Jul 16, 1999
Consumer Inquiries: 888-INFO-FDA
SERIOUS MANUFACTURING DEFICIENCIES
WITH ABBOKINASE PROMPT FDA LETTER TO ABBOTT LABS
WASHINGTON D.C. (www.SafetyAlerts.com)
- The Food and Drug Administration has informed Abbott Laboratories of additional concerns
related to manufacturing deficiencies for urokinase (Abbokinase).
Abbokinase is used in the United States to
dissolve blood clots in the lungs and heart. It is also used to help clear intravenous
catheters. Abbokinase is derived from cultures of human kidney cells from newborns who
have died of natural causes
During inspections of Abbott Laboratories and of
BioWittaker, Inc., Abbott's supplier of human kidney cells, FDA identified numerous
significant deviations from current good manufacturing practice (CGMP) regulations
designed to assure product safety.
Until these problems are corrected, further
distribution of Abbokinase would violate federal laws designed to assure the safety of
drugs for patient use. FDA's concerns about the product relate to serious deficiencies in
the manufacturing processes, the testing of the product, and the screening and testing of
the donors of the kidney cells used to make Abbokinase.
Compliance with CGMP is important because products
manufactured from human sources have the potential to transmit infectious agents. CGMP for
products such as Abbokinase requires important, overlapping safeguards in the production
process, including adequate
- screening of donors and testing of the cells,
- controls for proper harvesting, storage, and
handling of materials used in all stages of manufacturing, and
- processes to remove or inactivate infectious agents
from the product.
Over the past several months, the firm has
reported to FDA that a number of in-process lots of Abbokinase were contaminated with
microorganisms. Six such lots were found to contain various strains of reovirus, a virus
that usually results in no symptoms or causes minor respiratory or gastrointestinal
symptoms. Association of reovirus infection with other human diseases has been reported,
although a causal link has not been established. Another in-process lot was contaminated
with mycoplasma, a microorganism that can cause respiratory infections, and, on rare
occasions, other infections that may be serious. Abbott has assured FDA that none of these
in-process lots were manufactured into final product or distributed.
These recent findings of contamination and
Abbott's inability to locate the source of the problem have raised further concerns at FDA
about Abbott's entire manufacturing process for Abbokinase. Abbott's deviations from CGMP
could significantly impact the safety of the product. One FDA concern is that deficiencies
in manufacturing practices could also lead to the product being contaminated with
microorganisms that have not yet been detected.
In January 1999, FDA issued a letter to health
care providers in order to alert them to important safety information regarding the use of
Abbokinase. The letter included information about the potential risks of the product for
transmitting infectious agents. It also recommended that Abbokinase be reserved for only
those situations where a physician has considered the other available treatment
alternatives and has determined that the use of Abbokinase is critical to the care of a
specific patient in a specific situation. In addition, at FDA's request, Abbott changed
the labeling of the product to include additional information to reflect these safety
concerns so that physicians would have a clear understanding of the risks of using
However, since the January letter to health care
providers, FDA obtained additional information regarding the inadequacy of the screening
and testing of the mothers and donors of the human kidney cells used to produce
Abbokinase. Information was also obtained regarding the seven instances of in-process lots
of product being contaminated with reovirus and mycoplasma.
In the letter to Abbott, the agency has detailed
the steps Abbott needs to take to correct the serious and significant manufacturing
deviations. These include:
- completing a thorough and adequate investigation of
the reovirus and mycoplasma contamination, including the source of the contamination,
- manufacturing Abbokinase using human kidney cells
that have been obtained, processed, and tested through adequate methods, and
- assuring that fully validated methods are used in
the manufacturing process to test for infectious agents and remove them.
The limited number of lots of Abbokinase shipped
early this year were distributed only after they were tested for certain infectious agents
and found negative by Abbott Laboratories and FDA. Abbott Laboratories has not distributed
any new lots of the product since then.
The actual risk to patients of developing an
infectious disease as a result of using Abbokinase is unknown.
Patients should discuss any concerns they may have
about prior use of Abbokinase with their physicians.
Physicians should continue to report any adverse
events, including infections that may be attributable to Abbokinase. These reports can be
made to Abbott Laboratories, Pharmaceutical Products Division, North Chicago, IL. at
1-800-633-9110 or the FDA via the Medwatch program by phone at 1-800-FDA-1088, by fax at
1-800-FDA-0178 or via the Medwatch website at www.fda.gov/medwatch/.
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