By Chris Stumpf, PhD, Greg Murphy, and Steven F. Eaton
Figure 1. An internal review of the quality control (QC) testing environment highlighted a wide variety of testing software and equipment as well as many testing steps that used paper.
IMAGE COURTESY OF WATERS CORP.
Figure 1. An internal review of the quality control (QC) testing environment highlighted a wide variety of testing software and equipment as well as many testing steps that used paper. This shows the manual collation of results from multiple sources to create a certificate of analysis (COA).
Pharmaceutical companies continuously strive to improve manufacturing efficiency in order to increase profitability while maintaining product quality. To achieve these objectives, many pharmaceutical organizations have adopted Lean Six Sigma process strategies. Although improving operational control of manufacturing often leads to better overall efficiency, most companies still use paper to document the manufacturing and testing steps taken to satisfy regulatory requirements. Migrating to electronic documentation offers an additional opportunity to improve operational efficiency and meet compliance standards.
Despite initiatives to reduce bottlenecks on the manufacturing floor, most companies still rely on paper documentation to ensure that they meet regulatory requirements. The reluctance to employ an electronic documentation system can be attributed to somewhat dogmatic cultural philosophies, primarily represented by these statements: 1) “This is how we’ve always done it;” 2) “Current paper process is validated, so why change?;” and 3) “The operational approach of the competition doesn’t warrant any change.” This article describes a case study in which competitive pressures compelled a global pharmaceutical company to change paper-based data management and documentation processes specifically related to certificate of analysis (COA) to an electronic solution.
Ideally, a pharmaceutical manufacturer’s finished products should ship immediately after the completion of quality control (QC) testing. A slow product release process can be costly; any delay may translate into lost product and lost revenue. Although the software solutions presented here are well suited for accelerating the COA process for products with relatively short shelf lives, they also address many of the challenges associated with inefficient paper documentation processes in the pharmaceutical development life cycle, including research and development.
Figure 2. Consolidation of all chromatography data system (CDS) platforms onto a single compliant-ready solution simplified the CDS testing environment.
IMAGE COURTESY OF WATERS CORP.
Figure 2. Consolidation of all chromatography data system (CDS) platforms onto a single compliant-ready solution simplified the CDS testing environment.
Managing QC Operations
Due to a series of strategic acquisitions, the global pharmaceutical company we focused on operates manufacturing facilities across multiple geographies. In addition, many of the individual sites lack centralized QC laboratories because of plant layout. An internal review of the overall QC operation revealed that testing equipment, data management, and documentation processes differed from site to site, which limited standardization (see Figure 1, p. 23). The organization sought to overcome this lack of standardization to streamline the COA process.
Chromatographic System Control
Using operating equipment supplied by multiple vendors created inefficiencies within the QC workflow, such as repetitive training and difficulties sharing and reviewing data from different systems. Consequently, the first step toward standardization involved identifying opportunities to control instrumentation using fewer instrument acquisition-and-processing platforms. A comprehensive evaluation indicated that significant benefits at both lab and organizational levels could be gained by consolidating the company’s numerous chromatography data systems (CDS) into a single platform (see Figure 2, above). A compliant-ready CDS was selected to provide acquisition control, data processing, and result generation for all existing CDS software. The solution leveraged existing capital investments, reduced the training effort, and streamlined the review and sign-off of chromatography test results.
Figure 3. Data and test results from the consolidated chromatography data system (CDS) platform and results from other analytical testing equipment were centrally captured into the scientific data management system (SDMS).
IMAGE COURTESY OF WATERS CORP.
Figure 3. Data and test results from the consolidated chromatography data system (CDS) platform and results from other analytical testing equipment were centrally captured into the scientific data management system (SDMS). The consolidated test results from SDMS are then sent to the log inventory and management system (LIMS) for summarization into a certificate of analysis (COA).
Data Accessibility and Review
In addition to the CDS solutions, the pharmaceutical company’s QC laboratories employed a broad range of analytical instruments to meet their testing needs. Managing the vast quantities of information generated from these disparate technologies and geographic locations limited accessibility, hindered collaboration, and negatively affected workflow. A scientific data management system (SDMS), which functions as a centralized, compliant-ready data warehouse, automatically captures and catalogs analytical data while test results are printed into the repository, using print-to-database technology (see Figure 3, below). The pre-existing data management process used a combination of paper, CD/DVDs, and network file servers. Conforming to compliance regulations with respect to long-term data retention and creating easy access to test results to expedite completion of COAs continued to be a challenge, however. The SDMS serves as a single repository that provides storage, accessibility, data review, and archiving of all QC testing results, including those from CDS and other analytical instruments. The information is then consolidated and sent to the log inventory and management system (LIMS).
Reduce Error and Compliance Concerns
To eliminate manual data transcription from analytical instruments into individual LIMS solutions, the pharmaceutical company adopted a new LIMS to manage most of the QC testing and reporting operations. The LIMS architecture allowed for background secure data transfers primarily using web services in a globally centralized architecture. Users who log into the LIMS set up work lists and download them directly to the CDS. Work lists can also be sent to end users for specific tests on non-chromatography instrumentation. All printed results are sent to the SDMS database, and the critical information from each report is automatically extracted and sent to the LIMS for compilation into a finished COA. Now, fewer software interfaces are required between the LIMS and other databases, further simplifying the QC workflow.
With results automatically sent to the LIMS from the SDMS, manual transcription has been eliminated, reducing the error rate to near zero. And because all QC testing data is captured electronically, the risk of data retention non-compliance and the cost associated with data storage have been reduced. This standardized data management strategy has streamlined the COA process; the entire product inventory and release process is now handled by an enterprise resource planning system that interacts with the LIMS to collate test results that were electronically provided by the SDMS to generate the COA.
Figure 4. An analyst electronically completes compliant-ready worksheets within the electronic laboratory notebook (ELN) capability of the scientific data management system (SDMS).
IMAGE COURTESY OF WATERS CORP.
Figure 4. An analyst electronically completes compliant-ready worksheets within the electronic laboratory notebook (ELN) capability of the scientific data management system (SDMS). The solution serves as a single point of access for the analyst by directly interfacing with common laboratory data sources such as balances, log inventory and management system (LIMS), and inventory systems.
Eliminating Paper SOP Worksheets
The next step toward improving the COA process was implementing a system that eliminated the paper standard operating procedure (SOP) worksheets used in routine laboratory testing such as solution preparation, gravimetric calculations, and the documentation of observations ordinarily recorded in a paper notebook (see Figure 4, left). Because maintaining SOP worksheets can be time consuming and error prone, the task represents a significant burden for the QC analyst. Additionally, the documentation review and sign-off process can stall, further increasing the potential for bottlenecks. The SDMS selected to streamline the COA process provides an analytical electronic laboratory notebook (ELN) capability. The ELN has an electronic SOP form and documentation workflow system that is designed to improve documentation efficiency (>60%), reduce transcription errors (0%), and reduce review and sign-off times (50% faster). This strategy creates a 100% electronic audit trail of the exact steps in the manufacturing QC process.
The next phase of this project leveraged the standardized data management strategy outlined here to improve QC documentation efficiency, streamline review and sign-off, and provide greater transparency in the manufacturing and QC testing operation.
Summary
A global pharmaceutical organization implemented a standardized CDS and SDMS platform to improve their COA process and, ultimately, to reduce manufacturing cycle time. The new data management strategy allowed the company to achieve several key tactical objectives, including:
This standardized data management strategy has streamlined the COA process: The entire product inventory and release process is now handled by an enterprise resource planning system that interacts with the LIMS to collate test results that were electronically provided by the SDMS to generate the COA.
* managing compliance documentation requirements with greater ease;
* reducing the number of software interfaces necessary to gain access to QC data;
* minimizing manual transcription;
* reducing training costs; and
* streamlining the sign-off and review process so that COAs are generated more rapidly.
Finally, the organization was able to evolve and enhance current LIMS methodologies by managing raw analytical QC data via a global, centralized repository that accelerates product release and virtually eliminates errors.
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