PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 280

Of maximum risk in the packaging operation is the potential for product
mix-up. Providing the wrong product or the wrong dose can result in serious
harm to the patient and send regulatory agencies to your door for investigation.
A product mix-up can occur in any facility that manufactures more than one
product or product dose. A few situations where product mix can likely occur
are as follows:
• on packaging lines that process multiple products and is typically the result
of inadequate cleaning of the line between different product batches;
• on packaging lines that are dedicated to one product but are adjacent to
another line dedicated to a different product; and
• where the final package contains a combination of more than one dose,
(usually two or more distinct dosage forms, typically identified by different
product colors or shapes).
In all cases, key to avoiding product mix-up is separation or isolation of
different products or product doses. The risk assessment should focus on adequate
separation between packaging areas and for combination packaging, separation
between the different doses. Here are some areas to consider when doing the risk
assessment:
• product flow;
• packaging line clearances (e.g., proper bulk, labels, containers before

startup);
• personnel process intervention, interaction with other lines, and work flow
(e.g., operators handle more than one packaging line, one operator collects
samples or conducts in-process challenges on multiple packaging lines);
• in-process sampling and/or routine challenge test sample handling and rec-
onciliation (e.g., samples used to challenge automated vision color or shape
detector);
• packaging line equipment cleaning; and
• facility design.
Tablets may be packaged in a variety of ways, such as in a bottle, a blister
pack, or a sample packet. In each case, the equipment must be properly set up so
that the tablets are aligned to fall into the package opening in the correct amount.
Missing or inadequately filled product containers may result in the risk that the
patient will not be properly treated. On the other hand, the patient may become
overdosed if the container is overfilled.
The package contains information needed by the patient that identifies the drug
and how it should be safely taken. The label on the package includes description
of the product, its approved indication, correct dosing regimen, warnings, and
expiration date. Incorrect product information is a risk to the patient who may
take the wrong product or take a harmful dose.
Package integrity keeps the drug product protected from contamination and
helps maintain its stability or potency over its shelf life. Having the proper