sterilisation at ≥160 °C for ≥2 h or terminal ionising radiation of 25 kGy.

14. Post-aseptic processing terminal heat treatment

A terminal moist heat process employed after aseptic processing which has been demonstrated to provide a SAL ≤10-6, but where the requirements of steam sterilisation (for example, F0≥8 min) are not fulfilled.

15. SAL (Sterility Assurance Level)

The SAL for a given sterilisation process is expressed as the probability of micro-organisms surviving in a product item after exposure to the process. An SAL of 10-6, for example, denotes a probability of not more than 1 non-sterile item in 1 × 106 sterilised items of the final product.

16. TAMC (Total aerobic microbial count)

The total aerobic microbial count (TAMC) is considered to be equal to the number of CFU found using casein soya bean digest agar.

17. z-value

The z-value is the change in temperature required to alter the D-value by a factor of 10.

Reference for Q 1 to 17:: 6 March 2019 EMA/CHMP/CVMP/QWP/850374/2015, Committee for Medicinal Products for Human use (CHMP), Committee for Medicinal Products for Veterinary use (CVMP), Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

18. Difference Between F0 and Fh Values

At this point of time, it’ll be better to differentiate the two i.e. F0 and Fh values.

F0 ValueFh Value
Used to evaluate the effectiveness of Steam SterilizationUsed to evaluate the effectiveness of Dry Heat Sterilization
The assumed z-value is 10°C for sterilization range of 100 to 130°CThe assumed z-value is 20°C for sterilization range of 160 to 200°C
Theoretical Requirement
121.1°C @ 30 min. of sterile hold time
Theoretical Requirement
170°C @ 32 min. of sterile hold time
Targetted to mitigate micro-organisms especially living endosporesTargetted to remove the bacterial endotoxins
Much more complicated because of steam quality requirementsLethality of the microbes is less than that of F0 at the same temperature

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