Professional Documents
Culture Documents
CLEANING VALIDATION
PROTOCOL
AT: <LOCATION>
INDEX
S. No. Content Page No.
1. Preapproval of Protocol 3 of 15
2. Introduction 4 of 15
3. Objective 4 of 15
4. Scope 4 of 15
5. Responsibilities 5 of 15
6. Protocol Training Record 6 of 15
7. Product Profile 6 of 15
8. Equipment Description 7 of 15
9. Methods of Cleaning 7 of 15
9.1 Cleaning Procedures 7 of 15
9.2 Materials and Equipments used for cleaning 8 of 15
9.3 Cleaning SOP Index for each equipment 8 of 15
10. Sampling Method 9 of 15
10.1 Selection of Sampling Method 9 of 15
10.2 Scientific rational for selecting Sampling Points 9 of 15
10.3 Visual Inspection 9 of 15
10.4 Swab Sampling for Chemical Analysis of API 9 of 15
10.5 Sampling Patterns 10 of 15
10.6 Swab sampling for Microbial analysis 10 of 15
10.7 Swab sampling Location 11 of 15
11. Analytical Procedure 12 of 15
12. Establishment of Acceptance Criteria 12 of 15
12.1 Visual Inspection 12 of 15
12.2 Active Residue 12 of 15
12.3 Rational to Calculate Maximum Allowable Carry-Over Taking the Worst-Case 12 of 15
12.4 Rational to Calculate Maximum Allowable Carry-Over Taking the 10 ppm Criteria 13 of 15
12.5 Establishment of Acceptance Limits 13 of 15
12.5.1 Acceptance Limits per Equipment (ALE) for API 13 of 15
12.5.2 Acceptance Limits per Swab (ALS) for API 13 of 15
12.6 Acceptance Limits for Microbial Bio-burden 14 of 15
13. Acceptance Limits for the Cleaning Agent 14 of 15
14. Hold Time Study 15 of 15
15. Revalidation Criteria 15 of 15
<COMPANY NAME>
<ADDRESS>
1.Preapproval of Protocol:
Signing of this Protocol indicates agreement with the Cleaning validation approach established for <LOCATION,
WHERE THE VALIDATION IS TO BE PERFORMED>. Further, if any changes in this Master Plan would be
required, it will be revised and duly approved.
Compiled By:
Functional area Name Designation Signature Date
Quality Control
Production
Quality Assurance
Head-
Quality Control
Head-
Production
Quality Assurance
Authorized By:
Functional area Name Signature Date
Head-
Quality Assurance
<COMPANY NAME>
<ADDRESS>
2 Introduction:
Cleaning Validation in the context of manufacture of the solid oral products at <COMPANY NAME> may
be defined as:
“The process of providing documented evidence that the cleaning method of the equipments and
ancillary utensils employed within the facility consistently controls potential carryover of product (including
intermediates and impurities), cleaning agents and extraneous material into subsequent product to a
level which is below predetermined levels.” (Source: APIC, September 1999)
It is necessary to Validate Cleaning procedures for the following reasons:
a) It is a customer requirement - it ensures the safety and purity of the product.
b) It is a regulatory requirement in Active Pharmaceutical Ingredient product manufacture.
c) It also assures from an internal control and compliance point of view the quality of the process.
3 Objective:
The objective of this protocol is;
Objective of Cleaning Validation is to establish and assure with documented evidence that the
cleaning procedures used after manufacturing of <PRODUCT NAME> is effective and consistently
performs as expected and produce a result that meets a predetermined acceptance criteria when
manufactured.
To provide documented evidence through the scientific data to show that the cleaning procedure
used after manufacturing of Tablet is effective and consistently performs as expected and produce
a result that meets a predetermined acceptance criteria when manufactured.
To establish that the cleaning process shall provide a high degree of assurance for removal of
residues of the last manufactured product, so that those residues are not transferred to the
subsequently manufactured product.
To prove that equipment is consistently cleaned of product to an acceptable level to prevent
contamination and cross-contamination
4 Scope:
The scope of this protocol is applicable for the Cleaning validationof<NAME OF THE PRODUCT
WITH API STRENGTH>
Also, to evaluate the acceptability of cleaning procedure used in cleaning of equipment using well-
established analytical and microbiological method to determine the chemical and microbiological
residue after cleaning of the equipment. This will also cover the responsibilities, sampling plan,
acceptance criteria, re-validation criteria, and change control procedure. This protocol is applicable
for <NAME OF THE COMPANY>.
<COMPANY NAME>
<ADDRESS>
5 Responsibilities:
– All the personnel involved in the cleaning validation activity, sampling and testing of cleaning
validation samples must be appropriately trained in their assigned job responsibilities and on the
Cleaning validation protocol.
– Personnel or operator who performs cleaning routinely should be trained and should be trained and
should be effectively supervised.
– Record the training details of the persons involved in the sampling and testing.
7 Product Profile:
7.1 <NAME OF THE API WITH STRENGTH>
STRENGTH>isis the existing product of the <LOCATION , WHERE
THE VALIDATION IS TO BE PERFORMED> of <COMPANY NAME> NAME>.
7.2 <A STATEMENT RELATED TO THE SOLUBILITY PROFILE OF THE API>
7.3 <IUPAC NAME OF THE API>
7.4 <CAS NUMBER
UMBER OF API>
7.5 Chemical Skeletal Structure the API <FOR EXAMPLE PARACETAMOL>
PARACETAMOL>:
8 Equipment Description:
Following Equipments of same design and operating principles shall be deployed for cleaning validation
of the three batches of <NAME OF PRODUCT>.
Surface **Surface
S. No. Name of Equipment Capacity ID Number 2 2
Area(cm ) Area(cm )
8.1. <EQUIPMENT 1>
8.2. <EQUIPMENT 2>
8.3. <EQUIPMENT 3>
8.4. <EQUIPMENT 4>
8.5. <EQUIPMENT 5>
8.6. <EQUIPMENT 6>
** Surface Area + 10% of Surface Area <This Neutralizes any Calculation Errors and also takes Ancillary
Equipments like Scoops, Spatulas etc in account>
9 Methods of Cleaning:
9.1 There are three types of cleaning procedures deployed at<COMPANY NAME>:
NOTE:
Equipments shall be cleaned as per the respective cleaning SOPs followed during product changeover
only <ALSO DESCRIBE IN DATA RECORDING SHEETS (DRS)>. Swabs of the cleaned equipments
shall be taken as per the sampling points given in the DRS.
<COMPANY NAME>
<ADDRESS>
10 Sampling Method:
The product contact surface area which is most difficult to clean shall be selected as sampling
point. The location selected for swabbing are generally those locations that are most difficult to
clean representative of different materials and representative of different functional locations
(side corners, agitator, blades etc.). If these locations are swabbed and if residues in these
materials are acceptable then residues on another location shall also be acceptable.
Performing swab on these locations and materials can be helpful in terms of providing higher
assurance in validation results.
After cleaning of the equipment visual inspection shall be done. To carry out a visual
inspection, use a torch if required and a mirror (attached to stainless steel rod) to inspect the
surface of equipment. This should be done under viewing conditions (Lighting, angle,
Distance), that simulate the viewing of Equipment.
Sampling error: During swab sampling following care to be taken: area of sampling (should not be less
2
than 100 cm ), apply proper force during collection of sample to avoid any sampling errors.
2 2
Sampling area: 10 x 10 cm. = 100 cm or equivalent (for the parts, where 100 cm is not available as
whole)
10.5 Sampling Patterns:
Wipe the defined area in zigzag directions as shown in the figure. Apply only one time at a
surface for one time only. Collect the swab by application of normal force.
Note: Avoid lifting the swab stick from contact surface during collection of swab.
10cm OR
End
10 cm 10 cm
Handling of swab Samples: Swab and Swabbing Media shall be prepared by quality control, The test
tubes shall be covered with paraffin film, proper precaution shall be taken during handling of swab. After
swabbing, each sample shall be placed inside the test tube duly labelled and covered with paraffin film
and should be sent to QC Laboratory for testing of determination.
10.6 Swab sampling for Microbial analysis:
– Sterile hand gloves and face mask shall be worn before taking the swab.
– Sterile swab shall be from the test tube and dipped into 0.9% sterile saline solution.
– Now the Swab shall be stroked over a 5 x 5 cm (or equivalent) of the product contact
surface.
– The strokes should be as per the procedure for chemical swab only.
– Immediately the Swab shall be processed as per the procedure for Microbial Testing.
<COMPANY NAME>
<ADDRESS>
Prior to swab sampling, cleaned equipment shall meet “Visual Clean” criteria. Sampling shall
be carried out as per current version of SOP. Chemical and microbial sampling location shall
be different from each other. The locations from where, swab sample is to be taken is
identified are below:
<EQUIPMENT
1 1>
<EQUIPMENT
2 2>
<EQUIPMENT
3 3>
<EQUIPMENT
4 4>
<EQUIPMENT
5 5>
<EQUIPMENT
6
6>
<COMPANY NAME>
<ADDRESS>
11 Analytical Procedure:
Analytical methods for Specific analysis were validated as per Analytical Method Validation Protocol.
Validated methods shall be employed to analyse the cleaning validation samples.
Based on the current scenario, we shall be taking 10 ppm criteria under consideration as the acceptance
limit obtained from MACO index is more than the acceptance limit obtained from the 10ppm criteria.
Swab samples for Microbial Analysis shall be collected from product contact surface area
immediately after the completion of cleaning activities and after specified hold time period of
total aerobic microbial count. The limits for microbiological bio-burden criteria for product
contact surface area is as follows:
2
Product Equipment Microbiological Bio-burden (cfu/ 25cm ) Corrective Action
Contact Surface (If the counts go beyond limit)
Total Plate Count Mould and Yeast
Alert Level <AS PER THE Absent No action required.
REQUIREMENTS>
Action Level <AS PER THE Absent Investigate possible causes
REQUIREMENTS> Perform re-cleaning
Perform extra microbial testing
To establish the effectiveness of cleaning process to remove the cleaning agent; i.e. <NAME OF THE
DETERGENT>, the acceptance limits shall be prepared based on the toxicological data of the
<DETERGENT>. The calculations are as follows:
NOEL= LD50 (of Detergent) x 70kg/2000
Maximum Allowable Carry-Over for Detergent(MACOD)= NOEL (of Detergent) x SBS/SF x MDDB
Where,
NOEL: No Observed Effect Level
2000: an empirical constant
LBSB= Largest Batch Size of Product B
MDDB: Maximum normal daily dose for next prod
Safety factor: 1000 (Constant for Oral Solid Dosage)
Thus, the Acceptance Limit per Swab (ALS) =<CALCULATE AND DEFINE THE LIMIT>
Note:Any change must be formally requested, documented with Change Control. The likely impact / risk
of the change on the product must be assessed and the need for the extent of re-validation should be
<COMPANY NAME>
<ADDRESS>
determined.
End of Document
<COMPANY NAME>
<ADDRESS>
R0 Sandeep Mehra
First issue.