# Risk Management in Good Manufacturing Practice (GMP) Radiopharmaceutical Preparations
## 2 Materials and Methods
### Operational Risks  
To assess the operational risk, a similar approach has been used, but rather than ISO9001, the Failure Mode and Effect Analysis (FMEA) methodology was used according to ICH Q9 because FMEA is able to identify and help us understand the risk sources, their causes, and their effects on the system by assigning priorities and implementing corrective actions to address the most serious risks.  
At the beginning, the production process was divided into the main activities and then each identified activity was analyzed for the identification of the risks. Figure 2 shows the main process subdivided into the principal activities.  
\begin{table}
\begin{tabular}{c c c} \hline
**Requirement 9001:2015** & **What Did We Ask Ourselves** & **Main Risks Identified** \\ \hline \multicolumn{3}{c}{**Performance evaluation**} \\ \hline \multirow{3}{*}{Management review} & Have we determined what and when needs to be monitored and measured? & The risk is linked to non-adherence to strategic objectives. \\  & Is the system reviewed to ensure alignment with & \\  & strategic guidelines? & \\ \hline \multicolumn{3}{c}{**Improvement**} \\ \hline Non-compliance and corrective and improvement actions & Do I keep track of non-conformances and take actions to keep them under control and correct & The risk is linked to the fact that I do not solve the problems. \\ \hline \end{tabular}
\end{table}
Table 1: _Cont._  
\begin{table}
\begin{tabular}{c c c c} \hline
**Impact/Probability** & **Not Very Likely** & **Likely** & **Very Likely** \\ \hline Low & Irrelevant & Tolerable & Moderate \\ Medium & Tolerable & Moderate & Effective \\ High & Moderate & Effective & Intolerable \\ \hline \end{tabular}
\end{table}
Table 2: Matrix for risk quantification, risk index.  
\begin{table}
\begin{tabular}{c c} \hline
**Risk Type** & **Action Required** \\ \hline Irrelevant & No Action required \\ \hline Tolerable & No further control actions are required. If necessary, improvement actions can be identified. \\ \hline Moderate & Risk mitigation actions are required. \\ \hline Effective & Resources must be assigned in order to reduce the risk. \\ \hline \multirow{2}{*}{Intolerable} & Activities should not be carried out until the risk is reduced. If it is not possible to reduce the risk even with the use of adequate resources, the activities cannot continue. \\ \end{tabular}
\end{table}
Table 3: Corrective and preventive actions based on risk index.  
By multiplying the severity of the damage (S) with the probability of occurrence (O) and the detection index (D), the risk index was obtained according to the formula RI = SxOxD.  
Based on the risk index (RI) calculated, 3 different risk categories are individuated:  
Risks with indexes 27, 18, and 12. They are high risk (NOT acceptable) and require immediate mitigation action.  
Risk with index 9 or 6 medium risk: requires corrective actions to be implemented as soon as possible (days).  
Risk with index from 4 to 1: low risk; they may require improvement actions to be implemented in the medium-long term (annual planning).