Comparing visual inspection methods for parenteral products in hospital pharmacy: between reliability, cost, and operator formation considerations

TL;DR

This study compares different visual inspection methods for sterile pharmaceutical products, finding manual and semi-automated methods more reliable than automated ones.

Contribution

The study evaluates the reliability, cost, and training requirements of visual inspection methods for detecting particles in sterile pharmaceuticals.

Findings

Manual and semi-automated visual inspection detected 100% of visible particles, while automated inspection detected only 28%.

Manual and semi-automated methods were more effective under ISO 8 pre-production conditions compared to automated methods.

All methods correctly analyzed particle-free vials and performed well under ISO 9 conditions.

Abstract

The COVID-19 pandemic has led to unforeseen and novel manifestations, as illustrated by the management of drug shortages through the development of hospital production of sterile pharmaceutical preparations (P2S). Visual inspection of P2S is a release control whose methods are described in monographs of the European Pharmacopoeia (2.9.20) and the United States Pharmacopeia (1790). However, these non-automated visual methods require training and proficiency testing of personnel. The main objective of this work was to compare the reliability and speed of analysis of two visual methods and an automated method for detecting visible particles by image analysis in P2S. Furthermore, these methods were used to evaluate sources of particulate contamination during pre-production processes (washing, disinfection, depyrogenation) and production (filling, capping).

Three pharmacy technicians examined 41 clear glass vials of type I, 10 and/or 50 mL through manual visual inspection (MVI), semi-automated (SAVI), and automated (AVI) inspection. The vials were distributed as follows: (i) 16 vials of water for injection containing either glass particles (224 µm or 600 µm), stopper fragments, or textile fibres; (ii) five sterile injectable specialties; (iii) 20 vials of water for injection prepared under different pre-production conditions.

MVI and SAVI detected 100% of visible particles compared with 28% for AVI, which showed a deficiency in detecting textile fibres. All three methods correctly analysed P2S that did not contain visible particles. The three methods detected particles in vials maintained under International Organization for Standardization (ISO) 9 pre-production conditions. However, detections by (i) MVI and SAVI, and by (ii) AVI of particles contained in vials maintained under ISO 8 pre-production conditions were deemed satisfactory and unsatisfactory, respectively.

The importance of visual inspection of P2S requires rapid, sensitive, and reliable detection methods. In this context, MVI and SAVI have proven to be more effective than AVI for a more competitive financial, training, and implementation investment.

Figures