CLEANING VALIDATION PROTOCOL

FOR

<<System Name>>
Version: xx
Date of Version: DD-MMM-YYYY
Document ID: xxxxxx-xxx
 /// THIS PAGE MUST BE DELETED BEFORE PUBLICATION

The purpose of this template is to assist in the interpretation, application, and preparation of the
Cleaning Validation Protocol.
• Paragraphs in blue italics font are meant to serve as instructions to the Author and should
be deleted in the final document.
• Paragraphs in black regular font are sample wording that may be used as is or modified as
needed. Should a paragraph not be applicable, delete it from the document altogether.
• Red text indicates example text, which may be used if applicable. If red text does apply to
your system/project, keep the text and convert the text color to black. Should the red text
not be applicable, delete it from the document altogether
• No sections, may be deleted from the document. If a section does not apply, the section
heading must remain and a statement of non-applicability must be added under that
section.
• Text in <<BRACKETS>> should be replaced with the appropriate information by the
Author.
• The date of the document version needs to be added. The date is to be in the format
DD-MMM-YYYY.
• The document ID is obtained by your company’s SOP.
• It is stressed that this document serves as a guideline only. It will require modification to
accurately reflect the specific project and computer system being implemented or
upgraded.
 Document Preparation Signatures
Prepared by:

<<First Name Last Name>>/<<Preparer Department>> Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee or consultant responsible for
preparing the document.

Reviewed by:

<<First Name Last Name>>/<<Reviewer Department >> Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee or consultant responsible for
reviewing the document.
 Document Approval Signatures
Business Owner:

<<First Name Last Name>>/<<Business Owner Department>> Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee who is the business owner of the
system.

Development/Technical Personnel:

<<First Name Last Name>>/<<Development/Technical Department>> Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee responsible for overseeing the
development and technical aspects of the system.

Validation Unit:

<<First Name Last Name>>/New Jersey Site Validation Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee responsible for the review and
approval of this document to ensure compliance with Xxxxxxxxxxxxxxx
validation practices.

Quality Unit:

<<First Name Last Name>>/Quality Assurance Documentation Compliance Date (DD-MMM-YYYY)

Signature by the Xxxxxxxxxxxxxxx employee responsible for system quality who
performs independent review of completed and/or executed validation
documentation.
 Version History

Version Date of Version Revised By Title/Department Description of Change

1.0 DD-MMM-YYYY First Issuance

/// Enter the relevant information into the Version History table for the Date (DD-MMM-YYYY
format), Revised By and Title/Department columns. The first approved version is always version
1.0 with a description of change being “First Issuance”. Subsequent versions require
description of change detailed by document section. ///
 TABLE OF CONTENTS
1 INTRODUCTION............................................................................................................................ 7
1.1 Purpose........................................................................................................................................................................ 7

1.2 Acronyms and Definitions ......................................................................................................................................... 7

1.3 Schedule....................................................................................................................................................................... 7

1.4 References ................................................................................................................................................................... 7

1.5 Teams and Responsibilities........................................................................................................................................ 8

1.6 Test instruments and materials ................................................................................................................................. 8

2 SAMPLING PLAN ........................................................................................................................ 10

3 ACCEPTANCE CRITERIA......................................................................................................... 11
3.1 Limits of the residual active ingredient .................................................................................................................. 11

3.2 Limits of the bioburden............................................................................................................................................ 13

3.3 Appearance inspection acceptance criteria ............................................................................................................ 13

3.4 Limits of the residual detergent .............................................................................................................................. 13

4 TEST METHODS .......................................................................................................................... 14

5 REVALIDATION REQUIREMENT .......................................................................................... 15

APPENDIX A: SIGNATURE LOG.................................................................................................... 16

APPENDIX B: ATTACHMENT LOG............................................................................................... 17

APPENDIX C: PROTOCOL VARIANCE LOG .............................................................................. 18

1 Introduction
1.1 Purpose
The purpose of this file is to document the <<Cleaning Validation Protocol >> of the <<System Common
Name>>.
1.2 Acronyms and Definitions
The purpose of this section is to define the terminology used in this validation document.

Term Definition
IQ Installation Qualification
OQ Operational Qualification
PQ Performance Qualification

/// All acronyms identified in the document need to be added to the table in the definitions and
acronyms section. All new entries to the table must be placed in alphabetical order. In
addition, any acronym removed from the document when detailing the template to a specific
project must also be removed from this table. ///
1.3 Schedule

/// Add a schedule identifying when will the protocol should be started. ///

1.4 References

Document Identification Document Title

/// Fill in the above table to reflect the appropriate references. At a minimum, any document
referenced within the body of the document needs to be referenced in the above table.. If there is
an approved GMP governing the creation of this specifications document a reference to that document
should be added to the references table above. ///
1.5 Teams and Responsibilities
The roles and responsibilities for the review and approval of this Protocol are referred to <<sop
name>>(xxxxxx-xxx). Signature on the approval page by these groups implies an assumed responsibility for
the content, accuracy and relevance of the signed document to the signer’s area of expertise as well as
agreement, resource commitment and accountability for document content and specified activities.
The following additional roles will be required in the execution of this Protocol. A complete list of roles and
their associated responsibilities is detailed in the following table.

Role Responsibility
Reviewer(s) ƒ Sign Signature Log.
ƒ Reviews execution of the testing and confirms that:
o All steps are complete and documented correctly.
o All supporting documentation is available, labeled, annotated, and properly
cross-referenced.
o Test Variances are documented and resolved.
o Test results meet acceptance criteria.
o The Signature log is complete.
ƒ Signs and dates the test script, as the Reviewer.
ƒ Provides test comments, if needed.

Tester(s) ƒ Sign Signature Log.

ƒ Verifies prerequisites are completed prior to test execution.
ƒ Executes testing as defined in the approved test protocols.
ƒ Provides required screen captures or printouts (output is initialed, dated,
cross-referenced to the appropriate test step(s), and retained with test
documentation).
ƒ Prepares any Protocol Variance report(s) that may be needed.
ƒ Provides test comments (if needed).
ƒ Signs and dates the test script.

/// Enter the other roles & responsibilities required for the testing execution of this project
1.6 Test instruments and materials
/// List the test instruments and materials that should been used in this protocol. ///
Name Type Instrument number
HPLC LC-10A xxxxxx

Name Quatity Material code

Cotton swab 100 xxxxxx
2 Sampling plan

Sequence number Frequency of the Sampling method The recovery of

Description of
of the sampling sampling the sampling
Sampling site
site method

/// A description in detail of the sampling site is needed, pictures which show the related site are expected here.
More attentions should been given for the sampling method, the recovery of the sampling method should be
evaluated before conducting of this cleaning validation. ///

/// The reason of why your choice the specific sampling method should be concluded here in detail. ///
3 Acceptance criteria
///A sample is given in the following section. To establish a test limit, we should list and evaluate the quality of
all products that should been produced at the same manufacturing line. ///

Name Solubility Hydrostatic/Reactivity/Inertness

Prod.A Hydropilicity , diffluent Runny/inertness

Prod.B Hydropilicity , diffluent Runny/inertness

Prod.C Hydropilicity , diffluent Runny/inertness

/// This is a complex issue. Typically, similar products are grouped to pick up a ‘worse case’ product. For
those highly toxic or sensitively products should be studied as the ‘worse case’ product individually.///

3.1 Limits of the residual active ingredient

/// The carry-over of product residues should meet defined criteria, which should include:
• No more than 0.1% of the normal therapeutic dose of any product will appear in the maximum daily
dose of the following product.
• No more than 10ppm of any product will appear in any product.
• No quantity of residue should be visible on the equipment after cleaning procedures have been
performed. Spiking studies should be used to determine the concentration at which most active
ingredients are visible.///

(The following is only a sample)

Limit Calculation Matrix

Equipment Surf. Area (sq.ft.) Prod. A Prod. B Prod. C
Piece 1 13.0 X X

Piece 2 34.2 X X

Piece 3 15.9 X X

Piece 4 * 0.0 X X

Piece 5 96.9 X X X

Piece 6 33.7 X X

Piece 7 Ded. X

Piece 8 111.1 X X

Piece 9 129.6 X X

Piece 10 Ded. X

Piece 11 Ded. X

Piece 12 Ded. X
 Shared Surface Area
Next Product
Previous Product
Prod. A Prod. B Prod. C
Prod. A XXXXX 193.7 337.6

Prod. B 193.7 XXXXX 96.9

Prod. C 337.6 96.9 XXXXX

Product Attributes
Lowest Potency Daily Dosage Units per Smallest Smallest Batch
Product
(mg) (units/day) Batch (kg)
Prod. A 200 4.5 375,000 150

Prod. B 5 4 1,500,000 660

Prod. C 25 2 8,000,000 600

Note: if compound has multiple actives, review each.

Maximum Allowable Residue is calculated by following formula, and the validation limit will be
whichever is lower, the derived limit or no more than 1ppm.

1/1000 SF:residue (mg/ft2) = 0.001 x low. pot. prev. prod. x units per small. batch next prod.
daily dosage next prod. x shared equipment surface area

NMT 1ppm:
residue (mg/ft2) = 1 mg prev. prod. x small batch next prod.
1 kg next prod. x shared equipment surface area

1/1000 SF Limit (from previous)

Next Product
Previous Product
Prod. A Prod. B Prod. C
Prod. A XXXXX 387.2 0.0015

Prod. B 2.2 XXXXX 206.4

Prod. C 6.2 96.8 XXXXX

 1 ppm Limit (from previous)
Next Product
Previous Product
Prod. A Prod. B Prod. C
Prod. A XXXXX 3.41 1.78

Prod. B 0.77 XXXXX 6.19

Prod. C 0.44 6.81 XXXXX

It’s apparent that product A residua in product C is the worst combination. So the ‘worse case’ product should
be product A, and the limits of product A residua should be 0.0015mg.

3.2 Limits of the bioburden

The total microorganism counter of the final rinse sample or wipe sample should meet the specification of the
WFI (USP).

3.3 Appearance inspection acceptance criteria

Any surface after cleaned by designed procedure should be no visible trace of the residual durg or any other
matter.

3.4 Limits of the residual detergent

/// This will be laid on the category of the detergent. The limits could be assessed as per recommends in
section 3.1 ///
4 Test methods

Test name Acceptance criteria Sensitivity SOP number

/// Analytical methods shall be validated before the cleaning validation study is carried out.
The analytical methods used to detect residues or contaminants should be specific for the substance to be
assayed and provide a sensitivity that reflects the level of cleanliness acceptable to your company.
The analytical methods should be challenged in combination with sampling methods used to show that the
contaminants can be recovered from the equipment surface to show the level of recovery as well as the
consistency of recovery. This is necessary
For cleaning validation purposes, the limit of detection and limit of quantification must be demonstrated for all
analytical methods. Analysts must also have demonstrated their competence to perform the required analyses
and this shall be documented. ///
5 Revalidation requirement
A routine monitoring plan should be established to assess the trend of residual cumulation.
In case of changes of cleaning methods or types of detergents that cause difference in data, revalidation
shall be carried out.
Appendix A: Signature Log
Description:
The Signature Log will ensure that all signatures contained within the protocol can be readily identified.
Procedure:
All individuals who participate in the execution of this protocol must complete the information listed in the
table below. A signature indicates that signer has read and comprehends this test protocol.

Printed Name Company Title Signature Initials Date

Reviewed By: Date:

Signature ID Sheet Page: _______________ of _________

 Appendix B: Attachment Log
Description:
The Attachment Log will ensure that all attachments are identified and properly labeled.

Procedure:
All attachments generated though the execution of this protocol must be listed in the table below.

Attachment No. Description No. of Pages Recorded By/Date

Reviewed By: Date:

Attachment Log Page: _________________ of _________

Appendix C: Protocol revises Log
Description:
The Protocol revises Log will be used to number, log, and track all revises produced through the testing
activities.
Procedure:
Record all revises observed during the execution of this protocol on individual Protocol revises Report
Forms. Record the Protocol revises Report ID#, Protocol Section, Page #, Date Initiated, and
Completed By on this log.

Protocol Revises
Protocol Section Page # Date Initiated Completed By
Report ID#

Total Number of revises: _______________

Reviewed By: Date:

Protocol Revises Log Page: _____________ of _________