Deviations as essential quality parameters in the pharmaceutical quality system

Dealing with deviations from processes and quality specifications - Background

Every pharmaceutical manufacturer must have and implement suitable processes for dealing with deviations from processes and quality specifications in order to continuously ensure the required quality of the products. There are many reasons for deviations. They range from quality problems in the raw materials, materials, equipment and devices used to inadequate description or implementation of the manufacturing, testing and quality assurance processes. A wide variety of reasons can lead to a backlog in the processing of deviations or deviation management. The workload associated with the processing of deviations and the associated commitment of personnel resources across all areas of the quality system can even become so great that batch-relevant deviations are not processed in time and these are not sufficiently taken into account for the release of the product batches. Supervisory authorities therefore regularly review the status and implementation of deviation management by pharmaceutical manufacturers in their inspections. This article illustrates the background and cites measures for preparing for this critical review.

Deviations or deviation management are reviewed as essential quality parameters in official inspections

According to the EU GMP Directive for medicinal products, the pharmaceutical quality system of pharmaceutical manufacturers consists of three areas: production, quality control and quality assurance. The qualified person has overall responsibility for the quality of each batch that is to be brought into the market and the associated product release. Since the qualified person cannot monitor and control compliance with all GMP-relevant processes alone, the practical implementation of these tasks is assigned to Quality Assurance. However, the tasks of monitoring and controlling GMP processes are also a workload that is almost impossible to manage for quality assurance. A contributing factor here is the fact that quality assurance within the areas mentioned is not uncommonly the one that is provided with the fewest resources by the company management and thus has an increased "susceptibility to process deviations" with regard to the fulfillment of its tasks. This is particularly true for smaller businesses (SMEs).
For the supervisory authorities, the status of deviation processing, in particular the handling of critical deviations, is an essential indicator of whether the pharmaceutical quality system is functioning.
Therefore, inspectors regularly check the lists of deviations from the current year and also from previous years with regard to the processing of the deviations. In this context, it is also checked whether the causes for the deviations have been correctly determined and suitable measures (corrective and preventive measures) have been defined and implemented, in order to reduce or prevent the recurrence of the deviations.

Deficiencies assessed as critical in this context include:

  • General lack of overview of responsibilities regarding the status of deviations and derived corrective and preventive actions (CAPA),
  • accumulation of deviations over years in some cases, the processing and conclusion of which must therefore be called into question,
  • processing of critical deviations that are not appropriate in terms of time and content,
  • lack of or inadequate root cause analysis, in particular in connection with inappropriate corrective and preventive actions (CAPA),
  • recurring deviations, in particular in connection with a lack of review of the implemented corrective and preventive actions (CAPA) with regard to efficiency,
  • lack of opening and processing of deviations that have demonstrably occurred or have been documented in processes. This also applies, for example, to deviations, which were identified during external and internal audits.

Once deviation management has gotten out of control, it can even happen that deviations are only partially recorded or not recorded at all. This can be area specific, e.g. for production or quality control, but also across all areas of a company.

The deficiencies described reveal to the authorities that the affected pharmaceutical manufacturers can no longer meet the necessary regulatory requirements. During inspections, such observations regularly lead to other core processes or tools of quality management being intensively reviewed.

If the authorities discover that relevant deviations have not been taken into account in the batch release, the authorities expect the manufacturer to take a suitable course of action for these affected batches. The manufacturer must prove that the batches meet the specified quality requirements despite the deviations present or, if this is not possible, if necessary, to recall the batches from the market. Such reprocessing for batches already on the market means a heavy workload and, in the case of recalls, also a high financial expense and, if necessary, negative impact on the reputation of the manufacturer.

How can pharmaceutical manufacturers prevent loss of control over deviation management and how can they restore the control, if necessary, with available resources?  

How to gain control of your deviation management

A review of the status of deviation processing indicates whether the associated processes are working and under control. However, a review of the lists of deviations alone is not sufficient for this. It must not only be checked that the list is up-to-date with regard to recently occurring deviations, but also that deviations that occurred in the previous manufacturing period have been completely recorded and processed and completed in accordance with the regulatory and internal company requirements. For this purpose, e.g. the manufacturing and quality control processes carried out are systematically reviewed. An additional factor for the success of the status check is that it is carried out by a neutral auditor.

Our Pharma Compliance Team will support you with appropriate audits that put your deviation management to the test.

We will discuss any defects found with you and jointly define measures to ensure efficient processing of the deviations in the future and to avoid a “deviation backlog” for the future.

If critical deficiencies have been identified as described above, only a pragmatic concept and approach will help to manage the heavy workload in a targeted manner. Our Pharma Compliance Team will also be happy to help you with this necessary task.

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