Applications of Fit-for-Purpose (FFP) Validation
Topic Leaders: Chad Briscoe, Patrick Bennett, Joseph Bower

• GCC issued White Paper as guideline for all CROs for Biomarkers screening, qualified and fully validated methods in 2012 (link: http://www.future-science.com/doi/pdf/10.4155/bio.12.197). However, it seems that CROs increasingly continue to be asked for full validation of biomarker assays vs. screening or qualified. This is very time consuming and challenging and very likely not needed based on the intended use of the data (e.g. exploratory biomarkers)

  • What can we do more as CRO community to convince clients to use the screening, qualified and fully validated approach?

  • How can we further apply/standardize our 2012 GCC White Paper to help all the CROs better manage these requests?

  • What about turning this White Paper in SOPs to better define the use of screening, qualified and fully validated methods?

• Fit-for-purpose validations - What to do when was asked for full validation even when it doesn't seem necessary based on the intended use of the data.

  • What is our regulatory risk of not doing a full validation and then not having control of the data that is generated?

  • When do CROs really see value for ourselves in doing FFP validation approaches?

• What are the issues, limitations, risks and benefits of performing early phase (or discovery) biomarker project at a CRO. This would include how best to manage method development and qualifications for discovery, FFP studies and how best to manage these as they progress towards use in GLP and GCP studies. It could be focused on LC/MS and or LBA, or can (and should) include flow cytometry.

• LBA support for ocular or tissue methods: Full Validation or FFP Validation?

  • Historically LCMS team would consider these all non-GLP and on rare occasion try to fully validate a method. For large molecules, most clients are tending to request LBA methods to be fully validated. However, this is very challenging and often not possible. Therefore, a topic to raise discussion on what other CRO are doing for ocular studies and tissue work in general may be of value to all.

2016 immunogenicity guidance and Recent and unexpected 483s on Immunogenicity Assays - Topic Leaders: Joseph Bower, Bruce Stouffer

• FDA 2016 draft guidance on ADA, Trends?

• CRO Experiences

• Recent and unexpected 483s on Immunogenicity Assays. It is very important to understand the reasoning behind this kind of 483s

Hybrid LBA/LCMS assays - Topic Leaders: Stephanie Cape, Mark Arnold

• How CROs are managing this?

• Has everyone decided to use ligand binding acceptance criteria?

• Are critical reagents being managed similarly to the processes in the ligand binding space?

Biosimilar - regulatory Feedback - Topic Leaders: Rafiq Islam, Yi Qun Xiao, Barry van der Strate, Dan Sikkema

• CROs'experiences and interactions with FDA

• Lessons Learned from CROs' perspectives

Bioanalytical laboratory's role in writing PK sample collection instructions - Topic Leaders: Roger Hayes, Shane Karnik, Mark Warren

• What parameters are BioA labs testing to provide these instructions?

• Are BioA labs training the clinics on how to collect the samples?

Cumulative Stability - Topic Leaders: Stephanie Cape, Mark Arnold

• Is benchtop stability for samples considered and managed cumulatively (e.g. if you have established 6 hours of wet ice stability, does this cover a situation where a sample is exposed to wet ice for 3 hours, frozen, then exposed to wet ice for 4 hours)?

• Tracking of stocks and intermediates to ensure cumulative time exposed to room temperature conditions (or wet ice as it may be) are covered by stability (this came up in a recent EMA audit);

• Tracking of blank matrix freeze/thaw cycles and time at room temperature (this also came up in a recent EMA audit)

Health Canada Oct. 8th Notice - compiling data and put together a position paper/ white paper - Topic Leaders: Rafiq Islam

• Almost all CROs have implemented Health Canada Oct. 8th Notice on how to perform sample stability even if other Regulatory Agencies are not asking to follow Health Canada procedure for now. There have been numerous discussions on the fact that this procedure is not "scientific based". Protocols have been already written to demonstrate the equivalence of multiple aliquots vs. single aliquot for stability testing.

• Other Regulatory Agencies have not decided yet on what procedure to enforce. From a CRO point of view this procedure implies unjustified extra cost without increasing quality. We should compile data from all CROs and put together a position paper/ white paper on trying to:

  • Influence other Regulatory Agencies and mainly the upcoming ICH M10 on BMV

  • Minimize unjustified extra cost for all the studies that are not submitted to Health Canada

Use of Chiral vs Achiral methods - Topic Leaders: Chad Briscoe

• EMA is requiring chiral method more often that FDA for BE studies. What's the CRO impact? Chiral methods are much more complicated to be developed and more expensive than achiral ones. Moreover, Regulatory Agencies issue deficiency letters more often for chiral methods for reproducibility and poor integration.

• Can CROs provide feedback and clarification on this topic and avoid regulatory findings by writing a paper/recommendation?

• Sometime Agencies ask for R, S and sum of them. Is the sum of R and S enantiomers equivalent to the results obtained with an achiral method?

• Can data of the Achiral method be provided to agencies rather than the sum of R and S?

• Is there any ion suppression with co-eluting enantiomers in the achiral method vs. sum of R and S? Please note that in incurred samples it is possible to have a large excess of an enantiomer vs. the other.

• Did any CRO find any ionization differences between R and S enantiomers?