With over 2000 different raw materials being analysed in its laboratory, a busy pharmaceutical company decided that a LIMS system could be justified on the basis of anticipated efficiency savings and improved GMP. John Dickson and Peter Sheppard outline the project and show how laboratory personnel became a key part in its success.
CP is a rapidly growing, fully independent, integrated pharmaceutical business based in Wrexham, UK. It employs over 450 people developing, producing and marketing branded and unbranded prescription medicines.
The company manufactures a range of pharmaceutical dosage forms at the Wrexham plant, including solid dose products, creams, ointments, liquids and sterile injectables.
As well as the manufacture of CP licensed products, the company provides contract manufacture and development services for a range of clients worldwide.
CP is currently nearing the end of a successful laboratory information management systems implementation of Nautilus LIMS within its quality control (QC) laboratories, in partnership with the informatics business of Thermo Electron.
The project commenced, with approval for purchase by the CP board of directors, in October 2000. The project was justified on the basis of anticipated efficiency savings and GMP improvements.
Ensuring that raw material, product and environmental testing specifications were in full compliance with regulatory requirements utilising the existing manual paperwork systems was a laborious and costly process.
New product introductions (a frequent occurrence at CP) required extensive laboratory input to provide the required documentation to support new testing methods and specifications. The implementation of Nautilus LIMS was an opportunity to replace many of the manual paperwork systems.
The CP core project team consisted of six personnel. Training of these individuals commenced at the end of October 2000, with all project members attending the Managing Nautilus course at Thermo's offices in Altrincham, UK.
The project commenced with five 5-day workshops run by Thermo consultants at CP. The purpose of these workshops was to review the manual systems and processes at CP and integrate them into the Nautilus application.
Where improvements to working practices could be instigated using Nautilus, existing systems were modified.
All project members were involved in all aspects of the workshop sessions. The workshops also served as system training for CP personnel, enabling them to continue the configuration of Nautilus and to set up all required workflows after the workshops were completed.
Using patent-pending workflow functionality in Nautilus, users can graphically design a workflow of a life cycle in the laboratory.
Workflows are best described as graphical representations of laboratory and business processes. The lifecycle of a new item such as a sample can be mapped onto Nautilus. This results in the assignment or creation of relevant aliquots, tests, results and associated reports, with no requirement to customise the LIMS by means of a programming language.
Other business priorities at CP during 2001 meant that each member of the project team was only spending about 25 per cent of their time on the project. Although the project continued to progress, the process was slowed down.
Refocusing the team
In January 2002, changes to responsibilities and structure within the QC department were implemented, which provided additional resource for the project.
One member of the project team was now dedicating100 per cent of their time to the project, with the other members of the team allocating approximately 50 per cent to 75 per cent of their time.
From this point onwards, the project teamwere able to concentrate their efforts on completing all test, aliquot, sample and study workflows, allof which were required for deployment of the system.
Configuration of all test workflows necessary for the first phase of the implementation (more than 1000) was the largest task. This required three hours per day from January 2002 onwards and involved a member of the project team and a senior lab analyst/technician, who was fully familiar with the method concerned.
Each test workflow was configured to include the various types of testing performed in the laboratory (such as product release, stability), calculations to determine final results, and reports to be utilised as laboratory worksheets.
During this period, other project team members were completing the set up of the remaining static data items while raising the necessary documentation for validation of the system.
The system went live during Summer 2003 for the following workflow types: raw materials, injectable preparations, water samples, viable microbiological environmental monitoring, instrument service & calibration, and operator training.
Other product types will be implemented in subsequent phases (three-month intervals approximately), when their workflows and validation testing are complete.
Following implementation, the system will be closely monitored to assess all improvements in efficiency and productivity.
Company lead times for QC testing will be amended on the basis of the new turnaround times for raw materials and products, from information derived directly from the system.
Analysts and technicians will be required to complete daily timesheets, detailing the time actually spent performing testing.
Any reductions as a result of the implementation of Nautilus LIMS will enable company standard product times to be reduced, which will have a direct financial benefit for the business.
Validation
CP Pharmaceuticals is subject to regulatory inspections from the MCA and FDA, and has successfully undergone a pre-approval inspection (PAI) for a US client company's new drug application (NDA). So the system must be validated to current MCA and FDA standards.
Since October 2002, the equivalent of two additional persons have been added to the project team to assist with the documentation and validation requirements, including validation protocols and reports, operating procedures, and training requirements for all QC personnel.
Currently, there is the equivalent of four persons working full time on this aspect. This level of resource will have to be maintained, up until the time the system is live.
Risk assessment has been used to focus testing requirements on areas of highest GxP impact. Validation testing has been minimised by restricting extensive structural testing to generic workflow classes, with data load verification only of other instances of the workflow class.
Ownership
It has proved possible to fulfill all CP's requirements without any custom programming. Also, following training and consultancy, the CP project team has gained sufficient expertise to undertake all the required data load and configuration of the LIMS itself.
There has been additional part-time involvement from outside the project team. This has included occasional additional consultancy from Thermo, as well as IT and validation assistance from other specialists from within CP. Nevertheless, the overwhelming amount of implementation effort has been undertaken by the core, laboratory-based project team.
An additional success factor has been the continuity of membership of the core project team, which has remained unchanged throughout. This has led to a deep understanding of the system by the people who are responsible for the information it holds.
And, perhaps most significantly, a genuine sense of ownership and pride in the LIMS within the laboratory community.
John Dickson is Senior Consultant in Informatics, Thermo Electron Corporation. Peter Sheppard is Quality Control Manager with CP Pharmaceuticals. For more information call Thermo Informatics on 866-463-6522 or e-mail info@thermoinformatics.com
