A collaborative study to establish a U.S. reference for tissue plasminogen activator (t-PA).

Area of Science:

• Biologics and Biotechnology
• Pharmacology
• Biochemistry

Background:

• The World Health Organization established the Second International Standard for tissue plasminogen activator (t-PA) in 1987.
• The Center for Biologics Evaluation and Research (CBER) initiated the development of a U.S. national reference t-PA for lot release potency testing.
• Alteplase, a licensed t-PA biologic, and other t-PAs in development require standardized potency assessment.

Purpose of the Study:

• To establish a U.S. national reference standard for tissue plasminogen activator (t-PA).
• To calibrate a candidate recombinant t-PA (rt-PA) preparation against the Second International Standard (2nd I.S.).
• To ensure accurate potency testing for t-PA products in the United States.

Main Methods:

• A collaborative study was conducted involving four laboratories, including CBER and three manufacturers.
• A candidate recombinant t-PA (rt-PA) preparation was donated by Genentech, Inc.
• Potency of the rt-PA preparation was established using a clot lysis assay calibrated against the 2nd I.S.

Main Results:

• The potency of the U.S. reference material for tissue plasminogen activator (t-PA) was determined to be 2900 international units (IU) per vial.
• The collaborative study successfully calibrated the national reference rt-PA against the international standard.
• Consistent results were obtained across the participating laboratories, validating the reference standard.

Conclusions:

• The established U.S. reference t-PA provides a critical standard for lot release potency testing.
• This national standard ensures the quality and consistency of t-PA products manufactured or developed in the U.S.
• The findings support the ongoing use of this reference material for reliable t-PA product evaluation.