Isolation, drying, milling (including micronizing), and packaging operations for nonsterile APIs should be performed using
a combination of suitably designed rooms and/or containment technology. The primary goals are to protect operators from exposure
via the containment of the API, to minimize the risk of contamination of the API and packaging materials from other compounds
and foreign material, and to minimize the risk of contamination of other compounds from the API. When evaluating isolation/packout
environments for the API, it is important to consider the risk factors for contamination and operator exposure. The steps
required to address the risks will vary based on processing step, equipment design, building finishes and design, and whether
the facility is multipurpose or dedicated. The use of cleanable/controlled rooms, for example, presents the least risk but
the use of engineering and processing controls can facilitate the use of other types of environments for isolating and packaging
This case study on packout remedies for mitigating contamination and exposure is the seventh of eight in a series put together
by the Product Quality Research Institute Manufacturing Technical Committee (PQRI-MTC) risk-management working group. The
series is meant to advance the understanding and application of the International Conference on Harmonization (ICH) Q9 Quality
Risk Management guideline by providing actual examples of risk-management assessments used by the bio/pharmaceutical industry.
The introductory article and first case study, on defining design space, appeared in the July 2011 issue of Pharmaceutical Technology (1). Subsequent case studies in the series (8 in total) can be viewed online at http://PharmTech.com/pqristudies.
In the current case study, the manufacturer identifies contamination and occupational exposure risk factors for final isolation
and packout of nonsterile APIs and uses quality risk management to evaluate the proposed alternatives to minimize these risks.
Risk question and risk assessment method
The risk question developed for the subject case study was: Are there effective room designs and/or containment technologies that may be utilized during packout operations at existing
facilities without significant capital investment to minimize the potential for cross contamination and operator exposure?
In this case study, the risk factors are more qualitative than quantitative. Therefore, the risk methodology selected for
the subject case study was: a decision table or modified hazard and operability (HAZOP) study.
Table I: Risk-evaluation levels.