eLN SUPPLEMENT


had reduced documentation considerably. Moreover, the overall quality of the documents was much improved. Compliance and quality audits were also


carried out during the pilots by both Development R&D and Operations QA groups.


Record (MBR) is the most appropriate place for this to be captured. In creating the MBR, one of the main jobs is to specify, in the batch instructions, points during manufacture where check-in must be carried out, to create a specific audit trail point. Based on a risk-assessment,


harmonising these working practices we recognised an opportunity to establish a defined business process for GMP manufacture of clinical trials API as part of a pharmaceutical quality system (PQS), all of which is in line with modern regulatory guidance (ICH-Q10).


Conclusion By employing an iterative pilot-driven approach to system design, we have devised an effective e-Batch record system for clinical trials API manufacture that provides major efficiency gains together with an improved system of quality management, which is in accord with principles outlined in ICH-Q9 and ICH-Q10. Effective collaboration between stakeholders from all interested departments was a vital element in developing a workable system that has been universally accepted by users. Improving the technical efficiency of information transfer between R&D and development manufacturing was the initial objective, whilst for QA improved quality management was a central goal. Taking a structured holistic approach to the execution and recording of manufacturing processes enabled us to


generate a global business process and harmonise activities.


The conclusion of the audits was that “overall the system is acceptable with regard to GMP compliance.” The R&D QA group was particularly pleased with the transparency of the documentation, which made the QA assessment easy to conduct and helped chemists gain more insight into manufacturing processes. Some important observations and issues were raised during the pilots and these enabled us to make further useful refinements to the e-Batch record system before it was launched for routine use in GMP manufacture. Also, based on the learning derived from the pilot studies, an internal guideline on data integrity was revised to take better account of electronic documentation systems. A key question that needed to be addressed


was, when and how will the Batch Record be updated during manufacture? The e-Batch Record actually comprises a sequence of files in the system audit trail representing each ‘check-in’ event, so the real question is, when is a check-in required? According to the principles of our system design, this should be defined by a risk-assessment (ICH-Q9) and the Master Batch


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points before and after key unit operations are defined for check-in and we have also generated a generic list of activities / events that trigger a check-in requirement. A specific weakness of the eLN is that it is a free-text system with no facility to lock-down text, so clear procedures and guidance was put in place to minimise this risk. Additionally, a system improvement plan was created with our vendor (Symyx) to ensure that future versions of the eLN system enabled lock- down of text sections in batch records. Counterbalancing these limitations of the electronic system there is the advantage, over a paper system, that valid timed and dated events are captured in the audit trail. Some of the questions raised by the QA


group during the trials helped drive more efficient working practices together with better quality procedures that could be harmonised across manufacturing sites. Additional efficiency benefits were derived by removing non-value adding procedures, and quality management was enhanced by clarifying the purpose and requirements for such things as in-process tests and controls. As we were changing and


John Leonardis currently a Principal Scientist at AstraZeneca in Global Pharmaceutical Development. His current prime responsibility is for Laboratory Automation and Informatics, strongly linked to synthetic route design and drug substance process development. John has


been working in pharmaceutical process R&D for over 10 years and has led both drug development and technology based projects. Previously he worked as a professor of organic chemistry at the University of Salford, following a number of industrial and academic research appointments, which included Columbia University and Shell Research. John is a Fellow of the Royal Society of Chemistry.


References


1. Electronic Records; Electronic Signatures Final Rule, 62 Federal Register 13430 (March 20, 1997)


2. Guidance for Industry Part 11, Electronic Records; Electronic Signatures - Scope and Application, FDA (August 2003)


3. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), Quality Risk Management Q9 (November 2005)


4. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), Pharmaceutical Quality System Q10 (June 2008)


European Pharmaceutical Review 19 Volume 16 | Issue 4 | 2011


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