The document discusses Alcon's Risk-based Exposure Evaluation Process (REEP) which aims to protect pharmaceutical workers from exposure to active pharmaceutical ingredients during manufacturing. REEP involves taking an inventory of all APIs, prioritizing them based on worst-case exposure scenarios, conducting breathing zone sampling during tasks using IOM samplers, analyzing samples using Bayesian Decision Analysis to calculate the required Assigned Protection Factor for respirators. Preliminary results from six sites found over 50% of 57 samples exceeded exposure limits, and improvements to controls are underway based on factors identified to contribute to high exposures such as work practices, engineering controls, and process design.

1. Risk-based Exposure Evaluation Process: Protecting Worker Exposure to
Active Pharmaceutical Ingredients
Alexandra J. Fields, Dr. Alisa Rich, and Janet Gruner
DISCUSSION / RESULTS
METHODS
CONCLUSION
Thanks to:
Janet Gruner
Kathy Meissner
Dr. Alisa Rich
Alcon Global HSE
The purpose of this project is to support Alcon’s Risk-based Exposure
Evaluation Process (REEP). The objective of REEP is to transfer Novartis’s
decision-making process from a hazard-based approach to a risk-based,
data driven approach in order to protect their pharmaceutical workers’
exposure to active pharmaceutical ingredients (APIs) during the
manufacturing process.
The first step of REEP is to take an inventory of all the APIs used at the sties,
and then create REEP Assessments. Next, the REEP Assessments are
prioritized based on which APIs could represent the worst case scenarios
when sampled. Breathing zone sampling is carried out at each site, using an
IOM sampler. Sampling data is collected for the duration of time to perform a
task – not an 8-hour time weighted average to avoid underestimating the risk.
During sampling, observation of the unit operation process is conducted and
critiqued. The samples are then sent to a qualified Industrial Hygiene (IH)
laboratory for analysis. Lastly, sampling results are statistically analyzed using
Bayesian Decision Analysis (BDA). BDA is used to calculate the Assigned
Protection Factor (APF) needed for a respirator to protect workers from over-
exposure.
Bayesian Decision Analysis
REEP is a continuous process that is
evolving into a fundamental tool to
track potential exposures, analyze
sampling results, and execute
corrective actions in order to protect
Alcon’s employees from harmful effects
of Active Pharmaceutical Ingredients.
These preliminary results revealed the
first set of risk-based API exposure
data for Alcon’s six pharmaceutical
sites. Based on the results,
improvements to multiple levels of
controls such as engineering,
administrative, and respiratory
protection equipment (RPE) are
underway.
From January 2015 – March 2016, all
six pharmaceutical sites collected a
combined total of 57 samples for 8
different APIs. 31 out of the 57
sampling results were above the
Novartis Internal Occupational
Exposure Limit (NIOEL) – about 54%.
After analysis and discussion with the
sites, the main contributing factors to
the high exposure results were found
to be:
1. Poor Worker Practices
2. Not Utilizing Engineering
Controls
3. Rare Steps in the Process
4. Poor Process Design
The sampling results which came back
under the NIOEL provided confirmation
that the engineering controls and
established worker practices are
effective at protecting the workers from
exposure.
INTRODUCTION / BACKGROUND
Plant A
API
Sampling
Date
NIOEL
(µg/m3)
Results
(µg/m3)
Tobramycin 17-Jun-15 150 726
Tobramycin 21-Jul-15 150 95.3
Pilocarpine HCl 23-Oct-15 50 14.8
Dexamethasone 14-Dec-15 8 7.46
62.9% certainty that an APF of 10 is
sufficient; 95.1% certainty that an
APF of 50 is sufficient