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A Standard MES for API Production in Biopharmaceutical and
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| Product Portfolio PAS-X BIOTECH |
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| Paperless API Production |
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The production of active pharmaceutical ingredients is a highly sophisticated task, based on technically demanding chemical and biochemical fermentation and synthesis processes and has to meet stringent validation requirements. Werum's advanced Manufacturing Execution System PAS-X BIOTECH can cope with all these demands and ensures reliable and fast production data management and facilitates cost-effective biopharmaceutical production procedures.
Process reliability is a key factor in the biopharmaceutical production process which is characterized by complex process descriptions for any process involved, such as inoculum, fermentation, purification, or filling.
This goal is achieved by integrating special quality management procedures enabling reliable approvals within a short time and ensuring process data documentation in compliance with GxP/FDA. It is of particular importance to detect discrepancies as early as possible to prevent jeopardizing effects for the production processes, which take several days or even weeks.
The production management system PAS-X BIOTECH meets these demanding requirements and creates the basis for paperless production by means of Electronic Batch Recording (EBR). The system ensures compliance with 21 CRF Part 11 rules for the handling of electronic records and electronic signatures (ER/ES) and guarantees a reliable archiving of process data.
PAS-X BIOTECH is tailored to meet the exacting requirements of the mentioned production procedures. Long-term experience and in-depth process knowledge based on a close cooperation with our customers in the field of active ingredient production helped us develop this best-in-breed product. PAS-X BIOTECH meets all the very specific requirements involved in this particular area of process engineering and manufacturing in the best-suited way.
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| PAS-X BIOTECH Benefits at a Glance |
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1. Shortening of lead times by filtering flood of information
Paper-based production documentation, which is still widely spread, often lacks a systematic structure and, therefore, can be confusing rather than informative at first sight. Quite often, the documentation is a mixture of manually collected data and data acquired with DCS or SCADA equipment. Thus, the process of reviewing a batch record, in which discrepancies are assessed and approved, becomes a very time-consuming task.
PAS-X BIOTECH provides configurable electronic approval workflows. Users can assess discrepancies on the spot by means of the process data that are available online. The electronic production report, which is essential for the approval, does not only contain the complete manufacturing documentation, but also the deviation report. This report comprises information on all the discrepancies and events and the data is provided in a clearly structured and summarized form. This allows all departments involved a fast, reliable and efficient assessment and electronic approval. Thus, lead times are reduced considerably.
2. Fast and reliable data acquisition
PAS-X BIOTECH carries out validity checks for manually acquired data relating to input materials, equipment used, or process parameters, and compares them to the batch record specifications. The software detects discrepancies and immediately issues an according message, thus enabling the user to take the necessary steps without any delay. Moreover, the system requests the user to enter a comment on the deviation. The entire process is documented in detail. The scanning of barcodes is a very efficient way to verify that the correct input material is used and to help establish a complete and consistent batch genealogy for subsequent tracking and tracing.
3. Efficient equipment management
An electronic equipment management enables powerful electronic logs and their automated administration. Comprehensive status monitoring and control functions effectively prevent the use of incorrect equipment, such as filters, tanks or containers which have not been sterilized or are not suitable.
4. Early detection of discrepancies to increase process reliability
The electronic process monitoring functionality has been designed as an early warning system, which alerts the user even before the limit values are exceeded. The system continuously monitors the process values and calculates trends. When it becomes evident that one of the parameters will probably reach the defined limit values, the system will report this critical trend. Thus, the operator will be warned with ample opportunity to take appropriate steps to correct the process.
The integration of production, in-process-control (IPC), and quality assurance facilitates process control and eventually minimizes the costs for rejected batches.
5. Transparency of process data evaluation
Using an MES you can easily analyze production, quality, and laboratory data, thus providing a sound basis for continuous process improvement.
The analysis of key performance indicators is of major importance. PAS-X calculates and evaluates KPIs and thus enables high performance and optimization of equipment usage.
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| Vertical Integration |
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Since process engineering in biopharmaceutical and API production is characterized by a high level of automation, involving complex automation systems to control the processes, an integrated overall approach is required. This approach should be based on the vertical integration of ERP level and automation level. It is the idea of such a concept to handle the administration of manufacturing specifications, control in-plant material flows, manage master batch records, generate control recipes and ensure their downloading to the process control and automation level in an integrated way.
Apart from automated production processes, biotechnological API production also requires manual workflows to be integrated. In this context it is of vital importance to guide the user reliably through the process. Such manual workflows also have to comply with cGMP/FDA documentation requirements.
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| Recipe Management: Centralized Graphic Generation of Recipes |
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The model of META recipes describes the entire process for the production of bulk for a biopharmaceutical product. META recipes include all the recipes required from the first through to the last fermentation step as well as the corresponding recipes for producing media, their processing, final purification, and drying.
The recipe control functions of PAS-X BIOTECH cover comprehensive process engineering and control functions
- for n steps of fermentation/manufacturing
- for CIP/SIP procedures
- for operating MES and DCS/SCADA systems
- providing flexible user prompting, e.g. by means of mobile workstations/terminals
- providing complex material flow management with e.g. pipelines, containers, reactors
- for cGMP/FDA-compliant documentation.
The MES administers the recipes centrally and downloads them to the DCS and SCADA systems, when required. In addition, PAS-X BIOTECH is able to flexibly distribute building blocks of recipes to the process levels, as required by the applied automation systems.
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| Electronic Batch Recording |
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PAS-X BIOTECH uses a graphical approach to facilitate the creation of master batch records, i.e. basic operations and functions can be combined by means of drag-and-drop functions. Reusable module libraries provide version-controlled standard operations and functions and thus support a consistent structure. For handling a large number of recipes, a product group inheritance concept is applied and the associated data is effectively administered in tree structures.
For any operation, from receiving of goods, throughout manufacturing and packaging, to the shipment of goods, PAS-X BIOTECH includes easy-to-operate, standardized operating screens. In addition to comfortable graphical user interface features, PAS-X BIOTECH provides the electronic batch record as "paper on glass", with a layout similar to a report on paper.
To support the approval process within the scope of electronic batch recording PAS-X BIOTECH generates a deviation report which summarizes all discrepancy details in a clearly structured form. The user no longer needs to check all the information contained in the manufacturing report and thus saves a lot of time. PAS-X BIOTECH features a fully automated approval workflow for electronic batch records.
PAS-X BIOTECH also supports the workflows for checking and approving master batch records. Any discrepancies detected during the manufacturing process are displayed on screen in a form that is similar to a report on paper. The user can enter production comments at any time
The "visual" quality control station is based on graphics representing various production areas. Traffic light icons show the progress of the production process and immediately reveal out-of-spec conditions.
The use of mobile work centers ensures a high level of operator flexibility. Pocket PCs and notepads of all leading manufacturers are supported.
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| Order and Material Flow Management |
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| The integration of the material flow management into the process workflows is of utmost importance to ensure a smooth production process. In view of finished product batches based on approximately 70-80 individual formulas, e.g. to produce the media required, reliable, in-time material staging is imperative. In this context, PAS-X BIOTECH takes charge of order control and the administration and labeling of any materials involved in the production process. The system provides where-used lists for batch input materials, administers materials down to transport container level and takes into account special requirements, such as the administration of silos or tanks. Such a function is of particular relevance if automated processes are combined with manual user inputs, manual activities or manual material adding. PAS-X BIOTECH coordinates and controls the interaction between users and automation systems. Material identification and verification are facilitated by the system, since operators can work with mobile data acquisition devices or workstations and are guided through the required operations by the system.
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| Deviation Management |
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PAS-X BIOTECH enables an overview of all the process steps and production stages. While DCS, SCADA and PLC automation systems focus on controlling the sub-processes in the individual process machines and fermenters, it is essential for operators and production managers to get a comprehensive overview of all the process steps. The quality control station of PAS-X BIOTECH provides this continuous and clearly-structured overall view throughout the entire production process.
The system makes it possible
- to log events
- to detect and assess deviations at a very early stage
- to document and archive deviations
- to take appropriate steps in due time
The quality control station signals any discrepancy from the process plan. Self-explanatory traffic light functions warn the user if the process exceeds defined warning limits. Thus, the user gets enough time to correct the process. Different employees of various departments can be authorized to assess the deviations. This way, appropriate steps can be taken at an early stage to prevent the rejection of a batch. |
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| Easy-to-operate |
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The operator obtains a homogenous view of the process, operates only the MES and is reliably guided through the process, even across several production stages. The system also ensures that the production documentation is GMP/FDA-compliant.
The graphic recipe structures created and administered in PAS-X BIOTECH follow S88/S95 standards. The system generates control recipes and downloads them to the automation level.
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| Step-by-Step Concept |
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The PAS-X BIOTECH portfolio offers scaleable products enabling you to define the scope of requested functions as best suited to your specific requirements and to implement them by means of standard solutions.
This way, in a first step, you can concentrate on the primary functions, using this effective and powerful product as a basic system, gradually extending it to a complete MES system.
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Management Summary
