1.
OBJECTIVE
To lay down the
procedure for validation of Analytical method for cleaning validation in
equipment surface samples for cleaning assessment.
2.
SCOPE
This procedure
is applicable for validation of Analytical method for cleaning validation by
swab method for the product chosen as worst case and manufactured at different
facility of Ajanta Pharma Limited.
3.
RESPONSIBILITY
3.1
Assistant
Manager or Designee Analytical Development Laboratory (ADL):
Preparation and execution of SOP.
3.2
Head
of Department (HOD) or designee ADL:
To check the SOP and to ensure activities
are performed as per SOP.
3.3
Head
or Designee of Research Centre (RC):
To review and authorization of SOP.
4.
PROCEDURE
Disregard
procedure for evaluation in chromatographic analysis. Maximum allowable
carryover (MACO) limit shall be provided by plant.
1.
On the basis of
limit of swab (MACO limit) the critical limit level concentration (CLLC) shall
be calculated as example given below and validation shall be carried out using
a specific written and authorized validation protocol considering critical
limit level concentration as 100%.
Examples to transform the
acceptance criteria value for swab in concentration units (µg/ml) is
presented as
1.
Equipment
surface to be swabbed is 5cm X 5cm = 25cm2
2.
Amount of drug
from the swabbed are (value provided from location side) = XYZ µg/swab.
3.
Sampling volume
e.g. 5mL, 10mL, 20 mL…..100mL
4.
Drug
concentration at acceptance level = 250 µg/25 mL = 10 µg/mL. Hence 10 µg/mL is
the critical limit level concentration (CLLC).
3.
Materials
required:
1.
Swab TX 714A
Large alpha swab
2.
Sampling
Template 1.5 mm thick white PVC sheet with 5cm x 5cm area cut on its surface,
5cm x 5cm coupon.
3.
SS Plate 316 or
any other material as per requirement such as sieves, roller etc.
4.
Swabbing procedure
1.
Wet the swab
with solvent given in respective protocol. Hold the swab at once corner and
wipe the surface of the coupon eight times using sampling template of size 5 x
5 cm in paint brush action as shown in figure 1 and 2, so that whatever amount
recovered remains in the swab only. Dip the swab in the glass beaker or conical
flask containing or measure volume of 25 ml of diluent or water and remaining
sample treatment as per the procedure given in the protocol.
2.
Calculation:
1.
For Swab
Sample:
2.
Amount of drug
in µg/cm2
Area of drug in spl.
Preparation Wt. of std.
std.dil.1
std.dil.2
---------------------------------------
X ------------------ X ----------- X ------------- X
Area of drug in std. Preparation
dil.
dil.1
dil.2
Sample volume i.e. 25, 50
or 100 mL 1
---------------------------------------------
X --------- =
mg/swab
25*
RCF
Where 25* = represents the
sample surface area (cm2)
RCF = represents the recovery correction
factor for the swabbed surface obtained from method validation
5.
Experimental
Design:
1.
Following
parameters has to be evaluated for cleaning validation by HPLC method and
following general criteria should be consider, if not mentioned in individual
protocol.
1.
System
suitability
2.
Specificity
3.
Limit of Detection
4.
Limit of
Quantitation
5.
Linearity
6.
Range
7.
Recovery
8.
Precision
9.
Intermediate
Precision (Ruggedness).
2.
System
suitability:
1.
Experimental
Design
Inject five/six replicate injections of Standard preparation
Acceptance criteria
1) % RSD for peak area
response of replicate standards : NMT 2.0% for five replicate injections
and NMT 5.0% for six replicate injections
2) Theoretical plates: NLT 2000
3) Asymmetry: NMT 2.0
3.
Specificity:
1.
Experimental
Design
Diluent,
Placebo and swab interference
Acceptance criteria
1) There should not be any
interference of peak from blank, placebo and swab at the retention time of main
peak.
2) Peak purity for the main
peak in Standard preparation and Spiked from coupon and swab should not be less
than 0.99.
4.
Limit of
Detection:
1.
The Limit of
Detection can be determined by any of the method given below.
Method I
Experimental
Design
Perform the linearity and
derive the curve by graph (Analyte concentration VS Response) and calculate,
3.3
× σ
LOD =
-----------------
S
Where, σ = the
residual standard deviation of the regression line from calibration curve
S = the slope
of the calibration curve.
Acceptance
Criteria
Report the
value of detection limit.
Method II
Experimental Design
The Limit for Detection is
established by signal-to-noise ratio (S/N) obtained from baseline noise using
following formula.
2H
S/N =
---------
h
Where,
S/N
= Signal to noise ratio
H
= Height of the peak of interest in mm.
h = Height of
the noise in mm.
Acceptance
criteria:
1) Report the
value of detection limit.
2) Limit of
Detection (S/N Ratio) should be about 2 to 3.
5.
Limit of
Quantitation
1.
The Limit of
Quantitation can be determined by any of the method given below.
Method I
Experimental
Design
Perform the linearity and
derive the curve by graph (Analyte concentration VS Response) and calculate,
10 ×
σ
LOQ =
-------------
S
Where, σ = the
residual standard deviation of the regression line from calibration curve
S = the slope
of the calibration curve.
Acceptance
Criteria
1.
Report the
value of Quantitation limit.
2.
RSD of area
should not be more than 10.0%.
Method II
Experimental Design
The Limit for Quantitation
is established by signal-to-noise ratio (S/N) obtained from baseline noise
using following formula.
2H
S/N =
---------
h
Where,
S/N
= Signal to noise ratio
H
= Height of the peak of interest in mm.
h = Height of
the noise in mm.
Acceptance
criteria:
1) Report the
value of Quantitation limit.
2) Limit of
Quantitation (S/N Ratio) should be about 10.
3) RSD of area
should not be more than 10.0%.
6.
Linearity and
range:
1.
Experimental
Design
1.
For the
establishment of linearity and range, a minimum 5 concentrations of standard in
the specified range as per method validation protocol. Linearity is evaluated
by visual inspection of a plot of signals as a function of analyte
concentration. Inject first level and last level six times and remaining all
the other levels in triplicate. Linearity shall be at LOQ level to 150% of critical
limit level concentration.
2.
Acceptance
criteria:
The correlation coefficient
should not be less than 0.99. The relative standard deviation at each level
should not be more than 10.0% for LOQ level and 5.0 % for all the other levels.
Report the value of slope of regression line, y-intercept and residual sum of
square.
7.
Accuracy
(Recovery):
1.
Experimental
Design:
1.
A known amount
of working standard solution containing placebo is spike on the swab or on the
coupon surface (5cm X 5cm) or on any other material as per requirement ( 5cm X
5cm) such as sieves, roller etc. and evaporate it as per the procedure given in
the protocol. Swab the surface and calculate the recovery. Accuracy shall be at
LOQ level to 150% of critical limit level concentration.
2.
Acceptance criteria:
Recovery at each level, mean
recovery and overall mean recovery from swab should be between 90.0% and 110.0%
with %RSD should not be more than 5.0%.
Recovery at each level,
mean recovery and overall mean recovery from coupon surface should be between
80.0% and 120.0% with %RSD should not be more than 10.0%.
Recovery at each level,
mean recovery and overall mean recovery from any other surface except swab and
coupon should be between 70.0% and 130.0% with %RSD should not be more than
15.0%.
8.
System precision:
1.
Experimental
Design:
1.
Inject five
replicate injections of Standard preparation
2.
Acceptance
criteria
% RSD for peak area
response of replicate standards: NMT 5.0%.
Theoretical plates: NLT
2000
Asymmetry: NMT 2.0
9.
Method
precision:
1.
Experimental
Design:
1.
Carry out
minimum six determinations of Recovery from coupon surface at Critical limit
level concentration.
2.
Acceptance
criteria
%RSD of recovery of six
replicate determinations should not be more than 10.0%.
The recovery should be
between 80.0% to 120.0%.
10.
Intermediate
precision:
1.
Experimental
Design:
1.
Carry out
minimum six determinations of Recovery from coupon surface at limit level
concentration on different days, by different analyst and using different
instruments.
2.
Acceptance
criteria
%RSD of recovery of six
replicate determinations should not be more than 10.0%.
%RSD of recovery of twelve
replicate determination (Method precision and Intermediate precision) should
not be more than 10.0%.
The recovery should be
between 80.0% to 120.0%.
5.
RELATED
DOCUMENTS
Nil
6.
REFERENCES
Nil
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