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Clean room HVAC Design for Pharmaceutical Facilities

Presented by: Mr. S. B. Khan M.Pharm Semester- I Department of Pharmaceutics, NDMVPS’s College of Pharmacy Nashik-422002.

Under Guidance of:

Dr. M. P. WaghAsst. ProffessorDepartment of Pharmaceutics,NDMVPS’s College of Pharmacy,Nashik-422002.

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Enclosures :

Sterile Manufacturing At Glance Cleanroom HVAC Design Clean Room : REGULATORY POINT OF VIEW Cleanroom Layout Contribution Of HVAC And The Meaning . . . Design Parameters Components Of HVAC System And Specifications HEPA FILTER : At Glance Monitoring And Testing Of HVAC Clean Room Validation Clean Room Of Future Cummary References

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Sterile Manufacturing At Glance

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Sterile preparations are products absolutely free of micro organisms, pyrogens and particulate matter.

Importance of sterile administration(Parentrals) Rapid in Action Produces a direct result Drugs are absorbed directly into the bloodstream

Do not irritate the digestive system

Precise dose to a targeted area

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Difficulties in sterile administration allergic reaction Introduction of microorganisms Injections can cause injury to tissue, nerves,

veins, and other vessels Needle can strike a bone Cost Communicable diseases

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Challenges in Clean room and sterile Mfg

contamination with micro-organisms, endotoxins and particles

ledges, shelves, cupboards and equipment Doors, ceilings Sinks and drains Personnel, clothing

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Cleanroom HVAC Design : Introduction

Federal Standard 209 In determination of key parameters like

temperature, humidity, pressures, filtration, airflow parameters and classification of cleanrooms.

Purpose limiting the presence of sub-micron particles and modifying inadequate

environmental conditions NEED electronic, high-tech, semiconductor,

pharmaceutical, aerospace, medical and many other industries

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Unidirectional And The Non-unidirectional Flow Design

Unidirectional

speed between 60 to 90 FPM

Remove particles before they settle onto surfaces

Remain parallel

used when low airborne concentrations of particles or bacteria are present

Air changes per unit of time greater in unidirectional flow design

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Cleanroom layout

Design Details

materials used must be nonshedding, nonporous and resistant to microbial growth finished surfaces must be hard, smooth and

easy to clean junctions of room surfaces withstand repeated disinfection number of openings in the clean-room fabric Concealed door-closer mechanisms

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Floors, walls, ceilings must be Chemical-proof Bacteriostatic Stable in dimension Colour fast Good resistance to surface spread of flame Sound absorbing Slip-resistant Resistant to abrasion Impact resistant Easily cleaned Colour-coded (between areas of different functions) “Soft” to walk on for operator comfort

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Classification Of Clean Room : REGULATORY POINT OF VIEW

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Clean

RoomClass

Class Limits "not to exceed" particles percu ft for particle sizes shown

0.1m 0.2m 0.3m 0.5m 5m

1 35.0 7.50 3.0 1.0 --

10 350 75.0 30.0 10.0 --

100 -- 750 300 100 --

1000 -- -- -- 1000 7.0

10000 -- -- -- 10000 70.0

10000 -- -- -- 100000 700

Classification Of Clean Room : REGULATORY POINT OF VIEW

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Contribution of HVAC

And The Meaning . . .

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Support the manufacture of quality pharmaceutical products

A heating system (“H” in HVAC) A ventilating system (“V” in HVAC)

A cooling system (“AC" in HVAC)

HVAC system design parameters Energy efficiency Cleanliness Cost Temperature

uniformity

Humidity control Chemical exhaust

efficiency Noise control

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Common problems of a wrongly designed cleanroom HVAC system Insufficient air flow Inadequate laminarity Fail to pressurize to specified pressure level Big stagnition zones Ineffective chemical vapor exhaust Too high noise Temperature variation above specifications Humidity variation above specifications

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“CLEANLINESS, CLEANLINESS and CLEANLINESS”

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What can HVAC do?

Control airborne particles, dust and micro-organismsMaintain room pressure (delta P)Maintain space moisture (Relative Humidity)Maintain space temperature

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What HVAC can’t do?

1. HVAC can not clean up the surfaces of a contaminated places, room or equipment

2. HVAC can not compensate for workers who do not follow procedures

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Components Of HVAC System

Block Diagram

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Local heating systems heat source, distributors, and Portable electric heaters, built-in electric resistance heaters, infrared heaters.

and wood stoves Local cooling systems Air circulation devices, such as

paddle or desk fans

Local ventilating systems Local air-conditioning systems

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HEPA FILTER : At Glance

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Conclusion:High Efficiency Particulate Aircapture a minimum of 99.97% of contaminants at 0.3 microns in sizeFiltration Mechanisms

Inertial Impaction1 micro or more Sieving 1 micro or more Diffusion retension 0.5 and less Electrostatic 0.5 to 1 micro Interception

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Components Frame Filter media Separator Adhessive Gasket

Testing Of HEPA Filter Efficiency : Hot DOP Integrity : Cold DOP Pressure Drop Air Velocity

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Monitoring and Testing of HVAC Clean Room

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: Monitoring and Testing of HVAC Clean Room

Physical Air borne particulate matter HEPA integrity : Cold DOP Air Changes per hour Flow pattern in room Pressure Diff across filter Temperature and Humidity

Microbiological Settling Plate Slit Plate Surface Sampling

Parameter Particulate monitoring in air HEPA filter integrity testing

(DOP testing Air change rates

Air pressure differentials

Microbiological monitoring by settle plates

Temperature and humidity

Test Frequency

6 Monthly

Yearly

6 Monthly

Daily

Daily

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Energy Efficient HVAC Cleanroom

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InteriorConditions

· Temperature setpoint 70 F +- 2 F· Relative humidity 45% +-3%

HVAC Air-Side Design

Air velocity 65 fpm· Exhaust air requirements 4.5 cfm/ft2 (based on 1997 UBC/UFC increased minimumventilation rate to 4 from 1 cfm/ft2)· Fewer or no silencers to dampen fan noise· Static pressure of 4” w.g. on makeup air units and 2” w.g. on recirculation air units· Fan efficiency 85%· Fan motor efficiency 94%

VALIDATION

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Design Qualification . Identification of various systems, their functions, schematics & flow diagrams,sensors, dampers valves etc.,

Layout plans,critical parameters

Operation Qualification various points of performance test readings, statement of compliance and noncompliance with the acceptance criteria

Performance Qualification Test readings of all critical parameters under full operating conditions and full

production

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Clean Room Of Future

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CUMMARY

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As Per US GMP, Design and Construction Features Standard 209

Air should be of a high microbial quality HEPA filter bank along with mandatory terminal filters filtration regime in generally three stages Critical areas should have a positive pressure differential

Remember, overstating quality requirements and tolerances may result in unnecessary costs . . . !

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References 1. J,E, F, Reynolds. Martindale: The Extra Pharmacopoeia, The Royal

Pharmaceutical Society: London, 1996, pp.1218-20. 2.Guideline on Sterile Drug Products Produced by Aseptic Processes, FDA, pub.

1987. 3.Guidance for Submitting Documentation for Sterilization Process Validation in

applications for Human and Veterinary Drug Products, FDA, pub. 1993. 4. ISO 13408-1 Aseptic Processing of Health Care Products. 5.Cleanrooms and Associated Controlled Environments, Classification of Air

Cleanliness. Contamination Control of Aerospace Facilities. Technical Order 00-25-203, U.S. Air Force, December l, 1972.

6. Current Practices in the Validation of Aseptic Processing. Technical Report No. 36, Parenteral Drug Association, Inc., Bethesda, MD, 2002.

7. ISPE. Pharmaceutical Engineering Guides for New and Renovated Facilities Bulk Manufacturing Facilities, 1996 8. ALLEN, EDWARD: HOW BUILDINGS WORK, OXFORD UNIVERSITY PRESS,

NEW YORK, NY, 1980.

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9. How Buildings Work provides a complete, introductory level look at all components of a

building. The chapter on air temperature and humidity control (pp. 75-90) gives a general introduction to

HVAC systems. 10. United Kingdom Accreditation Service. General Criteria of Competence for

Calibration and Testing Laboratories. M10. Middlesex: UKAS, 1989.

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