Ending the Paper Chase

Electronic notebooks (ELNs) have become a fixture of drug discovery laboratories, improving search capabilities, simplifying report generation, enhancing intellectual property protection and facilitating collaboration. Until recently, fundamental workflow and regulatory differences between R&D and manufacturing prevented many drug makers from using ELNs in post-discovery operations.

Responding to these different needs, ELN technology is evolving along two parallel paths: one optimized for discovery, the other for good laboratory and manufacturing practices (GLP and GMP) environments. Will these paths ever converge? Probably not, or at least, not for a while, experts agree (see "One Size Fits All?" below).

Compliance, operating cost reductions and the need for “right the first time” documentation will drive the use of electronic notebooks in manufacturing — in addition to keeping your staff from being suffocated beneath mountains of paper.

Nevertheless, pioneers have taken paperless compliance into more quality assurance and control laboratories, and a few are using it on the manufacturing plant floor. For example, Novartis has equipped operators and quality staff at its Suffern, N.Y. facility with ELNs for the past year and a half.

What exactly is an ELN? “The term means different things to different people,” says consultant Guy Talbot, based in Cedar Grove, N.J., who had spearheaded Purdue Pharma’s implementation of ELN technology in R&D and quality applications (see "Purdue Pharma Goes Paperless," Pharmaceutical Manufacturing, June 2004). Talbot defines ELN as a software application that accepts raw data in much the same way as a LIMS (laboratory information management system), but which also allows contextual annotation and data mining, while facilitating collaboration.

ELNS are integrating with laboratory information systems (LIMS) and other key IT applications. “The heart of ELNs is integration,” says Michael Elliott, president of Atrium Research, Inc. (Wilton, Conn.). “Any vendor that doesn’t offer that is not going to get very far.”

Most ELNs operate on open XML platforms and interface easily with document management systems (DMS), corrective and preventive action (CAPA), manufacturing execution systems (MES), enterprise resource planning (ERP) platforms and other software.

After a lab function has been completed and signed off on, for example, an ELN can automatically transmit data to an MES and become a means of controlling operations. A document management system can be linked with a notebook to ensure that lab analysts are using the proper procedures, then, once the lab has results, data can be sent back to the DMS, Elliott says.

The newer ELNs, on both the R&D and manufacturing sides, offer improved capabilities. At this point, Elliott says, ELNs are forcing more manufacturers to rethink their entire IT infrastructure. “Large pharmaceutical companies tell us that, as ELNs mature, they’re covering requirements that LIMS used to handle,” he says.

In research, the notebook serves as the nexus for laboratory work and everything associated with it: files, structures, spectra, printouts, raw data, structure-activity relationships, as well as notes. Where research notebooks needn’t tie in instrumentation as intimately, GLP and GMP notebooks must interface with instrumentation, sensors and machinery, and fit within the validation environment for those devices. In an analytical laboratory, the method includes instrument calibration and validation data, which may be viewed along with the result from any test.

As soon as you go into manufacturing, “everything changes with respect to documentation,” notes Ken Rapp, CEO of VelQuest (Hopkinton, Mass.). VelQuest’s SmartLab product is primarily used in QA/QC labs, which must meet both good laboratory and good manufacturing practices. “In GMP, the integration platform, by law, is the method,” he says.

“The method and instrument data are inseparable,” says Rapp. “The instrument has to be integrated directly into the method.” VelQuest’s ELN, for example, contains a library of hundreds of commonly used analytical instruments, and utilizes these as a Microsoft Windows computer would use printer drivers.

Variability is simply not an option. GMP users are looking not just for a data repository, but “metadata” — all the information about a data point that becomes relevant in a highly regulated environment. And more companies are approaching R&D ELN projects this way, with a view to making data accessible throughout their organizations.

Right First Time and ROI

Compliance, operating cost reductions and the need for “right the first time” documentation will drive ELN use in manufacturing. These goals have already been met or exceeded by ELNs deployed in QC analytical laboratories.

At Forest Labs in Dublin, Ireland, for example, quality manager Dennis McDaid says that in the year since Forest’s quality department has implemented ELNs, the technology has improved quality and compliance, as well as staff morale, and allowed management to monitor and trend data continuously. Forest expects the technology to pay for itself in another 1.5 to 2 years, based on a 30% reduction in product testing time, and 50% reduction in resources.

Those same benefits could make ELNs extremely attractive for manufacturing, especially considering the amount of time and resources spent on drug batch documentation today. ELNs would minimize the time that operators spend functioning as “scribes” and allow them to focus on production.