STEAM THERMODYNAMICS AND STERILIZATION

                             STEAM THERMODYNAMICS AND STERILIZATION

TEMPERATURE AND HEAT: Temperature is a measure of thermal energy, while heat is energy that is transferred as a result of a temp diff bet object and surrounding.

MECHANISM OF ENERGY TRANSFER:

1)   Conduction:  Transfer of energy through molecular agitation without any required motion of material as a whole.

2)   Convection: Transfer of energy resulting from contact with a moving fluid.

3)   Radiation: Transfer of energy through electromagnetic waves.

There is significant difference in energy content at a given temperature in various heating media. Heating media like super heated water, saturated steam, and steam air mixture contains different amount of thermal energy.

THERMODYNAMIC CHARACTERS OF STEAM: 

Saturated steam contains 2675 J/g at 100^oC, which consists of energy in the water 419J/g and energy required to create steam 2,256 J/g (heat of vaporization/condensation at 100 ^oC).

Hence The condensation of 1 gram of steam imparts 2, 256 joule to the object at 100 ^oC. 

-At 25 ^oC and 1 atm pressure, 4.1 Joule is required to change the temp of one gram of liquid water by 1 ^oC. The temperature will increase with input of energy until reaches 100 ^oC.  No further temp change will occur at 1 atm pressure  until an additional 2,256 joule have been absorbed by the water  to convert it to steam. The same amount of energy is imparted to an object when the process is reversed and steam is condensed to water.

Similarly at 2 atm pressure, the temperature will increase with input of energy until reaches 121 ^oC,  No further temp change will occur at 2 atm pressure  until an additional 2199 joules have been absorbed by the water  to convert it to steam. The same amount of energy is imparted to an object when the process is reversed and steam is condensed to water.

There is only one pressure that corresponds to a specific temperature on the curve when steam is saturated for example : at 1 atm saturated steam obtained at 100^oC, while at 2 atm it is at 121^oC. 

The energy properties contained by water and saturated steam at a definite temperature and pressure are already well known and constitutes steam table (Refer ASME International Steam table). Thus sterilization cycles are designed by considering these saturated steam temperature and pressure relations.

 If the values of Pressure and temperature are not in general agreement with established steam table then this may be an indication that the sterilization cycle is taking place without the full effect of the heat.

Also Flow of heat from heating media to a sealed container depends on:

1)   Temp difference  between container and heating media

2)   Geometry and characteristic of container

3)   Overall heat transfer coefficient: Overall heat transfer coefficient: is a complex function that includes the thermodynamic characteristics of the heating media. Apart from energy content difference of steam at difference temperature and pressure, there is difference in heat transfer rate of alternate Medias.

-  Saturated Steam: Heat Transfer rate –High

-  Steam Air Mixtures: Heat Transfer rate –Function of steam to air ratio and Flow velocity.

-  Super heated water :

Water Spray with air over pressure: Heat Transfer rate – Moderately High, Function of Flow velocity

Water Submersion with air over pressure: Heat Transfer rate - High but function of flow velocity.

^{______________________________________________}

Article Reference:  PDA Technical Report No.1 “Validation of moist heat sterilization process. Cycle design, development, qualification and ongoing control”

#1.2 STERILIZATION- F VALUE

Continued from #1.2

Lethal Rate:  can be calculated by

L_(Tref,Z)=10 ^(T-T_Ref^)/Z

Where

T= Temperature of item being heated

T _ref = Reference Temperature

Z = Z value of Challenge organism (10^oC if unknown)

Lethal rate is an exponential function; hence a small change in temperature difference can have a significant effect on delivered lethality.

For a BI system witha z value of 10^oC and T _ref -121 ^oC, decrease in lethality by decrease in 1 ^oC temperature can be calculated as:

L=10 ^(120-121)/10= 10^-0.1 = 0.79

It means for a BI with a Z value 10 ^oC one minute at 120 ^oC is equivalent to 0.79 minute at 121 ^oC in terms of lethality.

Microbial destruction at any temperature (120 ^oC in example) can be related to equivalent minutes at a reference temperature (T _ref ; in example 121 ^oC).

F_physical /F value: means the equivalent amount of time, in minutes at T _ref, which has been delivered to a product by the sterilization process".

F value is a measurement of lethality of a process.

F value is the calculated equivalent of time in terms of lethality at a reference temperature T _ref and a temp coefficient Z that is delivered to item being sterilized.

The F value is the integration of the lethal rates throughout the process.

F_ref = d(∑L)

Where:

d= the time increment between each temperature reading

L= Lethal rate calculated for each temperature reading.

F₀ Value:  is the number of equivalent minutes of steam sterilization at a temperature of 121 ^oC delivered to a container or unit of product using Z value of 10 ^oC.

F₀ of 8 minutes means sterilization effectiveness of that cycle is equivalent to 8.0 minute at 121 ^oC.

F _Bio: The term F _bio represents the delivered lethality measured by the actual kill of microorganism or in a BI System

F _bio = D_T×LR

D_T - D value of the BI at reference temperature

LR- Log reduction of BI population achieved during the cycle

^{______________________________________________}

Article Reference:  PDA Technical Report No.1 “Validation of moist heat sterilization process. Cycle design, development, qualification and ongoing control”

#1.2 STERILIZATION

Continued from #1.1

The semi logarithm relationship does not accurately fit all experimental microbial thermal destruction data, but to the date no other model is known that fits all experimental data.

In order to apply the semi logarithm model for survivor curve the challenge must consists homogeneous culture and a constant lethal stress must be applied to the challenge.

Considering sterilization by Thermal stress the survivor curve can be described as:

Log N_F = -F_(T,z)/D_T+Log N₀  (First order reaction) 

N_F: Number of microorganism after exposure of F equivalent minutes

F_(T,z): Equivalent lethality of a cycle calculated as minutes at a reference temperature(T) using a defined temperature coefficient (z)

D_T: Thermal resistance value_, in minutes of the microorganism at a specific temperature (T)

N₀: Number of microorganism prior to exposure

Graphical Representation for the above equation will be:

Resistance Value (D_T Value):  D_T value is the time in minute for a one log or 90% reduction of a microbial population under specific lethal condition i.e. temperature

One logarithm cycle on y axis represents a tenfold change in number of survivors or it can be said that 1 log reduction means a reduction of tenfold in microbial population.

D_T value is the time or equivalent time on x axis for the survivor curve to transverse 1 log cycle.

Temperature Coefficient (Z Value): Z value is the number of degrees of the temperature change necessary to change the D_T value by a factor of 10.

For example: D_T value of a BI challenge system with a Z value of 8^o will change by a factor of 10 for each 8^o change in temperature.

If the D₁₂₁ of the BI is 1.6 min then the D₁₂₉ will be 0.16 min and D₁₁₃ will be 16 min.

Moist heat sterilization processes are usually carried out within a small temperature change, 110 ^o to 135 ^o therefore experimentally determined z value is usually considered constant for practical purpose. Z value of 10^o is generally used.

^{______________________________________________}

Article Reference:  PDA Technical Report No.1 “Validation of moist heat sterilization process. Cycle design, development, qualification and ongoing control”

#1.1 STERILIZATION

Continued from #1

N / N₀ = 10^-kt  .....Equation 2   

Where     

N₀ - initial number of microorganism, t - elapsed exposure (= sterilization) time, N - number of microorganism after the exposure time t, K - reaction rate constant  which depends on the species and conditions of the  microorganism

As Equation 2 describes the survivor curve for microorganism and shows that number of microorganism decrease exponentially depending on sterilization time. 

The graphical representation of survivor curve (semi-logarithmic plot) shall be as follows:

The semi-logarithmic plot of the Survivor Curve has the difficulty of being undefined mathematically at zero, which is the definition of  “sterile”¹.

The sterilization reaction is therefore neither an "all-or-nothing" process nor a "potential barrier" process as its definition says2"Sterile" means absence of all viable microorganisms.

In the pharmaceutical industry the concept of “Sterility” expresses sterility as a probability in the region of the survivor curve below one surviving organism. This region has negative values for the log of concentration and is interpreted as non-sterile containers in a group being sterilized (e.g., one non-sterile unit in ten units for a survivor concentration of 10-1). This approach is called Probability of a Non-Sterile Unit (PNSU) or, as applied to all processes, Sterility Assurance Level (SAL) ¹.

^{______________________________________________}

¹Remington-Essentials of Pharmaceutics, Chapter 25 “Sterilization Processes and Sterility Assurance”

²F0 - A technical note – Doc. 352178v2 - Fedegari Group

KEY POINTS OF #1

#1.1

KEY POINTS “Sterilization", in a strictly biological sense, describes the destruction of all viable microorganisms. Death of microorganism can be accomplished by removing what they need to increase in number and the same can be accelerated by subjecting the microbes to some degree of stress (thermal, chemical, or ionic). Each death process of microorganism supposed to be following a chemical reaction that follows first order kinetics. First order reaction shows that number of microorganism decreases exponentially depending on the sterilization time.

#1.0 STERILIZATION

#1.0

1. Sterilization

"Sterile" and "sterilization", in a strictly biological sense, describes the absence, and respectively, the destruction of all viable microorganisms.

Microbial Growth and Death:

In order to increase in number (or replicate), aerobic and facultative microorganisms require: food, water & air. Hence death of microorganism can be accomplished by removing what they need to survive (i.e. food, water & air).

Death rate of microorganisms can be accelerated by subjecting the microbes to some degree of stress. The stress can be thermal, chemical, or ionic in nature (filtration is not a lethal process) in which the death rate is accelerated.

The mechanism of death may be fundamentally differ for all stress methods, but each death process follows a chemical reaction that follows first order kinetics.¹

A first-order reaction is a reaction that proceeds at a rate that depends linearly on only one reactant concentration.²

Example of Death model (in terms of first order kinetics)

Suppose a vial containing certain microorganism is subjected to stress condition via saturated steam. Under such condition thermal degradation of the microorganism supposed to obeys the laws of chemical reactions.

The variation in the number of microorganisms as the function of a chosen time “t” of exposure to the selected sterilization temperature can be written as:

 -K N=  dN / dt

Where:   N is number of microorganisms present in the system,

              K is a constant which is typical of the species and condition of the  chosen
               microorganism.

Or equation may be written as    -Kdt  =  dN / N

By converting from base e to base 10 logarithms, the following is obtained

log N = -k t + constant    .....Equation 1

Where, K = k/ 2.303 due to the shift from base e logarithms to base 10. 

At time zero or at initial,   t=0 & N=N₀, the equation shall become

log N₀  = Constant

Or ....Equation 1 can be expressed as:  log N = -k t + log  N₀ 

Or    log N / N₀ = -k t 

Or    N / N₀ = 10^-kt  .....Equation 2   

Where   
N₀ - initial number of microorganism, t - elapsed exposure (= sterilization) time, N - number of microorganism after the exposure time t, K - reaction rate constant  which depends on the species and conditions of the  microorganism      

.....Equation 2 shows that the number of microorganism decreases exponentially depending on the sterilization time.³

^{______________________________________________}

¹Remington-Essentials of Pharmaceutics, Chapter 25 “Sterilization Processes and Sterility Assurance”

²https://chem.libretexts.org/Bookshelves/Physical_and_Theoretical_Chemistry_Textbook_Maps/Supplemental_Module       s_(Physical_and_Theoretical_Chemistry)/Kinetics/Reaction_Rates/First-Order_Reactions

³F0 - A technical note –  Doc. 352178v2 - Fedegari Group