Professional Documents
Culture Documents
BANGALORE, KARNATAKA
ANNEXURE
Raosaheb Desai
1 NAME OF THE CANDIDATE Flat no 6, Krishna apartment,
ADDRESS #52/23, 21st main, 22nd cross,
Marenahalli, Vijaynagar.
Bangalore 560 040.
1
6.0 BRIEF RESUME OF THE INTENDED WORK:
6.1
NEED FOR THE STUDY:
Cleaning validation is a documented process that addresses special
considerations and issues pertaining to validation of cleaning procedures for
equipment used in the manufacture of pharmaceutical products. The document is
intended to cover validation of equipment cleaning for the removal of
contaminants associated with previous products, residues of cleaning agents as
well as the control of potential microbial contaminants. A validated cleaning
procedure is necessary for attaining cGMP in a pharmaceutical unit
manufacturing products using common equipments and also for regulatory and
compliance requirement1.
Cleaning is a challenging task and the design of the cleaning system depends
upon the equipment use (dedicated/multipurpose), manufacturing process
(continuous/batch), cleaning equipment (manual/automated), preparation
(commercial product/clinical supplies) and product formulation i.e., type of
materials being removed from the surface, drugs (low/high risk, sterile/non
sterile, solids/liquids) and solubility (soluble/ insoluble) of active ingredients.
The purpose of cleaning validation is to ensure that cleaning process adopted
after the manufacturing of candidate product is capable of limiting the residue
within acceptable limit that can be allowed to the next subsequent product batch
of different product2.
2
Cleaning validation is performed to validate the cleaning procedure and is
generally followed as per Standard Operating Procedure for cleaning the
equipment used in API manufacturing facility of the company consistently and
concurrently to yield the results not exceeding predetermined limit residues. The
matrix approach for the product manufactured in the facility shall be made and
the worst case was selected based on calculated Maximum Allowable Carryover
(MACO) limit1,
The limit for Maximum Allowable Carryover (MACO) shall be established
according to the following equation.
TDDprevious x MBS
MACO = ------------------------------
SF x TDDnext
Before testing the active ingredients in the cleaning sample (to evaluate cleaning
effectiveness) validated methods need to be developed or such methods should
be applied, if available. Before analyzing the sample analytical method to be
3
validated. Analytical methods should be validated for the parameters like
Specificity, Precision, Accuracy, Linearity & Range, Limit of Detection, Limit of
Quantification, Intermediate precision, Robustness, Ruggedness, and Solution
stability.3
6.3
The analysis method generally employed in cleaning validation
are listed below
4
Instrumentation15
UV VISIBLE SPECTROPHOTOMETER
HIGH PERFORMANCE LIQUID CHROMATOGRAPH
TOC (TOTAL ORGANIC CARBON)
UV Visible Spectrophotometer
UV Visible Spectrophotometer can be used to determine Active Pharmaceutical
Ingredients (API) residues in swab samples and rinse samples.15
5
7.0 REVIEW OF LITERATURE:
Detailed survey of the literature of the published works, books and periodicals
and internet, yielded the following information on Cleaning Validation of
Multiple Equipments in Active Pharmaceutical Ingredients Manufacturing Plant.
6
Edward K.White5 published an article about risk-based cleaning
validation in Biopharmaceutical API Manufacturing. In risk-based
approach, the clean in place will determine acceptable carryover and
ensure no product impact. Acceptance cleaning will depend to a given
extent on what other products are manufactured with same equipment.
7.1
MATERIALS AND METHODS:
SOURCE OF DATA:
Reference from library of MICROLABS Limited.
References from library of Al-Ameen College of Pharmacy.
Internet (www.chemexper.com, www.google.com, sciencedirect.com)
7
7.2 METHOD OF COLLECTION OF DATA:
8.0 REFERENCES:
1. Active Pharmaceutical Ingredients Committee. Guidelines to Cleaning
Validation in Active Pharmaceutical Ingredient Manufacturing Plants, Dec-
2000; 1-55.
2. International Conference on Harmonisation (ICH).Technical
Requirements for the Registration of Pharmaceuticals for Human Use:
Good Manufacturing Practices for Active Pharmaceutical Ingredients.
ICH-Q7A, Nov10, 2000; 1-49.
3. International Conference on Harmonisation (ICH).Technical
Requirements for the Registration of Pharmaceuticals for Human Use:
Validation of Analytical Procedures, ICH-Q2A, Geneva; 1995.
4. International Conference on Harmonisation (ICH).Technical
Requirements for the Registration of Pharmaceuticals for Human Use:
Validation of Analytical Procedures: Methodology, ICH-Q2B, Geneva;
1996.
5. Edward K.White, Risk-Based Cleaning Validation in Biopharmaceutical
API Manufacturing. Bio-pharm Int Nov 1,2005.
6. Eric Lingenfelter, Wes Atkins, Henry Evans, Cleaning Validation
Procedures. Aug 2009.
7. Richard J. Forsyth, Vincent Van Nostrand, Application of Visible-Residue
Limit for Cleaning Validation. Pharm Tech Oct 2, 2005.
8. Tara Lukievics, Julia Roberts, Richard J. Forsyth, Vincent Van Nostrand,
Correlation of Visible-Residue Limits with Swab Results for Cleaning.
8
9.0 SIGNATURE OF THE CANDIDATE
11.2 SIGNATURE
11.4 SIGNATURE
11.6 SIGNATURE
9
SIGNATURE Principal,
Al-Ameen College of Pharmacy,
Hosur Road, Bangalore -27.
10