Nucleic Acid Analysis with UV-vis and NMR - Spectroscopy

26 Spectroscopy 24(11) November 2009 www.spectroscopyonline.com
• FDA has now set postinspection
deadlines for responses by organizations.
The response time for firms to
respond has been halved to 15 working
days. This is not just to send a letter
to begin a cozy correspondence with
the agency but to have a complete
response to all the 483 observations.
If the compliance problems are significant,
the timeframe for the response is
critical and the response must be full,
adequate, and complete. The letter will
not be able to show that the problems
have been resolved for all but the simplest
observations but will demonstrate
how they will be resolved and in what
timeframe. If a response is not received
in this time or the response is inadequate,
then the agency can start work
on a warning letter or other enforcement
action. We’ll take a look at ways
to respond to a 483 or warning letter in
a later section of this column.
An important point to understand
here is that the FDA now takes the
systems-based approach to inspections
and coupled with ICH Q10 on
pharmaceutical quality systems (6)
you will need a different approach to
respond to 483 observations. If there
is an observation that has an impact
outside of the area inspected, you will
be expected to fix it as part of the systems-based
approach. Remember, the
wording at the end of virtually every
warning letter on the FDA website:
“this letter is not intended to be an
all-inclusive list of the violations at
your facility. It is your responsibility
to ensure compliance with applicable
laws and regulations administered by
FDA.” However, there is an onus on
the inspector to discuss findings with
management to minimize surprises
and errors when issuing the 483 at the
inspection closing meeting.
• The warning letter issuing process
is being streamlined and speeded
up by the FDA. Instead of the FDA
lawyers reviewing all warning letters,
only those where there are significant
legal issues will now get the legal eagle
eye. The agency will not delay issuing
a warning letter if you are late in
responding to the 483. Even if your
response to the 483 is perfect, the FDA
does “not plan to routinely include a
response on the apparent adequacy
of the firm’s corrective actions in the
warning letter (4).” Instead, the agency
will respond to evaluate both your
response to the 483 and the warning
letter together. Therefore, the message
is clear to all: Your 483 response must
be timely and complete, or else you
could end up with a warning letter on
the front doormat pretty quickly afterwards.
• Next, the FDA will prioritize
enforcement follow-up. After a warning
letter is issued or a major product
recall occurs, the FDA will make it a
priority to follow up promptly with
appropriate action, such as an inspection
or investigation to assess whether
or not a company has made required
changes in its compliance practices.
• In the past, it was not uncommon
for a company to have a number
of warning letters after several inspections;
it may be the companies