In the current case study, risk-reduction and acceptance decisions centered on patient safety. Despite the apparently low
number of empty/low fill capsules that may be present, there was no assurance that the numbers of empty capsules in the market
was low. There was little ability for a pharmacist or patient to detect an empty or partially filled capsule. Most importantly,
the potential medical consequence for some patients due to receiving and administering an empty or partially filled capsule
was severe. As a result of the potentially high risk associated with some patients taking empty/low-fill capsules, and the
inability of the firm to implement appropriate risk mitigating actions to lower this risk (i.e., severity and ability to detect)
to an acceptable level, the decision was taken to initiate a product recall.
Risk documentation and communication
Site procedures require preparation and Quality division endorsement of a deviation report. The risk assessment output was
incorporated into a number of existing work processes and their associated documentation. To prevent reintroduction of rejected
product to the product, an automated sensor was incorporated into the empty-capsule reject reservoir. When activated, this
sensor automatically shuts down the encapsulation machine should rejected capsules in the reservoir reach the sensor level,
thereby preventing overflow. The overflow sensor with automated equipment shutdown was applied to all encapsulation machines
at the firm. Additionally, the results of the FEMA analysis and recommendation for product recall were presented at an internal-management
notification process meeting and minutes of risk analysis and associated conclusions were documented. Affected regulatory
agencies were formally notified of the recall decision.
Risk review and conclusion
Evaluation of product complaints, adverse-event reports, and further examination of product received from the product recall
may potentially be used to gain additional understanding of the extent of the defect that reached the market.
Ted Frank is with Merck & Co; Stephen Brooks, Kristin Murray,* and Steve Reich are with Pfizer; Ed Sanchez is with Johnson & Johnson; Brian Hasselbalch is with the FDA Center for Drug Evaluation and Research; Kwame Obeng is with Bristol Myers Squibb; and Richard Creekmore is with AstraZeneca.
*To whom all correspondence should be addressed, at firstname.lastname@example.org
1 . T. Frank et al., Pharm. Technol.
35 (7), pp. 72–79.
2. T. Frank et al., Pharm. Technol.
35 (8), pp. 72–75.
3 . T. Frank et al., Pharm. Technol.
35(9), pp. 82–84.