Risk Analysis: What Does it Mean for 21 CFR Part 11 Compliance

Victoria Lander, Nugenesis

The new FDA Draft Guidance Document discussing the revised scope and applicability of 21 CFR Part 11 clearly adopts a risk-based approach to Part 11 compliance. This is certainly a very pragmatic approach and one that many regulated firms had adopted even before the recent release of this document. This seminar will discuss the particulars of a risk-based approach to Part 11 compliance. The favored risk assessment protocols such as HACCP, FMEA and FMECA will also be addressed as well as how one can apply them to 21 CFR Part 11 compliance.

Topics include:

·     What has recently changed with regard to the new FDA approach to 21CFR Part 11
·     Discussion of the new FDA Draft Guidance Document for Part11interpretation
·     What is a "risk-based" approach to Part 11?
·     Why do a risk assessment?
·     What are the commonly industry accepted risk management approaches?
·     How to apply HACCP, FMEA and FMECA to risk assessment for Part 11
·     Moving forward with your Part 11 remediation plan

Qualification and Validation of Laboratory Networks

Bob Giuffre, Agilent Technologies

As chromatographic data systems (CDS) move from isolated, stand-alone systems into a networked environment, monitoring the health and status of the network becomes increasingly important; not only to insure adequate data transfer rates but also because the network infrastructure is also part of the qualified environment for those laboratories working within the 21 CFR Part 11 guidelines.  In addition, these systems operating within a qualified environment need to be monitored for any changes that may have occurred within the network infrastructure.

Analysis of Peptides via Capillary HPLC and Fraction Collection Directly
   onto a MALDI Plate for Off-line Analysis by MALDI-TOF

Luke Roenneburg, Gilson

Off-line coupling of capillary HPLC to mass spectrometry has significant advantages to current on-line methodology. Both the HPLC and MS parameters can be individually optimized and off-line coupling provides a means of "capturing" the HPLC run in time. All proteins and peptides that are separated through the capillary HPLC system are "captured" on a MALDI target and are analyzed
through the MALDI-TOF MS at a convenient time.

MALDI-TOF MS provides a means of "freezing" the sample in time, which allows re-analyzing of the collected fractions from a chromatographed sample as many times as are needed. Hence, fraction collecting the entire sample to a MALDI plate ensures that all information from the chromatographic analysis is retained (i.e., nothing is lost).

  LC/MS & LC/MS/MS Instrumentation & Method Considerations

Ken Rosnack, Waters

This talk is intended to enable discussion and consideration of the various types of LC/MS & LC/MS/MS instrumentation including Quadrupole and Time-of-Flight systems.  In specific, discussions will include differences in single quads, triple quads, time-of-flight, and hybrid MS systems.  HPLC details will be reviewed including choices in solvent systems, additives, flow rates, columns, etc. and hence their effects in LC/MS analysis.

Several application examples will be included for illustration purposes.

Topics on next generation liquid chromatographs and novel mass spec hardware will be included.

Understanding Column Selectivity to Expedite Method Development

Tivadar Farkas, Phenomenex

Outline:

1.    The evolution of the liquid chromatographic column
2.    Mechanisms of interaction between analytes and HPLC sorbents
3.    Testing protocols used for the evaluation of sorbents
4.    New generation HPLC columns
5.    HPLC method development based on making use of specific column properties
6.    Identifying series of columns with "orthogonal" behavior
7.    Method development based on screening a set of specific HPLC columns


Abstract:

Over two decades of efforts in HPLC column development have produced hundreds of columns offered to the analyst, each of them meant to be "the solution" for a separation problem at any given time.  Instead of being a comprehensive tool kit for the chromatographer, this myriad of HPLC columns available can be a rather confusing one, given the shier number of columns to chose from, and also because of numerous columns being quite similar to one other.  The picture is further complicated by the fact that at times the success of separating a particular mixture resides in minute differences in the behavior of columns, differences that are not easily recognized and exploited.  Often times, even experienced chromatographers find it difficult to select the best column for a specific application without undertaking lengthy column comparison experiments.

The purpose of this seminar is to present testing protocols standard to the industry used to characterize the chromatographic behavior of HPLC sorbents, and to identify useful differences between HPLC columns.  These tests explore properties like stationary phase hydrophobicity, methylene selectivity, hydrogen bonding capacity, residual silanol activity, and most importantly, phenyl and polar selectivity.

We will also share our experience in identifying the right column for a given application by taking into consideration the chemical structure of the sorbent stationary phase and of the sample components.  Suggestionswill be made for the rational selection of chromatographic conditions like mobile phase modifiers and gradient slopes that will allow for each sorbent surface to exert its specific mode of interaction and reveal its specific selectivity.

Most importantly, we present a protocol for the rational selection of a specific set of columns to be screened in the initial stages of method development. In turn, this set will have the most promise for yielding a solution to the majority of your separation challenges.  The principles used to develop this set result in columns that possess "orthogonal" chromatographic behavior, and thus separate sample components based on different mechanisms of sorbent-solute interactions.  Such a set has the promise of promptly revealing the appropriate column capable of resolving a critical pair of analytes. Method conditions can then be optimized,employing the most effective column for the desired separation.

Hints and Recommendations for Maintaining your HPLC and Establishing
Reliable Integration Techniques


Wilhad Reuter, Perkin Elmer
(Abstract yet to be received)

How Large Volume Injection Techniques, Two Dimensional Chromatography,
   and Deconvolution can Improve Your Laboratory Output

Diana Baker, Thermo

The pressures today are endless.  There is a drive towards shorter runtimes to increase throughput and profitability.  Within many regulatory agencies, the movement is towards lowered detection limits as toxicologists begin toacknowledge the effects of chronic low level exposure.  Finally, as the analyte list in many analyses continues to grow, it creates a need forbroad spectrum screening procedures that retain much of the matrix in order to also retain the many classes of compounds.

This talk with be a technical explanation of some of the recent technical advances within traditional gas chromatography that facilitate these changing analytical needs.  Large volume injections, defined here as 50 ul and above, for split/splitless inlets (SSL), pressure temperature vaporization inlets (PTV), and oncolumn injectors will be described.Fast GC for EPA volatiles methods will be presented with its complementary software for report writing.  Finally, to accommodate more complex matrices, three solutions, MS/MS, deconvolution and comprehensive chromatography (GCxGC) with their accompanying hardware and software will be examined.

Application of GC-MS for the Analysis of Polymers using Pyrolysis

 Tom Wampler, CDS Analytical

Although gas chromatographs are designed for the analysis of organic compounds which are volatile within the column oven range, they may easily be extended to the study of polymers and polymeric materials such as paint, rubber, glue, ink and textile fibers by the addition of a pyrolyzer as a sample introduction unit.  Control of the sample temperature permits both the release and analysis of intact semivolatile additives and the conversion of the polymer itself to volatile molecules which retain much structural and compositional information.

Interpretation of the data produced by pyrolysis requires an understanding of how different polymer types react at high temperatures.  In general, they may fragment to smaller pieces of the polymer, unzip to monomer or monomers, or release small molecules consistent with the polymer structure.  Copolymers, blends and finished materials follow the same paths, making the analysis of complex products relatively straightforward.

This seminar presents the basic chemistry involved in polymer pyrolysis, with interpretation based on GC-MS data.  Features required of pyrolysis instrumentation are discussed, as well as interfacing to GC systems.  Examples will show the analysis of complex “real world” materials, using temperature as the sample preparation and injection device.  Suggestions are given concerning the selection of analytical conditions to simplify the analysis of complicated products in a step-wise fashion.   

Last modified:07/07/04
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