Overview:
Validation of test methods is a critical requirement for the drug development process. Bioassays are used to support biologics in the drug development process and in post-market analytical support.
Unlike analytical test methods for small molecules, bioassays have
unique requirements due to the variable nature of some critical
components. Although some variability may be inherent, careful attention
to setting appropriate limits and to robust qualification of critical
components enhances the likelihood of success during validation.
Regulatory agencies expect pharmaceutical companies and
biopharmaceutical companies to use validated methods for late phase
work. The methods are used to test large molecule drug substance or drug
product for identity, purity, and potency. Poorly developed and
inadequately validated methods often have high failure rates when in
production. Data submitted from poorly developed/validated methods is
subject to additional scrutiny due to the excessively high failure rate
that lowers confidence in the data that is produced.
Cell-based methods may be difficult to validate due to a lack of
extensive testing during the development phase. Method validation
requires careful design of the method during development and seamless
implementation to meet regulatory agency expectations for the quality of
assay methods used in testing of biopharmaceutical or pharmaceutical
compounds.
Cell-based methods have additional complexities that may contribute to
variability. With appropriate controls in place in the method
variability can be minimized leading to successful validation and sample
analysis using the cell-based method.
This webinar will address several parameters that are important for the
successful validation of a bioassay. Included in this discussion are
multiple challenges that often lead to rework and failure that if
appropriately addressed during development should not become issues that
hinder validation. This webinar addresses the importance of method
development in successfully overcoming difficult validations. Specific
topics are unique challenges for cell-based methods, use of DOE to
define method parameters, and creating unambiguous methods.
This webinar will provide attendees with an understanding of handling
critical reagents as well as challenges faced in cell culture. Details
important in the written method as well as details for the validation
that reduce analyst variability and improve efficiency will also be
addressed. This webinar will not just define challenges but will also
guide professionals working with cell-based methods toward important
concepts that promote success in method validation.
Appropriate training and documentation of the method are critical
elements for successful transfer of a method from the development phase
into the validation procedure. Accomplishing the validation of a
cell-based method with little or no rework can occur with careful
planning and attention to an appropriate timeline. An important factor
that contributes to failure is rushing into validation without
collecting the data required to support fully a decision to move toward
validation.
This webinar addresses those issues that may lead to failure of
validations of cell-based methods while providing solid suggestions for
best practices that support success.
Why you should Attend:
Bioassays, especially cell-based methods are a necessary component of
assays providing data supporting large molecule therapeutics. Typically,
these methods are required to establish potency, a critical quality
attribute, in either release or stability assays. The live cell quality
of these assays may introduce a layer of uncertainty regarding the
ability to build a method that meets requirements for ruggedness.
Cells that express the receptor responsible for the mechanism of action
may be a transfected clonal line or may be a cell expressing the native
protein. The growth characteristics of the cell that promote expression
levels with good signal-to-background in the method are an important
quality to address as development of the assay begins.
A key question may be how much prework to perform to guide development
of the assay. Live cells are not as simple to control as individual
reagents in a method. Live cells respond to components in media,
environmental factors, and seeding densities in a manner that may have
an impact on growth characteristics, receptor expression, and signals in
cell-based methods.
These issues should be assessed fully and examined in early development
work to direct the lab toward the parameters likely to produce an assay
with a low rate of failure. This complexity often leads to problems when
factors that contribute to ruggedness in cell-based methods are not
assessed and addressed during the development phase. Successful
validation is achievable with careful consideration of the cells as the
primary critical reagent.
Control of the assay starts with control of the cells. While sufficient
time is needed to perform development using design of experiments,
moving from development to validation should be based on the quality of
the data observed in the assay and not inordinately pushed forward.
Areas Covered in the Session:
- Method selection
- Understanding the variable nature of cell-based methods
- Understanding the critical characteristics of cell-based assays that may affect performance
- Characterization of the cell line
- Details of cell maintenance, cell culture prior to performing the method
- Defining parameters to monitor
- Defining critical reagents
- Selection and certification of the reference standard
- Setting appropriate limits for reagents
- Reagent supply and sample handling
- Pre-test of critical reagents
- Setting intermediate performance controls
- Testing robustness/ruggedness/selectivity/specificity prior to validation
- Analyst training
- Peer review of the test method
- Statistical analysis
- Validation protocol and templates
- Preplanning
- Documentation of deviations and failures
Who Will Benefit:
- Validation scientists in bioanalytical or clinical laboratories
- Development scientists in bioanalytical or clinical laboratories
- QA Documentation Specialists
- Regulatory Specialists
- Consultants
- Directors of Outsourcing
- Method trainers
- Statistical staff