Biomedical Engineering Reference
In-Depth Information
For the predicate rules regarding GMP processes, see 21
CFR 211.192, Production record review:
Any unexplained discrepancy or the failure of a
batch or any of its components to meet any of its
specifi cations shall be thoroughly investigated. The
investigation shall extend to other batches of the
same drug product and other drug products that
may have been associated with the specifi c failure or
discrepancy. A written record of the investigation
shall be made and shall include the conclusions and
follow-up.
We take “unexplained discrepancy” to imply an observation,
“other batches” to imply tracking and trending, and
“conclusions and follow-up” to imply remediation.
9. 21 CFR 211.100.
10. 21 CFR 211.25(b).
11. See also 21 CFR 211.192 “Production record review.”
12. This is explicit in 21 CFR 211.22; it is more implicit in
21 CFR 1271.160. Again, all these controlled documents
are referred to herein as “procedures” or “SOPs.”
13. 21 CFR 1271.160 (b)(3). See also Tim Fields (2008).
14. See Lee Vanden Heuvel and Christine Robinson (2005).
Their Figure 1 provides a very useful overview of the
tradeoff between level of effort versus return in a RCA.
The ICH (2009) has stated that “The level of effort,
formality, and documentation of the investigation
should be commensurate with the level of risk.” Jerome
Spear (2002) discusses setting priorities in such a real
world.
15. See also James Sandler (2008); Emma Barsky and Len
Grunbaum (2008); and Doug Bartholomew (2006). For
a discussion of the problems of “silo thinking,” “fi nger
