Drug products critical parameters

An approach to drug product development using a combination of risk management and scientific knowledge to understand the relationship between process parameters and unit operations to API and/or drug product critical quality attributes (CQA). 

Another difference from drug therapy is that the dosing interval of a nutritional supplement is often not a critical parameter for a positive outcome. This lack of a strong dose-response relationship is an important consideration in setting of standards for dietary supplements and is in stark contrast to the situation for drug products. 

In the initial design of an oral MR drug product, a number of parameters often dictate feasibility and as such need to be critically evaluated. These important parameters include... 

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. 

These processing parameters could have a significant impact on in vitro dissolution of drug product. They should be understood and controlled for critical parameters. 

Retrospective validation may be conducted for a well-established proeess used without significant changes to [drug product] quality due to changes in raw materials, equipment, systems, facilities, or the production process. This validation approaeh may be used where 1. Critical quality attributes and critical process parameters have been identified... 

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