PROCESS VALIDATION PROTOCOL Autoclave

1.         PRE-EXECUTION APPROVAL

Successful completion of this protocol will provide documented evidence that all key aspects of the Autoclave used in LARGE VOLUME PARENTRALS SECTION adheres to appropriate application criteria, comply with standard operating procedures, and meet current Good Manufacturing Practices (cGMP) requirements.

1.1       SIGNATORY LIST

The signature below indicates approval of this protocol and its attachments for execution.

	Name & Designation	Signature	Date
Prepared By
Checked and Reviewed By
Approved By

1.2              Validation Team

All individuals participating in the execution of this protocol must fill out a row in the table below.

Name & Designation	Responsibility	Signature & Initial	Date
	Prepare the protocol and coordinate the validation study. Generate amendments to the protocol as required
	Microbiological validation of the sterilization process. document the microbiological aspects of the study
	Protocol training of operators and provide the resources for validation study

2.0       GLOSSARY OF TERMS

2.1       List of Abbreviation

CGMP             Current Good Manufacturing Practices

FDA                 Food and Drug Administration

GAMP              Good Automated Manufacturing Practice

GMP                Good Manufacturing Practice

IQ                    Installation Qualification

OQ                  Operation Qualification

2.2       Definitions

Acceptance Criteria                Agreed standards or ranges, which must be achieved.

Critical component                  A component within a system where the operation, contact, data, control, alarm, or failure may have a direct impact on the quality of the product.

Critical Instrument                   Any instrument that directly affects product safety, purity, or efficacy.

Direct Impact System             An engineering system that may have a direct impact on product quality.

Factor Acceptance Test         Documenting the performance characteristics of equipment prior to shipment to site.

Impact Assessment                The process of evaluating the impact of the operating, controlling alarming and failure conditions of a system on the quality of a product.

Indirect Impact System           An engineering system considered not having a direct impact on product quality.

Installation Qualification          Documenting the process equipment and ancillary system are constructed and installed according to pre-determined specifications and functional requirements.

No Impact System                  This is a system that will not have any impact, either directly or indirectly, on product quality. These systems are designed and commissioned following Good engineering Practice only.

Non-critical Component          A component within a system where the operation, contact, alarm or failure may have an indirect impact or no impact on the quality of product.

Operating Limits                     The minimum and /or maximum values that will ensure that product and safety requirements are met.

Operational Qualification        Establishing confidence that process equipment and ancillary systems are capable of consistently operating within established limits and tolerances.

Performance Qualification      The documented verification that al aspects of a facility, utility or equipment that can affect product quality perform as intended meeting pre-determined acceptance criteria.

Performance Testing              The process by which the performance of interdependent system is demonstrated as within the required tolerances, the output of interdependent system is demonstrated as delivering the required duty or capacity, the interdependent functions of system are interdependent to be as specified and appropriate.

Piping and Instrumentation

Diagrams                                Primary source of design information for utility systems and process equipment. They are used to depict the process flow, equipment configuration, process parameters, instrumentation, and materials of construction. They also are used to perform overall material and energy balances and pressure balances.

3.0       INSTRUCTION

3.1.      General Instruction

All performers and reviewers must complete qualification forms using the following guidelines:

·                     Complete all items on a form in full, except the optional comment’s section.

·                     Document any deviation from defined protocols and expected results. Owner approval of protocol deviations must be documented before final approval signatures can be obtained.

·                     Write additional comments on an addendum sheet when there is not enough space on a form to accommodate all comments. Use these three steps when adding an addendum sheet.

1.         Number the page alphanumerically.

2.         Initial and date additions.

3.         Insert the addendum sheet behind the original page.

·                     Make all entries in permanent black or blue ball pen.

3.2       Correcting Entries

If you need to make corrections on a form, use the procedures described below:

3.2.1    Correcting Short Entries

To correct a short entry [such as a single word or test result] on a form:

1.         Draw a diagonal line, bottom left to upper right, through the miss entered or incorrect information.

2.         Write the correction to the upper right of the original entry.

3.         Give brief explanation of change

4.         Initial and date the change.

3.2.2    Correcting Long Entries

To correct a long entry or information block on a form:

1.         Draw a diagonal line, bottom left to upper right, through the miss entered or incorrect information.

2.         Write the correction on a separate addendum page.

3.         Give brief explanation of change.

4.         Initial and date the changes.

5.         Number the page alphanumerically

6.         Place the addendum page behind the original page.

3.3       Marking Elements That Are Not Applicable

Mark each element carefully according to the instruments below, so that it will be clear that the element is unnecessary and that you have not skipped or forgotten the element.

1.         Draw a diagonal line, bottom left to upper right corner, through the element that is not required.

2.         Write the letters NA [Not Applicable], your initials, and the date above the line. Include comments above the line or on the form to document the reason the element is not required.

3.         Where NA is indicated as an option, select this field.

The performer and reviewer must sign and date all forms, as usual, even when part or all of the form is marked “NA”.

Note:               All original entries must remain legible after any corrections have been made.

3.4    Caution

The following conditions require “re-qualification”;

·                     When a Instrument modification has been completed, it affects the installation qualification.

·                     When the software or firmware has been upgraded or changed

·                     When this Instrument is being removed from where it was originally installed.

3.5       Re-calibration / Re-certification Requirements

The following conditions require “re-calibration / re-certification;

·                     For a pre-determined period of time or use.

·                     After any minor service has been done or replacement of parts.

·                     When this Instrument is being removed from where it was originally installed.

4.         RESPONSIBILITIES

4.1       Validation Team

·                     Prepare and approve the validation protocol.

·                     Provide training to the personnel regarding protocol execution.

·                     Assure complete adherence to the protocol during the execution

·                     Generate amendment to the validation protocol, as required.

·                     Document any deviations that occur during protocol execution.

·                     Document Operator SOP Training.

·                     Provide the resources required in executing the validation protocol.

4.2       PRODUCTION MANAGER

·                     Review the validation protocol and the final reports

4.3       QUALITY CONTROL/ASSURANCE MANAGER

·                     Approve the validation protocol and the final reports

5.0     Objectives:

To verify and establish that the Autoclave is working as per recommendations of the manufacturer.

6.0       Scope:

This validation protocol is applicable to the Autoclave intended to be used for steam sterilization in LARGE VOLUME PARENTRALS SECTION.

The protocol will be implemented under the following conditions

§         The validation of sterilization process using saturated steam as the steriliant

§         Prior to the production of a new sterilizer.

§         A change In the load design or weight that would result in a load that is more difficult to sterilize.

7.0       Equipment Identification

Equipment Name	Autoclave	Verified
Model Number		Yes ¨  No ¨
Serial Number		Yes ¨  No ¨
Make		Yes ¨  No ¨
Asset No.		Yes ¨  No ¨
Location		Yes ¨  No ¨

It has the following sub-components

S. No.	Description	Check
1	Time controller	¨
2	Pressure controller	¨
2	Temperature  controller	¨
3	Pressure gauge	¨
4	Safety Valve	¨
5	Thermometer	¨

Completed By:__________________                          Date:_____________

Reviewed By:___________________                                    Date:_____________

8.0       EQUIPMENT DESCRIPTION

The Autoclave intended to be used for steam sterilizations process. It has following specifications:-

S. No.	Parameter	Range	Readability	Check
01	Timer	0—60 min	1 min	¨
02	Pressure	0—60 Lb/inch²	2.0 Lb/inch²	¨
03	Temperature	0 –150°C	0.5°C	¨

8.1        LOAD IDENTIFICATION

Nature of load	1000ml bottles
Quantity of load	2000 Bottles

8.2       STERILIZATATION CYCLE PARAMETERS

Sterilization set point	106°C
Temperature range	106°C +0.5°C
Expose time	45 minutes

8.3       Equipment Used for PROCESS VALIDATION

Equipment	Calibration		Certificate No.	Issue Date
	YES	NO
Recording potentiometer	¨	¨	___________	________
Thermocouples & lead wires	¨	¨	___________	________
Biological indicator i.e. B. stereothermophyllus	¨	¨	___________	________

Completed By:__________________                           Date:_____________

Reviewed By:___________________                                    Date:_____________

9.0    strerilizatation procedure:

§               Place six thermocouples in the load at the slow to heat points as determined

        Previously by(Heat Distribution and Heat Penetration studies)

§               Place thermocouples exterior and near to (Penetration TC)and expose to  chamber steam distribution TC)

§               Place BIs (Biological Indicators) at each of the slow to heat penetration location.

§               Load autoclave extend TC out of autoclave and attach to potentiometer

§               Position one TC by controller record sensor

§               Close autoclave door

§               Perform, function check of TC .replace if defective.

§               Replace autoclave sensor chart with a new one

§               Check to make sure that cycle parameters are set

§               Set potentiometer for a 3.0 Hours scan cycle.

§               Initiate sterilization cycle and potentiometer cycle at same time                 

§               Allow cycle to continue until it is completed. Collect all potentiometers, controls and computer control record and place with protocol.

§               Have computer graph results and calculate Fo value. After load has cooled, remove BIs and have tested

§               Incubate BIs in incubator at 55Cº for 48 hrs

10.0             ACCEPTANCE CRITERIA

1-       BDS Strip

All four colors segment of the processed indicator are black. If all other critical process parameters such as temperature, pressure and sterilization are in accordance with cycle reference.

2-       Bio-Indicator i.e. B. stereothermophyllus

No growth should be observed after incubation for 48 Hours.

10.1            Results

Temperature                  :           106°C

Pressure                       :           10 Lb/inch²

Sterilization Time           :           30 minutes

1-      Evaluation of the BDS strip.

S.#.	Position of Indicator strip	Stick BDS-test indicator strip on	Acceptance Criteria		Results
			All four color segment of indicators strip are black
			Yes	No
1			¨	¨
2			¨	¨

2-      Evaluation of the Bio-indicator i.e. B. stereothermophyllus

S.#.	Position of B. stereothermophyllus			Acceptance Criteria		Observation
				No growth is observed after incubation for 48 Hours
				Yes	No
1	Front/top left	Fornt/bttm center	Middle /centleft	¨	¨
2	Middle/ bttmleft	Rare/top center	Rare/bttm left	¨	¨
3	Front/top center	Front/bottm center	Middle/cent left	¨	¨
4	Middle/bttm right	Rare/top bottom	Rare/bottm center	¨	¨
5	Front/top right	Front/ bottmleft	Middle/ center	¨	¨
6	Middle/ Bttm/Cent	Rare/top right	Rare/bttm center	¨	¨

All acceptance criteria have been met.                             Verified By / Date

Yes ____________No _____________                             _____________

If No or N/A, explain in Comments.

 Comments:_____________________________________________________________

 Completed By:__________________                                            Date:_____________

 Reviewed By:________________                                               Date:_____________

11.0.   Incidents/Deviations

To document any discrepancy or variations noted during the execution of the Process Validation Protocol. Any action to be taken to resolve an outstanding issue is to be identified within the incident report.

INCIDENT #	DESCRIPTION OF INCIDENT	RECORDED BY	DATE

COMMENTS: ____________________________________________________________ ____________________________________________________________

12.0     Final Comments about PROCESS VALIDATION

________________________________________________________________

________________________________________________________________

________________________________________________________________

________________________________________________________________

13.0             SIGNATURE IDENTIFICATION SHEET

This sheet is a record of each individual who signs or initials any page included in this protocol or in the attached document. Each person shall be identified by typed or printed name.

Name                                Signature and Initials                                 Company

__________________       _________________________                _____________________

__________________       _________________________                _____________________

__________________       _________________________                _____________________

__________________       _________________________                _____________________

__________________       _________________________                _____________________

__________________        ________________________                 _____________________

__________________        ________________________                 _____________________

__________________        ________________________                 _____________________

__________________       _________________________                _____________________

FINAL APPROVAL OF QUALIFICATION

This document certifies that the process of Autoclavation has been validated as specified and complies with Standard Operating Procedures, and satisfies the requirements for cGMPs.

	Name & Designation	Signature	Date
Prepared By	Tahir Ibrahim Quality Assurance Executive
checked and Reviewed By	Abdul Hafeez Production manager
Approved By	Tajjamal A Qurashi Manager Quality Control

PROTOCOL TRAINING

Training Session Date         :        ____________________

Instructor                               :        ____________________

Protocol Reference             :        ____________________

Name	Title	Signature	Date