ENVIRONMENTAL ENVIRONMENTAL

MONITORING IN MONITORING IN BIO PHARMACEUTICAL BIO PHARMACEUTICAL

INDUSTRYINDUSTRY

BRIEF HISTORY OF THE COMPANYBRIEF HISTORY OF THE COMPANY

• SHANTHA BIOTECHNICS was started by SHANTHA BIOTECHNICS was started by Dr.K.I. Varaprasad Reddy.Dr.K.I. Varaprasad Reddy.

• This company has led to the launch of This company has led to the launch of SHANVAC-B. SHANVAC-B.

• It is an rDNA Hepatitis-B vaccine.It is an rDNA Hepatitis-B vaccine.• It is the first Indian Hepatitis-B vaccine It is the first Indian Hepatitis-B vaccine

pre qualified by WHO-Geneva.pre qualified by WHO-Geneva.• It is the India’s first recombinant human It is the India’s first recombinant human

health care product in 1997.health care product in 1997.

Products of Products of SHANTHA BIOTECHNICSSHANTHA BIOTECHNICS““Shanvac™Shanvac™®-B®-B” -----r-DNA Hepatitis ” -----r-DNA Hepatitis

B vaccineB vaccine “ “ShanferonShanferon™”™” -----r-DNA Interferon -----r-DNA Interferon

Alpha-2b drug.Alpha-2b drug. “ “ShankinaseShankinase™”™” -----recombinant -----recombinant

Streptokinase Streptokinase Injection. Injection.

“ “ShanpoietinShanpoietin™” ™” -----recombinant -----recombinant Human Erythropoietin Injection.Human Erythropoietin Injection.

“ “ShantestShantest™-HBsAg Elisa” ---- ELISA ™-HBsAg Elisa” ---- ELISA forfor

“Shantetra™” ----- recombinant vaccine for Diphtheria, Tetanus, Pertussis and Hepatitis B vaccine

“Shantrip™” -----Adsorbed Diphtheria Toxoid, whole-cell Pertussis and Tetanus Toxoid. “ShanTT™” ----- Adsorbed Tetanus Toxoid vaccine. “Shantest™ - AFP” -----[ ELISA for the determination of Alpha-fetoprotein]

ABSTRACTABSTRACT

• Environmental conditions to be Environmental conditions to be maintained in critical and non critical maintained in critical and non critical regions of production.regions of production.

• They should be monitored according They should be monitored according to their specifications.to their specifications.

• Environmental monitoring is classified Environmental monitoring is classified into two types.into two types.

1.Viable monitoring.,1.Viable monitoring., 2.Non viable particulate count 2.Non viable particulate count

monitoring.monitoring.

• Viable monitoring includes counting Viable monitoring includes counting of colony forming units.of colony forming units.

• Non viable monitoring includes Non viable monitoring includes particle counting particle counting

INTRODUCTIONINTRODUCTION• PURPOSE – Environmental monitoring is PURPOSE – Environmental monitoring is

to identify microbiological and to identify microbiological and particulate control concepts and particulate control concepts and principles.principles.

• They relate to the manufacture of They relate to the manufacture of sterile pharmaceutical products.sterile pharmaceutical products.

• These concepts also can be applied for These concepts also can be applied for non sterile product manufacture.non sterile product manufacture.

• The focus is environmental monitoring The focus is environmental monitoring as it relates to facility control and as it relates to facility control and compliance.compliance.

ENVIRONMENTAL CONTROL PROGRAM- ENVIRONMENTAL CONTROL PROGRAM- SUPPORTED BYSUPPORTED BY

Sound facility design and maintenance.Sound facility design and maintenance.Documentation systems.Documentation systems.Validated / qualified sanitization / Validated / qualified sanitization /

disinfection procedures.disinfection procedures.Reliable process controls.Reliable process controls.Good housekeeping practices.Good housekeeping practices.Effective area access controls.Effective area access controls.Effective training, certification / Effective training, certification /

qualification and evaluation programs.qualification and evaluation programs.Quality assurance of materials and Quality assurance of materials and

equipmentequipment

HVAC SYSTEM COMPONENTSHVAC SYSTEM COMPONENTS

• Fan(s) to circulate the supply air(SA) and Fan(s) to circulate the supply air(SA) and return air(RA).return air(RA).

• Outside air device Outside air device • • Condenser(s)Condenser(s)• Mixed air chamber Mixed air chamber •• Pump(S) Pump(S) • Filter section(s) Filter section(s) • Water boilers• Water boilers• Heat exchanger(s) Heat exchanger(s) • Steam boilers• Steam boilers• Auxiliary heating devices Auxiliary heating devices • Water chillers• Water chillers• Compressor(s) Compressor(s) • Cooling • Cooling

towerstowers• ControlsControls

Aim and ScopeAim and Scope

• To achieve aseptic conditions in the To achieve aseptic conditions in the production unit.production unit.

• To reduce air borne contamination where To reduce air borne contamination where air is not critical in causing air is not critical in causing contamination.contamination.

• Using HEPA filters which filter up to Using HEPA filters which filter up to 0.599.97% efficiency is to be obtained.0.599.97% efficiency is to be obtained.

Materials RequiredMaterials Required

• Air samplerAir sampler• SCDA platesSCDA plates• RODAC platesRODAC plates• Peptone water bottlesPeptone water bottles• Sterile garmentsSterile garments• Particle counterParticle counter• Thermo-hygrometerThermo-hygrometer• Isopropyl alcohol (70%)Isopropyl alcohol (70%)• Mop clothMop cloth

MethodologyMethodology VIABLE MONITORING:VIABLE MONITORING:1.1. Active air samplingActive air sampling2.2. Passive air samplingPassive air sampling3.3. Surface monitoring by swab methodSurface monitoring by swab method4.4. Personnel monitoring by RODAC platesPersonnel monitoring by RODAC plates

METHODOLOGY:METHODOLOGY:

ACTIVE AIR SAMPLING:Ensure that the pre-filled plates are at the room temperature before use.Check the SCDA plates for contamination.Enter the production area/filling area by following entry/exit procedures.Transfer the air sampler sanitized with 70% IPA and using autoclaved sieve into the process area through material entry.Swipe the exterior of the plate with 70% IPA using a mop cloth to prevent external contamination.form.

•Keep the sterilized aspirating head ready.•Operate the air sampler as follows.(Ref: SAS instruction manual)•Select the air volume to be sampled (1000L)•Label the plates with location, date, and signature.•Insert the plates and remove the lid.•Place the aspirating head.•Press START button to start the cycle.•At the end of the cycle, remove the aspirating head.•Close and remove the contact plate.1.Send the plates to Quality Control for further testing along with a test request

CLASS A

(CFU/m³)

CLASS B

(CFU/m³)

CLASS C

(CFU/m³)

CLASSD

(CFU/m³)

SPECIFICATIO

NS<1 <10 <100 <200

ALERT

LEVEL

≥1 >10 >100 >200

ACTION

LEVEL

2 CONSECUTIVE COUNTS

AT

ALERT LEVEL

PASSIVE AIR SAMPLINGPASSIVE AIR SAMPLING1.1.Check the SCDA plates for contamination.Check the SCDA plates for contamination.

2.2.Enter the production area/filling area using Enter the production area/filling area using personnel entry/exit SOP.personnel entry/exit SOP.

3.3.Transfer the plates to the controlled area of Transfer the plates to the controlled area of the production block.the production block.

4.4.Swipe the exteriors of the plate with 70% Swipe the exteriors of the plate with 70% IPA using a mop cloth to prevent external IPA using a mop cloth to prevent external contamination.contamination.

5.5.Place the plates in the pass box and switch Place the plates in the pass box and switch on the UV lamp.on the UV lamp.

1. Take out the SCDA plates from pass box.

2. Label the plates on the lower lid with location number, date and signature.

3. Identify the location to be monitored as monitored in the respective grid and start and exposing the plates from inside at first and outside at last, thereby avoiding air disturbances over the exposed plates.

1. During exposing of plates, place the lid in inverted position adjacent to the plate. Expose the plates for 4 hours at operational height.

2. After exposure collect plates from all the location and transfer back through pass box.

3. Transfer the plates to Quality Control for further testing along with test request form.

CLASS A

(CFU/m³)

CLASS B

(CFU/m³)

CLASS C

(CFU/m³)

CLASSD

(CFU/m³)

SPECIFICAT

IONS<1 <5 <50 <500

ALERT

LEVEL≥1 >5 >50 >100

ACTION

LEVEL

2

CONSECUTIVE

COUNTS AT ALERT LEVEL

SURFACE MONITORING SURFACE MONITORING BY SWAB TEST:BY SWAB TEST:

• Collect all the required material for the Collect all the required material for the monitoring program and transfer them monitoring program and transfer them to the controlled area of the to the controlled area of the production block/filling area.production block/filling area.

• Enter the sterile area using the Enter the sterile area using the personnel entry/exit SOP.personnel entry/exit SOP.

Remove the swab dipped in 0.1% peptone water bottle.

Transfer the samples to the Quality Control laboratory along with the test request form.

Place all the testing material in the pass box and switch on the UV light. Close the door.

Identify the location to be monitored as mentioned in the respective RST

CLASS A

(CFU/m³)

CLASS B

(CFU/m³)

CLASS C

(CFU/m³)

CLASS D

(CFU/m³)

SPECIFICA

TION<1 <5 <25 <50

ALERT

LEVEL

≥1 >5 >25 >50

ACTION LEVEL 2

CONSECUTIVECOUNTS

AT

ALERT LEVEL

PERSONNEL MONITORING PERSONNEL MONITORING BY RODAC PLATES:BY RODAC PLATES:

Collect all the required material for Collect all the required material for the monitoring program and transfer the monitoring program and transfer them to the controlled area of the them to the controlled area of the production block/filling area.production block/filling area.

Enter the area using entry/exit SOP.Enter the area using entry/exit SOP.

Swipe the exteriors of the plate with 70% IPA using a mop cloth to prevent external contamination.

Place all the testing material in the pass box and switch on the UV lamp.

Take the impression on the personnel after growing with RODAC plates from fore head, chest, left hand and right hand.

.

Label the plates with location, name of the person, date and shift.

Instruct the personnel who underwent sampling to change garments and gloves after the procedure

LOCATION OF

THE PLATE

SPECIFICATIO

NS

ALERT LEVEL ACTION

LEVEL

CLASS A B C

A B C 2

CHEST <1 <5 <50 ≥1 >5 >20 CONSECUTIVE

FORE HEAD <1 <5 <50 ≥1 >5 >20 COUNTS AT

LEFT HAND <1 <5

<50

≥1 >5 >20 ALERT

RIGHT HAND <1 <5 <50 ≥1 >5 >20 LEVEL

•after the procedure.

NON VIABLE NON VIABLE MONITORINGMONITORING

PARTICLE COUNTINGPARTICLE COUNTING

• It is useful in detecting significant It is useful in detecting significant deviations in gas or liquid deviations in gas or liquid cleanliness.cleanliness.

• It is useful as a tool for qualification It is useful as a tool for qualification and monitoring before, during and and monitoring before, during and after operations.after operations.

ENVIRONMENTAL MONITORING PROGRAM ENVIRONMENTAL MONITORING PROGRAM SCHEDULE:SCHEDULE:   In addition to the regular schedule, In addition to the regular schedule, environmental monitoring shall be environmental monitoring shall be carried out in the effected area after anycarried out in the effected area after any intervention that includes area intervention that includes area modification and repairs. Such records modification and repairs. Such records shall be a part of the area qualification shall be a part of the area qualification exercise.exercise.

AREA

VIABLE PARTICLE

COUNTING

SCHEDULE

NON-

VIABLE

PARTICLE

COUNTING

TEMPERATURE,

PRESSURE,

RELATIVE

HUMIDITY

PROCESS

AREA

WEEKLY ONCE MONTHLY

ONCE

DURING EVERY

SHIFT

FILLING

AREA

THRICE DURING

EVERY FILLING

PROCESS(BEGINNIN

G,

MIDDLE AND END)

THRICE

DURING

EVERY FILLING

PROCESS(BEGINN

ING,

MIDDLE AND

END)

DURING EVERY

SHIFT

SUMMARY:SUMMARY:• Environmental monitoring program is a key element Environmental monitoring program is a key element

of contamination controls. The contamination of contamination controls. The contamination controls take a comprehensive view of al l the controls take a comprehensive view of al l the potential vector that is potential vector that is

• AirAir

• PersonnelPersonnel

• SurfaceSurface

• DesignDesign

• Contamination control can be achieved by design, Contamination control can be achieved by design, how ever its maintenance should be achieved on a how ever its maintenance should be achieved on a critical basis only by moderate marinating critical basis only by moderate marinating mechanism as in study conducted.mechanism as in study conducted.

  

THANK YOUTHANK YOU