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Exposure Risk Assessment Challenges:Exposure Risk Assessment Challenges:Occupational Hygiene in the PharmaceuticalOccupational Hygiene in the Pharmaceutical
and Chemical Industriesand Chemical Industries
AIHA 2013AIHA 2013
Asia Pacific OH Conference, SingaporeAsia Pacific OH Conference, Singapore
Maharshi Mehta, CSP, CIHPresidentInternational Safety Systems, Inc., Washingtonville New York, USAwww.issehs.com
Samson PonselvanHead, Corporate EHSShasun Pharmaceuticals Limited, Chennai, India
Agenda: Two Part PresentationAgenda: Two Part PresentationPart 1: Maharshi MehtaPart 1: Maharshi Mehta
Growing need for sustainable Industrial hygiene Growing need for sustainable Industrial hygiene and process safety in Emerging Economiesand process safety in Emerging Economies
Introduction to potential health and process Introduction to potential health and process safety risksafety risk
Risk Assessment and Risk ControlsRisk Assessment and Risk Controls Challenges EncounteredChallenges Encountered Approaches adopted Approaches adopted Lessons Learned Lessons Learned
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Part-2 : Samson - AgendaPart-2 : Samson - Agenda1. Background /Introduction
A. Why is this important ?B. HSE Trends in Asian countries C. IH in Pharma and Chemical industries
2. Challenges in managing potential health risks and solutions
3. Hierarchy of controls - At Source / At Path / At Work
4. IH Management System Models
5. Integration of IH and handling of potent APIs
6. Conclusion Slide Slide 33
IntroductionIntroduction Pharmaceutical manufacturing is growing 8% to
12% per year in emerging economies India is the world’s largest producer of bulk drugsworld’s largest producer of bulk drugs Supply chain, third party manufacturing are Supply chain, third party manufacturing are
increasing rapidlyincreasing rapidly Outsourcing expected to exceed $53B Outsourcing expected to exceed $53B More than 100 FDA-approved pharmaceutical
facilities are in India- the largest number in any country outside the U.S
44
InfrastructureInfrastructure
Over 450 Over 450 colleges/departments offering colleges/departments offering degree and other education degree and other education programs in pharmaceutical programs in pharmaceutical sciencescience
More than 50,000 students More than 50,000 students graduates/yeargraduates/year
Manufacturing equipment, Manufacturing equipment, containment technologies containment technologies
R&D centers , laboratoriesR&D centers , laboratories
Two colleges offering Two colleges offering Master in Industrial Hygiene Master in Industrial Hygiene ProgramProgram
150 Industrial Hygienists for 150 Industrial Hygienists for all companies in India totalall companies in India total
5 CIHs5 CIHs Safety professionals or Safety professionals or
occupational physicians occupational physicians practicing IHpracticing IH
No Accredited Lab for No Accredited Lab for API/SurrogateAPI/Surrogate
55
Pharma Manufacturing EHS
Introduction-Pharmaceutical and Introduction-Pharmaceutical and Chemical IndustriesChemical Industries Active Pharmaceutical Ingredient (API) Active Pharmaceutical Ingredient (API)
Manufacturing similar to typical chemical industriesManufacturing similar to typical chemical industries– Bulk drug is manufactured Bulk drug is manufactured
– Potential process safety risk and chemical exposure risk is Potential process safety risk and chemical exposure risk is highhigh
– Large volume potential solid exposure risk is high after Large volume potential solid exposure risk is high after solid liquid separation solid liquid separation
Formulation or Dosage FormFormulation or Dosage Form– Solids and liquid pharmaceuticals are madeSolids and liquid pharmaceuticals are made
– Potential solid API exposure risk is highPotential solid API exposure risk is high
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API/Chemical Manufacturing –Process Safety API/Chemical Manufacturing –Process Safety – The highest priority– The highest priority
Low flash points solvent. Most commonly used:Low flash points solvent. Most commonly used:– Toluene, Methanol, Dimethyl Formamide, AcetonitrileToluene, Methanol, Dimethyl Formamide, Acetonitrile
Unit operationsUnit operations– Tanker unloading and tank farm, barrel transferTanker unloading and tank farm, barrel transfer– Reactor vessel charging and cleaningReactor vessel charging and cleaning– Solid liquid separation, distillationSolid liquid separation, distillation
Most common Contributory factorsMost common Contributory factors– Open handling of solvents Open handling of solvents – Validation of inertingValidation of inerting– Non-conductive container handlingNon-conductive container handling– Effectiveness of grounding and bonding Effectiveness of grounding and bonding – ““Explosion Proof” lightingExplosion Proof” lighting
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Example of Process Safety IncidentExample of Process Safety Incident
A massive explosion and fire gutted a pharmaceutical supply plant, killing at least three people and injuring more than two dozen others -- about 12 of them critically.
A massive explosion and fire gutted a pharmaceutical supply plant, killing at least three people and injuring more than two dozen others -- about 12 of them critically.
A volatile mix of air and suspended dust caused the explosion The explosion was so powerful it blew doors open on houses more than a mile away and sent debris flying, with some pieces landing more than two miles away
Authorities recommended residents within a mile radius around the plant to evacuate
Process Safety - Most Process Safety - Most common recommendationscommon recommendations
Process safety risk is manageableProcess safety risk is manageable Awareness and Risk Assessment (HAZOP)Awareness and Risk Assessment (HAZOP) Storage tank integrity, flame arrestor Storage tank integrity, flame arrestor
breather valves, dykingbreather valves, dyking Validation of inerting-flow rate, volume, Validation of inerting-flow rate, volume,
O2<4%. Inerting of not just process O2<4%. Inerting of not just process vessels – Centrifugevessels – Centrifuge
Static electricity controlsStatic electricity controls
– Painted surfacesPainted surfaces
– Continuity, resistance and earthingContinuity, resistance and earthing Conductive containersConductive containers Specifics on intrinsically safe lighting Specifics on intrinsically safe lighting
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Industrial HygieneIndustrial HygieneHazard 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
Hazards – Exposures – Controls - and Hazards – Exposures – Controls - and Risk: example…Risk: example…Low RiskLow Risk Compression Compression ActivityActivityHealth Hazard: API
Enclosed compression machine
Potential for exposure from fugitive emission
Reduced risk due to effective use of airline respirator
Industrial Hygiene - MethodologyIndustrial Hygiene - Methodology(Compression)(Compression)
Health Hazard IdentificationHealth Hazard Identification– Obtain hazard data for API from MSDS and labelObtain hazard data for API from MSDS and label
Exposure/Risk AssessmentExposure/Risk Assessment– How frequently and how long compression How frequently and how long compression
machine is running? machine is running? – How frequently compression machine is cleaned?How frequently compression machine is cleaned?– Are exposure controls effective in reducing Are exposure controls effective in reducing
exposure?exposure?– Are recommended RPE/PPEs used?Are recommended RPE/PPEs used?– Is exposure monitoring conducted? Is exposure monitoring conducted? – Is the exposure below OEG?Is the exposure below OEG?
Hierarchy of ControlsHierarchy of Controls Elimination – Avoid Compression?Elimination – Avoid Compression? Substitution – Use of low potency Substitution – Use of low potency
compound?compound? Process Changes – Vacuum transfer blend in Process Changes – Vacuum transfer blend in
compression hopper?compression hopper?– Not feasible due to business constraints e.g., product Not feasible due to business constraints e.g., product
validation and registration process validation and registration process Engineering Controls – Complete enclosure of Engineering Controls – Complete enclosure of
compression machine and tablet container?compression machine and tablet container? Administrative Controls – Reducing or restricting Administrative Controls – Reducing or restricting
exposure duration?exposure duration? Personal Protective Equipment and Respiratory Protective Personal Protective Equipment and Respiratory Protective
Equipment – Eye Protection, cleaning disinfecting Equipment – Eye Protection, cleaning disinfecting respirator, storing respirator in a zip lock plastic bag?respirator, storing respirator in a zip lock plastic bag?
API Chemical Plants: Health API Chemical Plants: Health Hazards - SolventsHazards - Solvents
Toluene and DMFToluene and DMF– Potential reproductive hazardsPotential reproductive hazards
AcetonitrileAcetonitrile– CN formationCN formation
Tetrahydrofuran (also peroxide forming agent)Tetrahydrofuran (also peroxide forming agent) IsopropanolIsopropanol Small Volume Highly Toxic compoundsSmall Volume Highly Toxic compounds
– AnilineAniline– IodineIodine
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API/Chemical Plants: Solvent API/Chemical Plants: Solvent Exposure Potential to Exceed Exposure Potential to Exceed OELOEL Solid liquid separation – Centrifuge - Manual Solid liquid separation – Centrifuge - Manual
diggingdigging Short term exposure – Tanker/barrel QC Sample Short term exposure – Tanker/barrel QC Sample
taking, tanker hose disconnecting, residual taking, tanker hose disconnecting, residual tanker solvent collectingtanker solvent collecting
Reactor, vessel cleaningReactor, vessel cleaning Distillation residue collectionDistillation residue collection
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API/Chemical Plants: Solvent API/Chemical Plants: Solvent Exposure ControlsExposure Controls Agitated Nutche Filter/Filter Agitated Nutche Filter/Filter
Dryer in place of CentrifugeDryer in place of Centrifuge Tanker QC sample from Tanker QC sample from
bottom nozzle and not by bottom nozzle and not by opening domeopening dome
Nitrogen for pushing Nitrogen for pushing solvents before opening solvents before opening hose after tanker unloadinghose after tanker unloading
Local Exhaust Ventilation Local Exhaust Ventilation
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Acute Pharmacological Effects Acute Pharmacological Effects
Pharma compound Exposure Incident: An operator Pharma compound Exposure Incident: An operator working on the manufacture of working on the manufacture of a product containing a product containing Barbiturates Barbiturates was admitted to hospital in was admitted to hospital in hypoglycaemic coma and the report of a study by the hypoglycaemic coma and the report of a study by the Pharma company found that operators absorbed Pharma company found that operators absorbed through skin significant levels of through skin significant levels of BarbituratesBarbiturates. .
Health effects described in this and subsequent slides potentially could occur from overexposure when effective exposure controls are not in place.
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HormonesHormonesEndocrine Gland Hormone Main function(s)
Pancreas Insulin Regulates blood sugar levels.
Thyroid Triiodothyronine and
thyroxineDevelopment of the brain and reproductive tract, and regulation of metabolism
Adrenal Cortisol Immune suppression and stress response
OvaryEstrogens (estradiol,
estrone, estriol)Growth promotion, maintain elasticity of connective tissues, preserve bone mass and, vascular compliance,
Testosterone Precursor for oestrogen and acts on libido.
Testis TestosteroneGrowth of male secondary sexual characteristics, sperm production and libido
Dihydrotestosterone Some male secondary sexual characteristics.
Placenta Progesterone Maintenance of pregnancyOverexposure to hormone during manufacturing, development and testing may result in elevated levels of hormone in the body and affect the normal functions of the related endocrine gland.
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Steroids – Health EffectsSteroids – Health Effects Male Employees: Male Employees:
– Gynecomastia (excessive development of the mammary Gynecomastia (excessive development of the mammary glands), decreased libido, reduced testicular size, glands), decreased libido, reduced testicular size, increased pigmentation of the nipple area, nipple increased pigmentation of the nipple area, nipple sensitivity, dysspermia (the occurrence of pain during sensitivity, dysspermia (the occurrence of pain during ejaculation), weight loss, and headaches ejaculation), weight loss, and headaches
Female Employees:Female Employees:– Menstrual disorders (such as increased flow or Menstrual disorders (such as increased flow or
intermenstrual spotting), nausea, headaches, breast pain, intermenstrual spotting), nausea, headaches, breast pain, leukorrhea (vaginal discharge), and swollen ankles leukorrhea (vaginal discharge), and swollen ankles
Adverse effect on skin such as acne and erythemaAdverse effect on skin such as acne and erythema
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Antibiotics - Health EffectsAntibiotics - Health Effects Allergic reactions: Allergic reactions:
– Itching and redness of eyes, runny nose, skin rashes, Itching and redness of eyes, runny nose, skin rashes, asthma, anaphylaxisasthma, anaphylaxis
Vitamin deficiency:Vitamin deficiency:– Workers with repeated exposure to antibiotics Workers with repeated exposure to antibiotics
experience change in number and type of bacteria experience change in number and type of bacteria which are normally present in intestines which break which are normally present in intestines which break down and absorb vitamins in intestinesdown and absorb vitamins in intestines
Fungal infections: Fungal infections: – Daily exposure to antibiotic dust can lead to fungal Daily exposure to antibiotic dust can lead to fungal
infections of the skin and nails. infections of the skin and nails. – Women workers may develop vaginal yeast Women workers may develop vaginal yeast
infections following exposure to antibioticsinfections following exposure to antibiotics
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Acute effects: severe soft-tissue damage, fetotoxicity, Acute effects: severe soft-tissue damage, fetotoxicity, headaches, lightheadedness, dizziness, nausea and allergic headaches, lightheadedness, dizziness, nausea and allergic reactionsreactions
Effect on growth and reproduction of the normal cells as Effect on growth and reproduction of the normal cells as Cytotoxic drugs may not distinguish between normal and Cytotoxic drugs may not distinguish between normal and cancerous cells cancerous cells
Other secondary malignancies, such as bladder cancer and Other secondary malignancies, such as bladder cancer and lymphomalymphoma
Chromosomal damage (e.g., Chlorambucil)Chromosomal damage (e.g., Chlorambucil) Testicular and ovarian dysfunction, including sterilityTesticular and ovarian dysfunction, including sterility Biological effects (even at very low levels of absorption)Biological effects (even at very low levels of absorption)
Antineoplastic - Health EffectsAntineoplastic - Health Effects
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OELs OELs Occupational Exposure Limits (OELs) Occupational Exposure Limits (OELs) Airborne concentration limit of a substance to which it is believed that Airborne concentration limit of a substance to which it is believed that
a worker may be exposed, without adverse health effects, expressed as a worker may be exposed, without adverse health effects, expressed as an average concentration. an average concentration.
The time weighted average concentration for 8 hr work-day, 40 hour The time weighted average concentration for 8 hr work-day, 40 hour work-week , to which nearly all workers may be repeatedly exposed, work-week , to which nearly all workers may be repeatedly exposed, day after day, without adverse effect. day after day, without adverse effect.
An OEL is substance-specific and is a level at which workplace An OEL is substance-specific and is a level at which workplace exposure is expected to be without detectable pharmacological or exposure is expected to be without detectable pharmacological or toxicological effect in occupational circumstances. toxicological effect in occupational circumstances.
Industrial Hygienists conduct personal exposure monitoring to assess Industrial Hygienists conduct personal exposure monitoring to assess employees’ exposure relative to these levels.employees’ exposure relative to these levels.
Exposure limits are nota fine line between safe and dangerous concentrations
Adjusted Occupational Exposure Limits (AOEL)*Adjusted Occupational Exposure Limits (AOEL)*
Activity Duration Activity Multiplier (AM)
Up to 10 min 5
> 10 to 30 min 3
From > 30 min up to 1 hour
2.5
From > 1 hour up to 2 hours
2
From > 2 hours up to 4 hours
1.5
From > 4 hours up to 8 hours
1
*AOEL = AM X OEL-TWA (basis ACGIH Excursion Limits)©International Safety Systems, Inc. ©International Safety Systems, Inc. www.issehs.comwww.issehs.com
Occupational Exposure Bands (OEBs) – Categorization Occupational Exposure Bands (OEBs) – Categorization
OEB 2 1000 - 100 ug/m3
OEB 3 100 - 10 ug/m3
OEB 15000- 1000 ug/m3
OEB 4 10 - 1 ug/m3
1000
10
100
≤1
OEB 5 ≤1 ug/m3
Not harmful, not irritating, low pharmacological activity e.g. predicted therapeutic dose >100mg/day, Examples – many excipients
Harmful, may be irritant, Moderate pharmacological activity, predicted therapeutic dose >10 - 100mg/day, Examples – Loratadine
5000
Moderate toxic and /or high pharmacological activity, predicted therapeutic dose >1–10mg/day, Respiratory sensitizers and potent dermal sensitizers, Severe irritants and corrosives, also default category, Examples – many penicillin & cephalosporin antibiotics
Toxic Serious irreversible effects, Carcinogens, Mutagens, Reproductive and Developmental Toxins, Potent respiratory sensitisers, predicted therapeutic dose 1mg/day, Examples –Corticosteroids, some oncology drugs
Extremely toxic and or extremely high pharmacological activity predicted therapeutic dose 1mg/day, Serious irreversible effects, Potent Carcinogens, Mutagens, Reproductive and Developmental Toxins, Examples - potent hormones or hormone effectors, select anti-cancer drugs©International Safety Systems, Inc. ©International Safety Systems, Inc.
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Risk Assessment ModelRisk Assessment Model
Most model considersMost model considers– PotencyPotency
– Frequency duration of exposureFrequency duration of exposure
– Air-borne Potential Air-borne Potential
– Exposure ControlsExposure Controls Formulation Formulation
– Small volume, less frequency/duration high potent Small volume, less frequency/duration high potent compounds considerationscompounds considerations
Potential skin and ingestion risks are also criticalPotential skin and ingestion risks are also critical
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Risk Ranking Criteria are summarized in next 3 slides
High Potent Compound in High Potent Compound in Chemical Industries Chemical Industries
Beryllium - OEL 2 ug/m3Beryllium - OEL 2 ug/m3 Hex chrome – OEL 5 ug/m3Hex chrome – OEL 5 ug/m3 Ni Carbonyl – OEL 50 ppbNi Carbonyl – OEL 50 ppb Chloromethyl isothiazolone – Kethon – very low Chloromethyl isothiazolone – Kethon – very low
OEL used as biocideOEL used as biocide Bis chloromethyl ether OEL 1 ppbBis chloromethyl ether OEL 1 ppb
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Rank Frequency Duration Health Hazard Daily Weekly monthly Yearly Chemicals API
1Minimal (under 30 minutes)
Any / Minimal (under 5 hours)
Any / Minimal (under 20
hours)
Any / Minimal (under 250
hours)
OEL in range 3.1 to 10
mg/m3 or > 1000 ppm
OEB1, OEL >1000 µg/m3
2About 30 min
to < 2 hour5 to 15 hours
per week20 to 60 hours
per month250 to 500
hours per year
OEL in range 0.51 to 3
mg/m3 or 101 to 1000 ppm
OEB 2, OEL 100 µg/m3 - 1000
µg/m3
3About ½ Shift (2 to 4 hours)
15 to 25 hours per week
60 to 80 hours per month
Use More Frequent
Basis
OEL in range 0.01 to 0.5
mg/m3 or 10 to 100 ppm
OEB 3, OEL 100 µg/m3 - 1000
µg/m3
4 About ¾ Shift (4 to 7 hours)
25 to 30 hours per week
Use More Frequent Basis
Use More Frequent
Basis
OEL < 0.01 mg/m3 or < 10
ppm
OEB 3, OEL 10 µg/m3 - 100 µg/m3
5(over 7 hours)
Use More Frequent Basis
Use More Frequent Basis
Use More Frequent
Basis
OEB 4, OEL 1 µg/m3 - 10 µg/m3
6
OEB 4, OEL 0.01 µg/m3 - 1 µg/m3
7
OEB 5, OEL <
0.01 µg/m3
RankAirborne Potential
Engineering Control
Skin Exposure
Skin HazardExposure Potential
1 LowTotal enclosure validated by IH
monitoring
No skin hazard, temporary effects
2 MediumTotal enclosure NOT validated
3 High
4 Moderate (LEV)
validated
Probable skin irritants, materials may cause
dermatitis.
Short term skin exposure
5
6 Moderate not
Validated
7 Will cause skin irritation,
sensitizers, corrosives (acids, caustics, nickel).
Repeated-long Skin exposure
8 Non-fixed controls
movable LEV
9
10 No controlsMaterials toxic to skin
(ACGIH) Skin Skin exposure
certain
Final Risk Ranking CriteriaFinal Risk Ranking Criteria
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DescriptionFinal Risk Ranking
1-100Low Risk – process is well controlled and personal exposures are obviously unlikely to become significant – no further action required other than periodic review
1
100-200
Medium Risk - Further evaluation required by monitoring. 2
200-300
Potenial High risk - implement exposure controls, conduct exposure monitoring, control employee exposure using respiratory protection until engineering controls are implemented
3
> 300 Very High Risk -Implement exposure controls immediately 4
Quantitative Exposure Quantitative Exposure MonitoringMonitoring
Sampling pump
Sampling media
Sampling media
Calibrator
Important ConsiderationsImportant Considerations
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 identified contaminants
Are all personnel required to be sampled? – No, sample few from those having similar exposures
known as Similar Exposure Group (SEG) (e.g., charging personnel, Dispensing personnel)
Important ConsiderationsImportant Considerations
How many samples to be collected?How many samples to be collected? – 6 (minimum) for each contaminant in SEG6 (minimum) for each contaminant in SEG– Additional samples need to be collected for high potent Additional samples need to be collected for high potent
compounds or when variability in exposure results is compounds or when variability in exposure results is significantsignificant
Where to sample? Where to sample? – Areas/activities/operations with potential for exposures Areas/activities/operations with potential for exposures
defined during Industrial Hygiene Risk Assessment defined during Industrial Hygiene Risk Assessment When should the sampling be done? When should the sampling be done?
– Representative sampling in all shifts Representative sampling in all shifts – Different operators, different shiftsDifferent operators, different shifts
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Challenges in API Exposure Challenges in API Exposure MonitoringMonitoring
OELs are not available for large number of APIs and OELs are not available for large number of APIs and intermediatesintermediates
Validated methods are not available for large number of API Validated methods are not available for large number of API analysisanalysis
Potent compounds require meticulous handling of samples to Potent compounds require meticulous handling of samples to avoid cross contaminationavoid cross contamination
Limited accredited laboratories are available in USA for APIsLimited accredited laboratories are available in USA for APIs– Each API employee and swab sampling method validation Each API employee and swab sampling method validation
include sensitivity (LOQ lower than high API), desorption include sensitivity (LOQ lower than high API), desorption efficiency, number of spike samples and other critical efficiency, number of spike samples and other critical parametersparameters
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Addressing Challenges API Addressing Challenges API Exposure MonitoringExposure Monitoring
Use validated methods and accredited lab with API Use validated methods and accredited lab with API analysis experience especially for highly potent analysis experience especially for highly potent APIs as employee health depends on the resultsAPIs as employee health depends on the results
Follow rigorous validated sampling methods to Follow rigorous validated sampling methods to avoid sample contamination (disposal powder free avoid sample contamination (disposal powder free gloves, plastic Ziplock bag for every sample)gloves, plastic Ziplock bag for every sample)
Use surrogate monitoring if API validated methods Use surrogate monitoring if API validated methods are not available are not available
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Implement Established Exposure Controls following Control Banding Approach
Surrogate Monitoring Surrogate Monitoring Good Practices Guidelines - ISPEGood Practices Guidelines - ISPE
International Society for Pharmaceutical Engineering (ISPE)International Society for Pharmaceutical Engineering (ISPE) Standardized Measurement of Equipment Particulate Airborne Standardized Measurement of Equipment Particulate Airborne
Concentration (SMEPAC) CommitteeConcentration (SMEPAC) Committee ISPE Good Practice Guide: Assessing the Particulate ISPE Good Practice Guide: Assessing the Particulate
Containment Performance of Pharmaceutical EquipmentContainment Performance of Pharmaceutical Equipment Standardized method of measuring Standardized method of measuring
– Performance of containment systems against specific Performance of containment systems against specific challenge challenge
– Establish an agreed and valid method that can be used to Establish an agreed and valid method that can be used to meet the requirements of practitioners and supplier meet the requirements of practitioners and supplier organizationsorganizations
Example of Laminar Example of Laminar Flow Flow Booth Surrogate Booth Surrogate Monitoring at LFBMonitoring at LFB
API/Chemical Plants: Exposure Controls: API/Chemical Plants: Exposure Controls: Reactor ChargingReactor Charging
Potential for exposure during:Potential for exposure during:
– Manual charging of solids Manual charging of solids
– Handling of empty bags/super-sacks – Handling of empty bags/super-sacks – (major source of exposure) (major source of exposure)
Very effective: Charging booth
Effective: Reactor Charging with LEV
Empty bags collected in plastic bag from inside of glove box
API/Chemical Plants: Exposure Controls: Tanker API/Chemical Plants: Exposure Controls: Tanker Unloading Unloading
Nitrogen – pushing residual chemical
Secured connections with arrangement to rinse piping
before disconnecting
API/Chemical Plants: Exposure Controls: Tanker API/Chemical Plants: Exposure Controls: Tanker Unloading Barrel Transfer of ChemicalsUnloading Barrel Transfer of Chemicals
Potential for exposure during transfer with left in hose
A barrel decanting unit reduces leaks, spills and
exposures
Never to use air pressure
Dispensing and Weighing of Solids - Small Dispensing and Weighing of Solids - Small VolumeVolume
Not Effective: LFB are nt effective in reducing exposure below about 50 ug/m3
Dispense cell, isolator for high potent compounds
Solid Solid DischargingDischarging
Fully Contained Discharge Through Weigh Isolator
Ventilated Balance Safety Enclosure Ventilated Balance Safety Enclosure (VBSE)® – For High Potent (VBSE)® – For High Potent Compounds in laboratory Compounds in laboratory
Face velocityFace velocity
– Not too highNot too high
– Not too lowNot too low
– 50 fpm to 70 fpm50 fpm to 70 fpm HEPA filtrationHEPA filtration DuctedDucted Size of opening for weighing - Size of opening for weighing -
adjustableadjustable Air flow monitor and alarmAir flow monitor and alarm Can be customizedCan be customized
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Efficient LEV design Efficient LEV design
efficient LEV
Efficient LEV powder coating
Principles of General Ventilation SystemPrinciples of General Ventilation System
Maintain always negative air pressure in the contamination generating room with respect to rest of the building
Replace exhaust air by make-up air Do not install an exhaust fan near an intake opening
or window (e.g., contaminated air will be pulled back into building rather than exhausted)
Ensure contaminated air does not pass through breathing zone
Efficient Local Exhaust Ventilation (LEV)Efficient Local Exhaust Ventilation (LEV)
Inefficient ventilation system design is one of the most Inefficient ventilation system design is one of the most common walkthrough findingscommon walkthrough findings
The designing contractors are often not knowledgeable of The designing contractors are often not knowledgeable of design principlesdesign principles
Adequate capture efficiency has not been accomplished Adequate capture efficiency has not been accomplished despite money spent in energy consumptiondespite money spent in energy consumption
Knowing basic principles of ventilation system helps in (a) Knowing basic principles of ventilation system helps in (a) modifying existing ventilation systems and (b) in guiding modifying existing ventilation systems and (b) in guiding designing contractors towards efficient ventilation system designing contractors towards efficient ventilation system designdesign
In an efficient LEV, energy consumption is minimum and contaminant removal from operator’s breathing zone is maximum
HoodHood
Provide a flange or hood at the air inlet. 25% more energy is required to Provide a flange or hood at the air inlet. 25% more energy is required to capture contaminates from the front, when a flange or hood is not providedcapture contaminates from the front, when a flange or hood is not provided
Locate hood closed to contaminant generationLocate hood closed to contaminant generation
Air is drawn from back side also
Air drawn from front only
PreferredReduce distance if feasible
HoodHood
Tapered hood are more efficient than right angle hoodsTapered hood are more efficient than right angle hoods
Locate hood so that contaminants do not pass through the Locate hood so that contaminants do not pass through the breathing zone of an operatorbreathing zone of an operator
Enclose sides as much as feasible
DuctDuct
Straight duct is more efficient than a duct with many Straight duct is more efficient than a duct with many bends and elbows. Smaller duct length and smoother duct bends and elbows. Smaller duct length and smoother duct surface improves efficiencysurface improves efficiency
Abrupt change in duct diameter and branch entry reduce the efficiencyAbrupt change in duct diameter and branch entry reduce the efficiency
For most of LEVs, round duct is For most of LEVs, round duct is preferred over rectangular ductpreferred over rectangular duct
–Prevents accumulation of Prevents accumulation of solidssolids
–Makes less noiseMakes less noise
–DurableDurable
Examples of inefficient ducts
Application of LEVApplication of LEV
Solid charging
Empty bags are placed in this large bag
Solid filling in drums
Barrel decanting
Glove box for highly toxic compounds Portable extractor
Ventilation measurementsVentilation measurements
Velocity measurement on Velocity measurement on the face of the hood is best the face of the hood is best indicator of efficiency indicator of efficiency
Depending on the face Depending on the face area, measure air velocity area, measure air velocity at several points on the at several points on the face and determine face and determine average face velocityaverage face velocity
The face velocity to The face velocity to capture most of the capture most of the contaminants is 100 f/min contaminants is 100 f/min (0.5 m/sec)(0.5 m/sec)
Instruments used to measure face and duct velocities
11.1 Ventilation Log
Range of Capture VelocitiesRange of Capture Velocities
Condition of
Dispersion
Examples Capture Velocity (f/min)
Capture Velocity (m/sec)
Released with practically no velocity into quiet air
Evaporation from tanks; degreasing, etc.
100 0.5
Released at low velocity into moderately still air
Spray booths; intermittent container filling; low speed conveyer transfers; welding; plating; pickling
100-200 0.5-1
Active generation into zone of rapid air motion
Spray painting in shallow booths; barrel filling; conveyer loading; crushers
200-500 1-2.5
Range of Duct VelocitiesRange of Duct VelocitiesMaterial Example Duct Velocity
(f/min)Duct velocity
(m/sec)
Vapors, gases All vapors and gases 1000-1500 5-7.5
Spray painting Paint aerosols 1000-3000 5-15
Fumes Lead, welding 1500-2000 7.5-10
Dry dusts Fine rubber dust 2500-3500 12.5-17.5
General industrial dust
Clay dust, silica flour 3500-4000 17.5-20
Heavy dusts Sand blast dust 4000-4500 20-22.5
Heavy or moist dust
Moist cement dusts 4500 + 22.5+
Measuring Ventilation System Measuring Ventilation System Performance Performance
Manometer/Magnehelic gauge that continuously measures pressure drop across filter.
Assists in determining when to
change filter
HVAC System and Dust Collectors HVAC System and Dust Collectors
Directional flow in Room: Clean air flows top-down and Directional flow in Room: Clean air flows top-down and contaminated air flows bottom-side, away from operator contaminated air flows bottom-side, away from operator breathing zone breathing zone
Recirculation through HEPA filter is permitted for OEB1-2Recirculation through HEPA filter is permitted for OEB1-2 Recirculated air from OEB 3 and 4 API Rooms through dual Recirculated air from OEB 3 and 4 API Rooms through dual
HEPA HEPA OEB 4 compounds, “Sink” airlock to OEB 4 compounds, “Sink” airlock to provide negative provide negative
pressure gradients from both process area and common pressure gradients from both process area and common corridorcorridor
Bag-In/Bag-Out safe change system at exhaust grills to Bag-In/Bag-Out safe change system at exhaust grills to minimize duct contaminationminimize duct contamination
Zoning for High Potent Zoning for High Potent Compound HandlingCompound Handling RedRed
– Potentially contaminated areaPotentially contaminated area
– Not used for gowningNot used for gowning Yellow Yellow
– Less or no contaminationLess or no contamination
– De-gowning areaDe-gowning area Green ZoningGreen Zoning
– Clean non-contaminated areaClean non-contaminated area
– Paper work is donePaper work is done
– Gowning is doneGowning is done
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Importance of Swab Sampling Importance of Swab Sampling to determine degree of surface to determine degree of surface contaminationcontamination Determines degree of surface Determines degree of surface
contaminationcontamination Useful in determining if Green Useful in determining if Green
Zone is contaminated or not Zone is contaminated or not Contact Surfaces (door handles)Contact Surfaces (door handles) Acceptable Surface LimitsAcceptable Surface Limits Lessons learnedLessons learned
– Do no assume ethanol is good Do no assume ethanol is good decontaminating agents for all APIsdecontaminating agents for all APIs
– Do not assume cleaning method has Do not assume cleaning method has decontaminated areasdecontaminated areas
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Gowning –Degowning for High Gowning –Degowning for High Potent CompoundsPotent Compounds
Two pairs of disposableTwo pairs of disposable– GlovesGloves
– GownsGowns
– Shoe CoverShoe Cover Disposal of outer pair after work is done in Red Disposal of outer pair after work is done in Red
Zone just before entering Yellow ZoneZone just before entering Yellow Zone
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Challenges in Respiratory Challenges in Respiratory Protection Protection
Variable Assigned Protection Factor for Powered Variable Assigned Protection Factor for Powered Air Purifying RespiratorsAir Purifying Respirators– 50 to 100050 to 1000
Disposable Vs. Reusable hoodDisposable Vs. Reusable hood– Disposable preferred – cost is highDisposable preferred – cost is high
– Reusable – API contamination of PAPR hood Reusable – API contamination of PAPR hood identifiedidentified
Cleaning validationCleaning validation
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ChallengesChallenges
Limited Resources – IH professionalsLimited Resources – IH professionals QA in exposure assessment data QA in exposure assessment data Financial constrainsFinancial constrains
– Price ControlsPrice Controls– CompetitionCompetition
Manufacturing and outsourcing is increasing rapidly and Manufacturing and outsourcing is increasing rapidly and corporate EHS and other resources are decreasingcorporate EHS and other resources are decreasing
Trained corporate EHS professionals are unable to cop-up with Trained corporate EHS professionals are unable to cop-up with demand for assistancedemand for assistance
Distance, time differenceDistance, time difference Limited sensitivity of site professionals to potent compounds Limited sensitivity of site professionals to potent compounds
5959
Approaches: Corporate and Approaches: Corporate and Regional EHS Regional EHS
Commendable effortsCommendable efforts AuditsAudits Regional training programs and meetingsRegional training programs and meetings Strong contract manufacturing programsStrong contract manufacturing programs Emphasis on selection of credible, competent Emphasis on selection of credible, competent
and cost-effective EHS service providersand cost-effective EHS service providers Providing limited financial supportProviding limited financial support
6060
ApproachesApproaches
Education Programs in Industrial HygieneEducation Programs in Industrial Hygiene– University LevelUniversity Level– Pharma specific training modulesPharma specific training modules
Managing cost effectivelyManaging cost effectively– Cost effective consultingCost effective consulting– Exposure assessment strategy – three samples /HEG/API , Exposure assessment strategy – three samples /HEG/API ,
never 1 samplenever 1 sample– Analytical cost discountsAnalytical cost discounts– Return on investment (e.g., savings from loss of API)Return on investment (e.g., savings from loss of API)– Not loosing focus on QANot loosing focus on QA
6161
ApproachesApproaches Empowering region and manufacturing sites in EHSEmpowering region and manufacturing sites in EHS TrainingTraining
– At the foundation of sustainable EHS programAt the foundation of sustainable EHS program
– Site specific, anecdotal , workshop at the siteSite specific, anecdotal , workshop at the site
– One corporation spends closed to $1B in all trainingOne corporation spends closed to $1B in all training Qualitative Risk assessment and Control BandingQualitative Risk assessment and Control Banding
– If exposure is obvious, why do monitoring?If exposure is obvious, why do monitoring?
– Exposure control and then monitoringExposure control and then monitoring Sanofi approach of Industrial Hygiene Education Sanofi approach of Industrial Hygiene Education
AcademyAcademy
6262
Approaches – Supply ChainApproaches – Supply Chain
Corporate requirement for supplier to demonstrate exposure is Corporate requirement for supplier to demonstrate exposure is below OEL through surrogate monitoringbelow OEL through surrogate monitoring
Corporate and third party due diligence auditsCorporate and third party due diligence audits Local services provider to do hand-holding for some timeLocal services provider to do hand-holding for some time
– On site training on process safety and IHOn site training on process safety and IH
– Limited exposure assessmentLimited exposure assessment
– Periodic supervisionPeriodic supervision
– 7/24 support7/24 support Limit number of suppliers based on EHS performance Limit number of suppliers based on EHS performance Shutting down operation when risk is imminent- provide Shutting down operation when risk is imminent- provide
limited assistance in reducing risklimited assistance in reducing risk
6363
ConclusionsConclusions
Potential process safety and chemical exposure risks are high in Potential process safety and chemical exposure risks are high in pharmaceutical and chemical industries. The risks are manageablepharmaceutical and chemical industries. The risks are manageable– Understanding and communicating Understanding and communicating
– Empowering line managersEmpowering line managers
– Capitalizing on available resources Capitalizing on available resources
– Implementing feasible risk control measuresImplementing feasible risk control measures
Potential risk is even higher at supply manufacturing sites. The risk is Potential risk is even higher at supply manufacturing sites. The risk is manageablemanageable– Effective auditingEffective auditing
– Limited hand-holding Limited hand-holding
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