Thursday, August 26, 2010


Document No. :
Issue No. :
Issue Date :


Table of Content


1.0 Pre-execution approval 3
1.1 Signatory List 3
1.2 Validation Team 3
2.0 Glossary of Terms 4
2.1 List of Abbreviation 4
2.2 Definition 4
3.0 Instruction 6
4.0 Responsibilities 8
5.0 Objective 9
6.0 Scope 9
7.0 Equipment identification 9
8.0 Equipment description 10
8.1 Load identification 10
8.2 Sterilization parameters 10
8.3 Equipments used for process validation 10
9.0 Sterilization procedures 11
10.0 Acceptance criteria 12
11.0 Incidents/deviations 13
12.0 Final comments 13
13.0 Signature identification sheet 14
14.0 Final approval of qualification 15
15.0 Protocol training sheet 16


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.


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

Name & Designation Signature Date

Prepared By

Quality Assurance Executive

Checked and Reviewed By

Production manager

Approved By

Manager Quality Control

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

Q.Assurance Exe. Prepare the protocol and coordinate the validation study. Generate amendments to the protocol as required

Microbiologist. Microbiological validation of the sterilization process. document the microbiological aspects of the study

Production Pharmacist
Protocol training of operators and provide the resources for validation study


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.


3.1. 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.


4.1 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.

• Review the validation protocol and the final reports

• 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:_____________


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 •


Nature of load 1000ml bottles
Quantity of load 2000 Bottles

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

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

Completed By:__________________ Date:_____________

Reviewed By:___________________ Date:_____________


 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 55CÂș for 48 hrs

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.

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.





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

__________________ _________________________ _____________________

__________________ _________________________ _____________________

__________________ _________________________ _____________________

__________________ _________________________ _____________________

__________________ _________________________ _____________________

__________________ ________________________ _____________________

__________________ ________________________ _____________________

__________________ ________________________ _____________________

__________________ _________________________ _____________________


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

Quality Assurance Executive

checked and Reviewed By

Production manager

Approved By

Manager Quality Control


Training Session Date : ____________________
Instructor : ____________________
Protocol Reference : ____________________

Name Title Signature Date