The biotechnology industry has mushroomed over the past decade, with revenues increasing from $8 billion in 1992 to $39 billion in 2003,1 and it shows no signs of slowing down. New therapeutics are entering and pressing through clinical trials. Treatments are emerging from clinical trials ready for marketing and scaling up for commercial production, leading to a growing need for new facilities.
Added to the challenges presented by growth is the extraordinary pressure from investors to produce or improve profits within an unusually short timeframe. This pressure translates into getting a new facility up and fully running at lightning speed. In terms of assets, this means selecting (following GAMP 4 guidelines for steps such as User Requirements Specification [URS] development and gap analysis),2 installing, calibrating, and validating each piece of equipment, each instrument, and all related systems and processes. This process not only applies directly to the equipment and instruments, but also to systems used to manage ongoing calibrations, maintenance, and validations of those assets. With strict compliance goals, this means new facilities must be brought on line quickly, correctly (following all regulations), and on budget. These three objectives are rarely achieved simultaneously.
Maintaining the Validated State
Biotech companies are under intense regulatory scrutiny. The management of instruments, equipment, and processes must be accurate and carefully documented. To demonstrate that assets are properly managed, the assets must first be validated, documenting that they are working as required and promised by the vendor. This original validation requires documented evidence that the entire production system results in consistent output. This necessitates performing initial qualifications, including the design, installation, operation, and performance of new instruments, equipment, processes, methods, and systems. Then, over the course of the asset's lifetime, procedures must be in place to keep the asset in that validated state, including regular calibrations and maintenance, and revalidating the asset when something alters its operation, requiring complete approvals before it can be used again.
To achieve their goals, validation specialists use a wide range of systems and tools, including project management systems, document management systems, change control systems, and systems used to manage calibrations and maintenance. Changes to records in any of these systems must pass through a specific approval process before they can be accepted as part of the validated state.
Regulatory agencies expect to see evidence that routine calibrations are being performed to keep instrument readings within tolerances acceptable to the process involved. These calibrations include using an approved standard to take readings at different set points before and after any necessary adjustments are made to determine whether the asset was and is performing within the process tolerance. If the asset is found to be out of calibration, then products and processes affected by that asset need to be discovered and corrected.