Many leading life science companies
have cost reduction initiatives to
eliminate the routine, nonvalue-added
tasks through automation. In most
regulated companies, approximately 70%
of laboratory-based resources are focused
on compliance-related functions, while
the key needs in discovery/research are
intellectual property related. Within the
laboratory operations, the drive to go
paperless is a strategic initiative that will
yield operational benefits on productivity
and cycle time reductions. This electronic
environment enables short- and long-term
communications between the operational
data islands ranging from discovery, development,
pilot operations, and final quality
control laboratory results. Key operational
data will help in early development efforts
on new processes by enabling better Quality
by Design (QbD) experiments that are
based on real-world conditions. Interfacing
those disparate data sources and other
process information management technologies
(i.e., enterprise resource planning
[ERP] systems and LIMS) provides
enterprise-wide intelligence that can combine
to improve overall commercialization
cycle times. This paper outlines the
key functional requirements for discovery,
development, and cGMP electronic laboratory
notebooks (ELNs).
Industry challenges
The pharmaceutical, biotechnology,
and generic businesses are challenged
to improve product quality, productivity,
return on investments, and compliance,
while at the same time producing
double-digit growth for their stakeholders.
This will become more difficult due to
the large number of products coming off
patent over the next few years and vulnerable
new product pipelines. The entire
product life cycle (research, development,
and manufacturing) must be streamlined.
Within this environment, large amounts
of data are being generated across the
entire enterprise in support of operations.
Today, most laboratory operations rely on
the ubiquitous use of paper-based systems,
which are routinely fraught with potential
human-generated errors that require
constant checking and manual verification
procedures that add no value to the
operations and contribute significantly to
the costs. Also, compliance with regulatory
requirements is a special challenge
for the life science industries, with high
costs stemming from activities centered
on compliance.
As a new product emerges from R&D and
goes into commercial operations, 21 CFR
Part 11 and ICH guidelines impose additional
demands on the pharmaceutical and
biotechnology industries. These regulatory
demands do provide a rational framework
for quality systems and electronic records.
Key to the new strategy is a risk-based
approach as defined by impact on human
health. While most discovery and R&D
areas are low risk, the QC/QA functions—at both the clinical materials and product
release stages—within the pharmaceutical
production arena clearly fall into a “high-risk”
definition.
The paperless laboratory: ELNs in discovery, development, and cGMP QC
The automation initiatives in production
over the last decade were driven
by the need to precisely control production
processes and reduce costs. Supervisory
control and data acquisition
(SCADA) and manufacturing execution
system (MES) implementations
are good examples of such automation.
That environment is now being further
scrutinized, as the costs associated with
other closely related laboratory functions
that are nonvalue-added tasks are
being reviewed. One identified area is
the huge number of paper processes used
in research, development, and manufacturing.
These “e-laboratory” initiatives
have received attention as one of a small
number of critical-path issues that, if
solved, will yield significant cost savings
for decades. Going paperless in research,
development, and manufacturing laboratory
functions will allow the operations
to manage the master data across
the enterprise’s facility and geographical
locations. Some key insights obtained from a research survey conducted by
VelQuest Corp. (Hopkinton, MA),
entitled “Laboratory IT—Enabled Solutions
Research Report,” are revealing:
“Our company has a priority initiative
to delegate decision-making, enrich
jobs, and create accountability for
delegated decisions. We see paperless
laboratories as a tool to empower
analysts to fulfill this charter. We
also want to reduce the time laboratory
supervision spends on review
and investigations, so they can work
on process improvement.”
“We believe [that through paperless
laboratories] real-time feedback
enables analysts to reduce errors,
minimize rework loops, and correct
ambiguous results immediately.”
The key issues mentioned here are shortened
review times, reduced operator errors,
minimized rework and investigations, and
ultimately an enhanced work experience
for well-trained analysts and operators. All
of these issues contribute to costs and product
release cycle times, and, if eliminated
or minimized, will significantly affect the
operation’s bottom line.
Figure 1 - Documentation stage and fundamental ELN requirements from discovery to development to quality control.
As scientific documentation work moves
from discovery to development to commercialization
(i.e., production), the
fundamental informatics requirements
change dramatically. Attempting to find a
“one-size-fits-all” ELN product is unrealistic
at best and most likely impossible to
achieve. The fundamental needs evolve
from a free-form, open structure to a
structured (but flexible) experimental set
for ruggedization to a more rigid method/standard operating procedure (SOP)-based execution platform for quality control.
A brief overview of these concepts is
outlined in Figure 1.
Research-based vs cGMP ELNs
Electronic laboratory notebooks began
to appear in the late 1990s and were
mostly utilized in research laboratories
to document experiments and capture
any intellectual property that might
be required for potential future patent
defense purposes. In fact, many of the
early ELNs for research were simply a
secure word-processing software product.
Today, research ELNs include chemical synthesis programs and stoichiometric
calculations in the software product.
Key to research-based ELNs is their open
structure, which is required for general
observations and experimental detail.
Often modern research/discovery ELNs
are “structure-centric” and have sophisticated
search capabilities based on
structure and substructure drawings of
the experimental molecules. This capability
is important to effectively search
and communicate previous experimental
research with colleagues to eliminate
duplication of work.
Figure 2 - Research ELNs vs QC ELNs—open vs structured approaches.
When one approaches a QC/QA environment,
an open-structure environment
is not preferred and is in fact a
liability. In a cGMP QC laboratory, an
ELN must be structured and contain a
method-centric operational protocol,
with all laboratory systems (instruments,
SOPs, reagents, etc.) integrated
into the e-method. Rigorous attention to
compliance requirements for the GMP
ELN, including reagents, instruments,
and devices used in the execution of test
methods, must be automatically verified
for their “compliance state” prior to use.
In this way, QC data are validated in
real time. In general, the major differences
between research ELNs and cGMP
ELNs are outlined in Figure 2.