Affected Persons In The Industry,
I was recently surprised to again read comments that imply
drug firms can make seemingly arbitrary decisions about how they
define their "raw data" with respect to testing results from
computerized "chromatography" data acquisition systems.
Those regulated by the FDA should read and heed the detailed
definition of "raw data" found in 21 CFR 58 -- GOOD LABORATORY
PRACTICE FOR NONCLINICAL LABORATORY STUDIES.
That definition, found at 21 CFR 58.3(k) states,
"Raw data means any laboratory worksheets, records, memoranda,
notes, or exact copies thereof, that are the result of original
observations and activities of a nonclinical laboratory study
and are necessary for the reconstruction and evaluation of the
report of that study. In the event that exact transcripts of
raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature),
the exact copy or exact transcript may be substituted for the
original source as raw data. Raw data may include photographs,
microfilm or microfiche copies, computer printouts, magnetic
media, including dictated observations, and recorded data from
[NOTE: The definition set set forth in 21 CFR 58.3: a) has
been a part of the FDA's regulations since 1978 [43 FR 60013,
Dec. 22, 1978] and b) was last amended in 1989 [54 FR 9039,
Mar. 3, 1989].
1. Thus, if an AUTOMATED INSTRUMENT RECORDS DATA, that data, or
a true copy thereof, must be maintained -- it is RAW DATA.
2. Moreover, any and all COMPUTER PRINTOUTS generated, including
those that are generated but NOT used, or true copies thereof,
must also be maintained as, collectively, they are RAW DATA.
3. For chromatographic systems, each and every exact parameter set
used to process any raw data file, including the one used to
generate "initial results" as well as those used to reprocess
any raw data file and the final one used to generate the "final"
results used for decision making, must be maintained. This the
case since they are a key component of the RAW DATA "necessary
for the reconstruction and evaluation of the report of that
study" (the set of printed chromatograms containing the values
reported in this case).
Collectively, "1." through "3." constitute the set of data
that a knowledgeable FDA auditor will need to see in an inspection
before he or she will can evaluate the validity of the result values
reported in the hopefully readily available derivative records, logs,
notebooks, and controlled recording forms.
There are instances of which I am aware (on FDA Form 483's issued
in the 1980's and 1990's where pharmaceutical testing laboratories,
including contract labs, have been cited for DISCARDING set up, and
intermediate processing chromatograms (where one, or more, HPLC
chromatographic raw data files have been reprocessed) even though
the raw data files and the final chromatograms (and, in most cases,
their generating parameter set or sets) were available for review
by the FDA auditors.
These problems and the industry's desire to use computerized
systems in were the catalysts that led to 21 CFR 11 -- ELECTRONIC
RECORDS; ELECTRONIC SIGNATURES.
Hopefully, providing the preceding will help those working in
the pharmaceutical industry who are seemingly unaware of: a) the
definition provided in 21 CFR 58.3(k) or b) what data is required
to satisfy the " reconstruction and evaluation" requirements.
Paul G. King