Packaging is the final step in obtaining a finished pharmaceutical product. It is important because it ensures product integrity,
identification, and presentation, including primary information for the patient (1).
For this reason, the packaging process should be analyzed, and manufacturers should take into account the occurrence of deviations
such as equipment and component failures, human error, operational errors, and other deviations that negatively affect the
final process result (2–4). Risk analysis (RA) methods are valuable tools for mitigating fault events by focusing on the cause–effect
interrelations that create them. RA methods thus facilitate fault elimination or, when faults cannot be eliminated, fault
reduction.
In today's pharmaceutical industry, most processes are conceived and designed with a high level of automation to minimize
operator intervention. Nevertheless, economic considerations lead companies to retain manual operations in certain situations.
The packing process that is the subject of this study is one example. In such a process, a fault-tree analysis (FTA) approach
can greatly help determine critical process points. The approach also helps manufacturers introduce barriers against equipment
and operator failure and minimize their probability of occurring (5, 6). Following these considerations, the packing line
was arranged, bearing in mind the potential failures to which the final result could be exposed. The arrangement was validated
by challenging the process to demonstrate its effectiveness.
Packing process description and considerations
Figure 1: The packing process represented in a block diagram. QA is quality assurance.
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The packing process in general can be summarized in a block diagram (see Figure 1). According to in-house procedures, the
quality assurance (QA) department must verify the information from quarantined product and the corresponding packing material
for approval. A product-release document is therefore indispensable to starting any product packaging activity. A packing-order
document is created upon product release. This document matches the product vials and packing material that are involved in
the process.
Refrigerated product vials must pass a room-temperature acclimatization stage to eliminate external moisture on the vials
before they are labeled. All other product vials are directly transferred together with label rolls for automatic labeling
and imprinting. Printed packing material such as labels for multiple unit boxes (MUBs) and shipping boxes, as well as cartons
and leaflets, are semiautomatically imprinted, folded, identified, and prepared as needed. These items are then temporarily
stored together with the rest of the materials until vial labeling and manual packaging begins.
Figure 2: Packing area layout. MUB is multiple unit box.
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The original packing-area distribution was modified to physically separate the preparation of packing material from the labeling,
imprinting, and manual packaging operations of the main packing line (see Figure 2). Note that the contiguous packing line
included a Sensitive 350 labeling machine (Libra Pharmaceutical Technologies, Fairfield, CT) followed by a 6.65-m long conveyor
with speed control to transport labeled vials to manual packaging operators. According to the original arrangement, one of
the operators near the labeling machine (No. 8) acts as a buffer by collecting vials and returning them to the conveyor in
groups of five. The other operator next to the labeling machine (No. 1) simultaneously configures and distributes empty MUBs
using the same conveyor. The rest of the operators (Nos. 2–7) package product vials in individual cartons, including leaflets,
placing the packed units into the MUBs in groups of 10.
