SOPs and Validation Process

SOP (Standard Operating Procedure)

    

1.2    Introduction

1.3    Good Manufacturing Practice

Good Manufacturing Practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.

1.4    SOPs

A standard operating procedure, or SOP, is a set of step-by-step instructions compiled by an organization to help workers carry out complex routine operations. SOPs aim to achieve efficiency, quality output and uniformity of performance, while reducing miscommunication and failure to comply with industry regulations.

The quality assurance department is responsible for providing support to the parent company, affiliates, and contract manufacturers in the development, upgrading, and maintenance of GMP requirements. Validation SOPs is required to give step-by-step direction in performing validation.

Ø  Efficiencies, and therefore profitability.

Ø  Consistency and reliability in production and service.

Ø  Fewer errors in all areas.

Ø  A way to resolve conflicts between partners.

Ø  A healthy and safe environment.

Ø  Protection of employers in areas of potential liability and personnel matters.

Ø  A first line of defense in any inspection, whether it be by a regulatory body, a partner or potential partner, a client, or a firm conducting due diligence for a possible purchase.

Ø  Value added to your business should you ever wish to sell it.

1.5    Validation Process

Ø  Action of proving, in accordance with the principles of good manufacturing practice, that any    procedure, process, equipment, material, activity, or system actually leads to the expected result.

Ø  Documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes and characteristics.

Ø  Obtaining and documenting evidence to demonstrate that a method can be relied upon to produce the intended result within defined limits.

2.1 SOPs Management

2.1.1    SOP Preparation

Ø SOP should be written by individuals knowledgeable with the activity.

Ø These individuals are essentially subject-matter experts who actually perform the work or use the process.

Ø SOPs should be written with sufficient detail so that someone limited. Experience with or knowledge of the procedure, but with a basic understanding, can successfully reproduce the procedure unsupervised.

2.1.2    SOP Review and Approval

Ø SOPs should be reviewed by one or more individual with appropriate training and experience with the process.

Ø The finalized SOPs should be approval as described in the Organization’s Quality Management Plan or its Master SOPs.

Ø Generally the immediate supervisor and organization’s quality assurance officer review and approval of SOPs.

2.1.3    Revision and Reviews

Ø  Whenever procedures are changed, SOPs should be updated and re-approved.

Ø  If desired, modify only the pertinent of an SOP and indicate the change date/revision number for that section in Table of contents.

Ø  SOPs should be also systematically review on a periodic basis, e.g. every 1-2 year, to ensure that the procedure remain current and appropriate.

Ø  The frequency of review should be indicate by management in organization’s Quality Management Plan.

2.1.4    Implantation SOPs 

Ø  Organization shall have SOP on preparation, approval, revision and control of Standard Operating Procedure for better control and management of SOPs.

Ø  Generally, administrative aspects of the SOP system such as distribution and filing are well managed. On the other hand, overall system management, frequency characterized by the lack of a system owner, is generally poor. If system owner exists at all, his or her responsibility are limited.

Name of Facility _____________________________________________ Page________ Of ____

SOP Number _____________ Tittle ______________________________________________ Revision By _________________ Written By _____________________________ Edited By______________ Authorization Signature ____________________ Department _____________ Date__________ Effective Date _________________________________ Replaces _______________

Purpose:     WHY:        Why is this procedure written?        Why is a being perform?

Scope:       WHEN:            Indicate when this procedure needs to be performed.        WHERE:             Indicate where this procedure applied

Material and Equipment WHAT: What is needs to perform the test? The list should be completely specific.

3.1 Generation and Validation of SOP for Autoclave

3..2 Purpose:   

This SOP provides an authorized procedure to carry out calibration & validation of Autoclave.

3.3 Scope:   

This SOP provides the relevant methodology for the calibration and validation of Autoclave.

3.4 Responsibility:

Microbiologist

3.5 Accountability:

Manager-Quality Control

3.6 Definition:

·     An apparatus in which special conditions (such as high or low pressure or temperature) can be established for a variety of applications; especially: an apparatus (as for sterilizing) using steam under high pressure.

·     A quality assurance procedure used to ensure that the autoclave reaches adequate temperature for an adequate amount of holding time to sterilize biological agents and wastes.

   Will demonstrate that adequate temperature and holding time has been achieved in an autoclave; should be used during validation to ensure efficient sterilization.  The most commonly used biological indicator is Bacillus stearothermophius, being the most resistant to steam autoclaving.

Autoclave

3.7 Procedure:

3.7.1 Calibration:

• ·         Calibrate the temperature indicator, pressure gauge and probe once in a year by external agency or  whenever any replacement or maintenance done on the apparatus.
• ·         Place the Benzoic acid AR grade as a chemical indicator for temperature calibration in regular sterilization cycle. It melts at 121°C.

 Maintain the records, and abort the particular load used for calibration.

3.7.2 Validation:

• Perform the validation of autoclave during installation of Equipment and revalidation.
• Heat distribution studies on empty chamber 3 times by using a multi-point data logger.
• All probes must reach temperature 121°C to 124°C. Pressure must be within 15 to 18 lbs maintain the same for 15 minutes cycle.
•  Heat distribution studies on minimum load of a load pattern one time by using a multi-point data logger.
•  All probes must reach temperature 121°C to 124°C. Pressure must be within 15 to 18 lbs maintain for 15 minutes, & find the lag time.
•  Heat distribution studies on maximum load of a load pattern three time by using a multi-point data logger.
• All probes must reach temperature 121°C to 124°C. Pressure must be within 15 to 18 lbs maintain for 15 minutes, and find the lag time.
• Heat penetration studies on minimum load of a load pattern three times by using a multi-point data logger.
•  All probes must reach temperature 121°C to 124°C. Pressure must be within 15 to 18 lbs maintain for 15 minutes, and find the lag time.
•  Heat penetration studies on maximum load of a load pattern three times by using a multi point data logger.
•  All probes must reach temperature 121°C to 124°C. Pressure must be within 15 to 18 lbs maintain for 15 minutes, and find the lag time.
• With the above heat penetration study the maximum lag time plus 15 minutes is regular operating cycle of the validated load pattern.

3.7.3 Microbial Challenge Test:

•  Keep spores suspension of Bacillus Stearothermophilus of having population 10 6 at various location of the autoclave along with probes during maximum load heat penetration study.
• Sterilized spore ampules incubate at 55° to 60°C for 120 hours.
• Spore ampules should not show any colour change at the end of the incubation.

3.7.4 Cleaning:

• ·         Ensure that the equipment is isolated from the power before starting the cleaning activity.
• ·         The outside of the autoclave should be wiped with a wet sponge and allow to dry.
• ·         Clean the chamber with 0.1% SLS solution using the sponge.
• ·         Wash thoroughly with purified water till get free from the detergent.

4.1 Generation and Validation of SOP for Dissolution Apparatus

4.2 Purpose:

This SOP provides an authorized procedure to carry out calibration & validation of         Dissolution Apparatus.

4.3 Scope:

This Procedure is applicable to all dissolution test apparatus, installed in quality control laboratory

4.4 Responsibility:

Doing: Worker

Checking: Executive/Manager

4.5 Accountability

Head of Department

    

4.6 Definition:

Tablet Dissolution is a standardized method for measuring the rate of drug release from a dosage form and the key word here is “standardization" because for any results to be meaningful, it is essential that all the apparatus used for the testing, produces the same sets of results given all other parameters are equal.

A dissolution test is a means of identifying and proving the availability of active drug materials in their delivered form. A dissolution test simulates the availability of active substance and allows the prediction of the time for complete release of the material from the dosage form.

Dissolution Test Apparatus

4.7 Procedure:

·         Raise the motor driven to upper side by Up/Stop/Down Switch.

·         Switch OFF the instrument.

·         Switch OFF the main.

·         Cleaning Procedure for the apparatus

4.7.1 RPM Setting:

·         Press the RPM key from the front panel.

·         Set the RPM from 25 to 200 using the UP / DOWN / DIGIT SCROLL key as per requirement.

·         To start or stop the stirrer use F1 or F2 keys respectively.

4.7.2 Temperature Setting:

·         Press the TEMP key from the front panel. Set the temperature from 30.0°C to 40.0°C by using UP / DOWN / DIGIT SCROLL key.

·         Switch heater ON/OFF BY using the function key F1/F2 Press ENTER key to register the change.

·         “TEMP ON” LED on the front panel will glow after switching on heater. The pump and the Heater ON LED on temperature Controller Unit will glow.

4.7.3 Frequency: After Completion of every dissolution test:

·         Remove the bowl from the its place discard the medium of bowl and wash properly with purified water then keep inside the dissolution bath number wise.

·         Remove the basket from basket apparatus and then paddle/basket from dissolution test apparatus with the help of key, wash them purified water, dry with tissue paper and keep at proper place.

·         Keep the record in the instrument log card.

·         Cleaning procedure for water bath of dissolution test apparatus.     

4.7.4 Frequency: Once in the week or whenever necessary:

·         Remove the all bowls from the water bath and the apparatus.

·         Remove the lid of the water bath and discard all the water from the water bath.

·         Wash the bath with raw water, detergent solution and raw water sequentially unit no foam of detergent remain in the water bath. After complete removal of the detergent wash the bath with purified water.

·         Keep the bath to it’s the original place and clean the dissolution apparatus.

·         Record it as per Annexure

·         Put the lid of water bath and fill medium in the apparatus. Fill the bath with purified water up to level mark.

4.7 Power Fail Condition:

·         During test running time, if the Power fails then the Power Failure screen will be displayed when the power is resumed back.

·         The user can either start the test again or can stop the test by pressing the F1 or F2 key respectively.

·         If the F1 key is pressed, then the test will start from the point it has stopped and the instrument will display the Run Screen again.

4.8 Sample Withdraw Procedure:

Withdraw sample from a zone midway between the surface of the dissolution medium and top of rotating basket/paddle, not less than 10 mm from wall of vessel.

4.9 Dissolution Medium Preparation:

Prepare the dissolution medium as per specified under monograph or procedure, filter through 0.45 mm filter paper under vacuum and stirring.

Note: Replace the water from the bath weekly or early if required.

5.1 Generation and Validation of SOP for Centrifuge:

5.2 Purpose:

A centrifuge is a laboratory device that is used for the separation of fluids, gas or liquid, based on density. Separation is achieved by spinning a vessel containing material at high speed; the centrifugal force pushes heavier materials to the outside of the vessel.

5.3 Scope:

This sop covers operation procedure and calibration for centrifuge apparatus and this sop is applicable to Quality control department.

5.3 Responsibility:

Office Executive

5.4 Accountability:

Head of Department

5.5 Definition:

A machine with a rapidly rotating container that applies centrifugal force to its contents, typically to separate fluids of different densities (e.g. cream from milk) or liquids from solids.

An apparatus that rotates at high speed and by centrifugal force separates substances of different densities, as milk and cream.  

Centrifuge

5.6 Procedure:

5.6.1 Procedure for General Cleaning:

·         Clean the instrument with dry cloth from inside chamber and outside of the instrument.

·         Remove the glass pieces and solution immediately by removing centrifuge head of any breakage of centrifuge tubes observed.

·         Remove the centrifuge head once in a month, apply grease at threading and fix it properly.

5.6.2 Procedure for Operation:

·         Keep the instrument on stable platform.

·         Before operating the instrument, the speed knob and timer must be in ‘OFF’ position.

·         Put the main switch and the instrument switch to ‘ON’ position.

·         Place the equally filled tubes in the cavities of chamber and ensure the balance of centrifuge tubes by suitable selection of tube position.

·         Close the lid and set the desired time with timer knob. [The instrument can also be operated without using the timer.]

·         Slowly increase the speed with the speed knob to the required RPM.

·         After the time is completed slowly bring the speed knob to ‘OFF’ position, remove the tubes from the chambers, close the lid and switch ‘OFF’ the instrument.

5.6.3 For Vibration Free Performance:

·         Always keep the centrifuge tubes equally either side.

·         Use Rubber cushion for glass tubes.

·         In case, any discrepancy in instrument performance, inform to Utility department through department head for rectification.

5.7 Calibration:
RPM Calibration shall be done through utility department once a year and after each maintenance job.

5.8 Precaution:

·         Proper handling of the instruments.

·         Ensure level and stability.

·         Balance centrifuge tube equally.

·         Ensure the use of rubber cushions for the glass tube.

·         Bring the speed knob to “OFF” and increase speed gradually.

·         Do not open the lid in between the centrifugation cycle.