Ih presentation-singapore-confernce-mm

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

©International Safety Systems, Inc. ©International Safety Systems, Inc. www.issehs.comwww.issehs.com

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


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


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


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


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


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


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.


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.


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


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


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


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.

www.issehs.comwww.issehs.com

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


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


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

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


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


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


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


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


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


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


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


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


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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