Quality System Issues Most Frequent Cause of Drug Shortages, Survey Finds

ISPE’s Drug Shortage Survey, conducted between February and March 2013, found that quality system issues contributed to more than 24% of all drug shortages. Among the quality issues, underlying systemic issues were common, respondents said.

“While the ISPE Drug Shortage Survey answered many questions about possible root causes for drug shortages, the data overwhelmingly confirmed the multi-factorial nature of this global problem​,” according to the ISPE report​ on the survey.

Notably, the survey found that aseptic processing equipment was seen as a significant factor in shortages, according to the 175 individual and 37 company respondents. Of the company respondents, 62% were pharma and biotech companies, 7% were CMOs (contract manufacturing organizations), 2% were API (active pharmaceutical ingredient) or excipient suppliers and the rest were other service providers.

The US FDA previously told us​ about 75% of drug shortages were related to manufacturing issues.

The underlying causes of sterile and non-sterile drug shortages were “surprisingly similar​,” according to the survey data, with quality systems being the top cause for the shortages. Other manufacturing systems contributing to shortages were identical for sterile and non-sterile drug manufacturing, with material systems leading the way, and then production systems, laboratory control systems, facilities and equipment systems, and packaging and labelling systems.

Production System​

Respondents said that for their production systems, the issues were complicated and influenced by many factors, though there were “significantly more​” issues with facility layout or compliant design in non-sterile facilities than sterile facilities.

Within the production system, the most prevalent issues reported were:

• Non-conformance - 34% for sterile shortages/near misses, 33% for non-sterile shortages/misses;
• Process validation - 21% for sterile shortages/misses and 20% for non-sterile shortages/misses; and
• Change control systems - 19% for sterile shortages/misses and 16% for non-sterile shortages/misses).

But in terms of production equipment problems, the equipment itself was the major source of issues for sterile products while equipment qualification was the major source of problems for non-sterile products. Aseptic processing equipment was the major piece of production equipment reported as posing problems by both individual and company respondents.

Mitigation Strategies​

In addition to identifying the production and quality system deficiencies, the survey sought to reveal what mitigation strategies companies were putting in place to help pre-emptively prevent drug shortages from occurring.

More than half said they had a drug shortage prevention program in place, although of those with such programs, more than half said that system was still unable to prevent a drug shortage.

“While it is clear that an effective quality system and strong GMP profile remain essential to preventing shortages, respondents indicated that inspections and, to a lesser extent, product registration are significant factors in drug shortages, particularly for sterile products​,” according to the survey report.