Microbiology Sop's

SAIKA PHARMACEUTICALS

FOR RESTRICTED CIRCULATION

Title : SOP FOR ENVIRONMENT MONITORING

SOP No. – CP/MBS/001

Department : MICROBIOLOGY

Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012

Page No. : 1 to 8 Revision No. : 01

Approved by : Prepared by

Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

To lay down a procedure for Environment Monitoring.

2.

Scope:

The procedure of this SOP shall be applicable for Microbiology Department of Saika Pharmaceuticals, Rohtak

3.

Responsibility:

Microbiologist

4.

Accountability:

Q.C. Manager

5.

Abbreviations:

6.

S.O.P. :

Standard Operating Procedure

QC

:

Quality Control

QA

:

Quality Assurance

Procedure:

6.1

Record the temperature & humidity in the environmental monitoring chart.

6.2

Regulate the A/C or Dehumidifier if the temperature of a particular area is out of the prescribed limit.

6.3

The limit is specified below:



Title : SOP FOR ENVIRONMENT MONITORING



Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012

Page No. : 2 to 8

Approved by :

Revision No. : 01

Prepared by

Checked by

Q.C. Manager

Q.A. Manager

Signature Date

Area Corridors Raw material Stores (Non Beta & Beta) Instrument Room & Micro-biology Room Chemical Laboratory Quarantine & Control Sample Room Ointments & Lotions 2.

Temperature 25-27°C 23-27°C 25-27°C 28-30°C 25-27°C 25-27°C

Humidity 70% max. 50% max. 50%max 70%max 50%max 50-55%

Record the result in the following format :

Area Name: Date

Time

Temperature

Limit

Humidity

Limit

Checked by



Title : SOP FOR ENVIRONMENT MONIORING



Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012

Page No. : 3 to 8

Approved by :

Revision No. : 01

Prepared by

Checked by

Q.C. Manager

Q.A. Manager

Signature Date

A.

RECEIVING: Pre Entry Cleaning 1.

All containers and package must be effectively cleaned before entering to manufacturing areas. Cleaning is carried out as per suitable SOP.

2.

Vacuum Cleaner is used to prevent displacement of dust.

3.

Wooden cases and crates must be opened outside the stored area and empty aces & crates must be discarded.

4.

Interior surfaces of the areas where raw and packaging materials are received must not shed particles.

B.

SAMPLING: 1.

Elaborate SOP must be followed to ensure prevention of contamination of material.

2.

Sample only one material at one time and in a segregated cubicle or booth fitted with suitable air control systems will minimize the risk of contamination.

3.

Use dedicated tools for sampling. Prescribe and follow SOP for cleaning of tools used in sampling and periodically validated.

4.

Do not return residues of samples to original containers.

5.

Sampling of potent materials like steroids, hormones, beta-lacto, and cyto-toxic substances must be done under specific conditions or in separate areas to protect sampling personnel as well as other products.

6.

Sterile products must be sampled under aseptic conditions.






Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

C.

D.

DISPENSING 1. Dispensing stations or benches must be equipped with suitable dust extraction systems. 2. Dispense only one material at a time, use cleaned scoops or measures for dispensing each materials, even if the different materials are components of the same product. 3. Effectively clean weighing equipment and dispensing bench after dispensing each material. 4. As far possible encourage the use of disposable gloves etc 5. To prevent displacement of dust do not use ceiling or tabletop fans during dispensing. 6. Materials used for construction of inner surfaces of such areas must permit easy and effective cleaning and disinfections. PRODUCTION: 1. Efficiency segregates each production activity. 2. Provide adequate dust extraction equipment. 3. Evolve and follow suitable equipment cleaning procedures. Periodically validate them to confirm effectiveness. 4. Regularly check and confirm integrity of oil seals. 5. To the extent possible use dedicated accessories such as filter finger bags, dust covers, sleeves, etc. 6. Record the temperature & humidity in the environmental monitoring chart. 7. Regulate the A/C or Dehumidifier if the temperature of a particular area is out of the prescribed limit. The limits for different sections are specified below. 8. Record of Temp. & Humidity is maintained in the following format. 9. For aseptic areas validation of air supply systems is very critical and special care must be taken to ensure that contaminants are not introduced through air handing system.






Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

10.

Air supply for the production and dispensing areas must be designed to avoid contamination in to the airflows or to the manufacturing areas. The air supply system must be validated, monitored and controlled to deliver air of appropriate quality. Documentation of the same must be maintained.

11.

The recommended limits for airborne particles and microbial contamination are as follows:

12.

Gases supplied to manufacturing areas must be of the appropriate quality and care must be taken to see that they are not sources of contamination.

13.

Air compressors used for supply of compressed air for product contact purposes and cleaning product contact surfaces must be of the oil free type.

14.

Water and steam generation and distribution systems must be designed to protect contamination of products and manufacturing areas. Monitoring and controlling of quality of water and steam are of great importance especially in aseptic manufacture.

15.

Potent and sensitizing products causing anaphylactic reactions, like beta-lacto, geotaxis and sex hormones must not be manufacturing in a general purpose facility. Adequate segregation and/or separation must be ensured for handling these products.

16.

Microbiological contamination is done by plate count method, pathogens and fungal count should be nil in all sections.






Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

At rest Maximum permitted number of particles per cubic meter equal to or greater than

At actual or simulated working Maximum permitted number of Maximum permitted particles per cubic meter equal to number of viable or greater than micro-organisms per by settle plates method

A

0.5µm 3520

5µm 29

0.5µm 3500

5µm 29

<1

B

35200

293

352000

2930

5

C

352000

2930

3520000

29300

50

Grade

D

3520000 29300 Note defined Note defined 100 Grade Types of operations for aseptic preparations. A Aseptic preparation and filling. B Background room conditions for activities requiring Grade A C Preparation of solution to be filtered D Handling of components after washing For Non-sterile products Product Location Particles Particles Viable > 5.0 µ / m3 > 0.5µ / m3 micro-organisms Cfu / m3 Topical and Oral liquids Point of NMT 20,000 NMT 3,500,000 NMT 100 supply to mfg room where product is exposed

All other nonsterile products

Point of supply to mfg room where product is exposed

NMT 20,000

Not applicable






Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012


NMT 500


Checked by

Q.C. Manager

Q.A. Manager

Signature Date

E. GENERAL 1. Primary packaging components such as bottles, caps etc. that are used in packaging should be handled only for one product at a time. If exigencies demand handling of more than one product then segregate each primary packaging activity. 2. Effectively clean every packaging equipment used in primary packaging before using the same for packaging another product. 3. All personnel must be made aware of the hazards of contamination. 4. All operating personnel must be attired in clean and suitable garments. 5. Regularly train operating in their respective functions to perform their tasks in a manner that prevents contamination. 6. Ensure air supply is suitable filtered to minimize airborne contamination. 7. Water being the most widely used material, regularly monitors the quality particularly, to control microbial contamination. 8. All personnel involved in the manufacture of non-sterile formulations must wear appropriate head covers, dedicated footwear and clean overalls appropriate to the need for protection of materials and product. 9. Personnel working with processes where materials and products are exposed must wear gloves and excessive facial hair must be covered. 10. Personnel working in aseptic areas must use a fresh set of aseptic garments during each entry to aseptic areas. Gloves used in aseptic areas must be powder free. 11. Employees working in contact with material and products must be medically fit and free from contagious diseases.

12. Pipe works, light fittings and other service lines must be designed and laid in such a way that recess, which are difficult to clean, are avoided.



Title: SOP FUMIGATION OF MICROBIOLOGY LAB. SOP No. – CP/MBS/002


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1. 2.

3. 4. 5.

6.

Objective: Scope:

To lay down a procedure for Fumigation of Microbiology Lab. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance AHU : Air Handling Unit LAF : Laminar Air Flow Procedure:

6.1

At the last day of working (week end) and after completion of all the cleaning activities.

6.2

Prior to fumigation ensure no trace of water present on any place.

6.3

Fumigation container is placed near the door of each room i.e. sterility testing room, change room.

6.4

Shut down individual LAF & AHU.

6.5

Add 20 g of potassium permanganate to the fumigation container. Now add 100 ml formaldehyde in very slowly and gently to each container.

6.6

Close the doors.



Title : SOP BACTERIAL ENDO TOXIN TEST



Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1. 2.

3. 4. 5.

6.

Objective: Scope:

To lay down a procedure for Bacterial Endo toxin Test. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure:

6.1 6.2

Wash the all glassware with purified water twice then with distilled water once. Cover all the glassware with aluminium foil.

6.3

Heat all the glassware to be used for the Bacterial End toxin test at 240°C for 2 ½ hrs.

6.4 6.5 6.6 6.7 6.8

so as to make it dehydrogenated. Weigh the samples. Prepare the dilution of the sample and control standard end toxin. Dilute the LAL reagent with 1.2 ml LAL reagent water. Place the tubes over the heating blocks. First put water for NPC and CSE for PPC.

6.9 6.10

Now dispense the samples followed by LAL reagent. Place two tubes as blank.

6.11

Incubate at 37 ± 1°C.

6.12

Observe the tube after exactly one hour the PPC should have the gel formation (firm gel) and NPC along with blank should not have.



Title : SOP FOR CLEANING AND SANITATION OF MICROBIOLOGY LAB/ STERILITY ROOM SOP No. – CP/MBS/004


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6. 6.1 6.2 6.3 6.4

To lay down a procedure for Cleaning & Sanitation of Microbiology Lab / Sterility Room. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure: After completing work in the Microbiology Laboratory, remove all used and unused material immediately. Clean the LAF bench and floor with a dry nylon brush to remove the materials; like vials, bungs, aluminum foils, papers, waste media traces and seals etc. Collect all the wastes in a plastic tray and transfer it to the dust bean. First mop the floors and the walls of laboratory with the sanitation solution (Combatant DS) with the help of sterilized nylon cloth.

6.5 6.6 6.7 6.8

Mope the working table with a dry nylon cloth, than clean the table with the suitable detergent (Lanoline 0.5% solution) with the help of nylon cloth. Finally clean the table with nylon cloth soaked in sterile water in order to remove the traces of detergents. Swab the working table with suitable disinfectant (Combatant DS) and then by 70% IPA. All cleaning and sanitation activities shall be followed by the spraying disinfectant. This is applied for disinfections of the air of area as well as surface.



Title : SOP FOR CLEANING AND SANITATION OF MICROBIOLOGY LAB/ STERILITY ROOM SOP No. – CP/MBS/004


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

Cleaning Schedule of Microbiology Lab. Mon.

Tue.

Wed.

Thu.

Fri.

Sat.

Pre-Noon Savlon 2% Mopping

Dettol 2%

Fairgenol 2%

B.K.C. 2%

Savlon 2%

Dettol 2%

After Noon Mopping

Savlon 2%

B.K.C. 2%

Fairgenol 2%

Dettol 2%

Savlon 2%

Dettol 2%

Remarks: • Spray the area with 70% IPA before 30 mts. of starting the work.

• Spray with 2% Lysol daily after completion of work. • Fumigate the on every Saturday as per SOP No. CP/MBS/005



Title : SOP FOR STERILITY TESTING SOP No. – CP/MBS/005


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1. 2. 3. 4. 5.

6. 6.1

6.2 6.3 6.4

Objective: Scope:

To lay down a procedure for Sterility Testing. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure: Prepare the media Fluid Thioglycolate and Soybean casein Digest Broth according to specified dilution and transfer the same into glass test tubes. Autoclave it at 121°C temp and at 15 lbs pressure. Incubate the media at 32 ± 2.5° C for 48 hrs. As preoccupation. So as to check the proper sterilization of the same. Prepare 1 liter (0.1%) Peptone Water and filter it through 0.45µm filter paper and autoclave it at 121°C temp and 15 lbs. Pressure for 20 minute. Switch on the LAF and UV light 2hrs, before the sterility test.

6.5 6.6 6.7 6.8 6.9

Dissolve the sample in 100 ml sterilized peptone water and pass the solution through 0.45µm filter paper. Wash the filter paper with 1liter peptone water. Cut the membrane filter paper into two pieces with a sterilized blade. Inoculate Fluid Thioglycolate media with one piece and Soybean casein Digest Broth with another one. Incubate the Soybean casein Digest Broth at 22.5 ± 2.5°C and Fluid Thioglycolate Media at 32 ± 2.5° C. I.P. products are incubating for 7 days and B.P & U.S.P products for 14 days.

Observation: Fluid Thioglycolate Media is observed for aerobic and anaerobic Bacterial growth and Soybean Casein Digest Broth is observed for fungal growth.



Title : SOP FOR SWAB TESTING SOP No. – CP/MBS/006

Department : MICROBIOLOGY Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1. 2.

3. 4. 5.

6.

Objective: Scope:

To lay down a procedure for Swab Testing. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance

Procedure:

6.1

Prepare swabs by rapping cotton on glass rods.

6.2

Keep the swabs in test tube filled with distilled water.

6.3

Sterilized the tubes in Autoclave.

6.4

Prepare soybean casein digest medium as per microbiological media preparation SOP.

6.5

Take the swab from the critical / specified places.

6.6

Incubate the swab rods into the sterilized tubes of Soybean Casein Digest medium.

6.7

Incubate the tubes on 32 ± 2.5 °C to check the bacterial growth and on 22.5 ± 2.5°C to check the fungal growth.

6.8

Observe the growth in the tubes. Grade

Area

Contact plates (dia. 55 mm) cfu per plate.

A

Class 100

<1

B

Class 1000

5

C

Class 10000

25

D

Class 100000

50



Title : SOP FOR MONITORING OF ASEPTIC AREA BY SETTLE PLATE METHOD SOP No. – CP/MBS/007


Issue Date

Effective Date

Next Review Date

Jan. 2006

Feb. 2006

Jan. 2008



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6. 6.1 6.2 6.3

To lay down a procedure for Monitoring of Aseptic Area by Settle Plate Method. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure: Sterilized the petrel plates in DHS Prepare the media as per microbiological media preparation SOP Pour 20-25 ml media in Petri plate under LAF.

6.4 6.5 6.6 6.7 6.8 6.9 6.10 6.11

Allow the plates to solidify Pre incubate the plates for 48 hrs. at the temperature 300 to 350c. Transfer the pre-incubated plates in aseptic processing area. Put the plates on the specified location. Open the lids of Petri plates and expose for 2 hrs. Close the plates Incubate the plates at required temperature in BOD incubator / Bacteriological incubator for required time for fungus & bacteria. After completing incubation period count the colony forming units in individual plates.



Title : SOP FOR MONITORING OF ASEPTIC AREA BY SETTLE PLATE METHOD SOP No. – CP/MBS/007


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

Recommended Limits for Microbiological Monitoring of Aseptic Areas “In Operation” by SETTLE PLATE. Grade

Area

Settle plates dia. 90 mm Cfu / 2 hrs.

A

Class 100

<1

B

Class 1000

5

C

Class 10000

50

D

Class 100000

100



Title : SOP FOR OPERATION & CALIBRATION OF LAMINAR AIR FLOW BENCH SOP No. – CP/MBS/008


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6.

To lay down a procedure for Operation & Calibration of Laminar Air Flow Bench The procedure of this SOP shall be applicable for Microbiology


6.1 Ensure that the instrument is clean and free from dust and placed in such a position, that any air while opening the airlock door does not affect the positive pressure of the instrument.

6.2 Check the level of the instrument base. The base should posses uniform level with no up’s and down’s. 6.3 Switch on the mains. 6.4 There are three switches and a pressure barometer on the instrument These switches represent: 1) Air flow 2) Ordinary light 3) UV light 6.5 Switch on the No.1 switch to start airflow. 6.6 Press switch 3 to start the UV light. 6.7 The airflow and UV light should be kept on for about 2 hours before carrying out any work under laminar airflow. 6.8 Switch off the UV light and put on switch 2nd for ordinary light. 6.9 Check the pressure barometer, the level of red oil indicator should be at 15 marks when airflow is on.



Title : SOP FOR OPERATION & CALIBRATION OF LAMINAR AIR FLOW BENCH SOP No. – CP/MBS/008


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

7

The function of instrument in to maintain the aseptic condition while carrying out any microbiological tests.

8

Flame the burner and put it inside LAF.

9

Done every work in front of the flame of the lamp.

Calibration 1.

The calibration is done by the plate exposure method i.e. Settle plate method.

2.

Prepare the plates of Nutrient agar media, and savored dextrose agar media.

3.

Switch on the LAF and expose the plates at different position in LAF for 2 hour.

4.

Incubate the plates of Nutrient agar on 32 ± 2.5°C savraud dextrose agar at 22.5 ± 2.5 °C.

5.

Observe the plates for no growth, Nutrient agar is used for Bacterial count and savraud dextrose agar is used for fungal count.



Title : SOP FOR OPERATION & CALIBRATION OF BACTERIOLOGICAL INCUBATOR SOP No. – CP/MBS/009


Issue Date

Effective Date

Next Review Date

Jan. 2006

Feb. 2006

Jan. 2008



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6.

To lay down a procedure for Operation & Calibration of Bacteriological Incubator. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure: Operation

6.1

Place the unit away from draft ventilating outlets, radiators or any other device that may cause sever changes in the temperature conditions surrounding the indicator cabinet. 6.2 Place the shelves in their positions provided inside the chamber before loading the material. Load the selves evenly. 6.3 Switch on the main switch, (main indicator of lamp Red, should glow) 6.4 Set the controller knob to indicate required temperature on its dial. 6.5 Allow the temperature to rise to required temperature and let it remain constant. 7.0 Calibration: 7.1 Dip the calibrated thermometer in Glycerin and keep it in the shelf No. 1, allow stabilizing the temperature for 15 minute. Note down the temperature displayed by the Instrument and the thermometer. Repeat the procedure No. 6 for all the shelves. 7.2 Correct the temperature required, with the help of temperature setting knob, first by the coarse and then by the fine knob. 7.3 Such calibration is done on monthly basis.



Title : SOP FOR OPERATION & CALIBRATION OF BOD INCUBATOR SOP No. – CP/MBS/010


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6.

To lay down a procedure for Operation & Calibration of Bod Incubator. The procedure of this SOP shall be applicable for Microbiology

Department of Saika Pharmaceuticals, Rohtak. Responsibility: Microbiologist Accountability: Q.C. Manager Abbreviations: S.O.P. : Standard Operating Procedure QC : Quality Control QA : Quality Assurance Procedure: Operation

6.1

Keep the instrument in a room having constant temperature and away form any heating device.

6.2

Switch on main button (red light will glow).

6.3

Adjust required temperature with help of coarse and finally with help of fine adjustment.

6.4

Digital display will show the desired temperature.

7.0 Calibration: 7.1. Adjust the temperature of the BOD incubator by the above procedure. 7.2. Put a calibrated zeal thermometer on the selves’ of the incubator. 7.3. Compare the temperatures displayed by the instruments and by the calibrated thermometer. 7.4. Repeat the same procedure with the other selves. 7.5

Calibrated the incubator on monthly basis.



Title : SOP FOR OPERATION OF MICROBIOLOGY SECTION SOP No. – CP/MBS/011


Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

2.

Scope:

3. 4. 5.

6.

To lay down a procedure for Operation of Microbiology Section. The procedure of this SOP shall be applicable for Microbiology


Operation of Microbiology Section is divided in the following activities: a) Double Door Entry to Microbiology Section. b) Preparation of the Equipment’s. c) Microbiological Testing. d) Cleaning of the Microbiology Section. Entry to Microbiology Section: a) The Person puts on the sterile garment and covers his/her shoe with shoe guard in the air lock. b) He / She washes his / her hand with disinfectant solution and put in sterile hand gloves. c) Opens the door by using his elbows and enter the Microbiology Laboratory. Preparation of the Equipment’s : a) The table top of laminar airflow workstation is cleaned with 70% IPA Solution. b) The culture tubes, inoculums, plates, inoculation spatula, membrane filtration assembly etc. are kept on the side table. c) The Bunsen burner is lit on and inoculation process is started. d) Once done each tube is closed by using the same “cotton plugs”.



Title : SOP FOR OPERATION OF MICROBIOLOGY SECTION SOP No. – CP/MBS/011


Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

Microbiological Testing: a)

The testing includes Microbiological Assay for Antibiotics & Vitamins.

b)

Total bacterial count.

c)

Total fungal count.

d)

Morphological testing after staining.

e)

Identification of individual or group of microbes etc.

f)

Bio burden analysis in bulk solution.

g)

Pathogenic analysis in DM water & water for injection. All these tests are done following official monographs like IP/BP/USP/IHS/SOP.

Cleaning of the area: i)

After the day’s operation the entire floor, furniture tops etc are cleaned by disinfectant solution as per cleaning schedule.

ii)

All the dirt and usages are taken out of the area.

iii)

The area is sprayed with 1% Gluteraldehyde in propylene glycol by using air guns.

iv)

Spray the area with 70% IPA before 30 mts. of starting the work.

v)

Spray with 2% Lysol daily after completion of work.



Title : SOP FOR PREPARATION OF MICROBIOLOGY MEDIA SOP No. – CP/MBS/012


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1. 2.

3. 4. 5.

6.

Objective: Scope:

To lay down a procedure for Preparation of Microbiology Media. The procedure of this SOP shall be applicable for Microbiology


6.1

Check the date of expiry of the media to be used.

6.2

Clean and dry the required glassware & accessories.

6.3

Check the suitability of glassware’s and requirement of preparation of media.

6.4

Weight the quantity of media according to the requirement.

6.5

Place the container on the magnetic stirrer with magnet bead and add the sufficient quantity of distilled water and add the weighed media in it.

6.6

Boil to mix the medium properly and make up the volume.

6.7

Check the pH with calibrated pH meter adjust if required either by 0.1 M NaoH for soyabean casein digest medium or by 1.0 M NaoH incase of fluid thioglycollate and pour it according to the requirement in the tubes.

6.8

Put the cotton plug in the tubes.

6.9

Keep the media in autoclave for sterilization and run autoclave for recommended time.

6.10

Cool down the media up to room temperature after sterilization and pre incubate the media for recommended temperature for 48 hours.



Title : SOP FOR CULTURE HANDLING



Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

To lay down a procedure for Culture Handling.

2.

Scope:

The procedure of this SOP shall be applicable for Microbiology Department of Saika Pharmaceuticals, Rohtak.

3.

Responsibility:

Microbiologist

4.

Accountability:

Q.C. Manager

5.

Abbreviations: S.O.P. :


6.

QC

:

Quality Control

QA

:

Quality Assurance

Requirement:

6.1

Pre Sterilised garments

6.2

Sterile Gloves

6.3

Sterile Loops

6.4

Sterilise Media



Title : SOP FOR CULTURE HANDLING



Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

7.1

Prepare the slants of agar medium & sterilise at 1210C for 200 minutes.

7.2

Incubate the slants at 300C to 350C.

7.3

Arrange the mother culture from authentic source.

7.4

Transfer the mother culture in sterilise agar plate.

7.5

Prepare the daughter cultures from mother culture.

7.6

Again incubate the daughter cultures at 350C for five days.

7.7

Label the daughter culture slants with name & ATCC No. Store the culture in the Refrigerator.

7.8

Repeat the same process to prepare the making culture.

7.9

Maximum five passages one allowed from mother culture to working culture.

7.10

Maintain the record by sub culturing at the register.



Title : SOP FOR SAMPLING PLAN OF STERILE RAW MATERIAL SOP No. – CP/MBS/014


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

To lay down a procedure for Sampling Plan of Sterile Raw Material.

2.

Scope:


3.

Responsibility:

Microbiologist

4.

Accountability:

Q.C. Manager

5.

Abbreviations:

6.

S.O.P. :


QC

:

Quality Control

QA

:

Quality Assurance

Requirement: 6.1

After getting the sample requisition slip from the Raw Material store the microbiologist will prepare the sampling plan for taking of sample.

6.2

Sampling has to be done from each container.

6.3

Sample No. of containers for sterility test as per following table.



Title : SOP FOR SAMPLING PLAN OF STERILE RAW MATERIAL SOP No. – CP/MBS/014


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

Less than 4 containers

Each container

4 containers but Not more than 50 containers

20% or 4 containers whichever is greater

More than 50 containers

2% or 10 containers whichever is greater

And for other analysis sampling has to be done from all containers. 1. Check the sampling requisition with labels of the containers and P.O. / Bill / Challan.

2. 3. 4. 5.

6. 7. 8. 9. 10.

Check the outer conditions of each drum / box. Sampling has to be done in aseptic area. Disinfect the outside of containers with 70% IPA with transfer it to aseptic area. Before starting sampling, check the following points in aseptic area : a. AHU & LAF should be ON. b. Temperature – NMT 250C. c. Humidity – as per product requirement. d. Proper cleaning of area. Draw sample aseptically from each container under LAF in sterilized and depyrogenated glass vials. Paste labels having no. of container and information regarding the material on sample vial / poly bags. Seal raw material containers / poly bags properly from which sample has been drawn. After drawing samples Q.C. person will paste a sampled sticker on the right hand side of under test sticker. Analyzed samples as per applicable protocol.



Title : SOP FOR INVESTIGATION OF THE OOS RESULTS IN ENVIRONMENT MONITORING SOP No. – CP/MBS/015


Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

1.

Objective:

To lay down a procedure for Investigation of the OOS results in environment monitoring.

2.

Scope:


3.

Responsibility:

Microbiologist

4.

Accountability:

5.

Abbreviations:

6. 6.1

6.2

Q.C. Manager

S.O.P. :


QC

:

Quality Control

QA

:

Quality Assurance

Action Steps: If the CPU count exceeds the Alert / Action levels at any location any day in the samples taken from the Environment or Personnel, the Production Head & QA Head will immediately be informed by QC Department with a dully filled “Action Taken Report Format”. Action Taken Report Format will contain the following details. a. Name of the Area. b. Date of monitoring c. Sampling method used d. Sampling location e. Microbial count exceeds Alert / Action limit





Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

6.3 6.4

f. CFU observed g. Action limits Investigation will be carried out in Quality control & Production department. Quality Control Department a. Results will be discussed with the Microbiologist for any unusual observations made in the area and for any difficulty faced during sampling.

b. Media Preparation & Sterilization Records and Negative controls of the Media will be checked for any abnormity. c. Identify the organism up to possible level from the plate showing O.O.S. result. d. Identify the organism isolated from other places which are having same colony characteristics to establish the possible source of contamination. e. Document the historical review of environmental monitoring results for the site in question. 6.5 If above observations do not confirm as a cause of analytical error then check at the production department. 6.6 Production Department. 6.7 The investigation will be carried out as per the checklist given in the Annexure the SOP. 6.8 The QA Head will investigate the cause of the O.O.S. results in co-ordination with Microbiology section (Q.C.) and Production Head. 6.9 After investigations are over the Plain manager will send dully filled action taken report along with the investigation report to Q.C. 6.10 O.O.S. Investigation for Alert level. 6.11 The alert level can consider as an “early warning” of potential drift from normal operating conditions and it allows the corrective actions to be taken before product quality is adversely affected. 6.12 Document the previous results for the affected site to determine the possibility of unfavorable and developed.





Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

6.13

Upon review of above determined results further investigation and / or additional sampling can be warranted. Instruct the in-charge (Operation in clean area) to take extra measures for disinfection of the site in question.

6.14

O.O.S. investigation for Action Level.

6.15

If there have been multiple excursions in excess of alert level or it the action level has been exceeded investigate the parameters shown.

6.16

On the basis of investigation made as per, establish the corrective action required and implement it.

6.17

After the corrective actions are taken check the effectiveness of these actions by suitable monitoring.

6.18

If count exceed alert / action level for Operator glove or gown check the following parameters : a. Operator activity b. Environment monitoring history of operator. c. Other environmental monitoring data in the working area. d. Periodic sanitization for groves. e. Types of organisms identified. f. Operator’s validation data during media fill.

6.19

Take the actions as mentioned in Step No. 4.21 to 4.23 for product release action. Also instruct the in charge for the re qualification of the operator and give and adequate training to the operator.





Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

QUALITY CONTROL DEPARTMENT SOP NO. QA 277 INVESTIGATION REPORT FOR O.O.S. RESULTS IN ENVIRONMENT MONITORING DATE OF O.O.S RESULTS

:

FACILITY

:

SAMPLE DETAILS

:

S. No.

Parameters Checked

Accep. Limit

1.

Temperature

2.

Relative Humidity

3.

Differential pressure of area

4.

Manometer reading of L.A.F.

5.

HEPA integrity checked last time on an result

6.

Cleaning & Disinfection of the area

7.

Disinfectant preparation date

8.

Cleaning & Disinfection of the area

Observations





Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012


Remarks


Signature Date

9.

Any Deviation observed during batch manufacturing

10.

Last fumigation recorded on

11.

Visual observations of the Area for any Abnormalities

12.

Any Power failure on that day If yes, mention duration

13.

Maintenance record for any

Checked by

Q.C. Manager

Q.A. Manager

recent activity in area 14.

Historical review of environmental monitoring for the site in question

15.

Identification of organisms and comparison with organisms isolated from other site to determine source PERSONNEL

16.

No. of persons working in area

17.

Personnel monitoring results if not satisfactory, give details

18.

Possible source of contamination with justification

19.

Reason for O.O.S.





Issue Date

Effective Date

Next Review Date

Jan. 2010

Feb. 2010

Jan. 2012



Checked by

Q.C. Manager

Q.A. Manager

Signature Date

ACTION TAKEN REPORT FORMAT From, QC – Microbiology Lab. To, The In-charge Production / In-charge Q.A. ……………………….. Find here the details of the environmental monitoring results, showing CFU exceeding the Alert / Action levels:

Date of Monitoring : Sampling method used : Location showing high counts : Alert limits : Action limits : Please investigate the matter and return the dully filled A.T.R. format to Q.C.

(Microbiologist) FROM PRODUCTION

(In-Charge Microbiology)

(Q.C. In-Charge) DATE:

On the basis of investigations made as per following actions were taken: (Chemist – Production)

(In-Charge Production)

Microbiology Sop's

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