Industrial Hygiene and PSM in Pharma industries Hangzhou, China 2013

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Applied Industrial Hygiene and Process
Safety In Pharmaceutical Industries
Maharshi Mehta, CIH, CSP
International Safety Systems, Inc.
Maharshi.mehta@issehs.com
+1 203 331 6464
www.issehs.com
The 9th RDPAC EHS Association
Conference, Hangzhou October 31, 2008

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About us

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What we do?
Industrial Hygiene Process Safety
Ergonomics Personal Safety

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Agenda
• Challenges in Emerging economies
– Companies
– Suppliers
• Applied Industrial Hygiene
• Applied Process Safety
• Approaches adopted

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Industrial Hygiene
Hazard Anticipation-Hazards likely to be present?
Hazard Recognition-What are health hazards?
Risk Evaluation-Exposed to health hazard? How much?
Risk Control-How can exposure be reduced?
And potential for occupational illnesses, material loss are
reduced and the company liability minimized
So that.. Health risk is minimized

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The Need
• Prevent occupational illness by reducing/eliminating
health risk
• Corporate Requirements
• Significant cost savings by reducing/recovering
particulate/vapor emissions
• Regulatory requirements
• Productivity increase

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Introduction
• Qualitative Exposure Assessment
– Determines exposure potential
– Based on process observations, health hazards, and interview
– Prerequisite for quantitative exposure assessment
– All processes, tasks, operations that use or create chemicals must
undergo this stage
• Quantitative Exposure Assessment
– Conducted by competent industrial hygiene professional
– Quantify magnitude of exposure
– Based on exposure monitoring methods
– Often used as primary means of determining exposures without
qualitative exposure assessment
Skip exposure assessment and place
exposure controls first when exposure is
obvious

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Exposure Assessment Model Developed for
Pharmaceutical Industry
• Health Hazard Ranking based on OEL for APIs
• Frequency/Duration Ranking
• Control Ranking
• Overall Risk Ranking

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Direct Reading Instruments
• Spot measurements
• Provide a quick indication of contaminant levels
• Not suitable for exposure determination
• Useful in identifying:
– Oxygen deficient atmospheres,
– Toxic levels of airborne contaminants,
– Flammable atmospheres,
– Radioactive hazards, and
– Leaks

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Direct Reading Instruments
• Portable gas chromatographs
– Measures organics more specifically and accurately
• Substance specific analyzers:
– Mercury vapor analyzer-gold film analyzer
– Ozone meter
– Oxygen meters
• Particulate monitors
• Combustible gas analyzers

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Calibration of Direct Reading Instruments
• Follow instrument’s instruction manual for calibration method and frequency
• The calibration substance should represent the substance for which the
instrument is designed to be used
• The calibration substance concentration should be close to the concentration of
concern (if you are interested in determining CO concentration around 30 ppm, the calibration gas
concentration should be around 30 ppm)
• Preferred Frequency of Calibration from Manufacturers:
– Once every six months to annually from the manufacturers
– Daily field calibration
• Confidence:
– In addition to calibration certificate, obtain data on the calibration
concentration, + and – error identified during calibration

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Colorimetric Detector Tubes-
Principle and Use
• Principle:
– Known volume of air is drawn through a detector tube
– Change in tube color is proportional to concentration and air volume
drawn
• Use:
– For quick indication of contaminant concentration
– For leak detection

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Detector Tubes- Strengths and
Limitations
• Strengths:
– Quick indication of concentration
– Does not require a laboratory to analyze the sample
– Readily available
• Limitations:
– Limited availability for organic and inorganic vapors/gaseous
compounds and some aerosols
– Can not be used for particulate contaminants
– Not suitable to determine exposure accurately (Accuracy is + / -
25%)
– Lack of specificity (many indicators are not highly selective and
can cross-react with other compounds)
– One brand of the tube can not be used with another brand of the
pump
– Shelf life at 25 °C of one to two years

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Passive/Diffusion Devices-
Sampling Method
• Select a passive sampler for a substance of concern
• Remove the sampler from the sealed pouch
(Keep all parts for future use)
• Record the start time on the sampler label
• Attach the sampler to the person with potential for exposure near the breathing
zone; the small holes should be facing out
• At the end of the sampling period, remove the sampler from the person, and
immediately seal it with cap and O-ring provided with the sampler. Record the
stop time.
• Document activity performed by the person
• Ship the sampler to an accredited laboratory (discussed later) for analysis
• Document temperature and humidity

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Industrial Hygiene
• Industrial Hygiene Field Sampling
(Quantitative Exposure Assessment)
– Conducted by competent Industrial Hygienist
– Quantify magnitude of exposure
– Based on exposure monitoring methods
• APIs, Chemical and Surrogate exposure
monitoring
– Active monitoring with sampling pumps

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Active Air Monitoring-
Survey Protocol Development
• What to sample? Contaminants with higher degree of
toxicity with potential for exposure identified during
qualitative exposure assessment
• Whom to sample? Personnel potentially exposed to the
contaminants identified
• Are all personnel required to be sampled? No, sample few
from those having similar exposures also known as
homogeneous exposure group (e.g., charging personnel)
• Where to sample? Areas/activities/operations with potential
for exposures defined during qualitative exposure
assessment
• How many samples to be collected? Six (minimum) for
each contaminant in a homogeneous exposure group
• When should the sampling be done? Representative
sampling in all shifts

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Air Monitoring
Sampling pump
Sampling media
Sampling media
Calibrator

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Air Monitoring
• Process:
– Air drawn with battery operated sampling pump
though sampling media in breathing zone
– Sampling media analyzed to determine weight of
contaminant
– Weight divided by volume of air drawn through
media to determine contaminant concentration
• Determines exposure during actual work duration. Not
instantaneous concentration determination as in direct
reading instrument
• Substance-specific accurate identification of exposure

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Personal Sampling and Area Sampling
Area Sampling:
• Collected at fixed location in workplace
• Collected to identify contaminant
concentration in general workplace and
potential exposure to people working in area
• Collected to evaluate efficiency and
sufficiency of control measures
• To identify source of contaminant
Personal Sampling:
• Collected in breathing zone of employee
• Preferred method to identify personal
exposure to employee
• Only method considered valid for accurate
determination of employee exposure
Area Sampling
Personal Sampling

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Pre-Sampling Procedure
• Calibrate air sampling pump
• Label sampling media
• Ensure proper connections in
sampling train
• Explain employee about need of
monitoring, function of
instrument and to perform work
as normal workday
• Write down,
– information about employee
and activity to be sampled
– start time
– Start air sampling
instrument
Pre Calibration
Air Sampling Train

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Placing Air Sampling
Pump
• Attach sampling media (e.g., filter cassette, charcoal
tube) in breathing zone a hemisphere in front of
shoulders with radius of 6 to 9 inches or (15 to 22.5 cm)
• Position sampling media outside respirator/hood and
protective clothing
• Ensure inlet is in downward vertical position
• Position sampling equipment and excess tubing to avoid
interference with work performance

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During Monitoring…
• Check pump every one hour to ensure it is
running
• Observe work practices to identify sources of
exposures
• Take digital pictures and make notes on
– Visible airborne contaminants
– Work practices
– Use of Personal Protective Equipment (PPE)
– Potential interferences
– Effectiveness of engineering and process
controls

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Post-Sampling Procedures
• At end of sampling duration,
remove sampling pump, cap media
and place it in refrigerator (for
solvents)
• Write down activities on that day,
deviation from normal work
practices and abnormalities, if any
(e.g., spill, leak)
• Post calibrate flow rate
immediately after removing
sampling pump
• Record all data in Chain-of-
Custody form
Post Calibration

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Sample Analysis
• Samples are shipped with chain of custody form to
American Industrial Hygiene Association accredited lab in
USA
• Laboratory reported results are interpreted
• The degree of exposure determined and compared with
occupational exposure limit

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Surrogate Monitoring
• Companies requires API supplier to conduct surrogate
monitoring
• Lactose with USP defined particle size and moisture
content is used
• Three personal samples collected with each operator
• Three area samples collected in each of the unit operations
• Background samples collected before lactose monitoring
began

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Surrogate Monitoring in Unit Operations

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Contributory Factors: Work Practices
• Material leaking from flange joints on Sieve and RMG
• Over filling of scoop while manual charging of
compression
• Shaking while emptying of Lactose with plastic bags
• Compressed air used for cleaning
• Dry sweeping in place of using a vacuum equipped with a
HEPA filter.

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Recommendations
• Containment and Local
Exhaust Ventilation
• Vacuum transfer
• IBC use and gravity feed
• Enclosure of compression
and de-dusting area
• HEPA equipped vacuum
cleaning
• PAPR

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Challenges
• High risk operations
• Trained professionals not available
• Quality Control
• Cost concerns
• Availability of resources
• Corporate EHS
– Not able to cop-up at manufacturing locations and
contract manufacturers (CM)
– Liability and public images continues to be a concern

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Our Experience with a Pharma Company –
Pant level - IH
• No IH process safety program in place
• Exposure monitoring data available
– All bellow exposure limits (??)
• Dust mask used
• Dry sweeping
• Containment not used or not validated
• Coporate Audit identified some of the concerns

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Our Experience with a Pharma Company –
Pant level – Process and general Safety
• Process Safety
– Open plastic bucket used for solvent transfer
– Reactor Inertting done
– Cylinders not labeled
– No Rota Meter to determine flow of ineting
– Inerting not validated with O2 Measurements
– Plastic hose used in Centrifuge
• General Safety
– Tanker unloading
– Nitrogen pressure used to transfer chemical

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Approaches adopted
• Walkthrough
• Exposure Assessment
• Process Safety Reviews
• Recommend Exposure Control Measures
• Developed SOPs
• Developed plant specific training manual with digital
images
• Conducted IH, PSM and Safety Workshop of 4 days at
plant site

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Outcome
• Reduced Process safety and IH risk
• Trained line managers and supervisors
• Self-sufficient program
• Limited involvement of consultant
• Limited involvement of Corporate IH Process Safety

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Our Experience with Contract Manufacturers
• Conducted IH and PSM review at 15 CMs
• Gross unsafe working conditions and unsafe work
practices
– Tanks with no vent
– Reactor with no ineting
– No reactor – open handling
• To keep us satisfied brand new gloves and respirator used

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Approached adopted
• Conducted baseline exposure assessment
• Recommended cost effective exposure control measures
• Develop easy to understand SOPs
• Few of the non-cooperative CMs removed from company’s list
• One unit was shutdown and allowed to start only after PSM
improvements are made
• Containment validation for new APIs
• Conducted a 3 day training program for all CMs
– 2 persons from each CM came
• Outcome
– Improved working conditions and work practices
– Reduced company liability

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Corporate Support
• Developed Industry Specific Training Manual
– Based on APIs manufactured
– Raw Materials used
– Operations and Activities conducted
– Reviewed by Corporate and Plant His
• Conducted one training program in each region
– Asia-Pacific, EU, US, LAM
– Program conducted at company’s manufacturing site
• Outcome
– 600 line managers trained in IH 101 in 22 training
programs conducted

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Raising bar.. Awareness.. At foundation

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