The importance of integrating analysis equipment in the modern pharmaceutical lab shouldn’t be underestimated, we find out why…
IN AN environment of extreme cost containment, integrated informatics solutions contribute significantly to today’s pharmaceutical manufacturing laboratories that require increased product quality and compliance with strict regulations. Modern LIMS (laboratory information management systems) serve as common platform frameworks that other informatics solutions, instrumentation, enterprise systems and communications tools can plug in to share common functions, without having to build them from scratch for each product. These systems can store data and methods safely and consistently, ensuring security and integrity as well as effective processing distribution. As a result, scientists and researchers can quickly and easily access data in order to make better-informed decisions.
Adopting a comprehensive enterprise level integration approach to streamline business processes can be beneficial, but can also present many challenges for modern pharmaceutical manufacturing laboratories. Global Pharmaceutical Supply Group (GPSG) Brazil – a unit of Janssen-Cilag Farmacêutica, Johnson & Johnson – has taken advantage of the latest technological advancements in its São José dos Campos laboratory complex in São Paulo. They have adopted Thermo Scientific Connects – a solution that includes laboratory instrumentation and informatics software, enterprise systems and document management tools to provide a fully integrated pharmaceutical manufacturing environment.
Pharmaceutical manufacturing companies are required to control the quality of their analyses according to specific US FDA guidelines, which apply to electronic format records that are created, modified, maintained, archived, retrieved or transmitted in their laboratories. These regulations are valid even for records that are not used in a submission, such as training records and SOPs. As a consequence, one of the major challenges facing the industry is the need to use validated CDS (chromatography data systems) and LIMS systems that enable compliance with standards and procedures enforced in this highly regulated environment. For many companies, a coherent strategy that integrates data between a LIMS, CDS, ERP (enterprise resource planning) and documentation system across the enterprise is a key business driver.
Additionally, pharmaceutical manufacturers face significant data security and consistency issues. They need to test a wide range of utilisation conditions prior to the implementation of any LIMS or CDS solution, thus establishing more trust in the system and in the information generated. Unless validation is carried out, a product’s quality may be undermined due to an error that might have been overlooked while the system was being implemented. During the validation process, the whole production environment is re-created, the systems are replicated in a “pre-production environment” and they undergo strict testing.
Traditionally, batch control has been a completely manual process, increasing the occurrence of information errors in documents. In addition, the manual detection of how many, which and at what time batch analyses should be carried out often caused delays in the dispatch of batches to be distributed or further processed. These shortcomings can only be addressed by implementing efficient CDS and LIMS solutions, which automatically track the batch.
A further significant challenge is the need to transfer the entire documentation from both production and quality control – consisting of countless technical specifications, standards, limits and analysis criteria – to LIMS. This can be a long and demanding activity requiring intense team involvement in the clear and detailed identification and description of the implementation tasks.
GPSG Brazil is a research-based pharmaceutical company specialising in pain management and fungal disease. Every month the manufacturing plant processes more than 10,000 analyses to assure the quality of nearly 2000 samples of raw materials, packaging materials, semi-finished and finished products, water and stability. The site is fully equipped with an incoming laboratory plus microbiologic, chemical, analytical development and research and development laboratories. The manufacturing plant handles both solids and liquids, including Tylenol 750mg tablets, Tylex tablets, Nizoral tablets, Tylenol drops, Nizoral cream and shampoo, and imported products such as Eprex, Risperdal tablets. In addition to holding a strategic position in the production of solids, liquids, creams and shampoos, GPSG Brazil imports a wide range of products while also exporting to many Latin America countries.
Given the high sample throughput and the high degree of reliability that is required of a pharmaceutical company, proven systems and equipment are vital to ensure maximum productivity and retain a competitive advantage. GPSG wanted to deploy state-of-the-art technology which delivered sufficient flexibility to meet the specific needs of the pharmaceutical industry, such as stability; supplier certification, microbiological analysis.
GPSG Brazil selected a LIMS solution to deploy in its laboratories to ensure integration with corporate enterprise resource planning package, SAP R/3. Between the production plant and the laboratory that analyses data from production, there is a need for regular exchange of information about quality and analysis values. In order to leverage the full benefits of modern ERP solutions, GPSG Brazil needed a solution to interface the LIMS with SAP so that the LIMS feeds data into the ERP. This would enable GPSG Brazil to expedite the data flow between the lab and the manufacturing functions, streamline data handling, and integrate data collection and reports. GPSG Brazil needed a validated product that provided sufficient flexibility to deliver all the requirements that a pharmaceutical plant has such as data security and consistent quality data; a centralised repository for the quality management data; fast and accurate data storage and recovery and all the industry functionality.
The LIMS has been implemented in all GPSG Brazil’s laboratories and is used by around 118 employees. In 2001, the company decided to also deploy a CDS solution to collect, process and ensure the safety of the chromatographic data generated within its laboratories. The CDS integrates 17 HPLC instruments in the chemical laboratory, enabling all the chromatographic data in the lab to be accessed via one central server and is used by approximately 37 employees. It was required as GPSG needed a validated system to control quality of the analysis in line with Johnson & Johnson guidelines.
The combined implementation of the two systems generated considerably higher data reliability, which led the company to upgrade to the latest versions of the systems and ensure their tight integration. The LIMS implementation was divided into cycles reflecting the production flow starting with raw materials through the packaging cycle, the semi-finished and finished products and stability. The CDS implementation was divided into four areas, namely solids, liquids, validation and residue analysis, because of the different types of inputs and reports specific to each one of these areas.
Seamless integration of laboratory instruments to the LIMS and the LIMS to the existing ERP systems at GPSG Brazil ensures full regulatory compliance (for example with the US FDA 21 CFR Part 11 standard that covers storage and integrity of computer systems data) at a lower cost. Controlled and traceable versions of the original data are created and the whole history of any modification carried out is securely stored, thus ensuring complete system validation. CDS/LIMS integration also supports and enables the periodical auditing of the supplier certification system utilised by the company to guarantee the quality of its raw materials.
The LIMS/CDS solution achieves quick and accurate transfer of high volumes of data, increasing sample throughput and improving laboratory productivity. Since the LIMS provides increased traceability, the system enables easy and quick access to background data associated with batches allowing for automated batch control. In the case of failed data, CDS/LIMS integration allows scientists to track both the original failed result and the actual chromatograph in the system. This enables users to find out if there was an operator error or a serious issue that would impact the quality of the product so as to take all of the appropriate action to protect consumers.
The integrated system detects changes in the production line, determining new analyses to be made. Chromatograms can be viewed during the analysis and the workbook can be customised in order to view analytical results. All required modifications may be performed in advance, preventing unnecessary and time-consuming rework.
The implementation has enabled GPSG Brazil researchers to view information that was previously only available in data reports. As a result, delivery of results has been accelerated since fewer steps are required within the analysis process. Further fundamental functions are also offered such as the ability to withhold and return acquisition queues, full-screen chromatogram expansion and baseline editing defects correction. Additionally, acquisition date is displayed on the chromatogram’s screen. This precludes an analysis sequence from being saved over another one, thus ensuring the integrity of the original data.
As part of its plan to implement tech¬nological innovations that promote operational excellence and regulatory compliance, GPSG Brazil is utilising the latest technological innovations in its São Jose dos Campos laboratory complex. The implementation, which connects GPSG Brazil’s laboratory into the enterprise decision-making, has enabled secure and seamless transmission of data, improving laboratory productivity and minimising costs.
The connected integration solutions deployed in its multiple laboratories help GPSG Brazil to guarantee tight quality control throughout its business processes, in compliance with strict regulatory controls – from material delivery, through production, packaging and distribution, to worldwide customer service. For GPSG Brazil, these systems are capable of storing data and methods in a safe and consistent way, thereby ensuring ultimate data security and integrity as well as effective processing distribution. As a consequence, GPSG Brazil is able to easily, timely and effectively access data in order to make better-informed decisions in a faster and more reliable fashion.