2 PDF

Vol. 1 No.
4 2012
Online Available at www.thepharmajournal.com
THE PHARMA INNOVATION
Cleaning Validation of Albendazole Tablets 400 mg
Bodavula Samba Siva Rao1*, Y. Surendhranath Reddy2, M. Jeybaskaran2
1. Department of Pharmacy, Khammam College of Pharmacy, Khammam, Andhra Pradesh, India

2. Browns College of Pharmacy, Khammam, Andhra Pradesh, India
The cleaning validation is to verify the effectiveness of the cleaning procedure for removal of
product residues, degradation products, preservatives, excipients and cleaning agents so that the
analytical monitoring may be reduced to a minimum in the routine phase. In addition one need to
ensure there is no risk associated with cross contamination of active ingredients. Cleaning
validation is intended to address special consideration and issues pertaining to validation
cleaning procedures for equipment used in the manufactured of pharmaceutical products,
radiopharmaceuticals, and biological drugs. The document is also intended to establish
inspection consistency and uniformity with respect to equipment cleaning procedures.
Keyword: Acceptable residual level (ARL), Cleaning equipment, Swabs and Wipes Method, Rinse
Method
INTRODUCTION: As a result of any Pierre Rousseau introduced matrix approaches to

pharmaceutical unit process, a residual level of the solved complex cleaning Validation
the drug substance remains on the equipment and Problems.
facility even after clean up. This residual drug
and possibly traces of cleaning agents may be Cleaning is a challenging task and the design of
carried over into the next product resulting in the cleaning system depending upon the
adulteration of the subsequent product. Hence, equipment use (dedicated/multipurpose),
the cleaning methods developed should manufacture (continuous/batch), cleaning
consistently lower the level of residual to the equipment (manual/automated), preparation
acceptable residual level (ARL). (commercial product/clinical supplies), product
formulation i.e., type of materials being removed
Formulation and Mullen of Eli Lilly Company from the surface, drugs (low risk/high risk),
established a method for finding out cleaning sterile/non sterile, solids/liquids and solubility
acceptance criteria limit for a multi-drug facility (soluble/insoluble) of active ingredients. An
in 1993. acceptable cleaning system should incorporate
the following elements.
Corresponding Authors Contact information:
Bodavula Samba Siva Rao* MATERIALS AND METHODS:
Department of Pharmacy, Khammam College of Pharmacy,
Khammam, Andhra Pradesh, India SAMPLING PROCEDURE
E-mail: siva69pharma@gmail.com
In order to evaluate a cleaning method it is
necessary to sample the product contact surfaces
Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 76

Bodavula Samba Siva Rao*, Y. Surendhranath Reddy, M. Jeybaskaran
of the equipment and establish the level of Limitations

residuals present.
Residues may not be homogeneously
distributed.
Inability to detect location of residues.
i) Swabs and Wipes Method
Rinse volume is critical to ensure accurate
Swabbing is the most widely used sampling interpretation of results.
technique. Swabs may be saturated with solvent
iii) Coupon sampling
such as water or alcohol, facilitating the
solubilzation and physical removal of surface Coupons of the same materials of construction as
residues. the item to be cleaned can be affixed to the
equipment, spiked with the product, subject to the
Advantages cleaning procedures and then submitted to the
Dissolves and physically remove sample. laboratory for direct analysis and recovery
Adequate to a wide variety of surfaces studies.
Economical and widely available. Advantages
Allows sampling of a defined area.
Allows for direct surface sampling.
Useful in cleaning method development.
Limitations Reduced variability in recovery.
Useful in evaluation of equipment
An invasive technique that may introduce materials of construction.
fibers.
Results may be technique dependent. Limitations
Swab material and design may inhibit Coupon may not be representative of equipment
recovery and specificity of the method. contamination or cleaning as it is separate from
Evaluation of large, complex and hard-to- primarily surface.
reach areas difficult (e.g. crevices, pipes,
valves, large vessels). Invasive
Might interfere with the cleaning process.
In obtaining rinse samples, location, timing and
volume are important considerations.
iv) Solvent Sampling

ii) Rinse Method This technique uses a solvent not normally
employed in the cleaning process to maximize
Advantages recovery residues.
Adaptable to online monitoring. Advantages
Easy to sample and non-intrusive.
Allows sampling of a large surface area. Commonly used in bulk chemical
Allows sampling of porous surfaces. facilities
Applicable for actives, cleaning agents,
excipients
Less technique dependent than swabs.
Usually affords more analytical
specificity, less recovery loss than swabs.

Allows sampling of a larger surface area. ACCEPTANCE CRIETRIA

Allows sampling of porous and delicate
surface Method of calculating Acceptance Criteria
Maximizes recovery to rinse. i) Based on Therapeutic Daily Dose
The principle for the requirement is that the
standard Therapeutic Daily Dose (TDD) of the
Limitations
following substance (contaminated substance, in
May require operator protection and other this called next) may be contaminated by no
safety and environmental protection more than a certain proportion (usually 1/1000
measures. part) of the TDD of the substance investigated in
May require more than one sampling for the cleaning validation (contaminating substance,
broad spectrum analysis. in this case called Previous). This method only
Reduced physical sampling of the surface. applies when the therapeutic daily dose is known.
May be difficult to accurately define the It generally used for final product changeover
controlled area sampled, therefore usually API Process A to API process B.
used for rinsing an entire piece of
equipment such as a vessel. PROCEDURE
May require the removal of solvent prior Establish the limit for Maximum Allowable
to equipment use for production. Carryover (MACO) according to the following
equation.
v) Placebo and Product Sampling TDDprevious x MBS

MACO =
Placebo sampling can be used to detects residues SF x TDDnext
on equipment thorough the processing of a place MACO: Maximum Allowable Carryover: acceptable transferred
to batch subsequent to the cleaning process. amount from the investigation product (Previous)
Product sampling is similar to placebo sampling TDDprevious: Standard therapeutic dose of the investigated
product (in the same dosage form as: TDD
except that it uses actual product. TDDnext: Standard therapeutic dose of the daily dose for the next
product.
Advantages MBS: Minimum batch size for the next product(s) (where MACO
can end up)
Points of product contact identical for the SF: Safety factor (normally 1000 is used in calculations based on
TDD).
two batches
Applicable for hard to reach surfaces.
Require no additional sampling steps. ii) Based on Toxicology Data
In cases in which a therapeutic dose is not known
(e.g. for intermediates and detergents), toxicity
Limitations data may be used for calculating MACO.
Procedure
Difficult to determine recovery
Lowers analytical specificity and inhibits Calculate the so called NOEL number (No
detectability Observable Effect Level) according to the
Residues may not be homogenously following equation and use the result for the
distributed. establishment of MACO.
No direct measurement of residues on
product contact surfaces.

MACO
CONC
MBS
MACO: Maximum Allowable Carryover: acceptable transferred
amount from the investigated product (previous). Calculated from
therapeutic doses and /or tox data.
MACOppm :Maximum Allowable Carryover: acceptable transferred
amount from the investigated product (previous). Calculated from
general ppm limit.
From the NOEL number a MACO can then be CONC: Concentration (kg/kg or ppm) of Previous substance in the
next batch. Based on MACO calculated from therapeutic doses and / or tox
calculated according to data.
MAXCONC: General limit for maximum allowed concentration
(kg/kg or ppm) of Previous substance in the next batch.
MBS: Minimum batch size fir the next product(s) (where MACO can end
up)
A general upper limit for the maximum

concentration of a contaminating substance in a
subsequent batch (MAXCONC) is often set to
MACO: Maximum Allowable Carry over: acceptable transferred ppm depending on the nature of products
amount from the investigated product (previous). produced from the individual company (e.g.
NOEL: No Observed Effect Level
LD50: Lethal Dose 50 in g/kg animal. The identification of the toxicity, pharmacological activity,) ppm in APIs
animal (mouse, rat etc., ) and the way of entry (IV, oral etc., ) is is very frequent).
important.
2000: 2000 is an empirical constant
TDDnext: Largest normal daily dose for the next product Note If you decide to employ the concept of
MBS: Minimum batch size for the next products (where levels of cleaning may be used for different
MACO can end up) levels. Especially if the product cleaned out is
SF: Safety factor
within the same synthetic chain and covered by
The safety factor (SF) varies depending on the the specification of the API, much higher
route of administration. Generally a factor of 200 (qualified) levels are acceptable.
is employed when manufacturing APIs to be If the calculated concentration (CONC) of the
administered in oral dosage forms. SF can vary previous (based on MACO calculation from
depending on substance/dosage form according to therapeutic doses/tox data) exceeds the general
(suppose tox values from oral administration) as upper limit (MAXCONC), then MAXCONC
for example as presented on the next page. level will be limit.
(iii) General Limit Swab Limits

If the calculation methods based on therapeutic If homogenous distribution is assumed on all
doses or toxicological data result in unacceptably surfaces, a recommended value can be set for the
high or irrelevant carryover figures, or content in a swab. This can be used as basic
toxicological data for intermediates are not know, information for preparation of a method of
the approach of a general limit may be suitable. analysis and detection limit.
Companies may choose to have such an upper
limit as a policy. The general limit is often set as Procedure
an upper limit for the maximum concentration Establish the target value for swab limit for the
(MAXCONC) of a contaminating substance in a whole equipment train, using the following
subsequent batch. equation:
The concentration (CONC) of the investigated
substance which can be accepted in the next
batch, according to dose related calculations, is:

Sample Standard
Sensitivity absorbance amounts
= x
level Standard of 10ppm
absorbance in 0.001%
Also other methods with different swab limits for

different surfaces in a piece of equipment and/or
equipment train can be used. Using this approach,
the total amount found on the equipment train has Standard amount of 10ppm in 0.001% is
to be below the MACO. 1mg.
SAFETY FACTORS2
Applicable approach may

Typical products be Cndd = normal daily = 0.1509mg
dose
Topical 1/10th to 1/100th of ndd Concentration of drug 0.101

= x 1 mg
th th
by 30cm2 in sample II 0.742
Oral 1/100 to 1/1000 of ndd
1/1000th to t/10000th of
Injections, Ophthalmics = 0.1361mg
ndd
Research & 1/10000 th to 1/100000th of 0.092

Concentration of drug
investigational ndd = x 1 mg
by 30cm2 in sample III 0.742
= 0.1240mg
RESULTS AND DISSCUSSION:
Swabbing is the most widely used sampling Average 0.1509+0.1361+0.1240

technique. Swabs may be saturated with solvent concentration of
such as water or alcohol, facilitating the 3
drug / 30cm2 of =
solubilization and physical removal of surface
residues (Sampling area: 30cm2). the whole
equipment
= 0.137mg
(i) Albendazole tablets to Paracetamol tablets BP

100mg The amount of drug present in 0.137
x5229
5229cm2 of Dispensing Booth = 30
Dispensing Booth
= 23.8793mg (or) 0.0238ppm

Dispensing Balance:
Concentration of drug 0.101 = 0.1354 mg

= x 1 mg
by 30cm2 in sample 0.742
= 0.1375mg
The amount of drug present in 0.1354
X1227
1227cm2 of Sifter = 30
78.75cm2 of Dispensing Balance x78.75 = 5.5378mg (or) 0.00554 ppm
= 30
Steam Jacketed Kettle
= 0.3609mg (or) 0.000361ppm
Dispensing tools: = 0.1132 mg

Concentration of 0.027
drug by 30cm2 in = x 1 mg
0.742
sample
= 0.0364mg Concentration of 0.092
1
drug by 30cm2 in = x
0.0364 0.742 mg
The amount of drug present in sample II
x60
60cm2 of Dispensing Tools = 30 = 0.1240mg
= 0.0728mg (or) 0.000073ppm
Sifter = 0.1186 mg
Concentration of 0.109 The amount of drug present in 0.1186

drug by 30cm2 in = x 1 mg x904.2
904.2cm2 of SJK = 30
0.742
sample I
= 3.5746mg (or) 0.00358 ppm.
= 0.1469mg
RMG
0.742
sample II = 0.08625 mg
= 0.1240mg

drug by 30cm2 in = x 1 mg = 0.2399 mg
0.742
sample II
= 0.1038 mg
drug by 30cm2 in = x 1mg
Concentration of drug 0.075 1 0.742
= x sample IV
by 30cm2 in sample III 0.742 mg
= 0.2938mg
= 0.1011 mg
Average of 0.08625+0.1030+0.1011
= 0.2577 mg
Concentration
3
of drug /30cm2 =
of the whole
equipment The amount of drug present in 0.2577 x
4225.2 cm2 of FBD = 30 4225.2
= 0.09705 mg
= 36.2945mg (or) 0.0363ppm.
The amount of drug 0.09705

present in 2101.8m2 of X2101.87 Cadmill
RMG = 30
Concentration of drug 0.472
= 6.7993mg (or) 0.0068ppm.
= x 1 mg
by 30cm2 in sample I 0.742
= 0.6361 mg
FBD
0.742
sample I
= 0.2722 mg Concentration of 0. 397
0.742
sample II
= 0.5350 mg
= 0.2251 mg

Average of 0.6361 + The amount of drug present in 0.5561 x

Concentration of drug 0.5350 2721 cm2 of Blender =
= 30 2721
/30cm2 of the whole
2 = 50.4384mg (or) 0.05044ppm
equipment
= 0.5855 mg
Compression Machine
The amount of drug present 0.5855 x Concentration of 0.251

in 923.4 cm2 of Cadmill = 30 923.4 drug by 30cm2 in = x 1 mg
0.742
sample I
= 18.0217mg or 0.018ppm.
= 0.3383 mg
Octagonal Blender
drug by 30cm2 in = x 1 mg = 0.2453 mg
0.742
sample I
= 0.5094 mg
= 0.2992 mg
0.742
sample II
= 0.5768 mg
= 0.2574 mg
0.742
sample III = 0.2850 mg
= 0.5822 mg

x
4608 cm2 of Compression
Machine = 30 4608
= 0.5561 mg = 43.776mg (or) 0.0438ppm

Average Equipment
S.
Concentrati in totally Acceptan
No
Equipmen
on of drug present ce Limit drug by 30cm2 in = x 0.1mg
t Name 2 0.742
. by 30cm amount(pp (ppm) sample I
(mg) m)
= 0.1698mg
Dispensing
1 0.137 0.0238 0.04615
Booth
Dispensing
2 0.1375 0.000361 3.065
Balance
= 0.1200mg
Dispensing
3 0.0364 0.000073 4.022
tools
4 Sifter 0.1354 0.00554 0.1967

= 0.1375mg
Steam
5 jacketed 0.1186 0.00358 0.2669
kettle
6 RMG 0.09705 0.0068 0.1148

= 0.1424mg
7 FBD 0.2577 0.0363 0.05712
8 Cad mill 0.5855 0.018 0.2614

x5229
9
Octogonal
0.5561 0.05044 0.0887
5229cm2 of Dispensing Booth = 30
Blender
= 24.8205mg (or) 0.02482ppm
Compressi
10 on 0.2850 0.0438 0.0524
Machine
Dispensing Balance:
II. Albandazole tablets to Chloroquine

phosphate tablets BP 100mg Concentration of drug 0.113
= x 1 mg
Dispensing Booth by 30cm2 in sample 0.742
= 0.1523mg
Standard amount of 10ppm in 0.001% is

1mg.
= 0.3998mg (or) 0.0003998ppm

Dispensing tools:
Concentration of 0.042 The amount of drug present in 0.1415

X1227
drug by 30cm2 in = x 1 mg 1227cm2 of Sifter = 30
0.742
sample
= 5.5378mg (or) 0.00554 ppm
= 0.0566mg
= 0.1132mg (or) 0.0001132ppm Concentration of 0.102

0.742
sample I
Sifter = 0.1375 mg
0.742
sample I
= 0.1644mg
= 0.1267mg
0.742
sample II
= 0.1186mg = 0.1321 mg
Average of 0.1644+0.1186 The amount of drug present 0.1321

x904.2
Concentration of drug in 904.2cm2 of SJK = 30
= 2
/30cm2 of the whole
equipment.
= 3.9815mg (or) 0.0039815 ppm.
= 0.1415 mg

RMG FBD
= 0.3262 mg
0.742
sample I
= 0.1092 mg
Concentration of 0.102 = 0.2830 mg
0.742
sample II
= 0.1375 mg
= 0.2412 mg
Concentration of drug 0.092 1
= x
= 0.1240 mg Concentration of 0.184

0.742
sample IV
Average of 0.1092+0.1375+0.1240 = 0.2480mg
Concentration of
3
drug /30cm2 of =
the whole
equipment
0.742
sample I
The amount of drug 0.1235
present in 2101.8m2 of x2101.87 Average of 0.3262+0.2830+0.2412+0.2
RMG = 30 Concentrati 480
on of drug
= 8.6525mg (or) 0.0086525ppm = 4
/30cm2 of
the whole
equipment
= 0.2746 mg

The amount of drug present 0.2746 x drug by 30cm2 in = x 1 mg
0.742
in 4225.2 cm2 of FBD = 30 4225.2
sample I
= 0.5553 mg
= 38.6745mg (or) 0.0386745ppm.
= 0.5094 mg
Cadmill
= x 1 mg
by 30cm2 in sample I 0.742
= 0.5553 mg
= 0.5809 mg
Concentration of 0. 371
0.742
sample II
0.5485 mg
= 0.5 mg
Average of 0.5553+0.5 The amount of drug present in 0.5485 x

Concentration of drug 2721 cm2 of Blender = 30 2721
= 2
/30cm2 of the whole = 49.7489mg (or) 0.0497489ppm
equipment
0.742
sample II
The amount of drug present in 0.5276 x
923.4 cm2 of Cadmill = 30 923.4 Compression Machine
= 16.2396mg or 0.016239ppm. Concentration of 0.262
0.742
sample I
Octogonal Blender = 0.3531 mg

Concentration of drug 0.192 S.

Average Equipment
Concentratio in totally Acceptanc
= x 1 mg Equipment
by 30cm2 in sample II 0.742 No Name
n of drug by present e Limit
. 30cm2 (mg) amount(pp (ppm)
m)
= 0.2588 mg
Dispensing
1 0.1424 0.02482 0.05151
Booth
Dispensing
2 0.1523 0.0004 3.42
Balance
= 0.2857 mg
Dispensing
3 0.0566 0.0001132 4.49
tools
4 Sifter 0.1415 0.00579 0.22
Steam
5 jacketed 0.1321 0.00398 0.298
= 0.3154 mg kettle
6 RMG 0.1235 0.008653 0.128
7 FBD 0.2746 0.0387 0.0638
Average of 0.3531+0.2588+0.2857+0.3 8 Cad mill 0.5276 0.01624 0.2917
Concentrati 154 Octogonal

9 0.5485 0.0498 0.099
on of drug Blender
= 4
/30cm2 of 10
Compressio
0.3032 0.04657 0.05845
n Machine
the whole
equipment III. Albandazole tablets to Erythromycin
= 0.3032 mg Stearate tablets 500mg
Dispensing Booth

x Sample Standard
30 4608 Sensitivity absorbance amounts
Machine = = x
level Standard of 10ppm
absorbance in 0.001%
= 46.5717mg (or) 0.0465717ppm
Standard amount of 10ppm in 0.001% is 1mg.

= 0.1307mg
78.75cm2 of Dispensing Balance x78.75
= 30
= x 1 mg = 0.4988mg (or) 0.0005ppm
by 30cm2 in sample II 0.742
= 0.1173mg
Dispensing tools:
= 0.0526mg

= x 1 mg
by 30cm2 in sample III 0.742 The amount of drug present in 0.0526
x60
= 0.0849mg 60cm2 of Dispensing Tools = 30
= 0.1052mg (or) 0.0001052ppm
Average 0.1307+0.1173+0.0849
concentration of Sifter
3
drug / 30cm2 of = = 0.1590mg
the whole
equipment
= 0.1109mg Concentration of 0.039
0.742
sample
5229cm2 of Dispensing Booth x5229 Concentration of 0.118
= 30 drug by 30cm2 in = x 1 mg
0.742
= 19.3300mg (or) 0.01933ppm sample I
= 0.1240mg
Dispensing Balance:
= x 1 mg
by 30cm2 in sample 0.742 = 0.1415 mg
= 0.1900mg

= 0.1483 mg
X1227
1227cm2 of Sifter = 30 Concentration of 0.107
0.742
= 5.7874mg (or) 0.0057874 ppm sample II
= 0.1442 mg
= 0.1361 mg
= 0.1213 mg
1
drug by 30cm2 in = x
0.742 mg
sample II
Concentration of drug 0.101 1

= 0.1321mg = x
= 0.1428 mg
Average of 0.1213+0.1321
= 2
/30cm2 of the whole The amount of drug 0.1428
equipment present in 2101.8m2 of x2101.87
= 0.1267 mg RMG = 30
= 10.0046mg (or) 0.010ppm.
The amount of drug present 0.1267

x904.2 FBD
in 904.2cm2 of SJK = 30
= 3.8187mg (or) 0.003818 ppm drug by 30cm2 in = x 1 mg
0.742
sample I
RMG = 0.1132 mg
0.742
sample I


0.742
sample II
= 0.5404 mg
= 0.1092 mg
= 0.1092mg = 0.5343 mg
0.742
sample IV

923.4 cm2 of Cadmill = 30 923.4
Average of 0.1132+0.1038+0.1092+0.1
Concentrati 092 = 16.4458mg or 0.01645ppm.
on of drug
= 4
/30cm2 of
the whole Octogonal Blender
equipment
= 0.1089 mg Average of 0.5283+0.5404
= 2
/30cm2 of the whole
equipment
The amount of drug present 0.1089 x
in 4225.2 cm2 of FBD = Concentration of 0.223
30 4225.2
= 15.34 mg (or) 0.01534 ppm 0.742
sample I
= 0.3005g
Cadmill
= x 1 mg
by 30cm2 in sample I 0.742 = 0.31 mg
= 0.5283 mg

= 0.2992 mg Average of 0.1078+0.1159+0.1105+0.1

Concentrati 146
on of drug
= 4
= 0.3033 mg /30cm2 of
the whole
equipment
2721 cm2 of Blender = = 0.1124 mg
30 2721
= 27.51mg (or) 0.02751ppm
x
Compression Machine
Machine = 30 4608
= 17.26mg (or) 0.01726ppm
0.742
sample I
= 0.1078 mg Average Equipment in
Acceptance
S. Equipment Concentration totally
Limit
N Name of drug by present
(ppm)
30cm2 (mg) amount(ppm)
Concentration of drug 0.086 1 Dispensing

= X 1
Booth
0.1109 0.01633 0.017212
by 30cm2 in sample II 0.742 mg
Dispensing
2 0.1900 0.0005 1.143
= 0.1159 mg Balance
Dispensing
3 0.0526 0.0001052 1.5
tools
Concentration of 0.082 4 Sifter 0.1415 0.00579 0.07335

drug by 30cm2 in = X 1mg
0.742 Steam
sample III 5 jacketed 0.1267 0.00382 0.09954
kettle
= 0.1105 mg
6 RMG 0.1428 0.01 0.04282
7 FBD 0.1089 0.01534 0.0213
Concentration of 0.085 8 Cad mill 0.5343 0.01645 0.09747

drug by 30cm2 in = X 1mg Octogonal
0.742 9 0.3033 0.02751 0.03308
sample IV Blender
= 0.1146 mg 10
Compression
0.1124 0.01726 0.01953
Machine

All the equipments were selected from cross

The cleaning validation for the equipment used in contamination point of view based on the matrix
manufacturing process of Albendazole tablets approach. Likewise, among the tablets
was carried out to provide that documented manufacturing facility, Albendazole tablet is
evidence with high degree of assurance that the predicted based on the worst case approach was
cleaning, when followed as per standard developed.
operating procedure, yields concurrently and
consistently the results which will be well within Then the acceptance limit is established to check
the acceptance criteria. the quantity of carryover of the drug
Albendazole. Form the previous product to the
The cleaning validation is carried out on the next product having the smallest batch size
equipment used for manufacturing of among all the product producing in the premises.
Albendazole tablets, after following the cleaning Chloroquine phosphate tablets is found to have
procedure as laid down in standard operating the minimum possible batch size (202kg) among
procedure for cleaning. Samples for the analysis all the products. The Erythromycin Stearate
were obtained by swab method. The different tablets is found to have the maximum formulae
changeover of total residue carry overs single dose 500mg per tablet. The MACO is
Albendazole in ppm by swab method was found determined on the basis of smallest batch size and
to be 0.188694, 0.1950662,0.1373352. All the largest single dose.
results were found to be well within the
acceptance criteria of 8.17117, 9.12046, The swab samples were taken from all the
3.047302ppm. The swab method is found to be a equipments but other samples were taken from
better sampling technique when compared to excluding compression machine analysis. The
acceptance limit to sampling amount. With the results of cleaning validation is found to be good
satisfactory completion of the cleaning validation. within the acceptance limit(Based on swab limit
It was concluded that the cleaning procedure and MACO approach) deals with the results and
followed is appropriate and satisfactory. discussion with representation of tablets.
From this study, it may be concluded that the

results of cleaning validation is found to be well
CONCLUSSION: within the acceptance limit and hence the
In the present work, an industrial project has objective of the company to have an effective
procedure has been taken in Global Remedies cleaning programme is well documented and
Ltd., (A subsidiary of Strides Arco Lab Ltd.,) ultimately the results were achieved.
Hosur. The project was identified to be validated
as Cleaning validation of Albendazole tablets 400
mg.
RERERENCE:
The purpose of cleaning validation is to establish 1. British Pharmacopoeia, Vol. 1, 1993, 365,611.
the documented evidence with high degree of
assurance that the cleaning process followed as 2. Cleaning validation Interpretation of the ICH guidelines
per standard operating procedure for cleaning the for API, Sec-12.7, Cleaning Validation.
equipment used for the processing of
Albendazole tablets, consistently and 3. ConstanceJ.A., Why some dust control system Dont
work, Pharm Eng., Jan-Feb, 24-26(1983).
concurrently yields the results not exceeding
predetermined acceptance limit of the
4. Destin A. LeBlanc, Cleaning Validation Technologies
Albendazole tablets. Technical Consulting Services August 2002.

5. FDA, Guide to Inspections of Validation of Cleaning

Processes, 1993
6. Fourman,G.L. and Mullen, M.V., Determining cleaning

validation acceptance limits for pharmaceutical
manufacturing operations, Pharm Technol. 1794), 54-60
(1993).
7. Gary L. Pourman and Michael V.Mullen, Determining

Cleaning Validation Acceptance Limits for Pharmaceutical
Manufacturing Operations, Pharmaceutical Technology
International, Jun 1993.
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Vol. 1 No.

THE PHARMA INNOVATION

Cleaning Validation of Albendazole Tablets 400 mg

Bodavula Samba Siva Rao1*, Y. Surendhranath Reddy2, M. Jeybaskaran2

1. Department of Pharmacy, Khammam College of Pharmacy, Khammam, Andhra Pradesh, India

INTRODUCTION: As a result of any Pierre Rousseau introduced matrix approaches to

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 76

of the equipment and establish the level of Limitations

iv) Solvent Sampling

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Allows sampling of a larger surface area. ACCEPTANCE CRIETRIA

v) Placebo and Product Sampling TDDprevious x MBS

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 78

A general upper limit for the maximum

(iii) General Limit Swab Limits

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Also other methods with different swab limits for

Applicable approach may

Topical 1/10th to 1/100th of ndd Concentration of drug 0.101

Research & 1/10000 th to 1/100000th of 0.092

Swabbing is the most widely used sampling Average 0.1509+0.1361+0.1240

(i) Albendazole tablets to Paracetamol tablets BP

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 80

Concentration of drug 0.101 = 0.1354 mg

Dispensing tools: = 0.1132 mg

Concentration of 0.109 The amount of drug present in 0.1186

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The amount of drug 0.09705

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Average of 0.6361 + The amount of drug present in 0.5561 x

The amount of drug present 0.5855 x Concentration of 0.251

The amount of drug present in 0.2850

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 83

4 Sifter 0.1354 0.00554 0.1967

6 RMG 0.09705 0.0068 0.1148

8 Cad mill 0.5855 0.018 0.2614

II. Albandazole tablets to Chloroquine

Standard amount of 10ppm in 0.001% is

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Concentration of 0.042 The amount of drug present in 0.1415

Steam Jacketed Kettle

= 0.1132mg (or) 0.0001132ppm Concentration of 0.102

Average of 0.1644+0.1186 The amount of drug present 0.1321

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= 0.1240 mg Concentration of 0.184

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Average of 0.5553+0.5 The amount of drug present in 0.5485 x

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Concentration of drug 0.192 S.

4 Sifter 0.1415 0.00579 0.22

6 RMG 0.1235 0.008653 0.128

7 FBD 0.2746 0.0387 0.0638

Average of 0.3531+0.2588+0.2857+0.3 8 Cad mill 0.5276 0.01624 0.2917

Concentrati 154 Octogonal

The amount of drug present in 0.3032

Standard amount of 10ppm in 0.001% is 1mg.

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 88

Concentration of drug 0.063

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 89

Concentration of drug 0.101 1

= 10.0046mg (or) 0.010ppm.

The amount of drug present 0.1267

Vol. 1 No. 4 2012 www.thepharmajournal.com Page | 90