Risk-Based Exposure Assessment and Control Guideline

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 E
xecutive Summary

The “Risk-Based Exposure Assessment and Control” guideline has been developed to assist
Environmental Health & Safety and Engineering professionals in the understanding of the

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process to be followed when determining potential inhalation/dermal exposure and selection of
exposure controls which may be necessary to manage the risk identified.

The process begins with a qualitative risk assessment that includes the collection and
organization of basic information needed to characterize occupational exposure risk associated
with the workplace, workforce, and chemical agents of the process being evaluated. This
information is used to understand the tasks being performed, raw materials and chemicals being
used, processes being run, and the controls in place so the potential inhalation/dermal exposure
risk ranking can be assigned.

The outcome of the qualitative risk assessment will determine whether or not a quantitative risk
assessment, requiring the collection of industrial hygiene personal monitoring data, is needed. If
the qualitative risk assessment is given a low ranking and the process does not require the use
of respiratory protection, the risk assessment and conclusion are documented and filed.
However, if the qualitative risk assessment ranking is high or inconclusive, or if respiratory
protection is required, a quantitative risk assessment must be performed.

The quantitative risk assessment, which includes that collection of industrial hygiene personal
monitoring data, is used to determine whether the risk posed by the exposure is acceptable.
Several samples must be collected (minimum of three) following validated sampling and
analytical methods. The sample analysis data results must be analyzed using Bayesian or
Descriptive statistics and compared to the Occupational Exposure Limit (OEL). Excursions
above the OEL require the use of exposure controls to manage the risk.

The primary objective of selecting the exposure control option is to reduce the exposure risk of
the workers below the Occupational Exposure Limit. There are numerous exposure control
options in which to choose. The decision may be to control the airborne contaminants at the
source, control the airborne contaminants within the room where the process is located, or rely
on personal protective equipment. Whatever control method is selected, industrial hygiene
personal monitoring data must be collected to confirm the exposure risk is below the OEL.

This guideline can be applied to all chemical risk assessments and exposure control and is
applicable to all Johnson & Johnson businesses worldwide. This guideline replaces the former
“Controlling Occupational Exposure to Active Pharmaceutical Ingredients (API) and Isolated
Process Intermediates (IPI)” standard operating procedure and guideline, which focused
primarily on active pharmaceutical ingredients.

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 Abbreviations
ACGIH - American Conference of Governmental Industrial Hygienists
ACPH - Air Changes per Hour
AHU – Air Handling Unit
API - Active Pharmaceutical Ingredients
BOD – Basis of Design
BSC - Biological Safety Cabinet
CAS - Chemical Abstracts Service
cGMP – Good Manufacturing Practice
CIP - Cleaning in Place
CSG - Containment Solutions Guide
DEA - Drug Enforcement Agency
DEL – Design Exposure Limit
EHS – Environmental, Health and Safety
FPM – Feet per Minute
HAZOP – Hazard and Operability
HHR – Health Hazard Rating
HEPA – High Efficiency Particulate Air
HVAC – Heating Ventilation and Air Conditioning
IBC - Intermediate Bulk Containers
IH – Industrial Hygiene
IPI - Isolated Process Intermediates
J&J - Johnson & Johnson
Kst Value – Dust Explosion Class defined as the rate of the pressure rise in bar meter/second
LAF - Laminar Air Flow
LEV – Local Exhaust Ventilation
μm - Microns
g/M3 - Micrograms per Cubic Meter
MOC - Management of Change
MIE – Minimum Ignition Energy
OEL – Occupational Exposure Limit
PA – Pascal
PAPR – Powered Air Purifying Respirator
PAT - Proficiency Analytical Testing
PM – Preventative Maintenance
PPE – Personal Protective Equipment
PPM - Parts Per Million
QA – Quality Assurance
RBEAP - Risk-Based Exposure Assessment Process
RTP - Rapid Transfer Port
SBV - Split Butterfly Valve
SEG - Similar Exposure Group
SME – Subject Matter Expert
SOP – Standard Operating Procedure
TLV – Threshold Limit Value
URS - User Requirement Specification
VBE - Vented Balance Enclosure
WG – Water Gauge
WIP - Wetting or Washing in Place (also sports radio station in Philadelphia)
WWEHS – Worldwide Environmental, Health and Safety

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Table of Contents

Executive Summary.................................................................................................. 2

Introduction.................................................................................................................... 6

1.1 Purpose of the Document....................................................................................... 6

1.2 Team Approach.......................................................................................................... 6

1.3 New versus Existing Processes................................................................................. 6

1.4 How to Use the Guideline........................................................................................... 6

1.5 Need for Documentation Trail.................................................................................... 6

1.6 Effort Scaled to Risk................................................................................................... 7

1.7 The Risk Assessment Process Diagram.................................................................... 7

1.8 Starting the Process................................................................................................... 7

1.9 Qualitative Risk Assessment...................................................................................... 7

1.10 Quantitative Risk Assessment.................................................................................. 7

1.11 Exposure Control Project......................................................................................... 8

1.12 Post Control Quantitative Risk Assessment............................................................. 8

2.0 Conducting a Risk-Based Exposure Assessment............................................... 10

2.1 Existing or New?...................................................................................................... 10

2.2 Qualitative Risk Assessment.................................................................................... 10

2.2.1 Data Gathering...................................................................................................... 10

2.2.2 Basic Information.................................................................................................. 11

2.2.3 Product.................................................................................................................. 11

2.2.4 Facility................................................................................................................... 12

2.2.5 Process................................................................................................................. 14

2.2.6 Manufacturing Processes...................................................................................... 16

2.2.7 Pre and Post Steps in the Process……………………………………………………19

2.2.8 Cleaning................................................................................................................ 19

2.2.9 Assembly & Disassembly of the equipment........................................................ 20

2.2.10 Maintenance of Support Utilities.......................................................................... 20

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2.2.11 Characterizing the Potential Source of Exposures............................................. 20

2.3 Quantitative Risk Assessment.................................................................................. 22

2.3.1 Unacceptable Exposure Risk............................................................................... 22

2.3.2 Quantitative Risk Assessment Outline................................................................. 22

2.3.3 Statistical Analysis................................................................................................ 23

2.4 Tools....................................................................................................................... 23

2.4.1 Risk-Based Exposure Assessment Process (RBEAP).......................................... 23

2.4.2 Industrial Hygiene Risk Assessment Forms.......................................................... 24

2.5 Conclusion of Quantitative Risk Assessment........................................................... 24

3.0 Engineering & Containment Solutions................................................................ 25

3.1 Exposure Control..................................................................................................... 25

3.1.1 Selecting Exposure Control Options..................................................................... 25

3.1.2 Containment Boundary.......................................................................................... 27

3.1.3 Hierarchy of Controls............................................................................................ 27

3.1.4 Personal Protective Equipment & Personal Hygiene............................................. 28

3.1.5 Administrative Controls........................................................................................ 29

3.2 Engineering Controls................................................................................................ 31

3.2.1 Closed Processes................................................................................................ 31

3.2.2 Downflow Booth Considerations............................................................................ 34

3.3 Facility..................................................................................................................... 41

3.3.1 Laboratory Ventilation Systems Summary............................................................. 41

3.3.2 Waste Water......................................................................................................... 42

3.3.3 Room Layout........................................................................................................ 42

3.3.4 Room Envelope..................................................................................................... 45

3.3.5 HVAC.................................................................................................................... 46

4.0 Forms..................................................................................................................... 50

4.1 Qualitative Risk Assessment form........................................................................... 50

4.2 Risk-Based Exposure Assessment (RBEAP) form................................................... 51

4.3 Containment Solution Guide template...................................................................... 52

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1 Introduction

1.1 Purpose of the Guideline

The Risk-Based Exposure Assessment and Control guideline provides a process by which the
potential exposure risk is assessed appropriately (for efficacy and cost) to ensure the controls
selected manages the risk. This document is not meant to address cGMP requirements.

The document is a guideline on how to perform a risk-based safety assessment, how to

determine whether the exposure risk is managed appropriately, and which options are available
when selecting exposure controls. Assessments are performed on a case-by-case basis where
the greatest exposure risk is given the highest priority.

1.2 Team Approach

To be effective this guideline requires the cooperation of all the stakeholders, including EHS,
Engineering, Maintenance, Operations, Quality, etc. If applicable, the product formulators,
technical transfer specialists, and other process knowledgeable personnel should be involved so
that processes chosen can address the manufacturing considerations and reduce exposure risk.

1.3 New Versus Existing Processes

The risk evaluation can range from assessing an existing process to determine if the exposure
risk will meet the OEL, to a new facility and process where nothing exists. Therefore, the
assessment has to be based on similar processes and professional judgment. When addressing
an external manufacturer attempts should be made to obtain qualitative risk assessments along
with any historical industrial hygiene data if available, otherwise conducting a risk evaluation
from the start may be required.

1.4 How to Use the Guideline

The guideline follows the natural progression of a Risk-Based Exposure Assessment & Control
project. This document is divided into 3 sections.

Section 1 is an overview designed for the first time reader, management and to get an overview
of the process.

Section 2 provides a risk-based exposure assessment, and is intended for those embarking on
a project to get a better understanding of the process and to highlight key factors to review. This
exercise is conducted using qualitative and quantitative risk assessments.

Section 3 provides a list of exposure control options that can be selected based on the outcome
of the quantitative risk assessment completed in section 2.

1.5 Need for a Documentation Trail

It is essential that all the steps be documented so that the decisions can be understood and
appreciated by others both now and in the future. This will ensure that the time and effort
expended are not lost and that the rationale for the decisions made is not forgotten.

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1.6 Effort Scaled to Risk
Effort is to be scaled to the risk. The magnitude of the risk assessment and associated
documentation should be commensurate with the scale of the risk. The risk assessments
should identify project line items that are not essential to a low risk (final packaging) project to
be deleted, while maintaining a format for larger risk (manufacturing process) projects. The
team should determine the scale of the risk involved in the project.

1.7 The Risk Assessment Process Diagram

The risk assessment process diagram is intended to provide a navigation map to the risk
assessment process and at its conclusion show that the industrial hygiene data collected are
below the OEL of the compound being reviewed. The diagram also illustrates that a risk
management document has been produced that records the steps, data and conclusions. Once
a process has shown that it statistically controls to within the OEL there is no need for re-
evaluation unless there is a change in process or an excursion event that requires investigation.
If respiratory protection is relied upon to manage the exposure risk, the quantitative industrial
hygiene data must statistically support the respirator assigned protection factor that is chosen.

1.8 Starting the Process

For existing processes the EHS professional can initiate and execute the assessment. However,
for new processes it is necessary to set up a team of stakeholders so that all aspects of the
proposed process can be assessed. Additionally, for technology transfers or external
manufacturing processes, a team approach is preferred as it lends itself to a clear
understanding of the risk assessment scope and the exposure risk management conclusion.

1.9 Qualitative Risk Assessment

At this point a qualitative risk assessment analysis is undertaken. This process has two distinct
phases; gathering information and evaluating that information. Data on such items as the
products and chemicals used are gathered to understand their hazards. In addition, a full
description of the processes and equipment are gathered so that the exposure risks inherent in
the process, its interventions, transfers, and cleaning can be understood. Obviously for a new
process the information may be preliminary in nature. It is also important not to rush to solutions
before all the relevant details have been gathered. It is best to design a practical solution and
then undertake the assessment rather than incorporating a wide range of engineering controls
that may not be necessary and/or could add considerable cost.

This is fully discussed in the qualitative risk assessment chapters in Section 2.

For new processes where historical IH data have not been collected, a qualitative assessment
can be made of the potential exposure risk.

1.10 Quantitative Risk Assessment

If the risk is not low, in other words the system will not perform within the OEL, then a
quantitative risk assessment needs to be performed. Once the IH data shows the results are
statistically within the OEL, the inhalation exposure risk is controlled. At this point, the risk
assessment process is considered complete and the risk management document is prepared,
circulated and archived. If respiratory protection is relied upon to manage the exposure risk, the
quantitative industrial hygiene data must statistically support the respirator assigned protection
factor that is chosen.

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1.11 Exposure Control Project
Upon completion of the qualitative and quantitative risk assessments a decision must be made
regarding the acceptability of the inhalation exposure risk-based on the IH data review. If the
statistical OEL is exceeded, historical IH data from similar processes indicate a high exposure
risk, or the qualitative risk assessment indicates the need for exposure control, an exposure
control project may be warranted. The project may be initiated by manufacturing management,
site engineering, EHS, or other impacted parties, however all interested departments should be
invited to participate on the project team.

The “exposure control” project key elements include:

1.11.1 Define the Project Scope. This is basically a summary of the unit operations, tasks and
activities that require exposure controls.
1.11.2 Assemble the Project Team. All stakeholders that can offer value are assembled: EHS,
Operations, Engineering, Maintenance, Quality and Regulatory.
1.11.3 Agreement of the Scope. The team reviews the project scope and amends it as
necessary.
1.11.4 Tools. The team uses the various tools described in Section 3 to select the appropriate
controls.
1.11.5 Implementation
 Select control measures
 Develop User Requirement Specifications
 Determine Cost of the control measures
 Obtain project approvals
 Contract with vendors
 Installation and commissioning
 Create operational SOP
 Qualify
 Hand over the controls to Operations (until verified by quantitative data, PPE shall be
used).

1.12 Post Control Quantitative Risk Assessment

A Quantitative risk assessment is conducted to demonstrate conformance with the statistical
OEL.

If the results are below the limit then the risk assessment and exposure control process is used
to record, document the results. If the results do not show conformance to the statistical OEL,
then additional controls to modify the existing controls are required in an effort to reduce
exposures below the OEL and/or the required level of respiratory protection needs to be
assigned and verified.

The process is shown diagrammatically below.

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 2 Conducting a Risk-Based Exposure Assessment
The qualitative risk-based exposure assessment is divided into the logical sequence of actions
required to complete the evaluation as shown in the preceding diagram. Each decision block
within the diagram is explained in detail below. Upon completion of the qualitative risk-based
exposure assessment, a decision can be made to determine if the potential inhalation exposure
risk is considered low and the risk for dermal absorption is under control. If a decision cannot
be made due to uncertainty or if a respirator is required for the task that was evaluated, a
quantitative risk-based exposure assessment is required.

2.1 Existing or New?

One basic question that needs to be asked prior to the review of a new process or chemical
introduction is whether the process is being installed into an existing or new facility. The options
afforded can be much more limited when introducing a new process or compound into an
existing facility or isolated piece of process equipment.

In many instances, decisions for new equipment must be made in the absence of industrial
hygiene data since the set-up is not yet operational. In this case the IH data from similar
equipment, e.g. Containment Solution Guides, from the same site or a different J&J site, may be
considered.

Controls offered in the Containment Solution section of this document can be selected based on
the OEL or Design Exposure Limit (DEL) to ensure the exposure risk will be properly managed.

The EHS professional needs to understand what controls are currently in place for the unit
operation as well as the room where the unit operation is located.

If the project involves a new facility, working with the project engineer in the early stages (Basis
of Design A) is required to ensure proper controls are included to manage the exposure risk
potential.

2.2 Qualitative Risk Assessment

A qualitative risk assessment is an evaluation, based on the integration of science, information
and judgment, providing a mechanism for identifying and prioritizing potential exposure risk and
safety considerations (e.g. Minimum Ignition Energy). The qualitative risk assessment includes
an evaluation of potential exposures via the various routes including inhalation, ingestion,
dermal contact, and injection. The predominant exposure determinants and events (such as
frequency, magnitude, and variability of exposure and tasks; route of exposure; and the
adequacy and potential for failure of engineering and work practice controls) should be
considered and documented as a part of the qualitative risk assessment.

It is important that the risk assessment information is well documented (see attached forms) and
that the process is conducted in a consistent manner. By doing so, the documentation can be
easily interpreted by other EHS professionals within the Operating Company as well as stand
the test of time. The recommended information to be collected is listed below.

2.2.1Data Gathering
It is essential that a clear definition of the scope is achieved and that the process is conducted
to avoid duplication. Much of the basic data are used in various ways and duplication of effort
has to be avoided if the process is to be efficient. It is also important to separate the data

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gathering and data evaluation stages so that evaluation is based on a full understanding of the
factors.

2.2.2Basic Information
This should include all the relevant information to describe when, where, and by whom the
assessment (analysis, evaluation, gap statement) or exposure control was conducted. Items to
be included:
 Date & Time
 Location (Bldg., Floor, Room)
 Unit Operation (Equipment)
 Assessor’s Name
 Assessor’s Contact Information (Phone & Email)

2.2.3 Product

2.2.3.1 Products Handled

A listing of all chemicals included in the risk assessment of the unit operation must be
documented including: hazardous solids, semi-solids, and liquids including: raw materials, APIs,
Active Ingredients, Isolated Process Intermediates, excipients, solvents, reagents, etc.

2.2.3.2 Product Information The chemical information should be provided, when applicable,
for each product handled. It is necessary to evaluate the physical and chemical
properties of the chemicals to be able to identify and prioritize potential exposure risks
and process safety risks. Many times a product Safety Data Sheet may provide valuable
chemical product information being sought. This includes:

 Chemical Name & Synonyms Different names are used for the same chemical, but
each chemical has a unique CAS number. A CAS (Chemical Abstracts Service)
Registry Number is a unique identifier that tells you, for example, that acetone and
dimethyl ketone is actually the same substance.

 Applicable OEL or TLV in Micrograms per Cubic Meter (g/M3) or Parts Per
Million (ppm) The OEL, identified for Active Pharmaceutical Ingredients and the TLV,
developed for other chemicals; give a classification with regard to toxicity. The monthly
updated J&J Global Occupational Toxicology HHR/OEL list should be consulted to find
the OEL, and/or HHR. The annually updated TLV and BEI booklet of the American
Conference of Governmental Industrial Hygienists (ACGIH) and local regulation should
be used to find the TLV value. List any particular characteristic, route of exposure or
warning properties.

 Batch Size (mass) in Kilograms The amount of the API used will vary depending on
the production activity (laboratory activities, pharmaceutical or chemical production).
The batch size range should be stated with the volume.

 % of Active Ingredient e.g. % API in the Batch The percentage of active ingredient in
the mixture that is handled can vary. In a pharmaceutical production environment the
API can be present for only a small percentage (for example 0.05% during compression
of tablets) where as in a chemical production environment the API is usually 100%
pure, not mixed. Many times the % of active is greatly reduced in the downstream
processing.

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  Solid, Liquid, Gel, or Cream Matrix The risk the API becomes an inhalation challenge
is much lower when the API is a liquid or mixed in a gel or cream. However, dermal
risks may increase.

 Particle Size Particle size (microns) is a critical parameter for the determination of the
exposure risk to dust. Depending on the size, particles are divided into an inhalable
(50% cut point of 100μm), thoracic (50% cut point of 10 μm) or respirable fraction (50%
cut point of 4 μm). This will determine where particles will settle down in the respiratory
system: the head airways region, the trachobronchial region or gas exchange region.

 Dustiness Relative to Sugar Versus Flour Dustiness is the most important property
for the determination of the exposure risk to dust. This determines how easily and for
how long the dust will be airborne. Large dust particles tend to fall out of the air faster
than small ones. This is due to their relative size and density as compared to air. Small
dust particles flow with the air and can remain airborne for a long period increasing the
chance of being inhaled. Dustiness can vary from high (baby powder, flour) to low
(sugar, sand).

 Vapor Pressure For chemical liquids, vapor pressure is the most important property
that will determine how easily vapors will be generated and become airborne when
handling the compound. Together with the vapor pressure, the process temperature
should be evaluated because vapor pressure and boiling point have an intimate
relationship.

 Process Safety Information In addition to the evaluation of the properties of the

chemical that can impact the exposure risk, the properties that influence process safety
should be considered in detail prior to design. MIE, Kst, Burning Class, Flash Point to
indicate Flammability or Combustibility – Based on these properties, with focus on
reactivity (stability risk) and flammability, proper selection of explosion-proof equipment
and area classification is performed and other intrinsic safety precautions should be
installed.

2.2.4 Facility
Describe the facility, use diagrams and photographs and describe the surface finishes.
Describe the HVAC system using diagrams and indicating pressure regimen, zones for air
handling units (AHUs), air changes per hour and whether the room air is once through (100%
exhausted to the outdoors) or partially recirculated, etc.

Indicate facility issues that need addressing. (e.g. absence of airlocks, finishes, etc.)
 What is the philosophy for the facility design?
 What is the intended use of the facility?
 What design concepts were used to meet occupational health and safety
requirements?
 Degowning space including respirator and/or Powered Air Purifying Respirator
(PAPR) storage & cleaning?

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2.2.4.1 Facility Block Plans
The facility block diagram should be legible and cover the area under discussion including the
architectural arrangements of the rooms, their purpose and identification. Sections are useful in
multi-story designs to show plant rooms and mezzanines etc.

2.2.4.2 Photographs of the facility

In many cases a drawing and photographs are better than a thousand words. A section
illustrating key features and key concerns with brief notation is an excellent tool to convey
information.

Drawings and diagrams are also helpful in understanding how a facility works. The types of
diagrams that best convey this information are listed below.

 Material & Product Flow Diagram This diagram traces the flow path of materials and
product to the point of use. It is useful in evaluating plausible pathways for any fugitive
emission from critical areas. This diagram also helps pinpoint potential mechanical transfer
routes, decontamination locations as well as waste flows. Decontamination points should be
shown and the means of conveyance stated such as intermediate bulk containers (IBC’s).

 Personnel Flow Diagram This diagram shows the “clean” and “dirty” flow of personnel into
and out of the facility. It identifies the gown and de-gown points. A brief narrative should
describe the gown/de-gown protocols.

 Clean and Dirty Equipment Flow Diagram This diagram tracks the route for clean and dirty
equipment as well as personal protective equipment (PPE) and identifies where the
equipment/PPE is decontaminated and where it is cleaned.

 HVAC Zone Diagram This diagram indicates the air handling unit (AHU) zones which
should provide a clear picture of which AHU serves which room, group of rooms or general
area (zone). The HVAC zone diagram should also indicate which system is re-circulation or
once through as well as room air changes per hour (ACPH).

 HVAC Airflow Diagrams

This diagram should provide a clear understanding of the locations and efficiencies of the
protective filters in the air distribution system. Other useful information shown on an airflow
diagram includes: AHU components, duct in-line devices, airflow rates and the existence of
any dust extraction system (dust collector).

 Finishes and Surfaces The finishes and features are described in outline with particular
reference to cleanability and penetration issues.

 HVAC Pressure Cascade This diagram shows the pressure cascade within the facility.
Pressure differentials should also be shown.

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2.2.5Process
Describe the processes and procedure for each activity with particular attention to the following:

2.2.5.1 QA Incoming Sampling

 Where are the samples obtained?
 Are exposures controlled when the samples are collected?
 Is the sample container a potential source of exposure risk?

2.2.5.2 In Process Sampling

 Methods used to perform sampling & analysis required.
 Methods used to control the potential exposure risk.

2.2.5.3 Charging/Discharging
 Type of charge? Bags, bins, drums, or totes, etc.
 Height of free fall? (i.e. the distance from the source to the target),
 How Performed? Scoop and dump. Flexible materials used, etc.
 Nature of charge, dustiness?
 The static charge of the particles?
 Total batch size?
 % of active pharmaceutical ingredient in the formulation?
 Procedure and work practices, etc.?
 Airborne vapors?
 Safety features present?
 Interventions

2.2.5.4 Blending/Mixing
 The severity of dust exposure?
 Wet or dry blend?
 Dustiness of material?
 Employee work practices?
 Airborne vapors?
 Interventions

2.2.5.5 Grinding, Sieving and Screening of Dry Powders

 The severity of dust exposure?
 Dustiness of material?
 Physical/chemical properties of the compounds?
 Employee work practices?
 Interventions

2.2.5.6 Vacuum Drying

 The severity of dust exposure?
 Dustiness of material?
 Physical/chemical properties of the compounds?
 Procedure and work practices, etc?
 Interventions

2.2.5.7 Spraying
 Rate of the spray?
 The size of the nozzle?
 The pattern of the spray?

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  The distance between the target and the nozzle?
 The properties of the chemicals used?
 Procedure and work practices, etc?

2.2.5.8 Weighing
 Type of container? Bags, Bins, drums, or totes, etc.
 How Performed? Scoop and Dump. Flexible materials used?
 Dustiness?
 The static charge of the particles?
 Total batch size?
 Procedure and work practices, etc.?
 Airborne vapors?
 Safety features present?

2.2.5.9 Dipping
 Properties of the chemical(s)? (e.g. vapor pressure)
 The operating temperature of the container?
 Entry and exit rate of the products being dipped?
 Procedure and work practices, etc?

2.2.5.10 Compression
 Charging method?
 Current controls if any?
 Discharge dustiness?
 Nature of de-duster and metal checker?
 Tablet testing describe
 Total batch size?
 Procedure and work practices?, etc:
 Interventions

2.2.5.11 Capsule Filling

 Charging method?
 Current controls if any?
 Dustiness?
 Nature of polisher and metal checker?
 Capsule testing describe
 Total batch size?
 Procedure and work practices?, etc:
 Interventions

2.2.5.12 Polishing & Buffing

 Dustiness?
 RPM of polish or buffing wheel?
 Direction of particle discharge?
 Particle capture mechanism (e.g. Local Exhaust Ventilation)?

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2.2.5.13 Procedure and Work Practices
 Are they contributing to exposure?
 Are best practices used?

2.2.5.14 Pre and Post Steps in the Process

 Where are chemicals coming from prior to the process, i.e. upstream equipment or
tasks?
o Is the upstream process an open (e.g. tray dryers) or closed operation?
o Describe any decontamination of the container?
 Where are the chemicals going after being processed, i.e. downstream equipment or
tasks?
o Are they contributing to exposure?

2.2.5.15 Product Packaging

 Describe with reference to exposure risk.

2.2.5.16 Cleaning
 Describe the current cleaning process with reference to exposure risk.

2.2.5.17 Interventions
Record all the interventions that occur:
 For set up
 For re-calibration
 For sampling or end point determination
 For recovery
 For cleaning

2.2.5.18 Qualitative Risk Evaluation

Up until this point, data have been gathered on what exists. Now with all the data gathered, it is
necessary to make an evaluation and assessment of the data.

The following reviews of the manufacturing process examples (not all inclusive) are intended to
aid and prompt the qualitative risk evaluation process. In undertaking the evaluation the data
collected are carefully reviewed to identify where emissions occur and if those emissions
contribute to exposure risk that may require exposure controls.

2.2.6 Manufacturing Processes

Equipment used to manipulate the product must also be understood when identifying the
potential exposure pathways. The equipment involved in the process step should be evaluated
to determine if it contributes to or reduces the inhalation exposure risk.

2.2.6.1 In-Process Sampling

Samples are required for QA use or end point determination at many stages in the process and
the extraction of samples represents an exposure risk. It is essential to describe every sampling
activity with details of how it is done, when it is done, the tools and methods used, the size,
number and the volume of the tools and containers used.

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2.2.6.2 Weighing
Weighing of dry chemical powders will generate airborne dust. The severity of the dust
exposure potential depends on the static charge of the particles, the quantity of material to be
weighed, the % active in the formulation, dustiness of material, size of source container,
frequency of weighing activities, employee work practices, etc. Weighing/preparation of liquid
chemicals (solvents, acids, bases) may generate airborne vapors depending on the vapor
pressure of chemicals, the temperature of the liquid, employee work practices, etc. The
exposure risk should be evaluated.

2.2.6.3 Transfer
Transfer takes place from one process to another. The current or proposed transfer system
should be described and any data on performance recorded. Not only the transfer device but
also the transfer container has to be described. A picture is often worth a thousand words. Can
the transfer be eliminated or improved?

2.2.6.4 Charging/Discharging
Charging bags, drums, or totes of dry powder will generate airborne dust. The severity of dust
exposure potential depends on the height of the freefall of dust (i.e. the distance from the source
to the target), the static charge of the particles, the total batch size, the % of active
pharmaceutical ingredient in the formulation, employee work practices, etc. Charging liquid
chemicals (solvents, acids, bases) may generate airborne vapors depending on the vapor
pressure of the chemical, the temperature of the liquid in the vessel, whether a nitrogen blanket
is present or not, etc.

2.2.6.5 Blending/Mixing
Blending/mixing of dry powders and excipients during the formulation process will generate
airborne dust. The severity of dust exposure potential depends on the static charge of the
particles, the % of active in the formulation, whether it is a wet or dry blend, dustiness of
material, the physical/chemical properties of the powders, employee work practices, etc.
Blending/mixing liquid chemicals (solvents, acids, bases) may generate airborne vapors
depending on the vapor pressure of the chemicals, the temperature of the liquid in the vessel,
whether a nitrogen blanket is present or not, employee work practices, etc.

2.2.6.6 Grinding, Sieving and Screening of Dry Powders

Can generate airborne dust. The severity of dust exposure potential depends on the static
charge of the particles, the % active in the formulation, batch size, dustiness of material,
physical/chemical properties of the powders, employee work practices, etc.

2.2.6.7 Vacuum Drying

Vacuum drying of powders/cakes will generate airborne dust. The severity of the dust exposure
potential depends on the dustiness of the material, the static charge of the particles, whether the
transfer in and out of the drying oven is an open or closed process, the % active in the
formulation, employee work practices, etc.

2.2.6.8 Spraying
Spraying chemicals can be controlled, however any open system has the chance of leading to
an airborne exposure potential. An example of a common spraying operation is a paint booth.
Although built to capture the paint particles that do not hit the target object, paint vapors require
the use of PPE. When a spray operation is being assessed, we need to understand the rate of
the spray, the size of the nozzle, the pattern of the spray, the distance between the target and
the nozzle, and the properties of the chemicals. Spray operations can be controlled with local

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exhaust ventilation. However, all aspects of the operation must be understood to select the
appropriate controls.

2.2.6.9 Dipping
This task is defined as the process of moving a product into a container (tank, vessel, bath, etc.)
that contains a chemical. Plating and cleaning operations in a maintenance shop is a good
example. We need to understand the properties of the chemical(s) (e.g. vapor pressure), the
operating temperature of the container, and the entry and exit rate of the products being dipped.
A higher temperature and/or a higher “drag-out” rate will increase the likelihood of airborne
exposure. Exhaust ventilation can be effective. However, the larger the container the more
exhaust air is required to ensure capture velocities are effective.

2.2.6.10 Compression (Tablet Press) It is the means by which powders are pressed into a
tablet. The age of the unit is a critical factor since newer units are more contained.
There are four main areas of focus:
 Charging – Adding materials to a compression tool can be done using gravity feed,
usually from a tote, via a closed system directly into the unit. Other operations may
involve open handling where operators scoop powder directly into the compression
hopper. The more open the operation, the more potential for airborne exposure of the
powder.
 Operation - These operations are very dusty in nature and can be equipped with
exhaust ventilation to minimize the dust accumulation in the tablet press cabinet. For
products with higher hazard ratings these units can also be equipped with a glove-box
type cabinet with alpha-beta connections and wash-in-place*. Another exposure
potential related to this equipment is maintenance work, including compression plate
removal and cleaning.
 Discharge – As the tablets leave the press an area of concern is the containment
controls on receiving vessels, de-duster, and metal detector. The more open the
operation, the more potential for airborne exposure of the powder.
 In-Process Control Samples - May be destructive or non destructive and a potential
source of airborne exposure.
* Bear in mind that most interventions for adjustment do not involve washing since the
adjustment will be made during a run to correct a critical parameter.

2.2.6.11 Capsule Filling

Capsule filling of dry powders may generate airborne dust in the absence of engineering
controls. The severity of the dust exposure potential depends on a manual versus automated
system, the static charge of the particles, the % active in the formulation, dustiness of material,
batch size, employee work practices, physical/chemical properties of the powder, etc.

2.2.6.12 Polishing & Buffing

Is the process of creating a smooth and shiny surface using a rubbing or chemical action,
leaving a surface with significant specular reflection and minimal diffuse reflection. Polishing and
buffing, when done dry, can generate dust that often leads to employee exposures. Often times
polishing is done wet, which can significantly reduce airborne dust generation. For dry
operations of polishing and buffing, local exhaust ventilation is used to capture the dust at the
point of generation.

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2.2.7 Pre and Post Steps in the Process
Tasks performed during disassembly and cleaning of the equipment may create a higher
exposure risk than normal production activities and exposure controls designed to meet the
challenges. While it is important to consider the operation and interventions required in the
process, it is just as important to understand the impact of maintenance, cleaning and other
tasks. For existing processes these activities can be reviewed by observation. For new projects,
it is essential to perform an assessment of these activities.

2.2.7.1 Corrective Action and Adjustment In many cases, intervention is required for
adjustment and correction during the process. It is imperative to solicit feedback from
the operators on interventions they have experienced to understand the exposures that
may result. In the case of a new process it is essential to fully debrief the supplier on
interventions and question any assertion that no intervention is required.

2.2.7.2 Upset Normally not reviewed under a normal risk assessment since this is an
unplanned event. A HAZOP or similar analysis should be undertaken to identify any
upsets that may occur and to describe mitigation in place to minimize the effects if
upsets occur.

2.2.7.3 Heel Recovery Most process equipment fails to achieve 100% discharge of the
product. In many cases the value of the “heel” (or remaining product) is such that it has
to be recovered. All interventions for heel recovery and the exposure created by such
intervention should be evaluated.

2.2.7.4 Raw Material Containers Another opportunity includes working with customers to alter
packaging to suit the needs of equipment.

If the upstream process is the responsibility of an external partner (e.g. raw material
supplier, external manufacturer), can we make agreements on the packaging material to
be used to increase containment?

Does the upstream process determine the packaging or are we free to choose an
optimum package for both processes?

Raw material containers should be suitable for charging and discharging at the right
containment level, but also be secure and save transportation. Cleanability of the
material is to be considered.

2.2.8 Cleaning
The key issue with cleaning from an exposure point of view is to understand the potential
contamination of the equipment to be cleaned. Also whether the “dirty” equipment needs to be
moved to another area for cleaning. Opening up the equipment to allow partial disassembly may
also be a contributing factor to exposure risk.

When evaluating the equipment to be cleaned, consider the impact of the following items being
used in the cleaning process:

 Detergents and/or solvents used i.e. solvent vapor exposure

 Cleaning in Place (CIP). In this case the equipment is completely cleaned in place
prior to disassembly (if necessary). The products handled inside the equipment are
completely removed so containment is assured.

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  Wetting or Washing in Place (WIP) or contained disassembly (e.g. split butterfly
valve). In this case the equipment is not cleaned, so this needs to be done in a central
cleaning facility. To avoid exposure during transportation the dirty equipment should
be completely enclosed or wetted prior to disassembly.

2.2.9 Assembly & Disassembly of the Equipment

As described in the previous paragraph, it is important to have clean or closed equipment when
starting to disassemble the installation. The risk assessment needs to account for the
transportation of the equipment to and from cleaning, such as whether the equipment is bagged
wet, immersion in a mobile tub, etc.

2.2.10 Maintenance of Support Utilities

The components of utility systems serving the process and rooms in which the chemicals are
handled should be evaluated. Examples of system components that warrant a qualitative
assessment include: removal/replacement of filters in dust collectors and HVAC systems,
maintenance/calibration of duct in-line devices in exhaust ductwork that convey dust from the
process, emptying and disposal of solid waste from dust collector hoppers, etc. HVAC airflow
diagrams are useful in identifying contaminated filters, major components and in-line devices.

2.2.11 Characterizing the Potential Source of Exposures

The way the products are handled in the unit operation must be documented and understood to
allow the EHS professional to determine the potential exposure pathway from the equipment to
the operator. In addition to the task performed, it is important to characterize each of the
contributing products. Knowledge of the products involved, the speed at which the task is
performed, as well as the operating conditions such as temperature and pressure can lead to a
clear understanding of the contributing factors to potential operator exposure. The following
questions can help identify potential sources.

2.2.11.1 Is There Relevant IH Data Existing From a Similar Process?

If the Operating Company has IH data from a similar unit operation, what can be learned from
it? Of course the EHS professional must ensure they are comparing similar operations and
products before drawing any conclusions. However, if the conclusion is that the operations are
similar, what do the historical data indicate? Does the historical report identify the source(s)
and/or contributing factors to the exposure?

2.2.11.2 Where are the Emission Sources?

Initially the EHS professional has to determine whether the operation is “open” or “closed”. For
example, in an open handling operation, the operator may be charging a chemical from a
container to an open vessel. With no controls in place, identification of the emission source is
quite simple. However, if the operation is closed, the emission source may be a leaking valve,
fitting, gasket, or other connection point. In many cases a semi-quantitative instrument (e.g.
particle counter, organic vapor analyzer) may be a useful tool when attempting to identify the
point(s) of emission. Pay particular attention to vented processes. Are the vent lines provided
with a means to prevent active materials from being transferred into the technical area or other
areas?

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2.2.11.3 Which Emission Sources Contribute to the Exposure?
After the EHS professional identifies the emission source(s), it is important to understand the
impact they may have on actual exposure to people. If the unit operation is located remotely
from people, or the people are remote from the emission source, are the emissions generated a
concern from an inhalation perspective? Answering this question requires more information,
such as “is the unit operation located in a room whose pressure gradient is positive or negative
to the outside hallway” or “what are the room cleaning procedures”? Additionally, information is
required relating to the duration of the operation and the allowable airborne exposure limit. What
is the impact of general room ventilation regarding the air currents in the area? Further, if the
emission is a powder, the associated particle size may suggest the material remains suspended
in air for long periods of time. The EHS professional must have knowledge regarding the
proximity of the operator to the emission source(s), the properties of the product, the impact of
air currents in the area, and the possibility for product migration to understand the potential
contribution to the inhalation exposure risk.

2.2.11.4 Characterize Each Contributor The EHS Professional needs to understand the
characteristics of each exposure source. This includes information such as the
chemicals involved, the operating temperature & pressure, the duration and frequency
of the operation, as well as specifics related to the actual emission source(s). This
information will prove helpful when exposure controls are being considered and when
evaluating the risk of exposure.

o Chemical Composition What is the physical state of the compound and how does
this impact the evaluation?

o Temperature & Pressure How do temperature and pressure affect exposure?

o Rate of Emission If possible, determine the rate of emission in unit terms of mass
per time (e.g. lbs/hr, mg/min). This also equates to product loss and need evaluation.

o Direction of Emission Define the direction (N, S, E, W) of the emission from the
point of origin to determine the risk of exposure.

o Velocity Determine the speed of the emission from the point of origin (e.g. m/s, ft/sec)
and evaluate its impact.

o Continuous or Intermittent Define whether the operation being evaluated is

unceasing or sporadic.

o Duration Define the length of time the operation being evaluated runs on a normal
workday. The degree of detail required in the qualitative assessment is to be
proportional to the hazard. If at the outset of the qualitative assessment it is clear that
the OEL is not a challenge and the processes are well controlled. There is little point
in conducting an exhaustive assessment so long as sufficient review is carried out to
identify any issues. One issue will be with high volume products with medium OELs,
if in doubt conduct a quantitative assessment.

2.2.12 Conclusion The conclusion to the qualitative risk assessment should: List all the issues
that potentially lead to exposure risk.

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  Is the process exposure risk low?
 If yes, is respiratory protection required?
 If the exposure risk is low and no respiratory protection is required, then the process
is complete and the reviewer can immediately complete the process by documenting
the Qualitative Risk Assessment. If there is uncertainty regarding the outcome of the
qualitative risk assessment, industrial hygiene data should be collected to confirm
your conclusion.
 If the exposure risk is not low or respiratory protective equipment is required then the
next step is to perform a quantitative risk assessment. However if the process is new
and quantitative data are not available from a similar operation and the conclusion is
that the OEL may be exceeded in the new process, then the next step is to establish
plans to address the exposure control.
 Where the assessment shows that a quantitative risk assessment is required, IH data
must be collected and statistically compared to the OEL.

2.3 Quantitative Risk Assessment

2.3.1 Unacceptable Exposure Risk

For unacceptable exposure risk (e.g., above the OEL or TLV) or if the exposure risk is uncertain,
or if respiratory protection is required, a quantitative risk assessment should be conducted to
confirm the conclusion from the qualitative risk assessment. A comprehensive review of the
entire risk-based safety assessment (qualitative and quantitative) may conclude implementation
of exposure or safety controls are required.

When conducting a quantitative risk assessment it is very important that the items identified as
critical in the qualitative analysis are incorporated in the sampling plan and that statistically
relevant data are collected.

2.3.2 Quantitative Risk Assessment Outline

The quantitative risk assessment, which includes the collection of industrial hygiene personal
monitoring data, is used to determine whether the risk posed by the exposure is acceptable.
Several samples must be collected (minimum of three) following validated sampling and
analytical methods. The sample analysis data results must be analyzed using Bayesian or
Descriptive statistics and compared to the Occupational Exposure Limit (OEL). The following
steps are normally conducted when performing a quantitative risk assessment:

 Identify agent (chemical, pharmaceutical, etc.) to be monitored.

 Select appropriate sampling methods and sampling media.
 Random selection of employees within the similar exposure group (SEG) to be sampled.
 Perform pre-calibration of sampling pumps at the desired flow-rate with sampling train
attached, including sampling media.
 After the pump is calibrated, attach the sampling pump and sample media to the
employee and ensure that the sampling media is located in the employee’s breathing
zone.
 Perform personal sampling for the duration of the task involving the agent of interest.
 Upon completion of the sampling episode, turn off the sampling pump and cap the
sampling media.
 Clean the sampling pumps using the appropriate detergent and water.
 Perform a post-calibration of the sampling pumps.
 Include a media field blank when submitting field samples for analysis.

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  Ship the sampling media and field blanks to an accredited IH laboratory for analysis.
 Once personal sample results are received, results shall be statistically compared to the
applicable ACGIH Threshold Limit Values, J&J Occupational Exposure Limits, or local
legislative limit, if more stringent.
 Communicate all results to sampled employees, SEGs and occupational health.
 If unacceptable exposure risks exist, the Industrial Hygienist has an obligation to partner
with Occupational Health to verify that appropriate medical surveillance is implemented.

2.3.3 Statistical Analysis

Utilizing statistical analysis (Bayesian or Descriptive Statistics) of industrial hygiene personal
exposure data, the organization shall establish, implement, and maintain a plan to reduce and/or
control employee exposures to below the applicable ACGIH Threshold Limit Value, J&J
Occupational Exposure Limit, or local legislative limit, if more stringent, with the goal of reducing
reliance on administrative and PPE controls. The plan shall address those contributing factors
that can potentially result in an occupational injury/illness or undesirable business consequence,
as well as the programs/processes that must be implemented and maintained to ensure
continued effectiveness and regulatory compliance.

2.4 Tools
A number of tools have been developed to aid and standardize the risk assessment process.
The value of these tools is that they provide a consistent format and provide a means to capture
data so that others can review it at a later date.

2.4.1 Risk-Based Exposure Assessment Process (RBEAP)

The RBEAP is a tool that can be used to complete the risk assessment of each unit operation
that involves the handling of chemicals/products. An example of a unit of operation is the room
or suite wherein a particular process (e.g. granulation) takes place. There are several steps
required to complete the RBEAP.

2.4.1.1 Define the unit operation and the different products and chemicals used for that
process. The chemicals/products (e.g. solvents, APIs, active ingredients, etc.) handled
for each unit operation are assessed to determine which chemicals have the greatest
potential to cause airborne concentrations and subsequent inhalation exposure risk
potential. This allows prioritization of sampling activities and surveys. The primary
factors that are considered in determining the RBEAP include:
 % of chemical in the batch
 Batch size (mass)
 Solid, liquid, gel, or cream matrix
 Particle size (if data available)
 Dustiness
 Vapor pressure
 Process safety information
 OEL/TLV
 Operating temperature

2.4.1.2 Based on the above product characteristics, each chemical/product is classified as high,
medium or low risk for airborne exposure potential. In addition to the exposure potential
characteristics, there are additional details recorded on the RBEAP form such as OEL,
type of respirators worn, etc.

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2.4.1.3 Following the classification of high, medium or low risk for airborne exposure potential, a
sampling strategy is developed to perform IH air sampling for those chemicals/products
that are classified as high risk. The sampling technique relies on traditional IH air
sampling techniques. The target is to collect 4 to 6 samples, the greater the number of
samples collected the less uncertainty that will exist when the statistical analysis is
completed. If further IH evaluation for a particular chemical/product is deemed
necessary, then additional samples may be collected.

2.4.1.4 Once all the sampling is completed, the data are statistically analyzed and the 95%
upper confidence level determined and compared to the OEL for each of the chemicals
handled. A determination of the type of respiratory protection required, if any, is
assigned. Based on the RBEAP assessment, the type of respirator required must be
assigned resulting in a level of protection that will be equivalent to or exceed the actual
protection required. If the IH data indicates the exposure risk is beyond the protection
factor of the respirator, engineering controls may be necessary.

The RBEAP should be re-evaluated in the event there are any changes to the process,
regulatory standard, procedures or chemicals/products that are handled for the unit operation
(linkage with existing “Management of Change”).

2.4.2 IH Hazard Assessment Forms [see Appendix]

 IH Qualitative Risk Assessment form
 Risk-Based Exposure Assessment Process form
 Containment Solution Guide template

2.5 Conclusion of Quantitative Assessment

If as a result of the quantitative risk assessment the OEL is met, then the Risk Assessment
process is documented, circulated and archived. If as a result of the quantitative risk
assessment the OEL is exceeded, then a strategy must be developed to determine the
appropriate exposure control plan selected in order to reduce the inhalation exposure risk below
the applicable OEL. The primary objective of selecting the exposure control option is to reduce
the inhalation exposure risk of the workers below the Occupational Exposure Limit. There are
numerous exposure control options in which to choose. The decision may be to rely on
personal protective equipment, control the airborne contaminants at the source, or control the
airborne contaminants within the room where the process is located. Whatever control method
is selected, industrial hygiene personal monitoring data must be collected to confirm the
exposure risk is below the OEL.

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3 Engineering & Containment Solutions

Introduction: The exposure control section of this document is intended to provide guidance to
the exposure control team based on the results of the quantitative risk assessment. Utilizing this
information, these technical details will provide the tools and direction necessary for selecting
control options that will help manage the risk identified. The exposure control solutions section
includes: reliance on personal protective equipment (i.e. respirators) options for engineering
controls at the unit operation (i.e. at the source), infrastructure considerations (room airlocks and
people/material flows), and design/filtration for HVAC systems.

3.1 Exposure Control

At this point a team has to be created to handle the exposure risk management project. The
team should be drawn from all the stakeholders that are relevant to the project. The following is
a suggested list. It is important to include all those who will influence the project, but should be
small enough to be manageable. The team should reflect the expertise required to understand
the exposure risk and recommended exposure controls. Potential team members (this should
be the same as the team listed up front) include:
 EHS
 Operations
 Operator
 Regulatory
 Quality
 Engineering
 Facilities
 Maintenance
 Project Management

Obviously some members will only attend relevant meetings. The team appoints a project
manager and at the initial meeting the team agrees to the scope and a timeline for the project.

3.1.1 Selecting Exposure Control Options

Many factors influence the choice of exposure control options. If the emissions can be
contained within the process at all stages of set up, run, charge and discharge, intervene,
sample and cleaning then other measures can be reduced or eliminated. As the exposure
boundary increases so does the difficulty of containing the compound successfully. The final
boundary is room or rooms in which the product is processed. The objective is to maintain the
corridors in a condition that meets all criteria for airborne and surface concentrations.

In undertaking the evaluation it is worth starting at the processes and working outwards to the
facility.

It is essential to consider the following factors when selecting exposure control options.
 Function; is the function possible with the controls in place?
 Can all the actions required for:
o Set up
o Operation
o Intervention
o Recovery from upset
o Sampling

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 o Cleaning including critical disassembly is completed successfully without injury,
ergonomic issues or discomfort?

In many cases the material handling aspects have to be considered to minimize the effort
required in performing the task. The processes should be carefully reviewed to see if they can
be simplified without impact to the product.

Transfer into and out of the process is often the key issue and a practical method that meets the
goals is required.

Finally, review the process in detail, preferably with the operators that have to perform the
process tasks so the issues are fully understood and addressed.

A key component of the selection of the exposure control options is the use of the Containment
Solutions Guide (CSG).

3.1.1.1 Containment Solution Guides (CSG)

CSGs are an engineering and industrial hygiene tool to support the J&J exposure control
programs for chemical agents. The CSGs are very inexpensive to generate and will require
approximately 30 minutes to develop. The CSG library is located on the WWEHS web site at:

Containment Solution Guides.url

o The value that the CSGs bring to J&J include:

 A tool to leverage existing capital and intellectual property
 Eliminate reinventing the wheel for engineering control technologies
 A format to capture and share best practices, solutions and lessons learned
 ‘Quick Wins’ based on existing J&J technology & experiences

o The CSGs will provide J&J sites and our external manufacturing partners with guidance and
information to:
 Design and install cost effective engineering controls based on proven technologies
 Use generic solutions for common unit operations: weighing, dispensing, compression,
reactor charging
 Help manage risks associated with chemical exposures
 Provide order of magnitude cost estimates and support capital planning

o The contents of the CSG include:

 Photos
Summary of the unit operation and activities
 Design features of engineering controls
 Cost of control technology
 Industrial hygiene data for the unit operation
 Training, cleaning guidelines, maintenance, work practice & lessons learned
 J&J site and vendor contacts

o The CSG can be used to support:

 Engineering design concepts and budget projections
 Technical transfer

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  \Sourcing decisions
 External manufacturing

3.1.2 Containment Boundary

Another basic question that requires answering is whether the compound can be contained
within the unit operation or room where it is located. When decisions are made regarding
exposure risk management typically the cost to contain the potential chemical exposure within
the equipment is more financially effective as opposed to using the room to provide the
containment, which leads to reliance on personnel protective equipment. Another benefit from
exposure reduction at the source is minimization of migration from the quality, cleaning and
exposure viewpoints. If the room must be used to provide the containment boundary, decisions
must be made to allow for the proper administration of personnel protective equipment.

Containment at the source is the preferred option if feasible.

A general practice is to maintain a boundary between the room(s) in which the compound is
processed and the common corridors defined as areas where people, equipment and product
could inadvertently be contaminated. If the chemical exposure is not contained at the source
(i.e. the OEL is exceeded) then measures to control transfer of people, equipment and materials
are required.

3.1.3 Hierarchy of Exposure Controls

In engineering solutions for exposure control three different levels can be determined:

3.1.3.1 Reduction at the Source, which gives the opportunity to eliminate or reduce the use of
PPE. Examples include the following:

 Containment: the process itself is completely closed and already contained by using
containment technology. Examples are isolator technology (both rigid and flexible),
contained connection systems (e.g. split butterfly valve and endless liner system) and
hard piped connections, (closed processes) including the right gaskets and fittings.
 Product Modification: the product is modified in formulation so that exposure is
minimized. Examples are wetting a powder (decreasing dustiness) or using solvents
at lower temperatures (decreasing the vapor pressure) and wetting a powder and/or
equipment (WIP) before opening/dismantling.
 Process Change: reducing the energy in the process. Examples are dipping versus
spraying, lowering internal pressure, changing an order of addition, increasing
packaging volume in order to reduce number of transfers.
 Substitution: In this case the hazard component is changed to a less hazardous one
so exposure will be removed or reduced. Examples are using less hazardous cleaning
solvents (if possible).
 Process Automation: By automating the process, operator intervention will be
reduced and the process can be controlled from a distance (e.g. control room). An
example is the automated dispensing of powders so no manual weight correction
needs to be executed.

3.1.3.2 Reduction at the Operator Product Interface This is accomplished by utilizing

measures outside the process boundary to keep the exposure of the operator to a
minimum e.g., local extraction. This gives the opportunity to reduce the use of PPE,
however limited. Examples include the following:

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  Local Exhaust Ventilation: creating a separation between the process (emission
source) and the operator. The direction of emissions is controlled and can be
redirected from the operator-breathing zone. An example is sampling from an open
drum in a laminar flow booth. It is important that the position of the operator doesn’t
influence the flow pattern. Another example to create a separation between the
process and operator is to use lamellas or a screen with operation through glove
ports.

 Local Extraction: If there is a single point or zone of emission, local extraction can be
used for capturing the emission at the source. Effectiveness of this exposure control
depends heavily on the design of the system. Capture velocity and hood design are
important parameters. These should be both aligned with the emission source and
emission velocity. Example is an air hood around the charging point and the
extraction on a bag discharge cabinet or a charge funnel. They can also be used to
augment the performance of simple split butterfly valves.

3.1.3.3 Reduction in the Surrounding Area Utilizing the facility design to keep the area of the
exposure to a minimum e.g., HVAC and compartments accomplish this. Use of PPE is
still required. Examples include the following:

 Ventilation: In an open area inside a building, HVAC ventilation can be used to

control the airflow patterns inside the building. The air can be directed away from
operator and other persons inside the building (e.g. a central corridor) to the sides
where the extraction system is located.

 Compartments: In order to prevent possible exposure to expand through the

surrounding area a process can be built in a compartment. The compartment should
have a negative pressure to the surrounding area to keep possible exposure inside
the compartment. Note, that for quality reasons an overpressure is preferable. Also
note, that in case of a compartment, the exposure level both in and outside the
compartment should be judged.

The approach for implementing engineering solutions should be according to the

hierarchy of control. This means that reduction at the source should be the first
priority. Highest containment levels are achieved through reduction at the source.

For all these engineering solutions it is important to review the exposure controls
during manufacturing, cleaning, dismantling and maintenance. Also check if the
current exposure controls perform as intended.

3.1.4 Personal Protective Equipment and Personal Hygiene

3.1.4.1 Personal Protective Equipment: Personal protective equipment (PPE) such as safety
eye glasses, gloves, coveralls and respirators help protect a worker by providing a
barrier from a chemical or work task. PPE is not a substitute for engineering controls.
PPE is normally considered a secondary control measure to protect the worker from the
environment when it is not possible to enclose or isolate a process or equipment,
provide local exhaust ventilation, or other engineering control. PPE may also be used
as a precaution to protect the worker from a potential spill and for short duration tasks
where engineering controls are not feasible.

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3.1.4.2 cGMP requires the operators to be properly garbed so gowning is inevitable. In
addition, since mechanical transfer of surface contamination at critical interfaces can be
transferred to skin and mucous membranes, the use of PPE to prevent such transfer
may be advisable even if respirator protection is not. The need for respiratory
protection is the key criteria as to whether exposure is controlled or not.

3.1.4.3 Use of PPE Does Not Eliminate the Risk. Selection of PPE must be carefully
considered and is dependent on many factors such as exposure level, compatibility,
durability and movement of the employee. Failure of PPE can result in exposure to the
contaminant. Chemicals providing a greater risk of absorption through the skin, such as
”skin notation” chemicals, must be factored into the PPE selection process to minimize
contact with exposed skin including the hands, forearms, face, and neck areas.

3.1.4.4 Personal Hygiene: Practicing good personal hygiene is important to minimize

incidental exposure to chemicals. Providing a readily accessible wash area near the
work area will allow for proper cleanup and minimize the spread of contaminants
outside of the immediate work area. Cleaning and removal of coveralls, respirators and
other contaminated equipment should be performed in a designated degowning area or
before leaving the work zone.

Bringing materials and equipment outside the work areas before proper cleaning may
result in contamination of the clean areas.

3.1.4.5 Degowning Procedures and proper handling of contaminated equipment is often

overlooked as a source of exposure. Washing hands with soap and water when
finished working with chemicals and when removing gloves will help prevent exposure
by removing any residual contaminants. Eating, drinking and the storage of food and
beverages should never be permitted where handling chemicals to prevent accidental
ingestion of chemicals.

3.1.4.6 Training in gowning and degowning protocols and the safe removal and disposal of
gloves is essential to minimize exposure & carry over.

3.1.5 Administrative Controls

3.1.5.1 Reducing Exposure Time: Administrative controls should be considered when

engineering controls and PPE cannot effectively reduce exposure. Job rotation
essentially reduces the time a worker is exposed to a hazardous work environment.
While job rotation may keep exposure below recommended limits, it has the potential to
expose more workers to the hazard.

3.1.5.2 Housekeeping: Good housekeeping practices play another key role in preventing the
dispersion of contaminants and in maintaining a safe work environment. Clean up
immediately after working with chemicals or when a spill occurs will minimize spread of
contaminants. Use of certain cleaning techniques such as wet wiping and/or use of a
HEPA vacuum will better control the spread of powders and is more effective at
reducing exposure than dry sweeping. Another consideration is the proper wipe down,
cleanup and storage of PPE such as respirators, reusable gloves and coveralls.
Equipment and tools should be cleaned before removing from the work environment
and stored in a location to prevent contamination or damage to the equipment.

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3.1.5.3 Maintenance Approach – Robust PM program: A maintenance program including a
preventive maintenance (PM) program should be implemented for maintaining
equipment and facilities in satisfactory operating condition by providing for inspection,
detection, and correction of potential problems or failures before they occur or before
they create a hazard. A robust PM program will measure effectiveness of engineering
controls such as fume hoods and local exhaust ventilation and help identify problems to
assure the equipment continues to operate as designed.

If ventilation systems are not well maintained it can lead to unnecessary exposure of
employees using the equipment as well as inadvertent exposures downstream of the
equipment. Maintenance of engineering controls and other equipment used in
production offer an additional source of exposure to personnel who maintain it. Routine
maintenance on dust collection systems, servicing of filters and other components can
result in significant short-term exposures if respirators and other controls are not in
place during servicing. Maintenance and other production support tasks should be
considered as part of your overall risk assessment.

The periodic testing of filters for integrity and a safe filter change out procedure for
expired filters is essential.

3.1.5.4 Employee Work Practices - A critical role is played by the operators with respect to
impacting the potential risk posed by chemical exposures in the workplace. When
performing a risk assessment, the EHS professional must note whether the operator
being observed is following the procedures and work practices that have been put in
place to minimize exposure risk. The following questions will assist in identifying
potential gaps in the area of employee work practices.

3.1.5.5 Are Controls Being Used as Intended? – Often there is a need for operator
involvement in order for exposure control devices to work as intended. For example, a
ventilated charge chute that is used to control dust when charging a vessel or reactor
will not be effective in reducing the potential exposure unless it is utilized. The dust
collector that is providing the exhaust from the ventilated charge chute will not be
effective unless it is turned on.

Another example involves using a DoverPak without securing the bag as required to
minimize dust leakage during a product transfer. A minor oversight can lead to major
exposure risks simply by not utilizing controls as intended.

3.1.5.6 Are Procedures Being Followed? – Many procedures are put in place to reduce
potential exposure risk and during a risk assessment the EHS professional must note
whether these are being followed. A procedure may require that parts are removed from
a chemical bath slowly so as not to drag out solvent vapors. The exposure risk is
minimized when the procedure is followed.

In a weighing operation, the procedure requires the scoop to be lowered to the powder
level in the “transfer to” drum in order to prevent a dust cloud. When this procedure is
followed, the exposure risk is minimized. When conducting the risk assessment the
EHS professional must be aware of the required procedures and ensure they are
followed and noted.

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3.1.5.7 Is Required PPE Utilized? – Often the EHS professional will rely on personal
protective equipment (PPE) to reduce potential exposure risk to operators. During a risk
assessment the EHS professional must note whether the appropriate PPE is being worn
as required. The exposure risk potential is minimized when the required PPE is worn
properly.

When conducting the risk assessment the EHS professional must be aware of the
required PPE, ensure it’s worn properly and utilized when required.

Is the operator satisfactorily trained to use the containment equipment and the PPE?

3.1.5.8 Is the Containment Equipment Used Properly? - Installing containment equipment

does not guarantee that you will achieve the expected containment level identified by
the supplier. It is of great importance that when installing new equipment employees are
properly trained and know how the use them. Detailed instructions need to be in place.
Evaluation and follow up during the first use is mandatory. Periodic inspections and
coaching afterwards is necessary.

3.1.5.9 Procedural

o Proper work practices should be established, workers trained and work practices
enforced.
o SOPs including required safety provisions should be developed. Good work practices
should be established, taught and enforced.
o Deviations from established work practices that result in increased airborne dust
levels and any potential for carryout of product beyond the processing area should not
be tolerated. Defined material and personnel flows should be established as part of
the control scheme.
o Training is required in the use of specialized containment equipment.

3.2 Engineering Controls

Introduction: The engineering controls section of this document is intended to provide
examples of exposure controls from which the team can select based on the results of the
qualitative and quantitative risk assessments. As stated previously, the exposure control
solutions section includes: options for engineering controls at the unit operation (i.e. at the
source), infrastructure considerations (room airlocks and people/material flows), and
design/filtration for HVAC systems.

Engineering Control Strategy: In order of preference.

 Closed material transfer
 Isolator
 Glove Bags
 Downflow Booths
 LEV

3.2.1 Closed Processes

In order for closed processes to be effective the system interface should address the following
activities:
 A contained way to charge and discharge
 Ability to contain interventions for sampling, adjustment and upset recovery

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  All vents are HEPA filtered
 Cleaning without opening
 Safe HEPA filter change
 Charging/discharging and transfers - bins, vessels
 Primary container from dispensing should align with process to get material into
intermediate bulk containers (IBCs), or each successive step should align with same type
of transfer methods.
 Gravity transfers should always be considered (Closed/Contained)

3.2.1.1 Isolators - Consult generic User Requirement Specification (URS) and decision logic
for isolators

Glove Box URS.url

The following considerations should be evaluated when designing and installing an isolator for
chemical exposure control:
 How to bring materials in and out are keys to successful operation.
 Drop through type to feed from drum to drum in controlled manner.
 Need to consider how labeling of weighed material will be handled.
 Consider scale calibration and accuracy in enclosed environment.
 Need to determine how unit will be cleaned as part of process.
 Difficult for handling multiple APIs, (e.g., validation and multiple incoming containers)
 Operator buy-in can be difficult.
 Developing implementation team before user requirements are written is a must to
assure implementation.
 Project and engineering expertise in containment equipment required
 Significant planning effort required upfront to align process, tasks and technology
 Design must be integrated with all the process activities that are required
 Defined cleaning strategy to be determined before URS.

3.2.1.2 Rapid Transfer Ports (RTP)

The following considerations should be evaluated when installing a RTP for chemical exposure
control:
 Can be docked to equipment to transfer either in or out through isolator.
 Can also allow sample collection in contained environment.
 Are generally used in conjunction with an isolator
 Design needs to be aligned with interfacing equipment and container sizing and handling

3.2.1.3 Vented Balance Enclosures (VBE)

The following considerations should be evaluated when installing a VBE for chemical exposure
control:
 Weighing and transferring activities involving chemical solids.
 VBE may also be used for containment of liquid aerosol generation from
manipulations with syringes, vortexing, or sonicating.
 Ventilated balance enclosures should be equipped with an in-line “safe change”
HEPA filter to capture the particulate, thus reducing the risk of room or ductwork
contamination.
 Ventilated balance enclosures tied into existing exhaust systems should be using a
thimble connection.

3.2.1.4 Flexible Material

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The following considerations should be evaluated when designing and installing flexible material
for chemical exposure control:

3.2.1.4.1 Bagging – can be in an enclosure if not utilizing a continuous liner and also in a
downflow booth with good work practices. Secondary bagging with continuous liner is
possible. Used with local exhaust ventilation (LEV) may achieve good results, but
difficult.

3.2.1.4.2 Dover Pacs & Hecht Bags– Flexible, detachable device is more cost effective than
solid wall isolator. Good results with low OEL materials are possible with good
operator technique.

3.2.1.4.3 Advantages of Flexible Material Include:

 No cleaning.
 Wet in place techniques can be used before removing.
 Continuous liners.
 Good method for smaller quantities, may not be practical for large quantities.
 Quick and inexpensive to design and install.
 Provides flexibility to change in future.
 Good operator work practices required.
 Possible required LEV for sleeve break.

3.2.1.5 Split Butterfly Valves (SBV)

The following considerations should be evaluated when installing SBV for chemical exposure
control:

 Used with docking stations or overhead connections to equipment.

 Can be used on equipment for feeding & discharge also.
 There are many different types of SBV vendors and design features. An assessment of
the different manufacturers and features is necessary. See Containment Solution Guides.
 Can be very effective at controlling exposures to low levels depending upon SBV model
and process.
 Should be purchased as an integrated system to other process equipment.
 A routine preventive maintenance program is required as SBV performance can degrade
over time.
 Material flow is an important design consideration.
 Inflatable seals – for sealing valve faces to equipment, also works with drum transfers
utilizing bagging sleeves.

3.2.1.6 Vacuum Transfers

The following considerations should be evaluated when installing vacuum transfers for chemical
exposure control:

 Typically for larger quantities of materials; secondary containers may need to be

designed for vacuum rating.
 Consider how equipment will break down and be cleaned and how to be transferred to
cleaning location.
 Can be very effective if closed system.
 Where is the vented air displaced? Needs to be addressed depending on type of filter
system utilized.

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  Assure product safety information is known (e.g. minimum ignition energy) before
designing vacuum or pneumatic transfer systems.

3.2.2 Downflow Booth Considerations

Consult generic URS and decision logic for downflow booths

Down Flow Booth URS.url

The following considerations should be evaluated when designing and installing a downflow
booth for chemical exposure control:
 Typically won’t control worker exposures below 100 ug/m3.
 Effectiveness will depend on worker’s work practices.
 Type and size of containers being handled will impact effectiveness.
 Method of material handling – scooping vs. vacuum transfer. Must also consider the
cleaning of the vacuum transfer equipment and other weighing utensils.
 Consider a booth with a physical barrier between the worker and the source. Critical to
design to actual handling in lower portion below head height of associate.
 Space consideration - one drum vs. 4 drums on a pallet.
 Energy considerations – energy consumption is high for this equipment.

3.2.3 Open Handling with Local Exhaust Ventilation (LEV)

 Open handling with local exhaust ventilation – this has limited ability to control.
 Depends heavily on operator technique and characteristics of materials.
 Design of LEV collection units should to conform to ACGIH capture velocities.
 Velocity requirements to be effective (refer to HVAC section).
 Generally not very effective for handling powders; acceptable for solvents
 Will not control exposure very effectively (< 1000 ug/m3).
 Can lead to migration of API from weighing location.
 Energy consumption and loss of material may outweigh return for control.
 Can be very effective for small-scale work.
 Requires excellent work practices by the operators.
 Enclosure should be equipped with waste discharge attachment.
 Exhaust emission control device may be required.
 Can be installed quickly, low cost and little engineering required.
Note* Incoming material container type & size, method to perform transfer (i.e. scooping vs.
vacuum transfer) must be taken into consideration.

Where an LEV is selected as appropriate it must be provided at the sources of contamination

using design criteria as recommended by the Industrial Ventilation guide from the American
Conference of Governmental Industrial Hygienists (ACGIH). Particulate/dust capture velocities,
duct transport velocities and hood face velocity criteria are published in the Industrial Ventilation
guide. For convenience, some criteria are included below.

3.2.3.1 Design Capture Velocities

Condition of Dispersion Example Capture Velocity
of Contaminant fpm (meters per
minute)
Released with practically Evaporation from tanks 50-100 (15-30)
no velocity into still/quiet
air
Released at low velocity Solids transfer / 100-200 (30-60)

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 into moderately still air Sampling
Active generation into Conveyor loading, 200-500 (60-
zone of rapid air motion aerosol dispersion 152)

Capture velocity is the air velocity at any point in front of the hood or at the hood opening
necessary to overcome opposing air currents plus the opposing momentum of the contaminant
dispersion to capture the contaminated air or dust particles at the dispersion zone and causing it
to flow into the hood. The lower values of the capture velocities listed above can be used if a
push-pull arrangement is designed. Down flow booths are an example of a push-pull design. In
the case of a downflow booth, air from the ceiling is supplied down through the dispersion zone
during solids transfer and captured by exhaust openings on the opposite end of the supply air.
The advantage of push-pull is that the push air will maintain velocity over larger distances than
the suction end. Push jet nozzles for example can maintain velocities for 20 to 30 feet per
minute whereas the velocity in front of an exhaust hood decays very rapidly as the distance from
the hood increases.

The table below summarizes the recommended duct transport velocities per Industrial
Ventilation. Maintaining appropriate transfer velocities is critical to avoid dust/contaminant
accumulation in ductwork.

3.2.3.2 Ranges of Minimum Duct Design Velocities

Nature of Examples Design Velocity
Contaminant fpm (meters per
minute)
Vapors, Gases, All vapors, gases and smoke 1000-2000 (300-
Smoke 610)
Very Fine Light Dust Powder 2500-3000 (760-
915)
Average Industrial Industrial Ventilation lists 3500-4000 (1060-
Dust materials that are not related 1220)
to typical pharmaceutical
materials. Some examples
listed are grinding dust,
coffee beans, silica flour,
etc. The engineer must
make an informed judgment
in selecting the appropriate
transport velocity per the
above examples.

In applications where the contaminant is being captured from a dispersion zone (dust cloud),
capture velocity and duct transport velocity are determined using the tables above. Consult the
ACGIH Industrial Ventilation Manual that provides formulas and diagrams to determine the
required exhaust airflow volumes based on the following variables:
 Distance from the hood face to the farthest point of contaminant release
 Hood opening face area
 Capture velocity required at the farthest point of contaminant release

3.2.4 Dust Collectors

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Dust collectors are used in applications that require removal of large quantities of dust from the
contained area. Dust collectors must be designed properly and adequately located to protect
maintenance personnel and to avoid contamination of adjacent facilities during removal of waste
and replacement of filters. They should be located as close as possible to the point of use.
 Dust collectors that serve a contained area should have bag-in/bag-out filter change
capabilities.
 The dust collector should allow for a contained method of waste removal, or should be
located in a containment area with maintenance personnel in PPE.
 Design for contained removal of waste can include a continuous liner in a sleeve
cartridge using the crimp and cut method or if low OELs are required, should be designed
with an Isolator. LEV and PPE will be required for the continuous liner approach.
 Requirements for explosion vents should be balanced with the risk probability and
capability of the collector. The risk assessment should include analysis of the
environmental impact of venting the collector contents outside when determining if the
dust collector should be designed to suppress an explosion rather than vent it through a
release panel. If a release panel is acceptable, the explosion discharge should be
directed to a non-occupied zone.
 Ductwork used to direct explosion venting should be properly designed to withstand
venting pressures without breaching.
 For new facilities, consider locating dust collectors that serve high containment areas in a
separate mechanical room designed for containment, including negative pressurization,
airlock and PPE or PAPR storage, removal and decontamination facilities. See the
section of this document under Room Containment Design Considerations.

3.2.5 Processes
 Where possible, process steps, transfer containers and equipment should be integrated
to minimize transfer points.
 Sampling should also be considered with the design of the equipment and facilities.
 Try to avoid open processes or equipment/activities that generate high dust levels or that
are difficult to contain. These may include open mixers, mills, tray dryers, sieves and
other equipment without enclosures and/or ventilation controls. Substitute
processes/activities that generate less dust or that are well contained.
 Eliminate unnecessary/redundant handling and processing steps consistent with lean
manufacturing techniques. Parts should be pre-cleaned and/or bagged in the
manufacturing area prior to removal.

3.2.5.1 Incoming Raw Materials

 Aligned to each step of process. For example, if the material is to be weighed can the
receiving container be docked to an isolator?
 Are they cleaned/decontaminated upon receipt?
 Can they be exchanged or transferred to an appropriate sized container? Where? How?
 Are there exposure risks to employees who are handling closed containers of raw
materials?
 Bulk active container handling – Where possible, align with the vendor to properly size
the container to facilitate ease of QA sampling and operations dispensing. Always need
to verify the vendor is sending a container that is free of contaminants on the external
surfaces. In case of actives with low OELs, consider delivery in rapid transfer port (RTP)
type containers or a safe area for repacking to facilitate the operations processes. Other
options include over-packing of container until it can be moved to a controlled area.
 Working with our purchasing associates, change in containers can be effected. Be aware
this may require more stability data.

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3.2.5.2 Incoming Raw Material Sampling
 The specific type of control will also depend on how much material is sampled, physical
characteristics and duration/frequency
 Eliminate sampling where possible.
 Proficiency analytical testing (PAT) potentials help with control strategy and may
eliminate need for samples.
 Avoid open handling unless risks are non-existent.
 Use a ventilated balance enclosure, especially if destructive testing of product is required.
 A downflow booth may be appropriate for some activities Most sites now utilize a
downflow booth however procedures and protocols are vital with a downflow booth for
raw material sampling and some actives
 Drug Enforcement Agency (DEA) controlled products can also require a segregated area
for sampling.
 Destructive testing should have a higher level of containment than simple sampling.
 Consider closed in-line sampling devices and systems.
 Separate samples (side stream samples) are ideal if the supplier will provide them and
the QA department will accept them (samples shipped in small separate containers with
bulk shipments).
 Ensure all necessary equipment is located within the containment unit before beginning
work.

3.2.5.3 In-Process Sampling

 Best if non-invasively obtained by proficiency analytical testing.
 Closed transfer of samples is best.
 Thief sampling of blends in bins is difficult but can be done.
 Essential to fully understand sampling requirements, normally a Quality function. Ensure
they are involved in the design of the system.
 Utilize closed sampling systems for in-process liquids (e.g., Dopak or Neotecha closed
sampling systems).
 Eliminate or reduce sampling if possible.
 Establish SOPs, training and ensure proper work practices are used to minimize
exposures.

3.2.5.4 Weighing/Dispensing
 Weighing should be done with the aid of engineering controls: glovebox (rigid or flexible),
downflow booth, LEV, etc.
 Typically screening or milling of material is required during the weighing process. Ensure
the equipment utilized is capable of containing this process and exposure during cleaning
of the equipment can be controlled.
 Rooms should be set up for this particular unit operation. Proper material flows to and
from storage through staging needs to be considered.
 Depending on level of containment being used, batch or weighing paperwork flows need
to be protected.
 Note incoming material container type & size, method to perform transfer, (scooping vs.
Vacuum Transfer).
 Flexible materials can be used for weighing and dispensing solutions – Incorporate drum
turner and continuous liner to maintain containment.
 Vacuum transfers for higher volume dispensing – Still may have to be done in a downflow
booth. Breakdown & cleaning of vacuum transfer unit needs to be thought out before
implementing. Depending on volume, several options exist.

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3.2.5.5 Solids Charging and Transfer
 Closed material handling and transfers with direct connection are generally
recommended.
 Controls that can be considered include isolators, split butterfly valve (SBV) (in
conjunction with IBC), RTPs, glove bag systems and vacuum charging.

3.2.5.6 Granulation
 Consider the type of technology (e.g. wet, spray, fluid bed).
 Tasks to consider include: charging, discharging, sampling, cleaning & filter changing.
 System to wet interior of chamber before opening equipment will assist in controlling
levels.
 Cleaning area for filters needs to be considered in room design. How to get to cleaning
area if not contiguous to room also needs to be considered.
 Closed system for charging and discharging.
 System may include vacuum transfers.
 Bottom discharge is helpful.
 Closed sampling techniques preferred.
 Techniques to remove and clean filters required.
 Glove bag techniques can be used for filter removal.
 Maintenance & cleaning of remote explosion relief valve needs to be considered.
 For fluid bed dryers, procedures that allow for adequate time to allow airborne particulate
to settle. Using a device to create vibration in the shell to loosen retained material is also
useful to minimize exposure when open.

3.2.5.7 Filtration
 Controls that can be considered include isolators, glove bag or downflow booth.
 Local exhaust ventilation (LEV) may be appropriate for material wet with solvent.
 Charging should be by direct connection.
 Discharge should be directly into a bag using a bag connection, rapid transfer port (RTP)
or intermediate bulk container (IBC).
 Heel should be removed safely with the use of engineering controls, (e.g. glove bag).
 Screens should be removed and cleaned while contained.

3.2.5.8 Drying & Mixing

 Charging and discharging should utilize IBCs or other containers that facilitate a closed
system.
 The interface between the IBC and the process equipment should be closed.
 A direction connection should be used via SBVs, RTPs or glove bag.
 If open handling, then LEV should be used if appropriate and effective.
 For discharging into drums, bag techniques should be considered.
 Isolators are available to transfer from IBC to drums in contained manner.
 Open mixers should be avoided because of the difficulty to control exposure.
 Review work practices and SOPs to reduce redundant handling and unnecessary
procedures.
 Try to avoid using tray dryer. If used, appropriate engineering controls will be required.
 Controls that can be considered include isolators, glove bag or downflow booth.
 The use of open front dryers is not recommended. If used, the front should be contained
with a glove box or flexible enclosure if the risk warrants controls.
 Charging tumble dryers should be by direct connection.

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  For drum operations, the use of bag techniques is recommended for dryer discharge.
Engineered LEV should also be provided (see HVAC section).
 The transition between the dryer discharge chute and receiving containers should be
closed. If bag is used it should be equipped with a bag ring connection, RTP or a
SBV/IBC.
 If discharging to an IBC, design consideration should include a continuous liner with an
inflatable seal. If additional containment is required the continuous liner should be
installed within a laminar air flow (LAF) or downflow booth.
 Parts should be cleaned while contained.

3.2.5.9 Reduction (milling, micronizing) and High-Energy Activities:

 Open process is not recommended
 Avoid hand scooping or manual feeding from container.
 Closed gravity feeding with use of inflatable seal or SBV offers better control.
 Performed with some type of control such as an enclosure, glove box or downflow booth,
LEV (at points of dust generation or emission). Sometimes the LEV can supplement the
primary control method to capture fugitive emissions.
 Closed discharging techniques should be used, (e.g. glove bags or continuous liners).
LEV can be used as a supplement control.
 Once enclosed, need to align possible nitrogen blanketing, depending on MIE, Kst and
static characteristics of the product.
 Consider how equipment will break down and be cleaned and how to be transferred to
cleaning location.
 Open charging hoppers are not recommended.
 Hoppers can be enclosed within a glovebox, glove bag, ventilated enclosure or downflow
booth.
 Equipment bodies should be gasket-sealed.
 Charging and receiving containers should be leak tight and use RTP canisters, IBCs with
SBV for connection to the mill and/or a mill glovebox.
 Closed connections between mill’s receiving and discharge points.
 LEV at connections is recommended to capture any dust emissions especially when
disconnecting (see HVAC section).
 Small-scale milling/sizing operations can be integrated into a ventilated enclosure.

3.2.5.10 Solid Dosage & Filling Operations:

 Closed charging of compression equipment via bins and SBV or some type of direct
connection.
 Inflatable seals can be used between different containers and equipment, depending on
material characteristics.
 Open charging/manual feeding is not recommended.
 Tablet presses and capsule fillers should be enclosed and equipped with LEV.
 Consider how operator will break containment for adjustments for in-process
adjustments.
 Wash in place equipment needs to be considered for some products, (e.g. risk
dependent). If not, consider how parts will be/can be wetted before disassembly.
 Need to consider where parts and tooling will be cleaned and stored.
 Consider handling Maintenance interruptions during a run.
 Sampling and in-process testing controls may be required, especially if destructive testing
is required.

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 Tablet presses should be equipped with tablet de-dusting apparatus. This and metal
checker should be closed/enclosed with separate LEV to dust collector. This will help
control exposure while charging coater.
 Several vendors now have experience in WIP type compression machine. J&J has
several different units already in–house to help decision to match requirements (See
CSGs).

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3.2.5.11 Inspection, Printing Packaging
 In general, very little risk will be present for these activities. If a risk exists then controls
that are appropriate include LEV or enclosures.
 If uncoated tablets, may require higher level of LEV or enclosures. Friability to be
considered. Capsule breakage potentials to be considered.
 Rework area may need to be segregated (based on risk).

3.2.5.12 Coating
 Dust levels should be very low for charging tablets that have passed through a de-duster.
 Depending on friability and static characteristics for the tablets to hold dust.
 If tablets are not de-dusted, then some closed connection between tablet container and
coating pan may be appropriate
 Risk during discharging should be very low given the fact that the tablets have been
coated.
 Need to consider the cleaning operations after coating, (e.g. cleaning of the discharge
filters).

3.2.5.13 Laser Drilling

 HEPA LEV.
 Dust collector (facility).

3.2.5.14 Packaging of Tablets/Capsules

 In most situations engineering controls will be minimal. Exceptions may be for products
with APIs that have very low OELs and that are un-coated.
 Special consideration may be made for the tablet-handling portion of the packaging
machine.

3.2.5.15 Parenteral
 Parenteral compounding
o Under laminar airflow (LAF) or other control.
o Consider closed transfer for lower OEL compounds.
 Parenteral solution filling
o General statement that only needed in situations where the OELs are very low and
when substantial aerosols can be generated.
o The potential for aerosols to be generated will be dependant upon the fill rate, the
type of filling equipment and material characteristics.
o External vial washing – consider regulatory and cGMP requirements.
 Parenteral powder filling
o Isolators and bulk RTP can be used to contain the powder filling area.
o Specialized LAF unit to contain fugitive dust generated during filling.
o Sampling & testing to be considered.
o Control of container exterior contamination.
o External vial washing – consider regulatory and cGMP requirements.

3.2.5.16 Parenteral Lyophilization

 Removal of/cleanout methods for broken vials.
 Integrated isolator may be required for lower OELs.

3.2.5.17 Document Transfer

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  Movement of documents into and out of contaminated areas and/or areas where
personal protective equipment is worn may present an exposure risk. Consider methods
to determine how documents are filled out and routed within the process to avoid
possible contamination to other areas.
 Consider use of paperwork glove-boxes or electronic documents.

3.2.5.18 Equipment Cleaning

 Parts should be pre-cleaned in the process area prior to removal to the cleaning area.
Bagging for transfer may be required.
 Removal of visible dust using either a portable HEPA vacuum or house vacuum system.
Pre-wetting of parts should be considered.
 Tooling final cleaning, maintenance, storage & testing should be considered part of
equipment cleaning process to review.

3.2.5.19 Maintenance
 Main issue is risk transfer to other areas during cleaning (equipment movement in and
out of contained area to cleaning/maintenance areas)

3.3 Facility
This guideline addresses room containment design, as opposed to cGMP requirements for
cleanliness and contamination control of facilities or processes. While containment and cGMP
cleanliness design for rooms share several design solutions, and many production operations
within J&J that require containment are also subject to cGMP regulatory requirements, the
containment requirements for a room should be identified and documented independently of
requirements related to the room’s cGMP requirements.

If the risk assessment of the process equipment and operations in a room indicate that
engineering controls cannot control the source to a level below the OEL then the room, as well
as the HVAC system, has to serve as a secondary containment. The risk assessment should
describe the key factors related to containment design of the room (see Risk Assessment
section):
 Level of contamination expected within the room for maintenance and/or abnormal
conditions such as spills or isolator failure.
 Probability of abnormal conditions such as spills or isolator failure as analyzed at each
process step.
 Level of risk from airborne contamination to facilities and environment outside of the
room.

3.3.1 Laboratory Ventilation Systems

Laboratory Ventilation Systems are installed as engineering and safety devices/equipment to
protect personnel, property, and the environment. Key components of the Laboratory
Ventilation Systems include:
 Chemical Fume Hood Performance: Fume hoods are the primary air contaminant control
system to contain chemical vapors and gases. The ACGIH Ventilation Manual details
technical standards that define methods for continuous system performance. This
includes proper fume hood system specification, airflow visualization tests, face velocity
measurements, and tracer gas containment.
 Biological Safety Cabinets: The biological safety cabinet (BSC) is the principal device
used to provide containment of infectious splashes or aerosols generated by many

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 microbiological procedures. It is imperative that BSC be tested and certified in situ at the
time of installation within the laboratory.
 Laboratory space air changes per hour, outside air requirements, pressurization
requirements, filtration level and room circulation patterns are a necessary component of
a proper Laboratory Ventilation Safety System. This secondary control system and
design, ensures general control of air contaminants and substances in the laboratory to
support the primary systems.
 Specialized ventilation and containment systems (isolators, ventilated balance
enclosures, etc.) are selected, designed, installed and maintained, to protect employees
from unique exposure risk.
 Fire prevention from static charges, unusual humidity levels and other unique
environmental conditions, are a design component of the proper Laboratory Ventilation
Safety System.

3.3.2 Waste Water

Consult with your environmental professional to determine how the waste generated (solid or
liquid) needs to be managed.
 Waste disposal options and regulatory requirements should be evaluated prior to process
startup.
 Water supplies in the containment room should have backflow protection.
 Floor drains in the containment room should not be directly connected to the domestic
drainage system.

3.3.3 Room Layout

Containment design for a room should address:
 Containment of airborne contamination by the physical room envelope (walls, floor,
ceiling) and room pressurization.
 Containment of liquid spills and fire sprinkler water.
 Handling of contaminated solid waste.
 Methods of moving people and materials in and out of the room without breaking
containment.
 Once the user requirements for containment are defined, the facility floor plan should
address key points in room containment design.
 Layout needs to comply with local building codes and regulations.
 Airlocks should be provided at the entrance and exit points for the room where room
pressurization is utilized for containment.
 Airlocks should be provided at exterior doors accessing the room under containment.
 Airlocks or gown rooms should be provided where personnel are required to use
respiratory protection in the room.
 Airlocks can be employed as cascade, positive (bubble) or negative (sink); refer also to
J&J Guideline 01042-03, Guideline for Clean Room Pressurization Design (see link
below). Combinations of these three basic types are sometimes necessary when trying to
meet conflicting requirements for containment and contamination control.

J&J WWERE Cleanroom Design Platform.url

The following airlock rationales are provided to assist the team in selecting the appropriate level
of airlock. Costs of construction and operation are associated with the complexity of the airlock
and should be selected commensurate with the risk.

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Airlock “A” provides the conventional cascade airlock for clean room design. The addition of
Airlock “B” as a pressure bubble airlock prevents air leakage from the containment room into the
corridor, while Airlock “A” prevents air leakage from the corridor into the clean room. Note that
neither airlock should be used for decontamination of material or equipment leaving the room.

JJ-III (ISO 8)
Corridor Containment
0"wc Room
0.06"wc (15 Pa)

JJ-III (ISO 8)
Airlock B
0.09"wc (22.5 Pa)

JJ-III (ISO 8)
Airlock A
0.03"wc (7.5 Pa)

Airlock Figure 1

Where the process is closed and controlled to the OEL, consideration could be given to a single
airlock B to maintain the pressure differential.
 An airlock can be used for both material and personnel access to a containment room
where traffic into the room is low and simple respiratory protection is used. Separate
gowning areas, however, should be considered wherever respiratory protection is
required, especially where there is lots of material and/or personnel movement into the
space.
 Separate gowning areas should be provided where over-gowning or PAPR use is
required within the room.
 Gowning areas should be sized to accommodate the level of gowning and respiratory
protection used as well as the number of people entering the room. Gowns and
respiratory protection that are worn more than once before cleaning should be stored
separate from clothing or personal effects. Mirrors should be provided to allow visual self-
inspection of gowning and respiratory devices.
 Personnel should remove used gowns and respiratory protection before leaving the
containment suite. A de-gown area outside of the contained process room should be
provided for this purpose. Degowning and decontamination of personnel exiting the
containment room should be designed based on the risk level in the room. Consider
providing a separate degown room where there is a high risk of surface contamination on
the gown from processes generating dust or aerosols.

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 Where a single room is used for gown and degown, an SOP should be developed to
prevent contamination of personnel entering the gown room before they have gowned.
This may include a time delay between degowning and access to the room for gowning to
allow for flushing of the room by the HVAC system.
 De-gown areas should be provided with hand wash facilities.
 Used gowns and respiratory protection should be decontaminated or bagged before
removal from the containment suite. Double bagging may be necessary for high-risk
areas or during clean-up of a spill or other abnormal condition.
 The facility layout should help ensure that gowns or plant uniforms worn inside
containment are not worn outside of the plant site or taken home. Consider providing
plant uniforms for personnel working in containment areas, with separate locker areas for
changing and storage of street clothing and adjoining toilet areas. Showers may be
desired, depending on activities within containment. Locker areas should be located for
logical personnel flow to the containment area.
 Housekeeping rooms or closets should be provided within each containment suite for
storage of vacuum cleaners and cleaning materials.

Degown
-0.03"wc (-7.5 Pa)

Misting Shower
-0.06"wc (-15 Pa)

JJ-III (ISO 8)
Containment
JJ-III (ISO 8) Room
Gown 0.03"wc (7.5 Pa)
Corridor 0.03"wc (7.5 Pa)
0"wc

JJ-III (ISO 8)
Airlock B
0.06"wc (15 Pa)

JJ-III (ISO 8)
Airlock A
0.03"wc (7.5 Pa)

Airlock Figure 2
 Where PAPR use is required, a separate room for cleaning and servicing of PAPRs
should be provided.

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  Access to containment areas should be restricted to authorized personnel. The layout
should separate visitor movement from that of authorized personnel to avoid visitors
having to enter containment. Where visitor viewing of operations is desired, windows or
cameras should be provided to permit viewing of the area from the outside containment
area.
 The layout should comply with local building code with regard to people movement and
emergency egress. Emergency exit doors from containment rooms may need airlocks,
depending on room pressurization and the nature of the risk.
 The amount of equipment transfer across the containment barrier should be minimized.
Where practical, equipment cleaning should be performed in place. Where equipment
movement is necessary, provisions should be made in the design for cleaning and
decontamination of equipment prior to leaving the containment room.
 Provisions should be made for decontamination or bagging or otherwise containing solid
waste before leaving containment. Waste from containment should be treated as
hazardous waste in accordance with J&J EHS requirements.
 The facility layout needs to accommodate maintenance of HEPA filters used for
containment. HEPA filter replacement should be performed either within the containment
area or through use of safe change (bag in/bag out) filter housings.
 Terminal filters located at the penetration of the room envelope should be designed for
access from the containment room (see the HVAC section for more information). The
layout of ceiling-mounted supply and return/exhaust filters should be coordinated with the
furniture and equipment layout in the room to allow for access to the filters. Where high-
bay ceilings are used, the procedure for access to ceiling-mounted filters should be
approved by EHS, maintenance and operations SMEs before the design is finalized. Duct
or AHU-mounted HEPA filters may be more appropriate in this situation.
 Room return/exhaust air terminal HEPA filters can be either ceiling or wall-mounted.
Where HEPA filters are wall-mounted the layout needs to account for the additional wall
depth needed for the filter support frame and air plenum behind the filter. See the HVAC
section for more details on recommended HEPA filter arrangements.
 Where the filters are remote from the room, safe change filter housings should be
provided, or conventional filter housings should be located in enclosed containment areas
that can be easily sealed for filter maintenance and easily decontaminated afterwards
(see the HVAC section for more information).

3.3.4 Room Envelope

 All surfaces should be hard, washable, coved and crevice free. Paint finishes with
pinholes should not be allowed.
 Where the containment room is also a clean room refer to J&J Guideline 01043-01,
Clean Room Construction Materials and Finishes (see link below) for guidance on
selection of construction types and finishes for walls, floor and ceiling. This guideline can
also be helpful in evaluating room construction for containment, given the similar
requirements.
 Conventional clean room wall construction should be sufficiently tight for control of air
leakage in a containment room. An additional level of sealing may be necessary for high
risk/high hazard situations, especially for piping and electrical penetrations.
 Room ceilings usually have more penetrations – light fixtures, HVAC diffusers, fire
sprinklers – than the room walls, making ceiling selection important in containment
rooms.
 Air-tight construction should be adopted so that there is no risk of contamination of
interstitial spaces.

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  Lay in grid ceilings should not be used in rooms that can be potentially contaminated
unless sealed air-tight. For new construction, an interstitial crawlway should be
considered.
 Lighting fixtures should be gasketed or sealed so that the separation of the room from the
ceiling space is maintained during lamp replacement. In new construction, top lamping
should be considered.
 Ceiling-mounted fire sprinkler heads in containment rooms should be pendant type with
the head and escutcheon plate sealed to the ceiling. Recessed heads or concealed
heads with cover plates should not be used since these cannot be sealed to the ceiling.
 Testing of the room envelope leakage rate is normally necessary only for high-risk
situations.

J&J WWERE Cleanroom Design Platform.url

3.3.5 HVAC
The HVAC system is an integral part of the facility infrastructure that provides secondary
containment to the process operation in a contained room. If the risk assessment of the process
equipment and operations in a room indicate that there is a high enough risk that the exposure
is not controlled at source to a level below the OEL, then the room as well the HVAC system,
has to serve as a secondary containment boundary. This section provides design considerations
for the HVAC system when required from the risk assessment to function as secondary
containment

Refer to J&J Guideline 01042-03, Guideline for Clean Room Pressurization Design (see link
below) for guidelines on airlock applications.

J&J WWERE Cleanroom Design Platform.url

There are no specific regulatory requirements for the amount of pressure differential for
containment purposes. A pressure differential of 0.03” to 0.06”WG (7.5Pa to 15Pa) is
recommended. Where an airlock is employed, the airlock pressure should be between that of
the adjacent areas. The recommended minimum differential pressure for monitoring and control
is 0.03”WG.

 Monitoring and alarm requirements for containment room differential pressures should be
established. Local room alarms that will alert the operator (inside and outside of the room) in
the event that the required pressures are not being maintained may be required.
 Negative differential air pressure in manufacturing rooms relative to surrounding rooms is
needed when secondary containment is required. Use of airlocks/gowning rooms for entry to
process rooms should be considered.
 HEPA filters should be housed in a safe change (bag in/bag out) system or be able to be
changed into the controlled area safely without occupational exposure.
 Both supply and exhaust ductwork should be considered contaminated up to a HEPA filter.
 High hazard rooms should have HEPA filtration at the room boundary if feasible.

3.3.5.1 Room Pressurization

Room pressurization for areas other than clean rooms or rooms containing cGMP activities
should be negative to surrounding areas, including outdoors, interstitial space above room
ceilings and adjacent mechanical rooms.

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3.3.5.2 Recirculation
Recirculation of the room air to save in energy costs should be considered when use of PPE is
not required in the room. HEPA filtration of the recirculated room air should be provided. A
second HEPA filter in series, with particulate monitoring and alarm between the upstream and
downstream HEPA filters, may be necessary; this should be confirmed with a risk analysis.

3.3.5.3 Supply Ductwork

It is recommended that supply air HEPA filtration be provided for a contained room as close to
the air discharge into the room as practical, to protect against migration of room air into the
supply ductwork in the event of an HVAC shut down or power failure. Terminal HEPA filters
mounted on the room ceiling or walls are preferred. An alternate and possibly lower cost option
may be an inline supply duct HEPA module per contained room located in an accessible area.
This assumes there is enough space in the mechanical room and that the room cleanliness
grade does not require terminal HEPA filters. The following are recommendations for both
alternatives:

3.3.5.4 Ceiling Mounted Terminal HEPA Filters

Filter replacement from inside the room. Does not need to be safe change (bag-in/bag-out).
Filter integrity testing required after filter maintenance or replacement.

3.3.5.5 Inline Supply Duct HEPA Housing System

Bubble tight isolation damper down stream to allow HEPA filter replacement. If bubble tight
isolation damper (see definitions) is used down stream of HEPA, the design does not need to be
safe change (bag-in/bag-out).
 Filter integrity testing required after filter maintenance or replacement.
 Down stream ductwork should be low leakage construction tested at 1% leakage.
 Avoid components and instruments requiring maintenance downstream of filters.
 Ductwork downstream of HEPA housing should be dedicated to contained areas by
product or other appropriate segregation in agreement with EHS.
 Provisions should be provided for cleaning and decontamination of ductwork downstream
(between housing and room) of the inline filter housing.

3.3.5.6 Return/Exhaust Ductwork

It is recommended for the return/exhaust ductwork from the contained area to have room
terminal HEPA filter housings mounted as close as possible to the exhaust/return grilles. This
prevents contamination of duct-mounted devices and air handling units, and migration of air
from a contained area to other areas. An alternate and possibly lower cost option may be an
inline return/exhaust duct HEPA housing per contained room located in an accessible area
assuming there is enough space in the mechanical room. The following are requirements for
both alternatives:

3.3.5.7 Wall Mounted Terminal HEPA Housings

 Filter replacement from inside the room. Does not need to be safe change (bag-in/bag-
out).
 Pre-filter upstream of HEPA filter (between HEPA filter and room) is recommended to
extend the life of the HEPA filter (may not be required in some clean rooms).
 Bubble tight damper located down stream of HEPA filter (between HEPA filter and
remainder of air handling system) for isolation from HVAC system during filter changing.
 Material of construction of terminal HEPA housings and grills are dependent on cGMP
requirements and/or room cleaning chemicals and operation.

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 Figure 3

 Where low wall installation is used provide enough wall space such that filters can be
replaced from within the contained area. See figure 3 for a typical side view installation
of a wall mounted terminal HEPA housing. It should be noted that the figure is just a
typical example. This figure shows two filter boxes, one with a HEPA and one empty to
allow for a second HEPA installation. This was done to provide flexibility in the event
where there is a concern of break-through of the first HEPA. Another recommendation is
to install a pre-filter to extend the life of the HEPA filter.
 The figure shows a break line that indicates the material of construction – stainless steel
on one side and galvanized on the other side. Contrary to what is shown on the figure, it
is advisable to save cost by minimizing stainless steel to only where it is necessary. For
example, stainless steel can be used from the bottom plenum and below to avoid
corrosion when exposed to cleaning agents and to meet cGMP industry practices
(stainless if exposed to the room).

3.3.5.8 Inline Return/Exhaust Duct HEPA Housing System

 Bubble tight isolation damper downstream to allow HEPA filter replacement.
 If the housing is located inside of the contained area and if a second bubble tight isolation
damper is used up stream of HEPA, the design does not need to be safe change (bag-
in/bag-out). If the housing is located outside of the contained area at a location that
cannot be easily cleaned after filter replacement, e.g. mechanical spaces, safe change
(bag-in/bag-out) design is recommended for both HEPAs and pre-filters.
 Up stream ductwork (between room and HEPA filter) should be low leakage construction
tested at 1% leakage.
 Avoid components and instruments requiring maintenance up stream of filters.
 Ductwork upstream of HEPA housing should be dedicated to one contained area (must
not have branches that serve other areas).
 Provide provisions for cleaning and decontamination upstream of inline filter housing.
 Include pre-filter upstream of HEPA to extend the life of the HEPA filter (may not be
required in some clean rooms).

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4 Forms
4.1 Qualitative Risk Assessment form

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4.2 Risk-Based Exposure Assessment form

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4.3 Containment Solution Guide Template

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5 APPENDIX

Definitions
Inevitably phrases and synonyms are used throughout that you may not know or where sharing
a common definition is beneficial to understanding in a multi-disciplinary environment.

Active Pharmaceutical Ingredients (APIs)

Any substance or mixture of substances intended to be used in the manufacture of a drug
(medicinal) product and that, when used in the production of a drug, becomes an active
ingredient of the drug product. Such substances are intended to furnish pharmacological
activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of
disease or to affect the structure and function of the body

Basic Characterization:
A process used to identify the agents handled by every employee in the workplace. The purpose
of the basic characterization is to have a complete inventory of chemical agents / hazardous
substances; the Health effects; OEL/TLVs; tasks/activities or unit operations and list of workers
or job titles.

Basis of Design (BOD)

A BOD is a set of conditions, needs, and requirements taken into account when designing a
facility or product.

Bubble-tight Damper
A bubble-tight damper is an isolation damper used primarily for isolation of a filter or filter bank
during the filter change-out process. The damper is tested for providing a "bubble-tight" seal
(zero leakage) at a differential pressure of 10"WC (2.5 kPa) at the damper's fully closed
position.

Exposure
Contact with a compound. It is variable and can be modified by a wide range of measures to
control risk.

Flash point
A flash point is the lowest temperature at which a liquid can form an ignitable mixture in air near
the surface of the liquid. The lower the flash point, the easier it is to ignite the material.

Hazard
Hazard is the potential for any compound to cause harm. Understanding the hazard allows risk
levels to be set. Every substance has some hazard. The terms hazard and risk are often used
interchangeably, this is incorrect since hazard is specific to the compound (s) of concern.

Health Hazard Rating (HHR)

A numeric system used to rate the relative health hazard of a substance. The health hazard
ratings are numerically set from 1 to 4. The health hazard ratings are 1) low, 2) moderate, 3)
high, and 4) extreme. Examples include HMIS and NFPA labeling systems.

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Kst
A powder or dust sample is dispersed within the sphere, ignited by chemical igniters, and the
pressure of the resulting explosion is measured. The sample size is varied to determine the
optimal dust cloud concentration. The maximum pressure and rate of pressure rise are
measured and used to determine the Kst value of the material

Minimum Ignition Energy (MIE)

The minimum ignition energy (MIE) test determines the lowest spark energy capable of igniting
a sample when dispersed in the form of a dust cloud. The test is used primarily to assess the
potential vulnerability of powders and dusts to electrostatic discharges, but is also relevant to
frictional sparks.

Occupational Exposure Limit (OEL)

Airborne concentrations of substances that will not result in adverse effects to most healthy
workers, exposed for 8 hours per day, 40 hours per week. Most OELs are established as an 8-
hour, time-weighted average. However, short-term exposure limits (STELs) or ceiling
concentrations may also be established for compounds that may result in adverse effects from
acute exposures. For operations that work a 10 or 12-hour shift, the Brief & Scala method
should be considered to recalculate the OEL accordingly.

Process Safety Management Hazard Screening Tool

A set of questions that help an Operating Company to determine whether a Process Safety
Management program is required for a facility or a specific process. This tool is located in
EDGE2 and the Worldwide EHS Standards (Chapter 21).

Qualitative Risk Assessment

Comprehensive qualitative evaluation of the workplace designed to recognize the risk to
exposures of each worker based on the basic characterization. The outcome of the qualitative
risk assessment is an identification of the hazards, and anticipation/estimation of workers’
potential exposures using professional judgment. One outcome of the qualitative risk
assessment is the development of a baseline-sampling plan.

Quantitative Risk Assessment

An assessment based on data rather than professional judgment. The source of data should
always be stated. Interpretation of data can be based on judgment so the method of
assessment, conclusion and who conducted the assessment should be stated.

Risk
Risk is the probability that a compound will produce harm under specified conditions of
exposure. Risk can be limited to safe levels by controlling exposure

Risk-Based
A risk-based evaluation utilizes many different aspects with regard to the decision making
process. For exposure potential, a risk-based decision would take into consideration the
chemical hazard, its physical form (solid, liquid and gas), quantity, current controls utilized,
duration of exposure, dustiness for powders/vapor pressure for liquids, etc. A risk-based
decision looks at all the possibilities that could potentially lead to exposure and takes them into
consideration when evaluating the controls used to manage the risk.

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Similar Exposure Group (SEG)
A similar exposure group (SEG), also referred to as a homogeneous exposure group, defines a
group of workers whose exposure to chemicals is the same for all workers in the identified
group.

Threshold Limit Value-Time Weighted Average (TLV-TWA)

The time-weighted average concentration for a conventional 8-hour workday and a 40-hour
workweek, to which it is believed that nearly all workers may be repeatedly exposed, day after
day, without adverse effect. The ACGIH TLV-TWAs have been adopted as J&J Occupational
Exposure Limits. For operations that work a 10 or 12-hour shift, the Brief & Scala method should
be considered to recalculate the TLV accordingly

Unit Operation
A unit operation includes the equipment required to produce a specific product as part of the
entire production process. Some examples include: a tablet press, a Sanpro machine, a
blender, and a filter press.

User Requirements Specification (URS)

A document used to communicate the users requirements to a vendor or other entity. It is critical
to the success of a development project. Requirements must be actionable, measurable,
testable, related to identified business needs or opportunities, and defined to a level of detail
sufficient for system design.

Vapor pressure
The vapor pressure of a liquid is the pressure exerted by its vapor when the liquid and vapor are
in dynamic equilibrium. It is important to specify the temperature when stating a vapor pressure
because vapor pressures increase with temperature. Also, be aware that there are several
different units of pressure. Vapor pressure and boiling point have an intimate relationship. The
boiling point is the temperature at which the vapor pressure of the liquid equals the external
pressure.

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