Improving a Pharmaceutical Water System based on a Risk Analysis Approach - Pharmaceutical Technology

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Improving a Pharmaceutical Water System based on a Risk Analysis Approach
In this study, fault tree analysis applied to a water pretreatment and purification installation exposed cause-and-effect complex interrelations in possible fault events.


Pharmaceutical Technology


Brief overview of the fault tree analysis method

The FTA method can diagnose the reliability and security of processes, mainly those that can be a potential source of hazardous and catastrophic events (8–10). Analysis starts from a top unwanted negative event and then developing all causal intermediate events in a descending way until reaching the final independent events of origin. From this analysis, a representative logical information flow diagram is obtained, in which special symbols depicting logical operators are used (11, 12).

FTA is useful for qualitative analysis because it reveals the various combinations of failures and cause-and-effect relationships that provoke the unwanted top event, as for quantitative analysis in case of calculating the top event occurrence probability from those to which the basic independent event can arise.

Brief overview of the failure mode and effect analysis method

FMEA can be used to discover and analyze all potential failure modes conceivable for a process or system and the effects they can cause as well as to determine how to correct or mitigate those (13–15). Correction is based on the evaluation of the degree of severity and criticality as well as their occurrence and cause detection levels. From there, the actions to be taken are determined.

A list in tabular form is then developed (16). For the WPP process, this list was organized in the same consecutive order of process stages, using the columns as follows (numbers correspond to columns matching the FMEA form):

1. Process equipment and components

2. Equipment and components function or operation

3. Related failure modes including those of nonimmediate detection

4. Effects of each failure mode


Table I: Severity index assignment criteria.
5. Severity index of each effect (S). For the WPP case, an assignment table was elaborated, which takes into account the impact on the WPP process and also on subsequent processes (see Table I).

6. Effect criticality, scoring a symbol if S ≥ 8

7. Potential causes ascribable to each failure mode

8. Cause occurrence probability index (O) through an assignment table found elsewhere (16)

9. Current existing controls

10. Control nondetection index (D) through an assignment table found elsewhere (16)

11. Risk priority number index calculation (RPN = S × O × D) for each cause, using maximum S value in case of several effects in a particular failure mode. RPN is used as a ranking of potential failure causes for assigning priority

12. Recommended corrective actions for avoiding failure causes.

In corrective actions, changes for improving process and its controls were taken into account. Such actions were defined for cases in which RPN > 100, as prioritized and for some particular situations in which RPN ≤ 100 also were considered critical.

Process improvement evaluation


Table II: Sampling plan for water pretreatment and purification system performance qualification.
Corrective actions executed from FMEA final results were considered as major changes to the WPP process. Therefore, according to house quality assurance (QA) policy, process revalidation was carried out according to a protocol specially elaborated for this purpose (17). After installation and operational qualifications, performance qualification was conducted for verifying change effectiveness during 15 days using offline measurements of those key variables better characterizing process functioning and based on a sampling plan summarized in Table II.


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