Remote assessment of data integrity in pharmaceutical processes

Abstract

The increased number of warning letters observed throughout the years led to concerns for manufacturers, regulatory authorities, and society, and the underlying causes for such an increase requires investigation. Acknowledging common breaches in data integrity mentioned in these alerts can be advantageous to the pharmaceutical entities undergoing inspections and can also be used to conduct gap analyses of the processes used in other firms to prepare for inspections by the European Medicines Agency or Food and Drug Administration. The aims of this research study were to identify areas of non-compliance in pharmaceutical processes and to propose measures to improve data integrity for an effective quality management system. During phase one of the study, a literature review was conducted using the search engine Hydi. Keywords ‘data integrity’ and ‘remote assessment’ were applied to find articles published in the last five years to identify data integrity related non-conformities. Non-compliance reports and warning letters between 2017 to 2022 were accessed on EudraGMDP and FDA databases to determine data integrity criteria. The compliance issues identified through literature, non-compliance reports and warning letters were analysed. Articles and guidelines were reviewed to identify the critical areas where there was breach of data integrity for the development of an SOP and checklist tool to be used as guidance to improve data integrity compliance. The SOP and checklist tool were validated by an expert group in data integrity. Forty-six and 168 warning letters issued between 2017 and 2022 by the EMA and FDA respectively were identified. From the identified warning letters, a total of 94 non-compliances identified by EMA and 453 non-compliances identified by FDA were observed. The majority of non-compliances were related to equipment or facilities (19%;n=103) followed by documentation (13%;n=72) and validation (13%; n=72). In the SOP, seventeen topics were included such as documentation and computer controls. The checklist covered sixteen topics related to data integrity including security and access control and audit trails. The identified non-compliances related to data integrity issues highlight the need for more education and training of personnel to minimise the occurrence of non-compliances and guarantee safety and quality of medicinal products.