After FDA updated the Information Sheet on Abbokinase (Urokinase) on March 16, 1999, Abbott Laboratories sent a "Dear Abbokinase Customer" message by Western Union Mailgram that evening. FDA has reviewed that message and issued a Warning Letter to Abbott Laboratories.
We are repeating the information in our March 16 update.
FDA is receiving new inquiries regarding a reported shortage of Abbokinase (Urokinase), a thrombolytic product manufactured by Abbott Laboratories (Abbott). The agency hopes that the following information will answer questions about this reported shortage.
In January 1999, Abbott implemented additional testing for finished lots of Abbokinase. Abbott has not yet completed validation of these additional tests. Additional finished lots of Abbokinase will not be available for use until further testing has been completed. FDA understands from Abbott that, due to shortage issues, Abbott has been distributing Abbokinase on an allocated basis.
In addition, three lots of in-process product, which were not manufactured into finished Abbokinase or distributed, have been found to contain reovirus. Reovirus is an adventitious agent that should not be present at any step in the production of Abbokinase. The presence of reovirus in the in-process product was discovered as a result of testing begun by Abbott this year at the request of FDA to correct deficiencies noted during FDA's inspection of Abbott last fall. Most reovirus infections are asymptomatic or produce minor upper respiratory or gastrointestinal symptoms. While association of reovirus infection with other human diseases has been reported, a causal link with other diseases has not been established.
Abbott is working to determine the extent and the source(s) of the reovirus contamination. Although a number of studies in the literature suggest that the heat inactivation step performed during the further manufacturing of the in-process product into Abbokinase should render reovirus non-infectious, FDA has received assurance from Abbott that any in-process product that contains reovirus will not be used to manufacture finished product. Moreover, if any lots of Abbokinase are found to contain reovirus, they will not be subject to distribution. Finished lots of Abbokinase currently on the market have tested negative for reovirus in Abbott's preliminary test; however, this test has not yet been validated.
The finding of reovirus contamination of in-process product illustrates the continuing concerns FDA has regarding the impact of deviations from Current Good Manufacturing Practice observed during FDA inspections of Abbott and its supplier of the human neonatal kidney cells used to manufacture Abbokinase. As a result of those inspections, on January 25, 1999, FDA issued an Important Drug Warning to Healthcare Providers regarding Abbokinase, which included the following information and recommendations:
FDA described Current Good Manufacturing Practice deficiencies noted during inspections of Abbott and its supplier of the human neonatal kidney cells that were used in the manufacture of currently available Abbokinase; the agency reported that the deficiencies could increase the risk of transmitting infectious agents.
FDA recommended that use of Abbokinase be reserved for only those situations where a physician has considered the alternatives and has determined that the product’s use is critical to the care of a specific patient in a specific situation.
- FDA discussed the risks associated with the use of Abbokinase and encouraged prescribers to consider the appropriateness of other treatment options for each setting in which the use of Abbokinase is being contemplated.
As set forth in the January 25th letter, FDA is not currently aware of any cases of infectious diseases that can be attributed to the use of Abbokinase. However, the likelihood that cases of infectious diseases caused by Abbokinase, if any, would have been recognized as such and reported to FDA is probably very low. Therefore, the actual risk to patients of developing an infectious disease as a result of using Abbokinase is unknown. FDA recommends that prescribers carefully consider this new information, as well as the information on manufacturing deviations set forth in the agency’s January 25th letter, in assessing the risks associated with the use of Abbokinase.