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

Concerning variables such as bioburden and endotoxin contents, which are determined out of line with a substantial delay, these variables can not lead to immediate actions in case of OOL detection and hence their monitoring cannot be considered as an effective barrier restricting related failure occurrence. This factor constitutes one of the process's major weaknesses.

In summary, the FTA model was mainly useful from the qualitative point of view. Thus the authors decided to appeal to the FMEA method for a more practical approach.

Results from failure mode and effect analysis application

Table III:Part of the FMEA applied to water pretreatment and purification process.
Table III shows part of the FMEA model applied to the WPP process, obtained as a listing record. Its elaboration was facilitated by using the available FTA descriptive model. As a result from this approach, potential process weaknesses were revealed as follows:
  • From a microbiological point of view, equipment based on fixed beds were restated as "critical," and the carbon-Silex mixed bed presented the highest risk level
  • From an operational point of view, the softeners battery, NaOH solution dosage system, pressure group, and the RO system high pressure pumps were also established as "critical"
  • There was a lack of consistency in performing important controls such as periodical checking of free chlorine in various points in the process, including water hardness at softeners battery outlet, visual indications of pressure distribution, pH, and EC at RO system, as well as systematic checking of pumps, dosage, and instrumentation functioning
  • A lack of consistency also was found in performing components periodical cleaning and disinfection, which is likely to generate microbiological contamination, including the same RO system.

A recommended corrective actions plan was aimed in principle to reestablish cleaning, disinfection, and process control activities in a better documented way through official records managed by the QA department. Equipment checking for maintenance and instruments verification and calibration was recommended. In addition, some specific controls must be improved, given the possibility of acquiring water hardness and free-chlorine measuring devices to quantify these variables online.

The authors also decided to incorporate new design elements mainly focused to ameliorate sanitary and operational conditions at the WPP process. The most important changes were as follows:

  • Replace the Silex fixed bed by a battery of two centrifuge filters arranged in parallel for retaining coarse particles of more than 50 μm.
  • Install a new digital device for controlling softeners' battery operations more precisely
  • Install a new totally automated pressure group
  • Replace the carbon-Silex mixed bed by a sodium meta-bisulfite (Na2S2O5) dosage system as the principal means of free-chlorine removal, apart from a battery of two carbon cartridge filters arranged in parallel as a safety alternative
  • Replace the RO system strengthened-polyester housings and pipes and fittings made of PVC by stainless steel AISI 316L elements. Likewise, all threaded connections between RO modules should be replaced by sanitary tri-clamp connections, the same as pressure-indicator instruments by installing them directly to the measuring points, thereby eliminating all impulse lines to the control board
  • Install new safety, drainage and protection elements in the outlet pipeline section from RO second stage to water product storage and distribution tank
  • Replace all PVC pipes and fittings through pretreatment stages by stainless steel AISI 304 elements, including sanitary connections as needed.

Results from process performance qualification

Process performance qualification results were documented in the corresponding final report (18). In principle, tap water was still arriving with good microbiological quality, and hardness and alkalinity (the latter related to some extent to carbon dioxide content) showed significant values that were similarly to previous studies. The WPP process still assimilated those loads effectively despite process changes that were directed to improve pretreatments operations with better sanitary conditions throughout the process and taking into account that the essential design of RO membranes arrangement in two stages was kept as originally conceived.


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