Risk analysis

Here you will find answers to the following questions:

  • Which tools may be used in order to define the adequate scope and extent of validation?
  • How may a risk analysis be performed?

1 Finding out the adequate extent of validation

The scope of the validation activities required depends on the type of manufacturing operation and the use of the product. It is easy to appreciate that a complex manufacturing process which requires technically sophisticated equipment, specially trained staff and permanent process monitoring and which concerns a product with a narrow therapeutic range for parenteral use must be validated more thoroughly than a skin antiseptic solution for use on intact skin. It is expected by authorities, that a systematic, documented approach is done for each validation project in order to determine how much validation work is necessary in the individual case. Nowadays risk analysis is the favourite tool to evaluate scope and extend of validation activities.

2 Carrying out risk analysis

Risk analysis should be carried out at the very beginning of each validation project to assess the individual product risk and the process risk. The "risk" is generally understood to be increased as probability of occurrence of product failures increases. It is also increased, as significance of product failures increases, but it is decreased, if there are means to discover the product defects. (See chapter 19.B Risk analysis.)

Figure 1 Fundamental questions for risk analysis

Fundamental questions for risk analysis

Product risk: Does the product itself present certain risks, e.g. due to its administration route (e.g. parenteral), its narrow therapeutic range or physicochemical properties (e.g. sensitivity to light)?

Process risk: Is the process complex? Does it consist of many individual steps? Does it have to be precisely monitored? Does it require specially trained members of staff? How much experience is there with the facilities/equipment used?

Quality assurance activities: Are there opportunities to detect any errors that may have occurred?

For the purposes of risk analysis, the entire production process is divided into individual processing steps and each processing step is assessed with regard to possible failures which might occur. Each failure is then assigned with probability and significance of occurrence, as well as detectability, in case the error really had occurred. There are various ways of grading these three factors, i.e. allocating numbers and calculating the risk of each processing step. The aide mйmoire "Inspection of qualification and validation in pharmaceutical manufacture and quality control" gives FMEA, fault tree analysis, fishbone analysis and the HACCP concept. Whichever technique is used, it is important that the result of the risk analysis identifies the "critical" and "non-critical" processing steps and that the process of decision is transparent and documented.

The risk analysis can be drawn up as a separate document or, for smaller validation projects, it may also be part of the validation protocol. Risk analysis can also be used in validation master plans, for example, in order to give weightings to sub-projects.


Risk analysis is a versatile tool for assessing and weighting possible or actual events. It is used, for example, in the planning stages of a validation to determine and justify which processing steps are to be considered as "critical". Risk analysis is also useful when allocating priorities in complex validation projects.