Clean room HVAC Design for Pharmaceutical Facilities

Presented by: Mr. S. B. Khan M.Pharm Semester- I Department of Pharmaceutics, NDMVPSs College of Pharmacy Nashik-422002. Under Guidance of: Dr. M. P. Wagh Asst. Proffessor Department of Pharmaceutics, NDMVPSs 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

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

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

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

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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Classification Of Clean Room : REGULATORY POINT OF VIEW

Clean Room Class Class Limits "not to exceed" particles per cu ft for particle sizes shown

0.1m
1 10 100 35.0 350 --

0.2m
7.50 75.0 750

0.3m
3.0 30.0 300

0.5m
1.0 10.0 100

5 m
----

1000
10000 10000

----

----

----

1000
10000 100000

7.0
70.0 700

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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)

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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 microorganisms Maintain room pressure (delta P) Maintain space moisture (Relative Humidity) Maintain space temperature

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What HVAC cant 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

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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 Air capture a minimum of 99.97% of contaminants at 0.3 microns in size
Filtration Mechanisms

Inertial Impaction Sieving Diffusion retension Electrostatic Interception

1 micro or more 1 micro or more 0.5 and less 0.5 to 1 micro

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 Components

Frame Separator Gasket Efficiency : Hot DOP Integrity : Cold DOP Pressure Drop Air Velocity

Filter media Adhessive

Testing

Of HEPA Filter

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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

Test Frequency

Particulate monitoring in air HEPA filter integrity testing (DOP testing Air change rates Air pressure differentials Microbiological monitoring by settle plates Temperature and humidity

6 Monthly Yearly 6 Monthly Daily

Daily

Daily
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Energy Efficient HVAC Cleanroom

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Interior Conditions HVAC AirSide Design

Temperature setpoint 70 F +- 2 F Relative humidity 45% +-3% Air velocity 65 fpm Exhaust air requirements 4.5 cfm/ft2 (based on 1997 UBC/UFC increased minimum ventilation 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%

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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 00-25203, 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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