17.03.2014 |

LOGFILE No. 10/2013 - Deviations - GMPnews FDA, India and EU

Deviations – Definition and Requirements

By Dr. Christian Gausepohl

In spite of qualified equipment, trained employees and validated processes, the daily routine in pharmaceuticals is rife with situations in which prescribed workflows are not observed or processes fail to deliver the expected results.

For this reason it is important not only to define the workflows for production in "normal cases," but also to specify how such deviations are to be handled. This will ensure that acceptable product quality can be obtained even in the event of unforeseen circumstances


There are many different contexts for use of the term “deviation”. No clear, sharply outlined definition can be found in the various regulatory documents in the USA or the EU. The terms used are not always the same either (for example, deviation, discrepancy, atypical situation, non-conformity).

Therefore, it is imperative for a company to define internally what is understood by the term deviation, in order to avoid vagueness and possible misunderstandings concerning workflows and responsibilities.

In the narrower sense of the word deviations represent a failure to meet specifications (such as parameter settings) in the production process, in-process specifications or production requirements. In a broader sense, however, deviations from other procedures or instructions can also be assigned to the deviation system. Depending on how the deviation system is interpreted in any given company, confirmed out-of-specification laboratory results (OOS results), for example, can also be introduced into the deviation system. The advantage of such a comprehensive structure is that relevant data from different areas can be gathered jointly and subjected to a comparative evaluation.

When deviations are being handled, interfaces with the CAPA system (Corrective and Preventive Actions) and the quality risk management system are created. In addition, deviations are taken into account in the Management Review as indicators of how stable processes and workflows are.

Table 1: Examples for potential deviations in different areas

Area & Examples

Production process

  • Manufacturing Formula
  • Process parameters 
    (e.g. machine parameters)
  • Process specifications 
    (e.g. target values in production process or yield limits)
  • Testing instructions for in-process controls
    (e.g. using obsolete versions)
  • In-process specifications
  • Anomalies in the process

Machines, plants, equipment, facilities, and media (including laboratory)

  • Machine defects
  • System failures
  • Temperature, humidity, number of particles or pressure differences outside of limits
  • Deviations in microbiological monitoring
  • Calibration results outside of limits
  • Failure to keep calibration or maintenance intervals


  • - SOPs

Quality control

  • Results out of specification (OOS)
  • Results out of trend (OOT)
  • Results close to specification limit
  • Using expired
  • reference standards


  • Anomalies in pest-control sector
  • Exceeding temperature limits
  • Anomalies in goods received procedures

Ordinarily, deviations are unplanned by nature. However, there are systems in which planned deviations are prospectively handled. This is especially true in the case of short-term deviations and/or changes in workflows or processes that are intended to run once only in a controlled manner, for instance as part of an experiment. Other examples can include taking additional samples during the manufacturing process or taking a risk when using a starting material for which the release testing has not been fully completed (for example, microbiological results not yet returned). These planned deviations are basically subject to the same requirements concerning risk assessment and additional safeguarding actions to be taken, if applicable. The important thing is to set planned deviations apart from a change within the framework of Change Control, which involves planned, permanent changes in existing rules or features. A deviation is no substitute for the Change Control procedure.

Requirements for deviation management

Certain things are always expected in dealing with deviations. For instance they should be thoroughly and completely recorded and investigated. The risk arising from the deviation must be assessed. It will also be necessary to look into whether or not other batches could be affected. Suitable actions for the affected batches must be specified, if applicable, and assessed with regard to their risk for other processes as well. The effectiveness of the actions must be examined. All this can basically be done in an integrated or a separate CAPA-system.

The information on the deviation as well as the assessment of the risk must be available to the Qualified Person, who must take this into consideration for a decision on the release. The individual aspects are explained below using the description of a workflow as an example.

Table 2: Elements of deviation management

Requirements for handling deviations

  • Complete record of the deviation
  • Complete investigation into root causes
  • Risk assessment of the deviation for the current batch
  • Expanding the search to other, possibly affected batches or products
  • Specifying actions for the affected batch
  • Specifying actions to prevent recurrence (corrective actions)
  • Assessing the risk from intended actions
  • Defining tests for effectiveness to assess suitability of the actions
  • Implementing the actions
  • Testing effectiveness of the actions
  • Periodic review of the system effectiveness


Dr. Christian Gausepohl
Rottendorf Pharma GmbH, Germany

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