Labcompliance News, October 2009
New USP General Chapter for Metal
Impurity Analysis under Development
The United States Pharmacopeia is in the
process to develop a new general chapter <231> on metal analysis.
Barbara Zink of USP told the audience of a joint USP/Agilent seminar
in Hyderabad/India details on the process and current status. A
milestone was a workshop in April this year with representatives
from industry, agencies and other Pharmacopeias. The purpose of the
Workshop was discuss new approaches for metal impurities in
pharmaceuticals and dietary supplements, including methodologies and
toxicological limits. One of the recommendations was to focus on the
top four metal impurities: inorganic arsenic, cadmium, lead and
methyl mercury. Other details and summaries on suggested methods,
limits, methodology and regulatory considerations are available on
the
USP website through several slide
presentations.
Averaging of OOS Test
Results Draws FDA Warning Letter
An API manufacturer's procedure allowed to average
in-specification tests results with out-of-specification (OOS) results. This
practice resulted in an FDA warning letter. The letter states: The API batches
were released based on reportable assay results obtained from the average of two
independent sample results. One of the sample results was out-of-specification
(ODS) while a second result was within specification. The averaged passing
reportable assay result was compared against the established specifications, and
the batches were released to the marketplace". According to the FDA this
practice did not conform with FDA guidance: Investigating Out-of-Specification
(OOS) Test Results for Pharmaceutical Products, The warning letter can be
downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 220).
To learn everything about FDA compliant handling of OOS test results and when
averaging of results is allowed, attend the upcoming
audio
seminar.
FDA Issues Guidance on Risk
Evaluation and Mitigation Strategies (REMS)
On Sept 30, The U.S. Food and Drug Administration
announced the availability of the first draft guidance for industry on Risk
Evaluation and Mitigation Strategies or REMS, which are required for certain
drugs or biologics. The guidance for industry titled “Format and Content of
Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and
Proposed REMS Modifications” provides FDA’s current thinking on the format and
content that industry should use for submissions of proposed REMS, it
describes each potential element and includes preliminary information on the
content of assessments and proposed modifications of approved REMS- To see the
press release,
click here. To download the guidance, click
here.
Missing Evaluation of HPLC
Detector Noise/drift Cited in FDA Warning Letter
FDA warning letters get more and more
specific. While neither FDA regulations nor guidance documents
specify what HPLC parameters should be tested FDA inspectors start
to cite missing or incomplete testing as deviations in warning
letters. Inspectors quote 21 CFR § 211.160(b)(4) with a
requirement to conduct adequate calibration of instruments. Example
citations are: "Your firm failed to conduct injector and detector
performance testing for the xxx system", "For example, no HPLC
injector and detector testing for linearity, accuracy, and precision
were conducted, such as evaluation of detector for noise/drift; and
carryover testing" This warning is a clear proof of FDA's much
tougher policy. It also is a clear statement that HPLC's require
full performance testing (OQ) and that system suitability is not
enough. The warning letter can be downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 221).
To learn everything about FDA expectations for HPLC initial and
on-going testing, attend the upcoming
audio seminar
New FDA Guidance for
Microbiological Data for Antibacterial Drug Products
The FDA has published a new Industry Guidance
on "Development, Analysis, and Presentation of Microbiological Data
for Systemic Antibacterial Drug Products.". The purpose of this
guidance is to inform industry of the FDA’s current thinking
regarding the types of microbiological studies, assessments, and
clinical trials needed to support an investigational new drug
application (IND) and a new drug application (NDA) for a systemic
antibacterial drug product. Recommendations i cover three
major areas: (1) conducting general nonclinical studies; (2)
conducting animal and human studies and clinical trials; and (3)
establishing and updating in vitro susceptibility test methods,
quality control parameters, and interpretive criteria. The guidance
can be downloaded from the
FDA website.
FDA's Current Inspection Focus is on
OOS, Failure Investigations and CAPA
FDA's focuses inspections on how companies follow up with
OOS situations. This once again became obvious in a warning letter to an API
manufacturer. The letter reads as violation: "Failure of your investigations of
out-of-specification results to determine if corrections or preventive actions
are needed. Your firm failed to continue its investigation of the OOS results
outside of the laboratory in order to determine the cause of the results."
Furthermore the FDA letter recommends "Any OOS result obtained should be
investigated and documented according to a procedure. This procedure should
include analysis of the data, assessment of the extent and cause of the problem,
allocation of the tasks for corrective actions, and conclusions." The warning
letter can be downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 209).
To learn everything about FDA compliant handling of failure investigations,
Out-of-specification and Out-of-trend test results, attend the upcoming
audio
seminar
Warning Letter: OOL/OOS Results
Generated by a Contract Lab not Investigated
During an inspection of a pharmaceutical
manufacturer the FDA found several several violations of cGMP regulations
related to inadequate handling of out-of-specifications (OOS), out-of-limit
(OOL) situations and failure investigations. Tests were conducted in contract
laboratory. The letter made stated that the sponsor company has to make sure
that Ouf-of-Limit (OOL) and Out-of-Specification (OOS) results obtained in a
contract laboratory should be adequately investigated, for example, the letter
states: "Although results above your alert limits may be an indication of an
ongoing uncorrected problem, no investigation was conducted to identify a
potential root cause of the problem". The warning letter can be downloaded from
the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 219).
To learn everything about FDA compliant handling of failure investigations,
Out-of-specification and Out-of-trend test results, attend the upcoming
audio
seminar
Labcompliance Network Compliance
Package Available as Download
The popular Network Quality&Compliance Package is
now available as download version, in addition to traditional
CD/Binder Version. The package includes 24 SOPs, a primer and a
project plan It also comes with 13 examples/checklists, two audio
seminars and two years free online updates. FDA and international
agencies require network infrastructure to be formally qualified and
tested. The package helps to develop strategies for network
qualification and it has the tools for trouble free implementation.
For details on content and ordering,
click here.
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: Reserve samples in Laboratories. To download
your free copy, go to the
Computer System Validation Package website. Scroll down
and click on the corresponding ICON on the left (offer expires on
October 30, 2009). Labcompliance offers more than 100 SOPs that help
to comply with FDA and ISO 17025 compliance. For titles and
ordering, click
here.
New Audio Seminar Schedule
New or Updated Sites