Risk analysis methods are used by many pharmaceutical manufacturers and suppliers today. Most companies choose methods referenced in guidelines. The methods listed in the ICH-Guideline Q9 Quality Risk Management are mostly a good starting point. The most used risk analysis method is the FMEA (Failure Mode and Effects Analysis) and derived methods out of it.
This article describes a risk analysis in brief that is especially developed for equipment and machinery suppliers. It can be easily used for all machines, facilities and equipment used in the pharmaceutical manufacturing. Those suppliers have to ensure that the GMP requirements are fulfilled when handing over the technical system.
The method is not appropriate for pharmaceutical process analysis. For such occasions the classical FMEA is more likely recommended. The classical method includes more features to improve manufacturing processes.
FMEA Risk Analysis Method
FMEA risk analysis methods often use the following parameters for evaluation:
According to the variation, the evaluation is done with ratings from 1 to 3 or 1 to 5. A rating from 1 to 10 is seldomly used in the pharmaceutical industry today. According to the definition of measures, a second rating process with consideration of the suggested measures is performed. This is usually performed only if the risk priority number was too high after the first rating round.
Waiver of Failure Detection Probability
While performing a GMP risk analysis one can realize that the probability of failure detection is the most used parameter to reduce the risk priority number. The measure is often the establishing of qualification tests. If one defines a qualification test the rating for the probability of failure detection decreases and with that the risk priority number.
Usually one cannot influence the severity of a failure. If you intend to reduce the probability of occurrence it is essential to make design or software changes. Often this is not easy to realize because alternatives are not always available.
On the other hand, suppliers have to demonstrate that the technical system fulfils the requirements including GMPs. Potential failures should not occur. For that reason the question is allowed whether the probability of failure detection is relevant for the rating within the qualification approach.
The evaluation of GMP risk analysis has shown, that mainly the following measures were adopted:
In the presented risk analysis RA2x5 only the probability of failure occurrence and failure severity is rated. If the product of the two values exceeds a specific level of the risk priority number, a qualification test has to be established.
Probability of Failure Occurrence x Failure Severity = Risk Priority Number (RPN)
Figure 1 shows the evaluation matrix for the rating of the probability of occurrence and severity of a failure with ratings between 1 and 5. It is obvious that the values with blue background ask for qualification tests.
Figure 1: Evaluation matrix
Figure 2: Template RA2x5
A template for the performance of such a risk analysis is shown in figure 2. It is noticeable that there is no second run necessary for the rating (as used in FMEAs). There is good reason for this efficient step. With the establishing of a IQ, OQ or PQ test it is sufficiently documented that the failure will not appear, respectively, the probability of occurrence is proofed.
Efficiency of Risk Analysis RA2x5
The risk analysis RA 2x5 wins people with its efficiency:
This type of risk analysis is already introduced and performed in projects and resulted in a significant improvement by risk analysis performance. Integration in existing quality assurance and management systems is possible with a justifiable effort.
Halfmann Goetsch Peither AG
Switzerland, Germany, Singapore
Maas & Peither AG
 ICH = International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use