Environmental Monitoring Performance Qualification (EMPQ) Risk Assessment

Environmental Monitoring Performance Qualification (EMPQ) Risk
Assessment
Producing non-terminally sterilized parenteral products requires strict

microbiological controls to mitigate potential contamination in highly controlled
environments. A holistic Sterility Assurance program is the combination of all
facility and process controls, practices, and procedures that ensure, with a high
degree of confidence, that products are free of microbial contamination. One of
most fundamental measures of Sterility Assurance program effectiveness is
Environmental Monitoring (EM). Although there is not a direct correlation
between EM data and product quality, it is a representative measure of holistic
environmental contamination control and capability representative of multiple
mechanism within a site’s Microbiological Control Strategy.
Environmental Monitoring Performance Qualification
It is critically important to assess the processing environment to determine those

areas that have the highest risk of microbiological ingress. This will develop a
deep understanding of the interplay of inherent facility/process contamination
risks and mitigations. Understanding these risks informs the sterility assurance
program and enables development of a robust EM program to measure per-
formance. Environmental Monitoring Performance Qualification (EMPQ)
provides documented evidence that an area is capable of meeting specified
levels for the proposed classification. This qualification activity is an overall
assessment of the design and environmental controls (e.g., HVAC, gowning,
disinfectants, behaviors, etc.) of a facility. The EMPQ should evaluate the
facility along with associated equipment (sterile and non-sterile) and processes
within the area. This activity allows the selection of routine sampling sites for
on-going facility environmental monitoring. The routine sites should be
determined based on risk assessment and include the following:
1. proximity to sterile components, equipment and/or product

2. duration of equipment exposure
3. personnel movement
4. duration of personnel exposure and
5. cleanability.
Execution of an appropriately designed EMPQ will inform the routine EM
program such that it is robust and representative.
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Risk Assessment Tool
Risk Assessment is a systematic process of evaluating the potential risks that

may be involved in an activity or undertaking. There are many types of Risk
Assessment/Analysis tools (e.g., failure mode and effects analysis (FMEA),
fishbone, process mapping, flow chart, etc.) available for use for the
biopharmaceutical industry. Any of these tools are acceptable for evaluating
risk. As stated earlier, the EMPQ is an evaluation for microbiological and
particulate levels within the facility being qualified. Therefore, an assessment
should provide an appropriate structure to evaluate microbiological or
particulate generation and/or ingress into the area. This risk assessment tool
allows the assessor a systematic approach to evaluate an area for
microbiological and particle hazard ingress.
Risk Factor and Ranking
Risk factor identification is a systematic use of information or data to identify

hazards the assessor will consider while executing the risk assessment. These
factors allow the assessor to evaluate the environment for risk of hazardous
ingress. The environment is assessed related to exposure to sterile components,
equipment, and product as it relates to proximity and the duration of the
exposure. Personnel activity is then evaluated, as personnel are the number one
source of microbiological contamination, along with the duration of the activity.
Cleanability of the environment including equipment in the area will allow the
assessor to determine the appropriateness of the area or equipment cleanroom
construction. Airflow Pattern Testing (AFPT) is another critical factor that
informs development of the EMPQ but is not directly assessed as part of this
risk assessment.
Ranking of the risk factors are critical, as these allow the assessor to
systematically rank risk associated with the area and/or process(es) during the
assessment. These rankings are comprised of numerical and qualitative values.
Both numerical and qualitative values are aligned to provide the assessor a
consistent risk ranking process, see Table 1. Along with providing numerical
and qualitative values for the risk factors, each must have clearly defined
descriptions for each factor that will be evaluated, see Tables 2-6. The
descriptions allow the assessor to consistently assess the area while executing
the Hazard Analysis Critical Control Points (HACCP) analysis.
Risk Assessment and Analysis
Defining risk factors and rankings ensures consistent execution of the EMPQ
risk assessment process. First, the assessor will need up-to-date drawings for the
facility to be assessed. Next, the assessor will delineate the facility into grids
based upon area classification. These grids are as follows: Grade A 1m2, Grade
B 2m2, Grade C 3m2 and Grade D 4m2, see Figure 1. The assessor will number
each grid from higher classification (Grade A) to lower classification (Grade D).
The assessor then develops a cross-functional team (Quality, Engineering,
Operations) to perform the risk assessment.
The cross-functional team will then evaluate each grid spatially and document
numerical risk ranking for each risk factor. The risk analysis is documented as
the cross-functional team moves through the facility grid. In addition to
establishing the grid and numerical risk factor rankings, the assessor documents
the following: 1) classification,2) grid activity 3) risk score and 4) rational for
risk factor rankings (see Table 7 for an example). The cross-functional team
will ensure the activity for each grid is clearly documented, along with the
associated risk rankings. The overall risk score is calculated by multiplying the
risk factor rankings. The risk score provides the overall risk associated to the
grid. It is imperative that clear rationale is provided for each risk ranking for the
associated risk factors. Documentation of all appropriate data and rationale, that
led the cross-functional team risk ranking, is critical to ensure transparent
communication of the risk assessment outcome to facility stakeholders. The
assessor then communicates, through document review and approval, the
outcome of the risk assessment to all facility stakeholders.
Risk Acceptance Criteria
The acceptance criteria for the assessment program is based on all possible
combinations (i.e., combinatorics) of risk factor rankings within the three risk
groupings (Low, Medium or High). The acceptance criteria were developed for
the equal distribution of qualitative risk rankings based on the total number of
possible calculated risk rankings. There are 21 distinct scores that can be
obtained from the 243 possible combinations derived from FIVE factors when
rated 1, 2, or 3. Table 8 provides the 21 possible scores with how many
combinations (“Count” in Table 8) each score can be obtained from (the counts
will add to 243). The 33% quantile is 12 and the 67% quantile is 36, which are
the demarcations for low and high risk, respectively.
After completion of the risk assessment, the assessor determines the overall risk
using the acceptance criteria discussed previously to determine overall risk
(‘Low’, ‘Medium’ or ‘High’) for each grid within an individual room. This
allows the EMPQ assessor to determine appropriate distribution of
environmental monitoring sampling sites, based upon risk, within the facility.
EMPQ results along with the risk assessment will drive final selection of routine
EM sampling sites, which facilitates evaluating if a manufacturing space
remains in a state of microbiological and particle control throughout production.
Summary
There are many ways to execute risk analysis of controlled and classified areas
within a manufacturing facility. This is an example of a robust integrated
HACCP approach to understanding contamination risk within production areas.
Evaluating the environment in this manner will allow the user to identify
locations with the greatest potential for microbial and particulate contamination
and enables risk- based selection for EMPQ sampling locations. Ultimately, this
process ensures robust detectability of the potential hazards that exist in the
routine production environment and activities, and in turn generates meaningful
data relating to environmental state-of-control during routine operations. Use of
this risk analysis builds an EM Program built on a foundation of scientific
rationale and excellence.

Environmental Monitoring Performance Qualification (EMPQ) Risk Assessment

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Environmental Monitoring Performance Qualification (EMPQ) Risk Assessment

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Environmental Monitoring Performance Qualification (EMPQ) Risk

Producing non-terminally sterilized parenteral products requires strict

Environmental Monitoring Performance Qualification

It is critically important to assess the processing environment to determine those

1. proximity to sterile components, equipment and/or product

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Risk Assessment Tool

Risk Assessment is a systematic process of evaluating the potential risks that

Risk Factor and Ranking

Risk factor identification is a systematic use of information or data to identify

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