Drug processing, computer systems

The computer systems that can directly impact the quality attributes of pharmaceutical drug products and associated production records include a wide range of applications. Typically candidate systems can include real-time process control/... 

A fundamental objective of a computer system applied to automate a pharmaceutical GMP operation is to ensure the quality attributes of the drug product are upheld throughout the manufacturing process. It is therefore important that quality-critical parameters are determined and approved early in the validation life cycle. The exercise should be undertaken to a written procedure with base information from the master product/production record file examined and quality-critical parameter values and limits documented and approved for the process and its operation. In addition, the process and instrument diagrams (P IDs) should be reviewed to confirm the measurement and control components that have a direct impact on the quality-critical parameters and data. This exercise should be carried out by an assessment team made up of user representatives with detailed knowledge of both the computer system application and process, and with responsibility for product quality, system operational use, maintenance, and project implementation. This exercise may be conducted as part of an initial hazard and operability study (HAZOP) and needs to confirm the quality-related critical parameters for use in (or referenced by) the computer control system URS. 

The computer system URS needs to describe the levels of functionality and operability required from the computer system, its application, and the location with regard to the process. Definition of approved and accurate manufacturing and process data is a key objective of the URS and is essential in order for the computer system supplier or integrator to fully understand and develop the computer application and to engineer the field instrumentation and electrical controls. This must include the quality-related critical parameters that are fundamental in determining and ensuring the satisfactory quality of a drug product. Parameters, data, and functions that are necessary to uphold GMP must always be considered as firm requirements and candidates for validation. 

The proliferation of computers in the production of pharmaceuticals resulted in the U.S. Food and Drug Administration (FDA) publishing the "Guide to Inspection of Computerized Systems in Drug Processing" in 1983. FDA Inspectors have been using this guideline for the past three years to cite firms for their failure to validate their computer systems. 

These principles apply to computer systems that can affect the quality of drug and healthcare products. Such computer systems include laboratory systems, process control systems, spreadsheet and database apphcations, business systems, and associated computer network infrastructure. 

Assess each computer system to determine whether or not it can influence the strength, identity, security, purity, or quality of a drug product. The assessment should be conducted in accordance with a defined process and the outcome of each assessment recorded. 

The preparation for inspections shonld inclnde a risk assessment based on the drug product being processed, the production process involved, and the technology mix including the use of computer systems and a review of the company s internal audit and regulatory inspection history. 

Several published articles discuss the recent advances in instrumentation and control (4-6) and may aid in the process of justification. Automation has rapidly developed in cases where documentation is required by U.S. Food and Drug Administration (FDA) regulations. These same regulations will continue to force development of computer systems for the oil industries and help justify the use of automated control systems. 

There would appear to be an appreciation amongst regulators that computer systems are extensively used throughout the drug manufacturing, packaging and distribution process. The computer systems covered by the inspections included MRP II, LIMS, spreadsheets, process control systems and network applications. Between these inspections, a large number of non-compliance observations were made and are summarized below. This summary is based on several hundred noncompliance observations made between the inspections. 

Moreover, the vahdation of a chromatography system is of great importance today. The U.S. FDA (Food and Drug Administration) defines validation as submission of documented proofs, which ensure the generation of a product by a specific process with a high degree of certainty to comply with certain specifications and quahty features that were determined beforehand. The integral parts of the validation process include Vendor Qualification (VQ), Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ), and a validated computer system. Installation Qualification, Operational Qualification,... 

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