Existing regulations involving quality-control (QC) monitoring for biopharmaceutical companies require review of production
control records and investigation of issues, including any signs of failures that could affect product sterility. Industry
guidelines call for quality data analysis to identify and respond to adverse trends. Visualization and trending tools allow
analysts to track adverse trends. As a result, companies must monitor in-process, utility-support systems, and the production
environment on a consistent and standard basis (1).
Currently, designing QC programs for water and utility systems includes the identification of critical monitoring points,
potential design flaws, and operator error. They also include continuous in-process monitoring, system validation, and system
maintenance. Although QC organizations provide sound monitoring systems, a shift from paper-based QC to automated QC will
help improve the management of the data being produced.
Figure 1: Using a quality-control repository allows for a smooth flow of information, automation of processes, and capture
of information. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
A paper-based QC process is still common for planning activities, collecting and processing samples, and analyzing data. Recording
data on paper and in spreadsheets is time-consuming and creates many opportunities for errors and delays. Production and QC
organizations each have responsibility for different parts of the monitoring process. This division of responsibility isolates
key information. For example, QC is typically responsible for monitoring microbial activity via manual samples processed through the laboratory. Production is typically responsible for the in-process and continuous-monitoring
points that provide indicators of microbial activity and process control. These disconnected sources of information and a
lack of standards for sharing data may result in critical information not being shared until after an out-of-specification
event occurs. The disconnected process results in increased labor costs, wasted time on recordkeeping, and delays in reporting,
which in turn leads to ineffective data analysis, a reduction in the overall effectiveness of the QC program, and potentially
the speed of product release. Automated processes provide an speed of product release.
Figure 2: The paperless quality-control process can eliminate11 of 25 tasks across the sample scheduling, collection, processing,
and reporting operations. Light blue boxes indicate eliminated tasks; darker blue boxes indicate retained tasks.
Automated processes provide an electronic representation of the QC program, eliminating many of the clerical steps required
in a manual, paper-based system—recording, reconciling, storing, and retrieving information. Compliant and accurate information
goes to a QC repository that is available on corporate networks providing comprehensive data on all key monitoring points.
Data are immediately available for reporting, trending, and investigative support through a variety of ad hoc analytical and
visualization tools, statistical process control software, and other widely used software packages for professionally formatted
Throughout the process, samples are collected containing information such as location, time, product/lot, and equipment traditionally
transcribed on paper. Specialized QC software allows this information to be recorded electronically at the point of sample
and prevents omission errors through the system by requiring entry of information into each field. It also can automatically
fill in correct information where possible and incorporate bar-coded information to further reduce the potential for handwritten
These samples are checked into laboratory storage or equipment such as incubators. The QC software controls which samples
can be submitted and their destination points, thereby further reducing the chance of error. To reduce the chance for deviation
from a procedure, controls also are in place to manage the duration of incubation/storage.
Samples are tested and results are read. Information is electronically recorded for these steps, and calculations are automatically
performed eliminating the risk of calculation error. Results are compared against the alert/action limits by the software
and users are notified when a sample is out-of-specification.
Lastly, these samples are ready to be reviewed. Reviewers are able to see all the information recorded during the previous
steps, including the task performers. Visual cues specify the samples that are out-of-specification. The data is available
for trending. Traditionally, paper information had to be entered into a spreadsheet or database then manually reformatted
for trending. The use of QC software allows the user to trend at the click of a button.
A typical paperless QC process starts by scanning a barcode to identify QC sampling requirements at a specific location such
as a cleanroom, utility port, or production line. The location at which the sample is taken, media used, equipment used (i.e.,
total organic carbon apparatus, conductivity meter, and pH meter) is recorded.
Wireless tablet personal computers, barcode scanners, and thermal barcode printers using sterile label stock can be used to
perform the mobile data acquisition. Sealed laptop computers can provide the capability to run the specialized QC software
as well as other software systems such as document management applications for standard operating procedure (SOP) access within
an aseptic production environment. This automated solution component eliminates the risk of introducing shed particles from
paper copies and helps to improve overall compliance.
Automation can reduce scheduling, sampling, and associated time for managing the monitoring routines by 35–50%, as reported
at Lonza's manufacturing facility for biopharmaceutical products in Walkersville, Maryland. Products range from research reagents
to licensed test kits to regulated parenteral products.