Air velocity and air flow and Air changes of AHU system in clean room

Air velocity: 
Speed of air under unit time, the units here are feet per minute(FPM).

Air flow measured in Cubic feet per minute(CFM):

= Air velocity(Feet per min) x Supply grill area(ft square)
= the results is in CFM.

Air changes per hour :

=Air flow x 60/ Total room area(Cubic feet)
= this gives air changes per hour
Limit is not less than 20 Air changes per hour

Limit of qunatitation-Requirements

The Quantitation limit or Limit of quantitation in short LOQ:

LOQ is the least level of concentration of an analyte(eg: Impurity-A) That an analtyical method can quantify precisely and accurately.

How to estatblish LOQ :

Method 1: Slope and standard deviation(=Steyx in Microsoft excel) method.

Inject low concentrations of an analyte  from the detection level about 3-4 concentrations and record the absorbances.

X= Concentration(% of impurity with respect to test sample concentration)

Y= Absorbances.

Now calculate slope and Standard deviation(SD) using Microsoft excel.

% LOQ = 10 x Slope/ SD

Method 2: Signal  to noise ratio method.

Prepare the analyte about 0.1% level and find the S/N ratio of the peak.

now estimate the concentration to get the  analyte peak signal to noise ratio is about 10:1

Inject the concentration to check the S/N is about 10:1

Now the estimated concentration is called LOQ concentration.

After obtaining the LOQ, we shall  prove this is precise and accurate.

Inject the LOQ concentration six times and check the  repeat-ability.( Precision)

Spike The LOQ concentration of impurity to the test sample and  verify the % recovery.(Accuracy)

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Limit of detection is 3.3 times less to the Limit of quantitation.

simply dilute 3.3 mL of LOQ solution to 10 mL with the diluent and analyse. the peak shall be visually detected and Signal to noise ration is about 3.

Usually LOD is not required for Quantification methods. It applies to the limit tests like TLC..

Description and solubility requirement as per USP/BP/EP

Description and solubility requirement as per USP/BP/EP :

These tests are only for information but not standards does not need to comply.

Long time ago, color and other organoleptic characteristics (taste, odor) and description (including the solubility and clearance of the solution) pertaining to an article, formerly included in the individual monograph, were considered subjective and general in nature. Now, this information is provided in the "Description and Solubility Section" of the USP-NF for those who use, prepare, and dispense drugs, solely to indicate descriptive and solubility properties of an article complying with monograph standards. The properties are not in themselves standards or tests for purity even though they may indirectly assist in the preliminary evaluation of the integrity of an article.

This explanation is so stated under the subtitle: “Description and Relative Solubility of USP and NF Articles” at the beginning of the section titled: “DESCRIPTION AND RELATIVE SOLUBILITY”.

Dirty equipment Clean Hold time studies :

Dirty equipment Hold time studies :

Now a days  the auditors are asking about the Dirty equipment Hold time study report in cleaning validation:

What is dirty equipment : 

Uncleaned equipment over a period of time

What is dirty equipment Hold time : 

The time between "after use" and "before cleaning" of equipment.


What to study : 
whether the cleaning process is capable enough to clean the dirty equipment and meets the acceptance criteria.

Plan :

Keep the equipment idle after usage(unload the material) and do not clean for 24 hours. collect the physical traces of sample after 8,12 and 24 hours respectively. then clean the equipment

Check for degradation using related substances method for the samples of 8,12 and 24 hours collected from different locations of the equipment.

Collect and check the rinse/swab sample after 24 hours for the product absence.

Clean hold time studies : 
The time period between "after cleaning and before use" of equipment.

Procedure :
After cleaning of an equipment, keep it idle for 48 hours and check swab sample for microbial counts.
TAMC : 1000 Colony forming units/swab
TYMC : 100 Colony forming units/swab

Temperature, Humidity and MKT in stability studies

Temperature, Humidity and MKT in stability studies:

*Relative humidity is a measure of how close the air is to reaching saturation with moisture

*Saturation is the point when the air can hold no more water vapor and is essentially full.

*Let us take  a glass filled with wine half full.

     The glass can hold 200 mL

*100 mL wine is in the glass - Absolute

*Content in % is 50 - Relative

Mean kinetic temperature :

*Across the year, temperatures vary from zero to 40°C

*The mean kinetic temperature will be the climatic condition.

*It is somewhat similar to average, But not exactly.

*It was calculated by using Arrhenius equation.

*For example, INDIA climate: 30°C / 75%RH.

*when Air becomes warm, Warm air can hold more moisture, because air expands

Relative humidity decreases.

*Air becomes cool, Relative humidity increases