CLEANING VALIDATION PROTOCOL模板

CLEANING VALIDATION PROTOCOL

FOR

<>

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.

?P aragraphs in blue italics font are meant to serve as instructions to the Author and should be deleted in the final document.

?P aragraphs 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.

?R ed 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

?N o 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.

?T ext in <> should be replaced with the appropriate information by the

Author.

?T he date of the document version needs to be added. The date is to be in the format

DD-MMM-YYYY.

?T he document ID is obtained by your company’s SOP.

?I t 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:

Date (DD-MMM-YYYY) <>/<>

Signature by the Xxxxxxxxxxxxxxx employee or consultant responsible for

preparing the document.

Reviewed by:

<>/<>

Date (DD-MMM-YYYY) Signature by the Xxxxxxxxxxxxxxx employee or consultant responsible for

reviewing the document.

Document Approval Signatures

Business Owner:

Date (DD-MMM-YYYY) <>/<>

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

system.

Development/Technical Personnel:

<>/<>

Date (DD-MMM-YYYY) Signature by the Xxxxxxxxxxxxxxx employee responsible for overseeing the

development and technical aspects of the system.

Validation Unit:

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

Signature by the Xxxxxxxxxxxxxxx employee responsible for the review and

approval of this document to ensure compliance with Xxxxxxxxxxxxxxx

validation practices.

Quality Unit:

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

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

Issuance

1.0 DD-MMM-YYYY First

/// 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

1INTRODUCTION (7)

1.1Purpose (7)

1.2Acronyms and Definitions (7)

1.3Schedule (7)

1.4References (7)

1.5Teams and Responsibilities (8)

1.6Test instruments and materials (8)

2SAMPLING PLAN (10)

3ACCEPTANCE CRITERIA (11)

3.1Limits of the residual active ingredient (11)

3.2Limits of the bioburden (13)

3.3Appearance inspection acceptance criteria (13)

3.4Limits of the residual detergent (13)

4TEST METHODS (14)

5REVALIDATION REQUIREMENT (15)

APPENDIX A: SIGNATURE LOG (16)

APPENDIX B: ATTACHMENT LOG (17)

APPENDIX C: PROTOCOL VARIANCE LOG (18)

1Introduction

1.1Purpose

The purpose of this file is to document the <> of the <>.

1.2Acronyms and Definitions

The purpose of this section is to define the terminology used in this validation document.

Term Definition

Qualification

IQ Installation

Qualification

OQ Operational

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. ///

1.3Schedule

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

1.4References

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.///

1.5Teams and Responsibilities

The roles and responsibilities for the review and approval of this Protocol are referred to <

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) Sign Signature Log.

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.

Signs and dates the test script, as the Reviewer.

Provides test comments, if needed.

Tester(s) Sign Signature Log.

Verifies prerequisites are completed prior to test execution.

Executes testing as defined in the approved test protocols.

Provides required screen captures or printouts (output is initialed, dated,

cross-referenced to the appropriate test step(s), and retained with test

documentation).

Prepares any Protocol Variance report(s) that may be needed.

Provides test comments (if needed).

Signs and dates the test script.

/// Enter the other roles & responsibilities required for the testing execution of this project

1.6Test 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

2Sampling plan

Description of Sampling site Sequence number

of the sampling

site

Frequency of the

sampling

Sampling method The recovery of

the sampling

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. ///

3Acceptance 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.///

3.1Limits 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 113.0X X

Piece 234.2X X

Piece 315.9X X

Piece 4 *0.0X X

Piece 596.9X X X

Piece 633.7X X

Piece 7Ded.X

Piece 8111.1X X

Piece 9129.6X X

Piece 10Ded.X

Piece 11Ded.X

Piece 12Ded.X

Shared Surface Area

Next Product

Previous Product

Prod. A Prod. B Prod. C

Prod. A XXXXX193.7337.6

Prod. B193.7XXXXX96.9

Prod. C337.696.9XXXXX

Product Attributes

Lowest Potency Daily Dosage Units per Smallest Smallest Batch Product

(mg)(units/day)Batch(kg)

Prod. A200 4.5375,000150

Prod. B541,500,000660

Prod. C2528,000,000600

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 XXXXX387.20.0015

Prod. B 2.2XXXXX206.4

Prod. C 6.296.8XXXXX

1 ppm Limit (from previous)

Next Product

Previous Product

Prod. A Prod. B Prod. C

Prod. A XXXXX 3.41 1.78

Prod. B0.77XXXXX 6.19

Prod. C0.44 6.81XXXXX

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.

3.2Limits of the bioburden

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

3.3Appearance inspection acceptance criteria

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

3.4Limits 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 ///

4Test 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. ///

5Revalidation 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.

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 _________

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 _________