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U.S. Department of Health and Human Services

About FDA

Collaborate in the development of a standardized Factor XIa reference reagent for Immune Globulin Thrombogenicity Testing

Description: Factor XIa content in plasma-derived immunoglobulin products has recently been shown by FDA scientists to be related to an increased risk of thromogenicity in product recipients. FDA scientists will collaborate with the WHO Expert Committee on Biological Standardization (ECBS) to develop and characterize the 1st International Reference Reagent for Factor XIa, and, to conduct thrombogenicity assay harmonization studies with the European Medicines Agency (EMA) and National Institute for Biological Standards and Control (NIBSC).

FY 2013 Updates

Milestone DescriptionMilestone DateMilestone StatusMilestone Completion Date

Reviewing final report on the collaborative study on the 1st international reference reagent for activated Factor XI; discussing the plans for the FXIa multi-assay performance study.

Quarter 1

Completed Quarter 1

Waiting for National Institute for Biological Standards and Control (NIBSC) study protocol to review.

Quarter 2

Completed Quarter 2

Waiting for NIBSC study protocol to review.

Quarter 3

Completed Quarter 3

Reviewed the “Final report on the evaluation of the WHO Reference Reagent (RR) for Activated Blood Coagulation Factor XI (FXIa), Human” from the NIBSC which was presented to the Expert Committee on Biological Standardization (ECBS) in Geneva, October 21-25, 2013. Reviewed ECBS 2013 document, “Proposal for the 1st WHO International Standard (IS) for Activated Coagulation Factor XI (FXIa)” also from the NIBSC. This will replace the Reference Reagent discussed above. OBRR decided to support the establishment of this new WHO standard. A principal NIBSC scientist on the 1st IS FXIa standard study, Dr. Elaine Gray, will be visiting OBRR on November 6, 2013 to specifically discuss the design of the study.

Quarter 4

Completed Quarter 4

FY 2014 Updates

Milestone DescriptionMilestone DateMilestone StatusMilestone Completion Date

CBER and the National Institute for Biological Standards and Control (NIBSC) (UK) are currently discussing design of the International Study CS504 to establish the 1st International Standard (IS) for Activated Coagulation Factor XI (FXIa), Human. The study is led by the NIBSC with the participation of CBER laboratory. The NIBSC study samples have been received by CBER laboratory on January 15, 2014. The primary goal of the collaborative study is to value assign the functional activity of the proposed 1st IS for FXIa, relative to the Reference Reagent for FXIa (NIBSC code 11/236). The secondary goal of the study is to explore the performance of the FXIa candidates and their use in the assessment of procoagulant activity by a variety of in-house and commercial methods used for release of Immune Globulin (IG), Intravenous or Subcutaneous products. The third goal of the collaborative study is specific to the CBER laboratory. We will evaluate the potency results, variability, and limits of detection of CBER’s investigational methods relative to other common tests and laboratories.

Quarter 1

Completed Quarter 1

1) Completed participation in the NIBSC study to develop the 1st WHO IS for FXIa, NIBSC 13/100; a preliminary report was issued by the NIBSC on 4 April 2014 to the participants for review. 2) Data were presented at two regulatory meetings, the 5 February 2014 FDA-EMA-HC Blood Cluster meeting and 18 March 2014 teleconference with the EMA-EDQM Meeting on Establishment of Common Test for Procoagulant Activity of Immunoglobulins. CBER presented data on the commutability of the NIBSC FXIa standard between 9 methods used for procoagulant activity testing. 3) OBRR started preliminary non-binding discussions with the USP on a collaborative NIBSC-USP-FDA-industry multi-laboratory study on the harmonization of IG thrombogenicity testing.

Quarter 2

Completed Quarter 2

 

Quarter 3

 

Quarter 4

Key Projects Legend

Milestone StatusDefinition
Not Yet StartedWork for specific milestone has not yet been started.
CompletedMilestone and/or overall project is completed.
On TrackMilestone - On track for completion by milestone deadline. Quarter status - Project is on track for completion based on overall milestone status.
On HoldMilestone - On hold, but deadline for completion has not passed. Quarter status - Project is on hold, based on overall milestone status.
DelayedMilestone - Delayed as it has not been completed and deadline has passed. Quarter status - Project is delayed based on overall milestone status.

Glossary

Note: The data provided on this website is produced on an ongoing basis for performance management purposes and is subject to change due to updates of preliminary estimates, corrections, or other reasons. In addition, FDA may change the type or amount of data provided on this website at any time. Information marked as "Completed" may include measures and/or key projects for which activities are ongoing but no longer tracked as part of FDA-TRACK.