Archived - Update Letter to Hospitals Re ABBOKINASE (Urokinase)

Starting date:

March 24, 1999

Posting date:

March 24, 1999

Type of communication:

Notice to Hospitals

Subcategory:

Biologic/vaccine

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-1700050

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  Affected products
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  Related AWRs

Notice about Health Canada advisories

Contact: BGTD

Therapeutic Products Programme

Tunney's Pasture

Address Locator #0603C

Ottawa, Ontario

KlA 0L2

March 24, 1999

Dear Sir/Madame:

The Therapeutic Products Programme (TPP) of Health Canada wishes to provide the following updated information regarding Abbokinase (Urokinase for Injection).

As indicated in our previous correspondence of February 4, 1999, Good Manufacturing Practice deficiencies were identified, last fall during inspections by the US FDA, of Abbott Laboratories and of its supplier of the human neonatal kidney cells used to manufacture Abbokinase. As a result of those deficiencies and as mandated by the US FDA:

1. additional in-process testing was implemented during production;
2. additional testing was instituted for finished lots of Abbokinase;
3. some process revalidation and other investigations were initiated.

As a result of the additional in-process testing, three unfinished lots of in-process material which were not manufactured into finished Abbokinase or distributed, were found to contain reovirus. Abbott is working to determine the extent and the source(s) of the reovirus contamination.

Reovirus is an adventitious agent that should not be present at any step in the production of Abbokinase. Although a number of studies in the literature suggest that the heat inactivation step performed during the further manufacturing of the in-process material into Abbokinase should render reovirus non-infectious, assurance has been provided by Abbott that any in-process material that contains reovirus will not be used to manufacture finished drug product. Moreover, if any lots of Abbokinase are found to contain reovirus, they will not be subject to distribution. Lots of Abbokinase currently on the market have tested negative for reovirus in Abbott's preliminary test; however, this test has not yet been fully validated.

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 has not yet completed validation of the additional tests requested by the FDA for finished product. Additional finished lots of Abbokinase will not be available for use until further testing has been completed.

Results of the investigations conducted by Abbott following the FDA inspection, indicate that the cell lines used during the past 2 years for the production of Abbokinase were free of HIV, HBV and HCV although the tests have not been fully validated. The revalidation of the inactivation of viruses by heat treatment and the removal of viruses during the purification process is ongoing; all these studies are scheduled to be completed by end of June 1999.

The finding of reovirus contamination of in-process product illustrates continuing concerns regarding the impact of deviations observed during the US FDA inspections and that the deficiencies noted could increase the risk of transmitting infectious agents. TPP would like to reiterate the information and recommendations in its letter of February 4, 1999 to Medical Chiefs of hospitals in Canada:

• The Therapeutic Products Programme (TPP) of Health Canada is recommending that Abbokinase be reserved for those situations where a physician has considered the alternatives and has determined that the use of Abbokinase is critical to the care of a specific patient in a specific situation.
• The TPP is not 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 the TPP is probably very low. Therefore, the actual risk to patients of developing an infectious disease as a result of using Abbokinase is unknown. For each setting in which the use of Abbokinase is being contemplated, we encourage physcians to consider the appropriateness of other treatment options.

Yours sincerely,

(Original signed by)

K. Bailey, D.Phil.

Director

Bureau of Biologics and Radiopharmaceuticals

Tel: (613) 957-8064

Fax: (613) 957-6302

E-mail: Keith_Bailey@hc-sc.gc.ca

Affected products

Related AWRs

Archived - Letter to Hospitals Re: Abbokinase

1999-02-04 | Health products

Advisory