At the 2nd European GMP Conference, held in Heidelberg, Germany, from 20 to 21
June 2007, Fred Blumenschein, Compliance Officer of FDA's CDER, gave a
first-hand presentation of the latest regulatory developments that the FDA is
For many years, the now almost 30-year-old cGMP Guide was
considered to be hardly changeable. As a consequence, a number of guidance
documents was created. The cGMP Guide defined in the Code of Federal Regulations
has thus not been changed so far. Since 1996, there has been a so-called
"proposed rule", which never got beyond the draft stage, however.
As a first step, the FDA will now withdraw its planned changes to 21 CFR 210/211
dating back to 1996, explained Fred Blumenschein, and then make a new attempt to
change the CFR. The FDA itself classifies the first changes as uncritical, since
they either represent an adaptation to the state of the art or serve to
re-enforce the certainty of the law by means of changes to the wording or have
been proposed by the industry itself:
- 21 CFR 211.48 (and 40 CFR 141): "potable water"
- in the future it can also comply with requirements other than those of the
USA (e. g. EU, Japan). Here, the FDA does not want to refer strictly to the
"Primary Drinking Water Regulations" by EPA (Environmental Protection
Agency) any longer - the more so since other authorities actually have
stricter water limits than EPA.
- 21 CFR 211.67 (a): Equipment that is to be sterilised
should be sterilised. One should think that this goes without saying.
However, the change increases the certainty of the law.
- 21 CFR 211.68: Omission of the second personnel check in
case of automatic equipment. Here, the CFR is adapted to the state of the
art, and one wants to facilitate the procedure for the industry.
- 21 CFR 211.72: Changing "no asbestos filters" to "no
particle-shedding material". Here, too, the wording was adapted to the state
of the art, since actually no asbestos filters are in use any more.
- 21 CFR 211.94 (c): The requirement that depyrogenisation
of sterile containers should be validated. These changes also serve the
purpose of increasing the certainty of the law.
- 21 CFR 211.110 (c): The requirement that bioburden
testing, if necessary, should be used as IPC. Also a measure of adaptation
to the state of the art.
- 21 CFR 211.113 (a): The requirement that the process of
aseptic filling and that of sterilisation should be validated. This change
links to the FDA Aseptic Guide. Both regulations should be congruent on this
After making the above changes (they are meant to be
implemented by the end of 2007), the FDA will initiate the second step, which
the Agency itself calls "controversial". Currently, the FDA is still discussing
how the future roll of QA should be defined and the text on validation and
Conclusion: The forthcoming changes in the CFR are a first step
within a far-reaching change to the cGMP Guide. They will be the first changes
since 1978, now that it is certain that the proposed changes from 1996 will not
come into force. Hence the now launched revision of the cGMPs represents a
consequent further development of the "cGMPs for the 21st Century" Initiative.
On behalf of the European Compliance Academy (ECA)