Cambridge Healthtech Institute’s 6th Annual
Optimizing Bioassays for Biologics
Merging Science and Statistical Methods for Successful Biological Assay Development
October 24-25, 2018
Bioassays, at their core, spring from a fusion of biological and statistical sciences, and are used to measure activity or function of a compound or group of compounds in samples. As the field evolves, new technologies and software are changing the way
scientists view experimental design and data analysis. The health authorities and USP have provided guidance for the design and validation of a bioassay; however, they do not discuss solutions to common problems springing from this revolution in technology.
At Cambridge Healthtech Institute's sixth annual Optimizing Bioassays for Biologics, leaders working in bioanalytical and bioassay development will come together to provide case studies and best practices for handling the most common
issues in biological assay development, validation, transfer, and maintenance. There will also be a focus on lifecycle management and design of experiments methods. In addition, new technologies and bioassay formats will be presented along with recommendations
for implementation to ensure a steady drug development pipeline.
Wednesday, October 24
1:00 pm Conference Registration (Foyer)
1:40 Chairperson’s Opening Remarks
Perceval Sondag, Senior Manager, Statistics, PharmaLex
1:45 KEYNOTE PRESENTATION: A Lifecycle Approach to Bioassay Validation
Timothy Schofield, Senior Advisor, Technical Research & Development, GSK
A bioassay can be viewed as a manufacturing process, with measurements the product. The customer is a decision-maker, and the “quality attributes” are related to accuracy and precision. The analytical target profile lists the requirements
for uses throughout the bioassay lifecycle. This talk will outline the stages and elements of a lifecycle approach to bioassay validation, highlighting the opportunities for ensuring the quality of bioassay measurement.
2:15 A Quality Approach to Stage One Bioassay Optimization
Steven Novick, PhD, Director, Statistical Sciences, MedImmune
The goal of stage one lifecycle management is to develop a reliable process for commercial manufacturing. It is imperative to develop robust bioassays to measure critical and key quality attributes, such as potency and purity of the drug substance and
drug product. This presentation will illustrate modern statistical methods applied to a response-surface design to determine the design space for multiple bioassays simultaneously by optimizing the probability to meet specifications.
2:45 Assay Performance Qualification: A Fit for Purpose Approach
Perceval Sondag, Senior Manager, Statistics, PharmaLex
Recently, the lifecycle management concept for analytical procedures was introduced. It is strongly related to the Quality by Design concept given in the ICH-Q8 guidance. This contrasts with ICH-Q2 recommendations that only focus on the validation step
to evaluate the performance of an analytical procedure. ICH-Q2’s well-known check-list approach fails to provide assurance of the quality of future results with respect to the intended use of the procedure. This talk proposes a fit for purpose
method for assay validation in a lifecycle paradigm, while maintaining a reasonable compromise between producer and patient risks.
3:15 BioAssay Express: Introducing BLAT, an Assay Registration System for Biologics
Samantha Jeshonek, PhD, Research Informatics Analyst, Research Informatics, Collaborative Drug Discovery
BioAssay Express annotates bioassay protocols using semantic web vocabulary, which makes them accessible to both humans and machines. New data is created using a web-based interface, and legacy text-based data is curated with the support of text mining
and machine learning methods. We will describe BioLogics Assay Template (BLAT).
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Edison D)
4:10 CPV Application in Bioassays – Strategies to Maintain Lot to Lot Consistency & Prevent Assay Drift
Mitra Azadeh, PhD, Principal Scientist, Bioanalytical & Biomarker Development,
Nonclinical Development, R&D, Shire
Continued process verification (CPV) is critical to bioassay life cycle management and essential in ensuring that the product output is within pre-established specifications. CPV components include systems for deviation identification, data collection
and analysis, and in-process evaluation of qualification standards, and assay quality controls remain central throughout the process. This talk focuses on the role of quality controls in assay trending and monitoring of calibration drift. Factors
critical to the production, qualification, and maintenance of quality controls as well as statistical versus graphical methods for control trending will be presented.
4:40 PANEL DISCUSSION: Statistical Approaches to Lifecycle Validation
- Opportunities to optimize each step of the lifecycle approach using statistical methods
- Common pitfalls and challenges in utilizing statistics for bioassay development
- Understanding regulatory guidelines (USP/NIBSC/FDA/etc.)
- Strategies for successful collaboration between statisticians and bioassay scientists
Moderator: Perceval Sondag, Senior Manager, Statistics, PharmaLex
Panelists: Timothy Schofield, Senior Advisor, Technical Research & Development, GSK
Steven Novick, PhD, Director, Statistical Sciences, Medimmune
Mitra Azadeh, PhD, Principal Scientist, Bioanalytical & Biomarker Development, Nonclinical Development, R&D, Shire
5:40 Dinner Short Course Registration
Recommended Dinner Short Course*
SC5: Back to Basics: Optimizing Bioassay Design and Analysis
* Separate registration required.
Thursday, October 25
7:30 am Morning Coffee (Foyer)
7:55 Chairperson’s Opening Remarks
Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting
8:00 Near-Universal Equivalence Bounds for Similarity in Bioassays
David Lansky, PhD, President, Precision Bioassay, Inc.
Testing for similarity via equivalence tests is an essential part of modern bioassay analyses. Sensitivity analyses show that scaled shifts in parameters measure non-similarity in ways that are assay-independent. These scaled shifts have lower bias and
variance than ratio estimates of parameter-specific non-similarity. Well-chosen equivalence bounds for scaled shifts yield assays with limited bias in potency due to non-similarity. This gives us a way to set equivalence bounds for non-similarity
informed by the product specification and analytic target profile.
8:30 Analytic Similarity: A Review of the FDA Draft Guidance on Evaluating Analytic Similarity
Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences
Analytics equivalence has historically been handled with a statistical test for differences. As the regulatory environment matures, newer statistical methods are being developed to help ensure that two analytic methods are in fact equivalent, and don’t
just suffer from a lack of difference. This talk will explore the statistical technique outlined in the draft FDA guidance document and discuss some of the perceived pitfalls associated with it.
9:00 NEW: Visual Tools for the Development of Equivalence Test Systems
Dr. Ralf Stegmann, Stegmann Systems
The development of test systems (assay and system suitability) making use of the equivalence test approach according to the USP <1032> is a challenging task especially for non-linear systems (e.g. 4-parameter fit). The question which and how many
different tests are required to qualify an assay run cannot be answered easily. New visualization and assay simulation tools help the scientist to verify that a developed test system is capable to sufficiently proving similarity between test and standard
curves as well as similarity between the assay run and development/validation data which has been used to develop the test system.
9:30 Problem Solving Roundtable Discussions
Wright / BannekerTable 6: Use of New Technologies in Bioassay Development
Moderator: Robyn Beckwith, PhD, Technical Development Scientist, Analytical Development and Quality Control, Genentech
Table 7: Benefits of Optimizing Bioassays with Design of Experiments (DoE)
Moderator: Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent
10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Edison D)
11:10 FEATURED PRESENTATION: Strategic Bioassay Design, Beginning with the End in Mind
Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little
The presentation covers the design and validation of a bioassay. It demonstrates how plate layout, dose selection, outlier identification and removal, curve weighting, replicate strategy, curve fitting method, systems suitability and validity criteria
all impact the invalid and OOS rate of the assay. A design of experiments approach to method robustness is presented. Establishing a design space for a bioassay, designing the validation protocols and acceptance criteria justification are presented.
11:40 Assessing Bioassay Validation Acceptance Criteria in Relation to Study Design
Keith M. Bower, Principal CMC Statistician, Process Sciences, Seattle Genetics
Limited guidance is provided in regulatory documents for bioassay validation acceptance criteria (AC). This presentation illustrates (i) the interrelationship between intermediate precision (IP) and the coefficient of determination, and (ii) how to assess
the likelihood of meeting proposed AC for a given study design. The use of a statistical performance assessment, relating IP to other AC is illustrated.
12:10 pm Using Critical Fold Difference to Ensure Assays Meet Proper Standards of Reliability
Nancy Sajjadi, M.Sc., Independent Quality Consultant
12:40 Sponsored Presentation (Opportunity Available)
1:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:40 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (Edison D)
2:20 Chairperson’s Remarks
Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent
2:25 Strategies for a Successful Bioassay
Stephen Hartman, PhD, Principal Scientist, AbbVie
Bioassays are a critical component of the development and testing strategy of biologic therapies. They are amongst the most challenging test methods to develop, implement, and maintain. The inherent variability of living cells, combined with complicated
multi-step procedures, biologically active reagents, long incubation times, diverse readouts and instruments, and complex data analysis come together to make bioassay development extremely challenging. Furthermore, modern biotherapeutics are ever
adopting new formats, modalities, novel mechanisms of action, and sometimes multiple mechanisms of action. As these therapies become more structurally and functionally diverse and complex, so do the bioassays needed to enable their development
and release. This presentation will provide an overview of strategies, considerations, and recommendations for developing bioassays that are accurate, precise, robust, MoA-reflective, “QC-friendly,” and phase-appropriate. We will also
discuss common pitfalls and oversights and how to avoid/prevent them.
2:55 Straight to Automation! The Benefits of Early Implementation in Bioassay Development and Optimization
Robyn Beckwith, PhD, Technical Development Scientist, Analytical
Development and Quality Control, Genentech
Bioanalytical testing environments routinely face constraints due to sample throughput, procedural variability, required hands-on time, cost and repetitive strain on analysts. Automation of discrete assay steps or entire end-to-end workflows can potentially
alleviate these issues, but practical implementation can be challenging given the inherent complexity of biological assay systems. Strategies for successful development and application of automation for biological assays will be explored, including
fit for purpose approaches to implementing new technologies.
3:25 Bioassay Development and Automation Strategies for Antibody-Drug Conjugates
Bharathi Govindarajan, Ph.D., Senior Scientist, CMC Bioanalytical development, Immunogen, Inc.
3:55 Close of Optimizing Bioassays for Biologics