This document discusses process safety management in pharmaceutical industries. It begins by describing several process safety incidents that occurred in pharmaceutical plants, including explosions caused by volatile dust mixtures and fires during chemical transfers. The document then discusses hazards like flammability, reactivity, and dust explosions. It outlines elements of a process safety management program including hazard identification, risk analysis, operating procedures, training, and emergency response. The document provides examples of risk controls and emphasizes the importance of process safety to protect people, the environment, and limit business interruptions.

1. www.issehs.com
Process Safety Management in
Pharmaceutical Industries
Ms. Lili Deng, EHS Specialist
(lili.deng@issehs.com), Maharshi Mehta, CSP,
CIH (maharshi.mehta@issehs.com)
International Safety Systems, Inc.
www.issehs.com
The 9th RDPAC EHS Working Group
Meeting
Hangzhou, China
October 30, 2008

2. www.issehs.com
Learning Objectives
 In this session, participants will learn:
– Process Safety Incidents in Pharmaceutical Industries
– Control of Process Safety Risk Lessons Learned
– Hazards: Flammability, Reactivity and Dust
Explosion Hazards
– Hazard Assessment Technique Review
– Risk Prevention and Controls
– Elements of Process Safety Management Program

3. www.issehs.com
Process Safety Incidents
 “Powerful explosion in
pharma firm” News
– Surrounding area up to 3
km affected
– Reactor in which
distillation was done
exploded

4. www.issehs.com
Another explosion incident..
KINSTON, North Carolina
(CNN) -- A massive explosion
and fire gutted pharmaceutical
supply plant, killing at least
three people and injuring more
than two dozen others
Volatile mix of air and suspended dust caused explosion The
explosion was so powerful it blew doors open on houses more
than a mile away

5. www.issehs.com
More Incidents..
 Suspended acetone bucket
caught fire during filling
 Explosion during vinyl
acetate transfer (same
operation conducted
number of times without
problems): External
paints prevented
grounding of the drum
 Centrifuge caught fire as
nitrogen purging was not
enough

6. www.issehs.com
Laboratory Accidents
 Mixing of incompatible waste (nitric
acid in ethanol rinsed bottle)
 Methylene chloride mixed with
oxidizer without knowing
incompatibility
– Hood and about 2000 sq feet of
laboratory area caught fire
– Broken glasses of bottles traveled 10
meters away and caused injuries

7. www.issehs.com
Common causes of PSIs
 Awareness and training
 Systems not in place
 Systems not implemented
 Preventive maintenance was reactive
maintenance

8. www.issehs.com
What is PSM
Managing process safety and
organization to reduce fire, explosion
and imminent health risk

9. www.issehs.com
Why PSM?
 Plant’s existence
 Harm to people, process and environment
 Process Interruptions
 Regulatory and Corporate Requirements
 Liability
 Return on Investment
– Recovery of resources
 Pre-requisite to participate in Global Economy
 Public Image

10. www.issehs.com
Hazards Considered
 Flammability
 Reactivity
 Dust Explosions
 Imminent health risk from acutely harmful
substances (will not be discussed due to
time limitation)

11. www.issehs.com
Fire Principle
 A fire in pharmaceutical industry
occur occur if ALL of the
following are present
– Fuel (e.g., methnaol) in sufficient
concentration in air
– Source of ignition
– Oxygen
 A chain reaction between oxygen
and fuel with sufficient
concentration of each is required for
a fire to occur and continue
 Removing one of the three
elements will prevent fire

12. www.issehs.com
Flammability Terms
 Flash Point
– Minimum temperature at which flammable chemical gives
off sufficient vapor to initiate fire with ignition source
– Lower the flash point, more flammable a chemical
 Lower Explosive Limits (LEL)
– Concentration of flammable vapor in %, below which fire
does not occur
 Upper Explosive Limits (UEL)
– Concentration of flammable vapor in % , above which fire
does not occur

13. www.issehs.com
Flammability of Solvents Used in
Pharmaceutical Industry
Chemical FP
0
C
LEL
%
UEL
%
Toluene 4 1.2 7.1
Methanol 11 6 36
Triethylamine -17 1.2 8
n-PA -37 2 10.4
Which chemical is more flammable?

14. www.issehs.com
Fuels in Pharmaceutical Industries
Solvents used in reactors and centrifuge (e.g.,
toluene and methanol )
Uncontrolled Inventory Flammable liquids in plastic containers

15. www.issehs.com
Static Electricity
Ignition Sources
Electrical fittings and apparatus
Open Flames
Overheated Heated apparatus
(vacuum pumps, hot plates,
ovens), distillation units

16. www.issehs.com
Ignition Sources
 Electrical (23%), Smoking (18%)
 Friction (10%), Hot Surfaces (7%),
 Overheated Material (8%)
 Cutting, Welding, Open Flames (4%)
 Static Electricity (1%)

17. www.issehs.com
Static Electricity
 Flammable chemicals accumulate static charges
readily as they have high insulating values
 Flow of liquid through pipe, strainers, filters
 Splashing of liquid jets
 Ejection of droplets from nozzles
 Stirring and Mixing
 Solid handling-Sieving, pouring and grinding

18. www.issehs.com
Activities with Static Electricity
Potential
▪ Flammable liquid loading,
unloading, transfer
▪ Flow of liquid through pipe,
strainers, filters, stirring and
mixing
▪ Solid handling-Sieving,
pouring, grinding,
micronizing, pneumatic
conveying

19. www.issehs.com
Potential Risk of Fire in Pharmaceutical
Process
 Tanker unloading and tank storage
 Reactors
– Charging of solids in reactor containing
flammable liquid
 Solid liquid separation – Centrifuge
– Methanol or any other solvent
– High static electricity during charging and
spinning
 Distillation
– Cooling stops
 Drying

20. www.issehs.com
Reactive Chemicals
 High reaction rate
 Reaction rate increases with temperature.
 If the reaction rate and resulting heat are not controlled , an explosion
could occur
 Heat initiated decomposition could result in explosion e.g., certain
peroxides
 Light could be initiator of an explosive reaction e.g., hydrogen and
chlorine reacts explosively in the presence of light
 Shock could initiate an explosion, e.g., acetylides, azides, organic
nitrates, nitro compounds and peroxides
 Picric acid becomes highly shock-sensitive when its normal water
content is allowed to evaporate

21. www.issehs.com
Incompatible Chemicals
 React dangerously when mixed with certain
other materials
 Spontaneous ignition or fire could occur
 Decomposition product may ignite or could be
harmful to health
 Examples
– Organics and Oxidizers
– Acids and Bases
More on Incompatible chemicals:
http://msds.chem.ox.ac.uk/incompatibles.html

22. www.issehs.com
Chemical Structure with Explosive
Tendencies
 -ONO2 nitrate R-NO2 aliphatic nitro
 -NH-NO2 Primary nitramine Ar-NO2
aromatic nitro
 -N-NO2 Secondary nitramine -N3
 -NO nitroso =N-X halamines
 -N=N-diazo -C=C-acetylides
 -N=N-S-N=N-diazosulfide
 Organic salts of chlorates, perchlorates,
picrates, nitrates, iodates.

23. www.issehs.com
Dust Explosion Potential
▪ Presence of Comustible Dust
▪ Oxygen concentrations 3% and above
▪ Small particle size (< 100 microns more potential)
▪ Minimum Explosible Concentrations (MEC)
▪ MEC for most materials is 10 to 500 g/m3
▪ 10 g/m3 dust concentration looks like dense fog
with visibility of 1Meter.
▪ More moisture less dust explosion potential

24. www.issehs.com
Activities with Dust Explosion
potential
 Fluidized Bed Dryers
 Dust collectors
 Solid charging in Reactors

25. www.issehs.com
Why Hazard Identification
“ For every dollar it costs to fix a problem in the
early stage of design, it will cost $10 at flow
sheet stage, $100 at the detail design stage,
$1000 afte r the plant is build and $10,000 to
cleanup the mess after an accident”
KLETZ

26. www.issehs.com
Hazard Identification
 Can the process/activity pose a threat to
health, safety, environment or property?
 INPUT: Properties of materials, historical
experience, knowledge of process
parameters, management system,
available safeguards, application of
analytical methods
 Output: List of potential problem
materials, process conditions, and
situations and understanding of what can
go wrong.

27. www.issehs.com
Process Hazard Analysis
 Hazards of Process
 Previous Incidents
 Engineering and Administrative Controls
 Consequence of Failure
 Human Factors

28. www.issehs.com
Process Hazard Information
Hazards Technology Equipment
Toxicity Block Flow
Diagram
Construction
Materials
PELs Chemistry Piping &
Instrumention
Physical Inventory Electrical
Reactivity Operating
Ranges
Relief Vents
Corrosivity Hazards of
Deviations
Design Codes
Stability Material Balances
Compatibility Safety Systems

29. www.issehs.com
Elements of Process Safety
Management and Hazard Analysis 1
 Process Safety Information
(Hazards, Technology, and Equipment)
 Prioritize the Process Hazard Analyses
(PHA)
 Conduct PHA
 Develop Operating Procedures
(for each operating phase and for safety
systems)
 Certify Current Employees Sufficiently
Trained

30. www.issehs.com
Elements of Process Safety
Management and Hazard Analysis 2
 Procedures for Maintaining Mechanical Integrity
 Document Process Equipment Inspections and
Tests
 Hot-work Permits
 Management of Change Procedures
 Incident Investigation
 Emergency Action Plan
 Process Safety Management Compliance Audits

31. www.issehs.com
Hazard Analysis - System Safety
 Depending on complexity of process, Hazard
Analysis is conducted using one or more of the
following methods:
– Job Safety Analysis (JSA)
– Preliminary Hazard Analysis (PHA)
– What-if and What if -Check List
– Hazard And Operability Analysis (HAZOP)
– Failure Mode and Effect Analysis (FMEA)
– Fault-Tree Analysis (FTA)
– Management Oversight Risk Tree (MORT)
– Human Reliability Analysis (HRA)

32. www.issehs.com
Principles-Risk Prevention and Controls
Elimination
Substitution
Process Changes
Engineering Controls
Administrative Controls
Personal Protective Equipment
Respiratory Protective Equipment

33. www.issehs.com
Risk Controls: Examples
Process change (seal-less pump) and engineering controls (Laboratory
Fume Hood and Local Exhaust Ventilation (LEV) on sink

34. www.issehs.com
Flammable Liquids-Controls
 Keep flammable liquids in covered containers when not in use
 Keep flammable concentrations below 25% of LEL when an ignition
source is present
 Use a calibrated detector to determine flammable vapor
concentration
 Provide grounding and bonding for static electricity controls
 Use of non sparking tools/ intrinsically safe electrical apparatus and
lighting
 Provide a non-return valve in flammable gas supply line
 Avoid using flexible hoses for transfer
 Provide and maintain explosion proof lighting

35. www.issehs.com
Solvent Storage Cabinets
 Flammable liquid limited to 60
gallons in approved cabinet
 Flammable chemical storage
cabinet to have 1hour fire
rating
 Cabinets to be labeled
"Flammable - Keep Fire
(ignition sources) Away".
 Vent through two ports on side
with flame arrestor

36. www.issehs.com
Flammable Chemical Storage
Room
 Allowable quantity 5 gal/sq feet of floor area when fire
protection is not provided and room fire resistance is 2
hrs
 Explosion proof electrical wiring
 Liquid tight room
 Ventilation to provide six air exchange rate per hour
 Provide clear aisle of 3' wide
 Stacking of containers one upon the other over 30 gallon
prohibited

37. www.issehs.com
Static Electricity Controls
 Bonding and grounding
 Metal to metal contact
essential (painted surface)
 Testing conductivity of
wire and connections
 Avoid free fall of liquid by
bottom entry or extend fill
pipe. Fill pipe to terminate
within 6” from the bottom
of vessel

38. www.issehs.com
Grounding bonding-Poor and best
practices

39. www.issehs.com
Dust Explosion - Prevention and
Controls
 Inerting, Purging, to keep oxygen
concentration below 3%
 Suppression
 Explosion Venting
 Process Isolation
 Pressure Vessel Design
 Control of Ignition Sources

40. www.issehs.com
Inerting
▪ An inert gas such as nitrogen is passed
through to remove oxygen
▪ Keep oxygen concentration to below
<3% to prevent a dust explosion or fire
▪ Ensure nitrogen is used and by mistake
other gases such as oxygen is not used
▪ Determine volume and flow rate of
nitrogen needed
▪ Ensure flow of nitrogen
▪ Provide low pressure alarm to warn
about loss of inerting

41. www.issehs.com
Tank Storage: Flammable Chemicals
▪ Do not overfill, level indicator
▪ Measure metal thickness
▪ Provide flame arrestor, breather valve with flame
arrestor preferred
▪ Level indicator
▪ Provide dyke of 1.5 times tank volume
▪ Unloading/Loading rack to be located at least 25 feet
away
▪ Steel support to be protected by 2 hour fire
resistance covering on batch tanks with supports

42. www.issehs.com
Unloading of Tank Cars/Trucks of
flammable liquids
 Metallic gauging rod prohibited when
electrical power line is within 20’ of tank
opening
 Setting of brakes, “STOP....” signs 25’ in
front
 Bottom unloading is preferred
 Continuous present of the operator
throughout unloading
 No smoking, grounding/bonding connection
 Applying chocks on wheels

43. www.issehs.com
Hot Work Permit
▪ Needed when welding, has cutting or
any spark producing work is carried out
▪ Define responsibility
▪ Remove all flammables, purge, cover
areas
▪ Close valve, block flow
▪ Provide fire extinguisher
▪ Test for presence of flammable vapors
▪ Randomly inspect
▪ Issue permit

44. www.issehs.com
Hazard Information
 Material Safety Data Sheets
– Manufacturer has legal duty to provide in most countries
– Available on Internet
 International Chemical Safety Cards
– International Labor Organization (ILO) publishes and contain
hazard information with terms used globally
 Labels
– Hazard Material Information System (HMIS) label
– National Fire Protection Association (NFPA) label
– Symbols and Risk Phrases used in European Community
 References
– Useful publications and Internet Sites

45. www.issehs.com
National Fire Protection
Association Label
 Used globally to indicate
flammability, reactivity
and health hazard
 Applied on chemical
containers, except those
container used in analysis
Container without a label or with
defaced label must be safely
discarded

46. www.issehs.com
Hazard Information-Websites
 Hazardous Substance Data Bank (HSDB) www.nlm.nih.gov
 European Agency for Safety and Health
– http://europe.osha.eu.int
 Asia Pacific Health and Safety Network from ILO
– http://www.ilo.org/public/english/region/asro/bangkok/asiaosh/
 Canadian Center for Occupational Health and Safety
– http://www.ccohs.ca/products/shop.html
 National Occupational Health and Safety Commission,
Australia
– http://www.nohsc.gov.au/