Labcompliance News, November 2009
FDA Continues to Enforce
Part 11
FDA is working on a new revision for Part 11.
In the meantime FDA officials refer to the Part guidance "Scope and
Applications" from 2003. According to the guidance FDA allows
enforcement discretion for some requirements, such as validation and
electronic audit trail. FDA inspectors frequently used enforcement
discretion from 2003 to 2006 and there was hardly any warning letter
related to Part 11 requirements. This has changed. In the last
couple years there were at least 30 warning letters with reference
to requirements as stated in Part 11, but the letter did not mention
Part 11 itself. It seems that industry cannot always rely on
enforcement discretion. An example is a Warning Letter as a result
from a clinical study inspection with deviations related to missing
electronic audit trails. The letter states: "All study data are
handled and controlled by your Study Coordinator, who enters the
data into an electronic data base. There is no audit trail or log of
data changes that are made to the information in the database". The
the warning letter can be downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 224).
To prepare your organization for FDA inspections, and to avoid FDA
warning letters related to Part 11, attend the upcoming
Audio seminar: FDA's New Enforcement of 21 CFR Part 11.
USP General Chapter Allows
more Flexibility for Method Changes
In December 2007 USP has updated chapter <621>
with parameters and limits on what and how much a method can be
adjusted before revalidation is required. For example limits have
been defined for column length ( 70%), column diameter ( 25%),
particle size (can be reduced by as much as 50%), and flow
rate ( 50%). In the meantime it has been recognized that the chapter
does not provide the necessary flexibility to change the
chromatographic column to accommodate columns with lower internal
diameters for significant solvent savings or to use ultrafast HPLC
without revalidation through packing material with lower particle
size. Starting December 1, 2009, as a first step USP will allow
additional changes in 32-2. For example, the column diameter
can be changed freely provided that the linear velocity is kept
constant by also adjusting the flow rate. This makers it easier to
save solvents by going to columns with smaller diameters. In a new
Stimuli Paper USP also indicates to allow flexibility in other
areas, for example, to reduce particle size. In theory some of these
changes will allow to transfer methods from standard HPLC to
(ultra)fast HPLC For more information on practical implementation,
attend the audio seminar:
FDA Compliant Transfer of Analytical Methods
"Missing
Method Validation Electronic Raw Data" Cited in FDA Warning Letter
FDA's inspection focus is on electronic
records. This became clear during an inspection of an API
manufacturer in March 2009. The company has lost raw data when
migrating to a new computer system. The letter states: "Your quality
unit failed to maintain complete laboratory control records for the
analysis of your APIs (including graphs, charts, and spectra from
laboratory instrumentation derived from all tests conducted) to
ensure compliance with established specifications and standards. For
example, raw data, e,.g. chromatograms, standard and sample weights,
calculations, standards, reagents, and instrument information for
xxx. method validation were not available during inspection. Your
quality unit personnel informed the investigators that the computer
software was upgraded and the raw data was lost during the software
upgrade, We have serious concerns about your firms
implementation of changes to your computer system (E.g., software
upgrade). It is your responsibility to provide the means of ensuring
data protection (e.g., back-up system) for your computerized system
to prevent the permanent loss of records". This is an other example
for recent enforcement of Part 11. The warning letter can be
downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 222).
To prepare your organization for FDA inspections, and to avoid FDA
warning letters related to Part 11, attend the upcoming
Audio seminar: FDA's New Enforcement of 21 CFR Part 11.
USP Plans General Chapter on
Transfer of Analytical Methods
In Pharmacopeial Forum 35 (6) USP has
published a 'Stimuli' paper: "Transfer of Analytical Procedures: A
Proposal for a New General Information Chapter". The purpose of the
transfer process is to qualify the receiving laboratory to perform
an analytical procedure that was developed in another laboratory.
This concept is similar to the verification process described in USP
General Chapter Verification of Compendial Procedures. A section in
the paper describes differences and similarities between
verification and transfer. This Stimuli article aims "to initiate
discussion and solicit stakeholder comments". For a detailed
discussion on the transfer process and to get a transfer master
plan, an SOP and a case study, attend the audio seminar:
FDA Compliant
Transfer of Analytical Methods
15 New SOPs from
Labcompliance
FDA and ISO 17025 require
routine activities to follow written procedures. Healthcare
professionals typically use Standard Operating Procedures (SOPs) to
address this. Since more than 10 years Labcompliance has been
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confirm their SOPs with external resources. Now we have added 15
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Inspectional Observations", "Measurement Traceability in Chemical
Analysis", "Conducting Laboratory Management Reviews", "Allocating
Analytical Instruments to USP <1058> Categories", "Validation of
Software and Computer Systems for ISO 17025" and "Measurement
Uncertainty in Chemical Analysis " In the meantime over 120 example
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Should Computer Based
Training Record Systems Comply with Part 11?
Electronic training management
and record systems systems may have to comply with Part 11. This
became obvious from a Warning Letter citation: "Training Database
software validation used to document employee training was deficient
in that the test scripts were not available to show the execution of
the software validation protocol."
Validation is one of the Part 11 requirements. Other requirements
are even more important, e.g., limited and authorized access and
e-audit trail. Let's assume a department has all training records on
a Laptop PC, no paper back-up. The Laptop and the records are not
secured in any way, so everybody can go in and make changes, e.g.,
if required trainings have not been provided in time. Or the lab
supervisor could go in and change training dates just before the
next inspection is coming without leaving a trace through electronic
audit trail. If the computer database is the only way to document
trainings, the system should comply with Part 11. The situation is
different if originally all training records are available and
maintained on paper and data are just entered into a computer data
base to easier search and find training information. This system
does not need to comply with Part11.
This situation is discussed as one of many case studies in the
upcoming
Audio Seminar: FDA's New Enforcement of 21 CFR Part 11. The
warning letter can be downloaded from the
Labcompliance Usersclub. Non members can
preview excerpts (scroll down to 206).
Free Primer on Analytical Instrument
Qualification and System Validation
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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: Disaster Recovery of Computer Systems. To
download your free copy, go to the
Computer System Validation Package website. Scroll down
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December 2, 2009). Labcompliance offers more than 100 SOPs
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New Audio Seminar Schedule
New or Updated Sites