eLN SUPPLEMENT


manufacture and documentation of pharma - ceutical production is strictly controlled by regulatory authorities. Good Manufacturing Practice (GMP) is the term used to describe the regulatory controls, which are enforced by strict internal compliance systems within pharma - ceutical companies. The industry has gained confidence in paper-based compliant GMP workflows, with wet-ink signatures, for


was transcribed into a Word-based format. Our first key question was whether it would be possible to create the Process Description within the eLN by ’cloning’ the experimental write-up and then simply making any required formatting changes to comply with the well established generic specification for a Process Description. The second key question was whether an eLN-based Process Description


provide manufacturing ’instructions’ for each batch of manufacture. As an additional bonus, it was found that the scaled instruction document could be followed and annotated during manufacture to provide an accurate Batch Record. Very quickly, we had devised the basis of an effective eLN-based Process Description and Batch Record system that both R&D chemists and manufacturing chemists were keen to develop into a working system.


Figure 1Transcription of documents in the paper workflow


manufacture of clinical trials API and there has been a reluctance to change to electronic records. Although external regulatory guidance on the use of electronic systems is strict, the regulations were not intended to preclude their use. Indeed, the FDA 2003 guidance2


states,


“These regulations, which apply to all FDA program areas, were intended to permit the widest possible use of electronic technology, compatible with FDA’s responsibility to protect the public health”. One of the primary challenges in imple -


menting an electronic lab notebook (eLN) is getting buy-in from the stakeholders who interact with the experimental data being recorded. Nowhere is this challenge more pronounced than in validated environments such as analytical GxP testing and GMP manufacturing. In these areas, the need to comply with strict regulatory mandates about how methods, processes and testing are documented and validated has led to even stricter internal controls than are codified in entrenched, paper-based workflows. In the first part of our pilot study, we chose


to avoid questions of GMP compliance and address some key questions regarding the potential effectiveness of the eLN to help with effective tech transfer. For each stage of manufacture the deliverable of the R&D department is a ’recipe’ for manufacture called a Process Description. This document is based on a laboratory experimental write-up (eLN) that


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European Pharmaceutical Review Volume 16 | Issue 4 | 2011


could be a more effective technology transfer format, enabling the manufacturing chemist to create a plan for larger scale manufacture by simply scaling the procedure and materials using the capability of the electronic system. To avoid compliance challenges we worked


on a non-GMP manufacture for the initial pilot study and quickly discovered that cloning an experimental write-up provided a very effective basis for the Process Description. The materials and quantities were already set and the write-up was easily modified to form a list of instructions as required in the Process Description


Addressing the GMP Compliance Challenge Although there was enthusiastic support from process scientists to develop the system for GMP manufacture, gaining approval for GMP-based pilot studies was a challenge. There was initial scepticism that the eLN system was not specifically designed as a tool for GMP manufacture and could not be used in accord with internal regulatory ER/ES guidelines. However, part of our case for continuing was that paper notebooks had not been designed for this either, but nonetheless had been successfully adapted for the purpose. We were convinced that it was only by trialling the eLN-based approach that we would learn more about how to design a workable electronic system. From the non-GMP trial the potential to build a better Quality Management system based on electronic records had been recognised and this motivated the stakeholders to embrace the possibility of moving from entrenched paper systems to new electronic ones.


Figure 2 Pilot-driven empirical iterative system design


document. Additional processing information was then added and the document was checked and approved by an R&D line manager. The chemist responsible for the manufacture also found significant advantages by cloning the Process Description and scaling the quantities to


Building internal and external partnerships


was the key to the ultimate success of the project. A small core team was built to drive the project and included representatives from Chemistry R&D, Development Manufacture and crucially a senior QA manager, as well as a Symyx


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