Manufacturing-related risk
Figure 3: Respondents indicate their level of concern about certain manufacturing-related risks, where the scale ranges from
1 to 5, with 1 meaning not concerned, 3 meaning concerned, 5 meaning extremely concerned.
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The most significant manufacturing-related risk as identified by respondents was contamination, followed in decreasing order
by human resources issues, and yield variability. Respondents were also concerned with increasing titers, but seemed less
concerned with the challenges posed by disposables (see section below). Respondents also identified a variety of other concerns
surrounding product validation, equipment reliability, and managing capacity. Securing sufficient supply and was also noted
among the respondents' comments (see Figure 3).
Four primary strategies are used to mitigate risks including training, statistical analysis, quality management techniques,
and a focus on improving both internal and external communication. About 40% of respondents identify training and education
as a key manufacturing risk-reduction tool, while more than 30% identify statistical analysis and quality management. Moreover,
respondents repeatedly highlight the positive impact of good communications both internally and with CMOs and suppliers on
manufacturing yields.
When addressed specifically, manufacturing contamination was reported to be a primary concern of 64% of the respondents
(see next section).
Contamination events
Figure 4: Respondents rank how frequent key risks become an issue.
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Of the various issues and concerns surrounding contamination, media contamination is by far the largest concern: 39% of respondents
identified this as their most significant contamination-related concern. Cross-batch contamination was a distant second at
19% (followed by lack of detectability of contamination, and extractables and leachables). To address these concerns, respondents
report primarily turning to high-temperature/short-time (HTST) pasteurization, physical segregation, and better assay technologies
at roughly equivalent levels (each by between 45% and 47% of respondents). About 60% report experiencing a contamination event
once or more a year, and roughly 14% experience such an event once a month or more frequently (see Figure 4).
Contract manufacturing
Figure 5: Respondents indicate their level of concern about certain contract-manufacturing risks, where the scale ranges from
1 to 5, with 1 meaning not concerned, 3 meaning concerned, and 5 meaning extremely concerned.
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Almost 60% of respondents report using CMOs for some or all of their manufacturing. Although respondents show concern about
all aspects of their relationships with CMOs (e.g., reliability, visibility, flexibility, and IP) the most dominant concerns
are around quality and compliance (these are the only categories for which a plurality of respondents indicated "extreme concern").
To address these risks, the most commonly noted approaches include a comprehensive focus on prescreening and monitoring CMOs,
frequent audits, and keeping a representative on the CMO site (and dual-sourcing where possible and reasonable) (see Figure 5).
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