Download Dept. of Quality Assurance

“EVALUATION AND COMPARISON OF CLEANING METHOD
VALIDATION TECHNIQUES”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,
BANGALORE
BY
PATEL SWETA NAVINBHAI
Under The Guidance of
MR. KRISHNANANDA KAMATH K.
M.PHARM.
DEPARTMENT OF QUALITY ASSURANCE,
SRINIVAS COLLEGE OF PHARMACY, MANGALORE – 574143
2010 – 2012
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE - II
REGISTRATION OF SUBJECT FOR DISSERTATION
1.0 NAME OF THE CANDIDATE
ADDRESS
PATEL SWETA NAVINBHAI.
DEPARTMENT OF Q.A.,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL,POST PARENGIPITTE,
MANGALORE -574143
2.0 NAME OF THE
INSTITUTION
3.0
COURSE OF STUDY &
SUBJECT
4.0
DATE OF ADMISSION
5.0
TITLE OF THE TOPIC:
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE.
MASTER OF PHARMACY
(QUALITY ASSURANCE)
31/05/2010
“EVALUATION AND COMPARISON OF CLEANING METHOD VALIDATION
TECHNIQUES”
6.0 BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR STUDY:
Good manufacturing practices require the pharmaceutical industries to strive for the
highest manufacturing standards. All phases of manufacturing process must be controlled
for predictability and for final production of a product that consistently meets
predetermined quality standards and specifications. Cleaning processes for manufacturing
equipment are closely inspected because inadequate cleaning procedures, method of
sampling analysis can result in adulterated or contaminated products. An important factor
in that control is validating cleanliness of equipment.
Cleaning validation is primarily applicable to cleaning process of manufacturing
equipment in the pharmaceutical industry. The scope of cleaning validation is that
cleaned surfaces, if inadequately cleaned, could potentially contaminate the product
subsequently manufactured in that same equipment.1
This should be performed to provide documented evidence that the procedure being
followed for cleaning of equipment and accessories is effective and removes residues of
previous product up to an acceptance level, using a well-defined protocol.
To check the efficiency of cleaning two methods are widely employed for sampling
during cleaning validation. They are rinse method and swab method.
The study involves comparing the cleaning method validation by Rinse and Swab
Sampling techniques. The API used is practically insoluble and more potent.
6.3 OBJECTIVE OF THE STUDY:
To compare the swab and rinse sampling techniques of cleaning method validation. The
study also involves finding out criteria for visual cleanliness limit for selected drug by
impregnating known amount of drug on SS. Plates.
Drug is selected based upon the solubility of drug in water, because water is major
solvent used for cleaning of equipment.
6.3 REVIEW OF LITERATURE:
A Review of literature on cleaning method validation was carried out in bellow manner.
The collection of references are reproduced below:
Current Practices: Various approaches are used for cleaning validation, including a
widely used technique called swab testing. Clean wet, swabs are applied to areas that
have been cleaned and an extract of that swab is analyzed to show the effectiveness of
that cleaning. Swab testing, however, is expensive and time consuming, but sampling
does not represent the entire part of equipment, subject to errors caused by factors such as
incomplete removal of contaminants. Cross-contamination can result from handling and
treatment of samples between swab collection and subsequent analytical work.
Unfortunately, no infallible algorithm has been identified for either cleanliness validation
or contaminant detection in final products, and validation practices normally depend on
previous experience. The most effective way to prevent the presence of a contaminant in
a finished product is to develop increasingly reliable and foolproof cleaning validation
methods.

Julie Thomas A.2 developed A Cleaning Validation Master Plan for Oral Solid Dose
Pharmaceutical Manufacturing Equipment. Validation are state-of-the-art is to
assemble a multi-discipline team from the Appropriate manufacturing sites that can
review and revise all components associated with cleaning validation. What follows
are excerpts from a cleaning Validation master plan that was painstakingly composed
and has now become the standard for planning and executing cleaning validations at
several manufacturing site.

Robert kirsch B.3 developed Validation of Analytical Methods Used in
Pharmaceutical Cleaning Assessment and Validation.Validation of cleaning process
following production of pharmaceutical products has received much industry and
regulatory attention, because companies are increasingly using multipurpose process
equipment and automated clean-in-place procedures, it has become even more
important to establish evidence that product is not contaminated. This method
discusses requirements for validating a Chromatographic procedure for assessing
cleaning efficiency and for cleaning validation purpose. Recovery experiments are
particularly important because firms must demonstrate removal of analytes at low
level from potentially active stainless steel and glass surfaces as well as from
polyester swabs to ensure the accurate evaluation of the cleaning process.

Pei Yang, Kim Burson, Debra Feder, and Fraser Macdonald4 developed Method
Development of Swab Sampling for Cleaning Validation of a Residual Active
Pharmaceutical Ingredient. Cross contamination with active ingredients is a real
concern. A swab-sampling method was developed for cleaning validation of a
residual active pharmaceutical ingredient in samples collected after cleaning of the
equipment. A summary of the strategies and results of the method development is
presented. The developed extraction method produced an acceptable level of recovery
and precision.

ICH Q2 guideline analytical method validation5, The discussion of the validation of
analytical procedures is directed to the four most common types of analytical procedures:
Identification tests, Quantitative tests for impurities' content, Limit tests for the control of
impurities, Quantitative tests of the active moiety in samples of drug substance or drug
product or Other selected component(s) in the drug product. Typical validation
characteristics which should be considered are Accuracy, Precision, Repeatability,
Intermediate Precision, Specificity, Detection Limit, Quantitation Limit, Linearity, and
Range for rinse and swab sampling techniques.

Ruey Ching Hwang6 developed how to establish an effective Maintenance Program
for Cleaning Validation Completing a cleaning validation study is a major task. When
a minimum of three cleaning validation runs are completed and the results meet the
acceptance criteria, the cleaning procedures are demonstrated to sufficiently and
consistently remove.
7.0 MATERIALS AND METHODS:
7.1
Source of Data:
Data will be obtained from the publication of USFDA Guidelines, Health Canada as well
as from Srinivas college of pharmacy library, Helinet, Science Direct and other internet
facility.
 Consultation with Industrial experts.
 www.sciencedirect.com
 www.pharmaifo.com
 www.pubmed.com
 www.jpronline.info
 www.google.com
ANALYTICAL METHODS:
The analytical methods should be validated before the Cleaning Validation Study is
carried out. The analytical methods used to detect residual or contaminant could be
specific for the substance to be assayed and provide a sensitivity that reflects the level of
cleanliness.
7.2 Method
The suitability of the material to be used for sampling and of the sampling medium
should be determined. The ability method to recover residue samples accurately. It is
important to ensure that the sampling medium and solvent are satisfactory and can be
readily used.
A. Swab sampling
After cleaning the equipment, product contact surface could be swabbed to evaluate
surface cleanliness. Swabs used should be compatible with the active ingredients and
should not interfere with the assay. They should not cause any degradation of the
compound and should not encourage degradation. This shall be evaluated during method
validation stage.
B. Rinse Samples
Rinse samples allow sampling of a large surface area. In addition, inaccessible areas of
equipment that cannot be routinely disassembled can be evaluated. A direct measurement
of the product residue or contaminant in the relevant solvent should be made when rinse
samples are used to validate the cleaning process. In method validation suitability of rinse
method for cleaning of active residue shall be evaluated.
C. Visual cleaning method
It is important to use visual inspection in addition to analytical methodology to ensure the
cleaning process is acceptable. The study involves finding out criteria for visual
cleanliness limit for selected drug by applying known amount of drug on SS plate before
taking swab samples for chemical analysis.
7.3 Does the study require any investigation to be conducted on patients or
animals?
No
7.4 Has the ethical clearance been obtained from your institution in case of 7.3?
Not applicable
REFERENCES:
1.
Destin LB, The applicability of cleaning validation. Cleaning Validation Technologies
cleaning memo October. 2000 http://www.cleaningvalidation.com
2. Thomas AJ. A Cleaning Validation Master Plan for Oral Solid Dose Pharmaceutical
Manufacturing Equipment. Journal of Validation Technology 2000; 6(2):522-530.
3. Robert KB. Validation of Analytical Methods Used in Pharmaceutical Cleaning
Assessment and Validation. Pharm Technol 1998; 40-46.
4. Yang P, Burson K, Feder D, Macdonald F. Method Development of Swab Sampling
for Cleaning Validation of a Residual Active Pharmaceutical Ingredient. Pharm
Technol 2005;84-94.
5. International Conference on Harmonisation (ICH). Harmonised tripartite guideline:
validation of analytical procedures: text and methodology Q2(R1). Geneva,
Switzerland: ICH; 2005. Available at
http://www.ich.org/LOB/media/MEDIA417.pdf.
6. Hwang RC. How to establish an Effective Maintenance Program for Cleaning
Validation. Pharm Technol 2000; 62-72.
7. Prabhu LS, Suriyaprakash TNK. Cleaning Validation and its importance in
pharmaceutical Industry. Pharma Times 2010; 40(7):21-25.
8.0
SIGNATURE OF THE CANDIDATE
Patel Sweta Navinbhai.
9.0
10.0
REMARKS OF THE GUIDE
NAME AND DESIGNATION OF
GUIDE
Forwarded for approval
Mr. Krishnanand Kamath K.
Assistant Professor
11.0 SIGNATURE
Dr. E.V.S. Subrahmanyam,
12.0 HEAD OF THE DEPARTMENT
Professor and Head,
Dept. of Quality Assurance
13.0 SIGNATURE
14.0 REMARKS OF THE PRINCIPAL
15.0 SIGNATURE
Dr. Ramakrishna Sharbaraya A.
Principal,
Srinivas College of Pharmacy,
Valachil, Mangalore.