Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Data integrity: Presentation of Measuring values in Module 3: Challenges for Regulatory CMC

Martina Luh (Abschlußjahr: 2016)

Summary
Language: English
Data integrity has been identified as an important element to ensure the quality and therefore also safety and efficacy of medicinal products (drug substances as well as drug products). Therefore, it is recommended by regulatory authorities respectively institutions to implement data integrity into the quality management system of pharmaceutical companies. Great importance is attached to adhering to the "ALCOA" principle which means that data have to be attributable, legible, contemporaneous, original and accurate.
Nonetheless, in cases when the quality dossier is written by Regulatory Affairs, it is also the department of Regulatory Affairs which is affected by the issue "data integrity". One task of Regulatory Affairs, especially Regulatory CMC is to present measuring values generated from raw data in the relevant modules of the quality dossier. Data reported in regulatory documents and therefore also in the quality dossier provide a basis for both marketing authorisation and – where applicable – for release of the drug product for the market.
So first it must be determined whether test results should be reported: as not numerical or numerical acceptance criteria. In cases of numerical values in general it is unusual to present raw data in the dossier. Therefore it has to be determined in which form numeric measuring values should be presented respectively processed in consideration of decimal places respectively significant figures, truncation, rounding etc. to ensure data integrity in the quality dossier.
For that reason a co-operation between the departments concerned is advisable. These departments are: Pharmaceutical Development / Quality Control (who generate the raw data), Regulatory CMC (who present the measuring values in the quality dossier) and Quality Assurance (who should implement data integrity into the quality management system).
After examination of recommendations with regard to data integrity the next step was to check relevant guidelines respectively chapter / sections of pharmacopoeias for presence of indications how measuring values should be reported. Importance of specifications set for the single pharmaceutical parameters has been emphasised. The specification set serves as a basis for reporting of values.
Following relevant literature has been checked in order to find possibilities of interpretation of regulation with regard to reporting of measuring values.
Finally, a Standard Operation Procedure for a fictive pharmaceutical company has been developed which shall ensure data integrity in the quality dossier. This SOP applies to QA, PD/QC and Regulatory CMC. One focus of the SOP is to check if requirements of data integrity, in particular the "ALCOA" principle, are met. A second focal point is to determine how measuring values for several pharmaceutical key parameters have to be reported in the quality dossier. For that reason a concept taken from literature has been implemented which is regarded as suitable.
According to this concept measuring values should be truncated and the values thus obtained should be reported with one more significant figure respectively decimal place as dictated by the specification set.
Pages: 53