Labcompliance News, August
2010
FDA Inspection Clarifies what "Readily Available Documentation"
Means
21 CFR Part 11 requires that electronic
records should be "instantly" retrievable and inspectors expect that
documentation is "readily" available. One of the most
frequently asked questions related to documentation and e-records is
what "instantly" and "readily" means in terms of absolute time. Now
an FDA inspection team has indirectly answered this question through
listing "documentation not readily available" in a 483 inspectional
observation from June 2010.. Inspectors have asked for 20 types of
documentation. The 483 states: "Records associated with drug product
production and control and within the retention period for such
records, were not made readily available for authorized inspection".
The 483 lists the dates when the 20 documents were
requested and when they were available. Furthermore, the inspector found that
"Stability information provided was not provided in an organized fashion on
06/30/10. I requested that the firm organize the information and bring in a
computer on 07/02/10 to view the contents of xxx". This frequently
happens: Inspectors as for printed documentation, and if the information is not
satisfactorily, they want to review the records on the computer. The 483 can be
downloaded from the
Labcompliance
Usersclub. Non members can
preview
excerpts. Scroll down to W-239. This information is
especially important in light of upcoming FDA Part 11 inspection with focus on
accuracy, integrity, authenticity AND availability of records. To learn about
and to download 30 other Warning Letters/483s related to computer validation and
Part 11 compliance book the Labcompliance
audio
seminar "Learning from Recent FDA Warning Letters Related to Computer
Validation and Part 11". To learn everything about FDA's new Part 11 inspection
program,
click here.
FDA Plans Using Internal Audit
Reports for Risk Assessment
The Food and Drug Administration (FDA) is
announcing the availability of the draft guidance entitled ``Medical
Device ISO 13485:2003 Voluntary Audit Report Submission Program.'.
Under this draft guidance, device manufacturers whose establishment
has been audited under one of the regulatory systems implemented by
the Global Harmonization Task Force (GHTF) founding members using
ISO 13485:2003 may voluntarily submit the resulting audit report to
FDA. If, based on that report, FDA determines there is minimal
probability that the company will produce nonconforming and/or
defective finished devices, then FDA intends to use the audit
results as part of its risk assessment to determine whether that
establishment can be removed from FDA's routine work plan for 1
year. Toi read the announcement,
click here.
Printed HPLC Chromatograms
not Considered a 'True Copy' of e-Raw Data
FDA's 21 CFR Part 211.180(d) requires that 21
CFR 211.180(d) requires records to be retained “either as original
records or true copies such as photocopies, microfilm, microfiche,
or other accurate reproductions of the original records. Examples
are chromatograms, inputs, outputs and audit trails generated by
computerized laboratory systems. The question has been heavily
discussed whether printed HPLC and GC chromatograms and other
records are considered 'true copies' of the electronic raw data
meaning that e-raw data can be destroyed after print-out. FDA makes
a clear statement in one of its
CGMP Q&A websites:
"How do the Part 11 regulations and
"predicate rule requirements" apply to the electronic records
created by computerized laboratory systems and the associated
printed chromatograms that are used in drug manufacturing and
testing?" The answer is very clear: The printed paper copy of the
chromatogram would not be considered a “true copy” of the entire
electronic raw data used to create that chromatogram, as required by
21 CFR 211.180(d). The printed chromatogram would also not be
considered an “exact and complete” copy of the electronic raw data
used to create the chromatogram, as required by 21 CFR 211.68. The
chromatogram does not generally include, for example, the injection
sequence, instrument method, integration method, or the audit trail,
of which all were used to create the chromatogram or are associated
with its validity. Therefore, the printed chromatograms used in drug
manufacturing and testing do not satisfy the predicate rule
requirements in 21 CFR Part 211". It s common FDA inspection
practice that FDA inspectors first review printed copies of
chromatograms but expect that the electronic version is maintained
and readily available for review if further information is required.
Attend the Labcompliance Audio
Seminar "Electronic Raw Data in Regulated Environments" to learn
everything about GMP and Part 11 requirements for raw data.
Availability of required e-records will also be part of FDA's
new Part 11 inspection program as planed for Q3/4 2010.
No Failure Investigations after Failed GC
Calibration Cited by FDA
The FDA expects to follow up on failed
laboratory instrument qualification to determine the root cause and
to initiate corrective actions to prevent re-occurrence. This became
obvious during a recent FDA inspection which resulted in a warning
letter with several violations. The warning letter reads: "There was
no documentation that an investigation was conducted to determine
the root cause of the failed calibrations of the Gas Chromatograph
(GC) on 9/18/08 and 10/20/08 that were identified and cited during
the May 2008 FDA inspection. In addition, your firm failed to
implement adequate corrective action to prevent recurrence.".
Furthermore the FDA inspector noted that the quality control unit
failed to adequately train personnel to perform their duties for
Operation of the Gas Chromatograph, and failed to follow procedures
in the conduct of GC Calibrations.. The Warning letter can be
downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts. Scroll down to
W-240. To learn everything about FDA and USP requirements for
analytical instrument qualification attend the
audio seminar "Calibration and Qualification of Analytical
Instruments".
FDA Video Training Updated
The FDA Center for Drug Evaluation and Research
has updated the popular continuing education program Drug Review and
Related Activities in the United States and has renamed the updated
program to reflect legislative changes and improved operations. The
new title is The Past, Present, and Future of FDA Human Drug
Regulation. For registration,
click here
Do You Know what FDA Does?
Learn about FDA Basics from the FDA.
Each month, different
Centers and Offices at FDA will host an session where the public can
ask questions to senior FDA officials about a specific topic or just
listen in to learn more about FDA. If you are interested,
click here. The website has also links to basic FDA information,
for example: What does FDA do, what does FDA regulate, how to
contact FDA, how is FDA organized, how many people are employed by
FDA and in what areas do they work?
FDA Warning for Insufficient
Number of System Suitability Test Runs
A drug manufacturer conducted only five test runs instead of six
for system suitability testing for a dissolution assay:
"System suitability conducted for Dissolution
Assay per laboratory test methods evaluates only five replicate
injections for Relative Standard Deviation (RSD). For NMT 3%. USP
requires six replicate injections for instrument precision and
accuracy". Other deviations included: E-Records not "readily"
available, impact of equipment failures on batch not investigated,
inadequate follow up of complaints, and, reference samples not
stored under conditions as recommended by the manufacturer. The
Warning letter can be downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts. Scroll down to
W-239. To learn about FDA and USP requirements for system
suitability testing attend the
audio seminar "System Suitability Testing for FDA and USP
compliance".
Free Document of the Month
As a 'Thank You' for our visitors
Labcompliance offers every month one document for free. This month's
document is the SOP Auditing Analytical Laboratories. To download
your free copy, go to the
ISO 17025 Laboratory Accreditation Package website. Scroll down
and click on the corresponding ICON on the left (offer expires on
August, 2010). Labcompliance offers more than 120 SOPs that help to
comply with FDA and ISO 17025 compliance. For titles and ordering,
click
here.
Audio Seminar Schedule
-
System Suitability Testing for FDA and USP Compliance
With 10+ Best Practices for easy Implementation
September 9, 2010
-
FDA Regulations for (Bio)Pharmaceutical Industry
Get an Overview on Principles and Key Requirements in just one
Hour
September 23, 2010
-
FDA Compliant Use of (Certified) Reference Material
With 10+ Best Practice Guides for Easy Implementation
October 7, 2010
-
Effective HPLC Method Development and Validation
Preparation, conduct and documentation for FDA/EMA Compliance
October 21, 2010
2-Day Workshop in Shanghai, China
New or Updated Sites