Streamlining the qualification of computerized systems in GxP-compliant academic cell therapy facilities

Compliance with Good Manufacturing Practices (GMP) is mandatory in the development and manufacture of advanced therapy medicinal products, pushing academic developers to implement methods for control and monitoring of bioprocess parameters that, until recently, were only found within large corporate environments [1]. These methods include computerized systems (CS), which contribute greatly to standardization; improvement of productivity while ensuring conformity of product specifications; removal of unnecessary duplicates; and reduction of downtime and human error. Indeed, the use of CS in the pharmaceutical industry has increased exponentially since the 1990s, and the growing field of cell therapy is no exception to this.The use of CS in public institutions is still limited, however, likely because of budget restrictions and the perceived complexity in obtaining qualification for information systems. Both American and European regulations devote significant attention to CS [2,3] and consider unqualified CS a serious deviation, particularly if their failure can compromise product quality, and therefore safety and efficacy. Any CS in operation in a GMP-compliant cell therapy facility must be qualified according to its architecture and validated for use.To achieve this, their acceptance criteria, protocols, procedures and records must be supported based on well-documented risk analyses that serve as the basis for leveraging the relative importance of the validation required, categorized according to the expected use of the CS [4].The International Conference on Harmonisation (ICH) defines “risk” as “the combination of the probability of occurrence of harm and the severity of such harm” [5]. Quality Risk Management thus emerges as a methodology to evaluate, monitor, verify and document quality risks throughout a product’s lifetime. According to regulatory authorities, Quality Risk Management is increasingly gaining acceptance as a valuable tool for achieving an effective quality system that considers the unavoidable existence of a basal level of risk in the production and commercialization of medicines. Both qualitative and quantitative risk analyses are accepted by regulatory agencies, although quantitative data are preferred because they are clearer, more intuitive and unambiguous [5]. Here, we share a simple methodology that complies with GMP regulations according to European Medicine Agency’s GMP 11th and 15th Annexes.We believe it is feasible to perform in academic institutions, and it has been used in our GMP-compliant cell therapy facility, which was inspected by regulatory authorities in 2010, 2011 and 2014 [1]. The approach presented here contributes to simplifying and streamlining CS qualification in compliance with pharmaceutical standards. Briefly, qualitative and quantitative risk analyses were performed using the Ishikawa and Failure Mode and Effects Analysis (FMEA), respectively, to determine potential causes of errors of the design, as well as installation, operation and performance of CS, based on the likely impact of CS on the specifications of cellbased products for clinical use (Figure 1A,B). First, an Ishikawa diagram is created as a preliminary risk analysis aimed at identifying and classifying the main cause(s) of deviation in product specifications.The simplicity of the initial Ishikawa risk analysis permits quick, qualitative identification of critical parameters that are classified in six groups (equipment,