# F0 Value in Steam Sterilization

The expected outcome of any sterilization technique, including the F0 value, is the microbial reduction to the pre-determined levels to maintain the safety, quality, sterility, and integrity of the pharmaceutical product. Various sterilization techniques practiced in healthcare facilities based on the type of application. Out of that, the F0 value (read as F Zero) designed in the industrial field of moist heat sterilization.

Before detailing the F0 value and its significance, it is important to understand the kinetics of moist heat and its mathematical versus biological angle.

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## Moist Heat Kinetics (Math vs. Bio)

Assume a system contaminated by microbial species in contact with saturated steam at a constant temperature. Therefore, sterilization develops like a first-order chemical reaction. Then, the rate of the reaction depicted below:

Where,

N – Number of microbes present in the system

t – exposure time to the microbes with steam

K – the rate of reaction’s constant (**species dependent**)

Re-arranging to integrate,

Now integrating,

Converting and simplifying the logarithmic value to exponential,

where,

N_{0} – no. of microbes initially

t – exposure time of steam (sterile hold time)

N – no. of microbes at the end of sterilization hold

k – the rate of reaction constant (**microbes dependent**); now this k = K / 2.303

The equation (1) hence shows that no. of microbes decreases exponentially with sterilization hold time. The time required to decrease the microbial amount to a pre-defined

### What is D-Value (Decimal Decay Time)?

The time (t) required at a specified temperature (T), to reduce the microbial population from 100% to 10% (1 log reduction). (Keynote – “

Definition of D-value“)Reduction of Microbial Population

D-value is reciprocal of rate of reaction constant (k) and therefore;

K = t^{ -1}

By putting this value in earlier equation (1) we get,

N = 0.1*(N_{0})

D-value plays an important role in determining hold time for the system under the sterilization. Equally important, D-value considered as “1” if there is no precise experimental data available. Typically, the range for D-value is 0 to 2 at around 121°C.

**D-Value vs. Time**

Let us understand the importance of D-value with an example where we want to reduce micro-organisms with moist heat sterilization.

- Initial no. of microbes = 100 i.e. 10
^{2} - Target reduction of microbes = 10
^{-6} - Constant Temperature of sterilization process (T) = 121°C

Table below represents figures based on an experimental data, which elaborates how the D-value affects microbial reduction time:

D-Value (min) | Time Required for Microbial Reduction (min) | Initial No. of Micro-organisms | Final No. of Micro-organisms |
---|---|---|---|

0.5 | 4 | 100 | 10^{-6} |

1 | 8 | 100 | 10^{-6} |

2 | 16 | 100 | 10^{-6} |

**Table: D-value vs. Time required for microbial reduction**

To summarize, the above table shows that residual contamination of 10^{-6} is gained from initial contamination of 10^{2}, at 121°C in

- 8 mins if D=1,
- 4 mins if D=0.5 and
- 16 mins if D=2.

For these numbers to understand, European Pharmacopeia introduced a concept called SAL (i.e. Sterility Assurance Level). SAL is the probability of identifying a non-sterile unit OR micro-organism in a batch or lot.

According to the Table above, SAL=100 and 10^{-6}. Therefore, the probability of identifying non- sterile microbe is one in 100 and one in a million, respectively.

### What is z-Value (Temperature Coefficient)?

Practically speaking, T

z-value: Number of degrees the temperature required to increase, which will effect a 10-fold variation of D-value. (Keynote – “

Definition of Z-Value”)Variation in D-value

Z-value considered as 10°C for steam sterilization temperature from 100 to 130°C.

Approximately D-value varies by 10 times for variation of 10°C. We must not interpret this that D-value varies by 1 time for 1°C variation. The rationale for this is beyond the scope of this topic. Only note that “** Variation in 1°C requires a variation of D-value by 25%**”.

The effect of temperature variation decreases considerably as:

1. Sterilization method change

2. Temperature raises

For dry heat sterilization of around 200°C, the

Summarizing the earlier dialogues: **D-value has a unit of time i.e. min and z-value is a temperature coefficient and has a unit of temperature i.e. °C**.

The upcoming part describes the application of these values (D and z-values) to make them accountable for the meaningful outcome for sterility measurement, i.e. F0 value.

## F0 Value Definition (Equivalent Exposure Time)

F0 value: Equivalent exposure time at 121.1°C to that of the actual exposure time at a variable temperature calculated with a temperature coefficient of the destruction of 10°C. (Keynote — “

F0 Value DefinitionEquivalent”)

where,

Δt – the time interval between two temperature readings

T – the temperature at time t of the product under sterilization

z – temperature coefficient (assumed as 10°C)

The term next to Δt is called Lethality Rate. You can calculate it individually or by averaging all the tabulated data, result will be equivalent.

### Testing F0 Value And Its Meaning

Consider sterilization hold time of 30 min. at constant 121.1°C, putting this in equation (2),

Solving we get, F0 = 30 min. (*This is an ideal cycle/condition for steam sterilization*)

Based on this, let’s see two further examples one below and one above ideal condition.

#### Example 1 (Below Ideal Condition)

Consider sterilization hold time of 30 min. at constant 110°C instead of 121.1°C, in a similar manner as above,

Solving we get, F0 = 2.33 min.

Hence, a 30 min. of sterilization at 110°C is lethally equivalent to 2.33 min. of sterilization at 121.1°C. *(Compare this sentence with the definition of F0 value for easy understanding)*

The crux of the example is,

121.1°C **→** 30 min. (Expected condition)

110°C **→** 2.33 min. (Actual condition)

Therefore, according to the expected condition; the effective sterilization cycle time was only 2.33 min. instead of 30 min. because of the lowered temperature of 110°C.

Let’s understand “how long will it take to complete the sterilization?” According to the above example, if we maintain temperature 110°C constantly, then it requires how much hold time to achieve F0 value as 30 min.

For instance, a reverse calculation can do this by fixing the F0 value as 30 min. The unknown part then would be Δt.

We have the following data with us:

F0 = 30 min.

Temperature T = 110°C

Apply these values in equation (2),

Solving we get, Δt = 386 min.

**When the temperature of the system under sterilization maintained at a constant 110°C, the time of 386 min. (i.e. Sterile Hold Time) would be required to achieve the lethal effect of 121.1°C @ 30 min.**

#### Example 2 (Above Ideal Condition)

Consider sterilization hold time of 30 min. at constant 125°C instead of 121.1°C, in a similar manner as above,

Solving we get, F0 = 73.64 min.

Hence, a 30 min. of sterilization at 125°C is lethally equivalent to 73.64 min. of sterilization at 121.1°C. *(Compare this sentence with the definition of F0 value for easy understanding)*

Simply put,

121.1°C **→** 30 min. (Expected)

125°C ** →** 73.64 min. (Actual)

Therefore, according to the expected condition; the effective sterilization cycle time was 73.64 min. instead of 30 min. because of the raised temperature of 125°C.

Let’s understand “how long will it take to complete the sterilization?” According to the above example, if we maintain temperature 125°C constantly, then it requires how much hold time to achieve F0 value as 30 min.

For instance, a reverse calculation can do this by fixing the F0 value as 30 min. The unknown part then would be Δt.

We have the following data with us:

F0 = 30 min.

Temperature T = 125°C

Apply these values in equation (2),

Solving we get, Δt = 12.24 min.

**When the temperature of the system under sterilization maintained at a constant 125°C, the time of 12.24 min (i.e. Sterile Hold Time) would be required to achieve the lethal effect of 121.1°C @ 30 min. **

## Conclusion

1. F0 value provides a simple idea of a lethal equivalence between ideal and practical conditions. Taking notes on practical values of lethal doses, D-value, and z-value become very important while evaluating F0 value precisely.

2. When the average temperature of the system is below the set value of 121.1°C, the sterilization cycle may lead to failure even if the sterile hold time completes. Ultimately, not bringing about a residual reduction of micro-organisms.

3. When the average temperature of the system is above the set value of 121.1°C, the sterilization may be lethally equivalent even before the sterile hold timer ends.

Note: This lethal equivalence has technical value only when the steam used for sterilization is **Saturated**. Otherwise, this equivalence is pointless.

For analysis of lethal equivalence, F0 value calculation considered useful post sterilization cycle as well. After that, the real-time calculation of the F0 value during sterilization requires a controller-based approach with a computerized system. This system requires efficiency to measure the F0 value and manage the sterilization cycle in real-time with proper programming and control mechanism.

Most of the pharmaceutical companies using steam sterilization rely on the calculation of F0 value for analysis purposes, though the logic-based controllers are capable to drive sterilization cycles based on F0 value. Whilst this article mainly focuses on the meaning and significance of F0 value theoretically.

Don’t miss-out the related articles

1. F0 Value and Sterilization Cycle Development

2. How Steam Quality has a significant impact on Sterilization?

3. F0 Value Calculator

Also, you may click here if interested in knowing the validation approach for the steam sterilization process in autoclaves.

## F0 Value Related FAQs

### What is f0 value?

It is equivalent time of exposure at 121.1°C to that of actual time of exposure at a variable temperature calculated with a temperature coefficient of destruction of 10°C. (i.e. Z=10)

### How do you calculate f0 value in autoclave?

To calculate F0 value, average temperature of all probes during sterile hold and sterile hold time values required. Also, z value for steam sterilization considered as 10 theoretically. Once these values become available, we input that in formula mentioned in this article earlier and get the F0 value in minutes.

### What is D value and Z value?

D Value or Decimal Decay Time: The time (t) required at specified temperature (T), to reduce microbial population from 100% to 10% (1 log reduction).

Z Value or Temperature coefficient: Number of degrees by which the temperature required to increase to effect a 10-fold variation of D-value.

This article clearly explains the significance of F0 value in steam sterilization.Thanks for explaining it clearly.

Hey Nikki! Glad that this added value to your know-how. More such content in pipeline. Stay tuned and take care 🙂

Because of examples, it was easy to understand D, Z and F0 value concept.

Hey Manisha! Thanks for that and wish you all the best!

Hi Saket. I found this article via LinkedIn. I am very impressed with the quality of the write-up. It is pretty easy to understand at the same time informative.

Hey Ranjeet! Thank you for your words and wish you all the best. Keep in touch.