Qualification of Automated Dissolution Systems

Pharmaceutical Development and Quality Products, Zymark Corporation, Hopkinton, Massachusetts, U.S.A. 

Dissolution is becoming one of the most commonly automated functions in the modern pharmaceutical development and quality assurance (QA) laboratory. To the experienced dissolution analyst the reasons seem obvious. Dissolution methods are time-consuming and require a significant amount of labor. Beyond the cost of labor, the true cost of increased regulatory requirements and documentation can be better managed through automation. Additionally, the increased pressure to 

Before describing the various considerations that go into designing a fully automated dissolution apparatus, it may be worthwhile to discuss automation in general for pharmaceutical applications. 

Automation at its basic level can be expressed simply with the statement that analyses that were traditionally manually performed are now performed mechanically through computer-controlled robotics or workstations. Designers typically have a strong desire to exactly reproduce the manual process. In reality, minor changes to the manual approach must be made in order to make the automated process reliable and efficient. 

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Validation of automated systems must demonstrate a lack of contamination or interference that might result from automated transfer, cleaning, or solution preparations procedures. Equivalency between the results generated from the manual method and the data generated from the automated system should be demonstrated. Since sensitivity to automated dissolution testing may be formulation related, qualification and validation of automated dissolution equipment needs to be established on a product-by-product basis (8,13) (see also Chapter 12 for a more detailed description of automation issues). 

System qualifications are quality checks. They are a part of the validation of a product. Validation is defined as, Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes (5). A product that is validated is considered to be of much higher quality than one that is not validated. Automated dissolution systems need to be validated as a requirement of their use in regulated laboratories. 

The cornerstone of validation and qualification is testing to a set of specifications. Without specifications, proper qualifications cannot be performed. For an automated dissolution system, the specifications originate from a few sources, which include the USP, the manufacturer s FRS, and the manufacturer s detailed design specifications, which may include HDS and SDS. 

Instrument qualifications should be executed on a scheduled basis that can be determined with the help of manufacturer s recommendations. Automated dissolution systems that are used regularly are typically re-qualified every six months to one year. Re-qualification is also recommended for other reasons including moving equipment or replacing parts. Below is a typical system re-qualification policy. 

The information in this chapter applies specifically to the first element sample preparation. The sample preparation steps are usually the most tedious and labor-intensive part of an analysis. By automating the sample preparation, a significant improvement in efficiency can be achieved. It is important to make sure that (1) suitable instrument qualification has been concluded successfully before initiation of automated sample preparation validation [2], (2) the operational reliability of the automated workstation is acceptable, (3) the analyte measurement procedure has been optimized (e.g., LC run conditions), and (4) appropriate training in use of the instrument has been provided to the operator(s). The equipment used to perform automated sample preparation can be purchased as off-the-shelf units that are precustomized, or it can be built by the laboratory in conjunction with a vendor (custom-designed system). Off-the-shelf workstations for fully automated dissolution testing, automated assay, and content uniformity testing are available from a variety of suppliers, such as Zymark (www.zymark.com) and Sotax (www.sotax.com). These workstations are very well represented in the pharmaceutical industry and are all based on the same functional requirements and basic principles. 

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