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Abstract. The importance of software validation increases since the need for high usability and suitability of software applications grows. In order to reduce costs and manage risk factors, more and more recommendations and rules have been established. In the field of pharmacy the vendors of so-called chromatography data systems (CDSs) had to implement the guidelines of the Code of Federal Regulations Title 21 (CFR 21) during the last few years in order to fulfill the increasing requirements. The CFR 21 part 11 deals with electronic records and signatures. This part is binding for each company in the regulated environment that wishes to create, edit and sign electronic information instead of printing them on paper. Subsection CFR 21 part 11.10(h) explains how to perform an input check for manual user entries as well as for data that will be collected from an external device. In this article we present an approach performing the double entry method on data provided by the hardware instrument in order to investigate possible influences on the raw data by the handling CDS. A software tool has been written which allows us to communicate with a high-performance liquid chromatography (HPLC) detector and acquire data from it. The communication is completely independent of a CDS which is started separately and connected to the same system. Using this configuration we made a parallel data acquisition of two instances at the same time possible. Two CDSs have been tested and for at least one of them it has been shown that a comparison of the acquired data can be done as with the double entry method for the data verification. For the second CDS we checked whether it would be applicable after a few modifications. The given approach could be either used for a live data verification of produced raw data or as a single test during a software operational qualification to verify the data acquisition functionality of the software.

Nowadays pharmaceutical analysis and industry could not be imagined without using chromatographic methods like the High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC). Therefore, the field of chromatography is already firmly anchored in the three important, regional pharmacopeias: EP, USP and JP. Deficits of specifications within these pharmacopoeias relating to the detector parameters sampling rate and signal filtration are the major motivation of this thesis. Furthermore investigations on the data acquisition and processing within the detectors and software products dealing with collected data were done. Several concepts like double entry method, smoothing optimization and signal filtration based on persistence have been developed and are used as tools to examine the data integrity of commercial Chromatography Data System (CDS), improve the signal-to-noise ratio of small peaks to lower the LOD and LOQ by efficient denoising, and determine the suitable filter parameters and sampling rates an user can apply on his system to accelerate the method development and validation. All developments have been tested on simulated and real chromatograms and have shown that they are suitable for their specific purposes. In the end optimizations in the concepts still exist but some new aspects in the long-term investigated field of chromatography have been discovered.

Traceability has an enormous value for companies, but especially for those working in the regulated environment. It plays a special role in the field of pharmacy with respect to manufacturing, controlling and distributing batches of drugs. Through the guidance of Good Manufacturing Practice (GMP) traceability should be ensured. An increasing number of pharmaceutical companies are member of one of the global pharmacopoeias (United States Pharmacopeia, European Pharmacopeia and Japanese Pharmacopeia). The specifications of these pharmacopoeias describe the best practice in documentation, control, qualification and risk management. But however, the pharmacopoeias are written very generally and do not distinguish between the vendors of the analytical instruments. Here, we analyze how chromatographic analyses and data acquisition rely on a specific vendor of the device and the chromatography data system (CDS), the controlling software. We present a way to compare the data acquisition of different CDSs communicating with HPLC instruments. A newly developed software called Data Collector allows the acquisition of data from a HPLC detector parallel to the controlling CDS in the same run. Two HPLC systems and two different CDSs using a well defined sample standard have been tested. The direct comparison of the acquired data precludes unexpected data manipulations of both tested CDSs and shows that there are primarily deviations between the CDSs due to time variations only which depend on the sampling rate. All in all the Data Collector can be used for the traceability of data acquisition.