1. Safety, Health and Environment (SHE)
Khairul Farihan Kasim
School of Bioprocess Engineering
UniMAP
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2. Biosafety In Biopharmaceutical Facilities
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3. Biosafety
Biosafety is a term used to describe efforts to reduce and eliminate the potential risk resulting from biotechnology and its product.
The potential risks can be grouped into the three areas of sustanable development:
Environment concerns (release to environment, biodiversity)
Social concerns (threat to human health from new allergens in the food system)
Economic concerns.
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4. Where Hazard Come From? Physical: Due to wrong operation of Equipment
Due to miss-use of Equipment
Due to lack of safety precaution during opearation
Chemical: Due to use of flammable or Biohazard chemicals outside Fume Cupboard
Not using suitable cloths, Gloves, Eye glass, etc….
Biological:
Emergency cases (leakage of hazard chemicals from broken tools & equipments)
Due to wrong use of biomaterials
-Use of MO in less safe lab. for its group
- Wrong decontamination protocol
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5. Before Running Experiment!
Types of biological materials used in experiment
The mode of modification applied and methodology
Type of Chemicals used and precautions of these chemicals
The different types of expected and unexpected biomaterials arised
Documents on the waste disposal regulation of the chemicals and biomaterials in each step
-Host (BI, BII, BIII, etc…., GRAS?)
- Vector
NO RADIOACTIVE MATERIALS ARE ALLOWED IN Biomanufacturing facilities
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6. Inside the Biotechnology Factory (Interferon Production Facility)
Working with hazardous chemicals (non-radioactive)
Working with B1 and B2 microorganism
Working with GMO Working with equipments with special requirements. (UV lamps, sonicators, etc….)
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7. Recombinant MO
If the wild strain considered as GRAS, its recombinant is not GRAS anymore.
The recombinant strain should not have any known combinant of pathogenicity, high colonization ability, and high genetic transfer competency.
The recombinant strain should not able to survive and colonize in the environment, and should not able to transfer any part of it’s genome to indigenous population.
Recombinant E. coli K-12 strains and their plasmidless hosts are unable to establish in environments consistent with various deliberate release scenarios. Moreover, those strains are non conjugating and apparently incapable of transferring genes to other organisms.
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8. Biosafety Levels BS Agents Practice
Safety Equipments (Primary Barriers)
Facilities (Secondary Barriers)
L1 & L1-LS
Not known to consistent cause disease for healthy personnel
Standard Microbiological Practice
Standard BSC Class I
Open bench top sink required
L2 & L2-LS
Associated with human disease, hazard , percutaneous injury. Mucous. Recombinant MO
BSL- 1 practice plus.
Limited access
Biohazard warning signs
Sharps precautions
Waste decontamination policy
Standard BSC class II
BSL-1 plus
Autoclave available.
L3 & L3-LS
Indigenous or exotic agents with potential for aerosol transmission, disease may have serious or lethal consequences.
BSL-2 practice plus:
Controlled access
Decontamination of all wastes
Decontamination of lab. Clothing before laundering
BSL-2 plus
- Physical separation from access corridors.
Self closing, double door accesss
Exhausted air not recirculated
Negative airflow in the laboratory L4
Dangerous/exotic agents which pose high risk of life-threatening disease
BSL-3 practice plus:
-Clothing change before entering
Sower on exit
All material decontaminated on exit from facility
Standard BSC class III or BSC class II in combination with full-body air supplied positive pressure
BSL-3 plus
- Separates building or isolated zone
-dedicated supply and exhaust vacuum
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11. Extra Requirement for Good Large Scale Practice (GLSP)
Implementation of a health and safety program.
Suitably trained personnel and written operational procedures.
Facilities, Equipment, protective clothing and practices appropriate to risk.
Regulatory compliance with regard to discharged to the environment
Minimization of aerosol generation to prevent adverse risk to employee health.
A spill control plan within the emergency response plan.
GLSP should preferably be designed to one level higher than the minimum acceptance biosafety level.
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12. Points of Potential Release of Controlled Material
Shaft seals (vessels, pumps)
Flanges (Pipes, Valves, Vessels)
Points of Probe and sensor entry
Perforated pipes, vessels, Equipment
Rupture Disk
Exhaust gases
Tubing and hoses
Pumps
Sample points
Gasket
Leakage into cooling water
Safety valves
Waster treatment system
Sanitary connections
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13. Biohazard from Biomaterials
Laminar Air – Flow
(Biological Safety Cabinet)
And
Decontamination System
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14. Biosafety Cabinet Type Face velocity (1fpm) Airflow Pattern
Radionuclides / Toxic Chemicals
Biosafety Level (s)
Product Protection
Class I open front 75
In a front:rear and top through HEPA filter No
2,3
Class II Type A
70% recirculated through HEPA; exhaust through HEPA
Yes
Type B1
100
30% recirculated through HEPA: exhaust via HEPA and hard ducted
Yes (low levels/volatility)
Type B2
No recirculation:total exhaust via HEPA and hard ducted
Type B3
Same as IIA, but plena under negative pressure to room and exhaust air is ducted
Class II NA
Supply air inlets and exhaust through 2 HEPA filter
3,4
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19. Decontamination Sterilization Disinfection Antiseptics
The use of a physical or chemical procedure to destroy all microbial life, including large numbers of highly resistant bacterial spores
The use of a physical or chemical procedure to virtually eliminate all recognized pathogenic microorganisms but not all microbial forms (bacterial endospores) on inimate objects
A germicide that is used on skin or living tissue for the purpose of inhibiting or destroying microorganisms.
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20. Decontamination Methods
Heat
Chemicals
Radiation
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21. Agent Selection Degree of microbial killing required
Nature of item/surface to be treated
Ease of use Safety
Cost
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22. Agent Efficiency Type of organism Number of organisms
Amount of organic material
Type & configuration of material to be treated
Time & concentration or exposure pH
Humidity Agent Efficacy
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23. Chemical Agent Selection
HLD-High level disinfection
ILD-Intermediate level disinfection
LLD- Low level disinfection
Sporocides Kills all microorganisms except high numbers of bacterial spores
Required 5-10 min. exposure
Examples: aldehydes, hydrogen peroxide, paracetic acid
-Tuberculocides Kills M. tuberculosis var. bovis and all vegetative bacteria, fungi, and most viruses
-Require minimum 20 min. Exposure
-Examples: phenolics, iodophores, chlorine compounds, alcohols.
Hospitals germicides used for housekeeping Kills most vegetative bacteria and some fungi, but not M. tuberculosis var. bovis
Require minimum 20 min. Exposure
Examples: quartenary ammonium compounds
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24. Decontamination Summary Sterilization
Bacterial Spores
B. Subtilis
Mycobacterium
MTB var. bovis
Non-lipid Viruses
Polio-
Rhino-
Fungi
Cryptococcus sp.
Candida sp.
Vegetative Bacteria
Pseudomonas sp.
Staphylococcus sp.
Salmonella sp.
Lipid Viruses
Herpes
CMV
HBV
HIV
2.10
Decontamination Summary Sterilization
HLD
LLD
ILD
Sterilization
HLD
ILD
LLD
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25. Different Types of Wastes in Biopharmaceutical Factory
Biohazard waste
(Containing Process related biomaterials)
Solid waste
Chemical wastes
Liquid waste
Non-Process related wastes
(wastes of non-production area)
Not contaminated with Chemicals or Biomaterials of process
Gas waste
Waste Management System in Factory is Important
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26. Waste Management System (Hazardous wastes) Solid and Liquid wastes
Segreagation and separation of different types in suitable container
Collection I
Collection II
Decontamination
Release of safe waste* (house hold level)
*, this step could be done by waste contractor (if available)
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27. The role of Biosafety Committee in Biopharmacetical factory
To Put A regulatory system to register and document all biomaterials
Establish a mechanism to handle requests for permits for certain activities, such as release of GMOs into the environment through the national biosafety committee
Establishing a mechanism for monitoring and inspections
Putting system to provide information for personnel (Training, workshop, Biosafety Guidelines, etc…)
Participate as consulting during the purchase of new equipments
Reviewing the SOPs of all department (safety of chemicals, method and suitability of biosafety level to the area classification.
Preparation of Biosafety Manuals
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