February 23, 2007
VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Manager, ADD Regulatory Affairs
Abbott Laboratories, Dept. 49C, Bldg. AP6C
100 Abbott Park Road
Abbott Park, IL 60064-6092
BLA STN #103766
ABBOTT PRISM HBsAg [Antibody to Hepatitis B Surface Antigen (Mouse Monoclonal IgM)]
BLA STN #103785
ABBOTT PRISM HBcore [Hepatitis B Virus Core Antigen (E. coli, Recombinant)]
Dear Ms. Sanborn:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed the product information sheets (PR1072D and PR1072B/R2-1), launch presentation (PR3041), and "Customer Letter - Living Donor Language and Informational Package Insert" webpages (at www.abbottdiagnostics.com, no ID number) for ABBOTT PRISM HBsAg [Antibody to Hepatitis B Surface Antigen (Mouse Monoclonal IgM)] and ABBOTT PRISM HBcore [Hepatitis B Virus Core Antigen (E. coli, Recombinant)] submitted by your firm under cover of Form FDA 2253. We reviewed the product information sheets that were submitted by your firm as well as the ones found on your website. These promotional materials are false or misleading because they fail to reveal material facts regarding the important risks associated with the use of the products and to provide adequate directions for use. Therefore, these product information sheets, launch presentation, and webpages misbrand these products in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. §§321(n) and 352(a) and (f)(1) and (2); cf. 21 C.F.R. 801.119 and 809.10(b). By failing to include sufficient information on risks and adequate directions for use, you have encouraged the potentially unsafe use of ABBOTT PRISM HBsAg and ABBOTT PRISM HBcore.
The ABBOTT PRISM HBsAg is an in vitro chemiluminescent immunoassay for the qualitative detection of hepatitis B surface antigen (HBsAg) in human serum and plasma specimens. It is intended to screen individual human donors, including volunteer donors of whole blood and blood components, and other living donors for the presence of HBsAg. It is also intended for use in testing blood and plasma specimens to screen organ donors when specimens are obtained while the donor's heart is still beating, and in testing blood specimens to screen cadaveric (non-heart-beating) donors. It is not intended for use on cord blood specimens.
The ABBOTT PRISM HBcore assay is an in vitro chemiluminescent immunoassay for the qualitative detection of total antibody to hepatitis B core antigen (anti-HBc) in human serum and plasma specimens. The product is intended to screen individual human donors, including volunteer donors of whole blood and blood components, and other living donors to prevent transmission of hepatitis B virus (HBV) from such donors. It is also intended for use in testing blood and plasma specimens to screen organ donors when specimens are obtained while the donor's heart is still beating. It is not intended for use on cord blood specimens.
These products are considered to be devices as defined in 21 U.S.C. 321(h) of the Act because they are an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, which is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease in man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary purpose.
Specific examples of risk information contained in each FDA-approved product labeling (PI) for these products include, but are not limited to, the following:
WARNINGS AND PRECAUTIONS
For In Vitro Diagnostic Use
The performance characteristics of this product have not been established for the laboratory diagnosis of HBV infection. (.)
CAUTION: This product contains human sourced and/or potentially infectious components. Some components sourced from human blood have been tested and found to be reactive for HBsAg/anti-HBc by FDA licensed tests. Refer to the REAGENTS section of this package insert. No known test method can offer complete assurance that products derived from human sources will not transmit infection. Therefore, all human sourced materials must be considered potentially infectious. It is recommended that these reagents and human specimens be handled in accordance with the OSHA standard on Bloodborne Pathogens. Biosafety level 2 or other appropriate biosafety practices should be used for materials that contain or are suspected of containing infectious agents. (.)
LIMITATIONS OF THE PROCEDURE (.)
Do not use specimens collected in heparin. Use of heparin as an anticoagulant may cause a reduction in Sample Net Counts and in S/CO for ABBOTT PRISM HCV; therefore, heparin is not recommended for any ABBOTT PRISM assay.
Failure to Reveal Material Facts
In determining whether promotional materials are misleading there shall be taken into account not only representations made or suggested by statement, word, design, device, or any combination thereof, but also the extent to which the materials fail to reveal facts material in the light of such representations, or material with respect to consequences which may result from the use of the article to which the materials relate under such conditions of use prescribed in the materials. See 21 U.S.C. §§321(n) and 352(a); cf. 21 C.F.R. 809.10(b)(5)(ii). For example, the product information sheet submitted by your firm as well as the one found on your website for the ABBOTT PRISM HBcore promote the indication, sample types, reactivity and sensitivity of the product but fail to present the warnings and precautions, or the limitations of the procedure reproduced earlier in this letter.
Similarly, both the ABBOTT PRISM HBsAg product information sheet submitted by your firm as well as the one found on your website, together with the launch presentation, promote the indication, sample types, reactivity and detectability of the product but fail to present risk information regarding the potential for transmission of infection. The product information sheet also fails to present the caution that specimens collected in heparin should not be used.
The ABBOTT PRISM HBcore product information sheet includes two tables but fails to provide important contextual information necessary to understanding the tables. These tables, titled "Reactivity of the ABBOTT PRISM HBcore assay in whole blood donors, in specimens from individuals with medical conditions unrelated to HBV infection, and in specimens containing potentially interfering substances" and "Reactivity of the ABBOTT PRISM HBcore assay in selected populations with HBV infection and at increased risk for HBV infection" correspond to Tables IV and VI, respectively, in the PI. However, the product information sheet omits all of the footnotes from these two tables that appear in the PI. These footnotes are necessary in order to put the data supplied by Tables IV and VI in the appropriate context. For instance, Table IV omits the footnote that defines all the terms used in the "Category" column, namely, IR (Initially Reactive), RR (Repeatedly Reactive), and CI (Confidence Interval); the list of additional tests for HBV markers that were performed to support a PRISM HBcore reactive test result; the categories of medical conditions unrelated to HBV infection and specimens containing potentially interfering substances; descriptions of the repeatedly reactive specimens; and a description of the specimens supported as positive by additional testing. Table VI, in addition to omitting some of the footnote information listed above, omits the footnote describing the categories of individuals at increased risk for HBV infection, as presented in the PI. See 21 U.S.C. §§321(n) and 352(a) and (f)(2); cf. 21 C.F.R. 809.10(b)(12).
Similarly, the footnotes are incomplete in the ABBOTT PRISM HBsAg product information sheet. For example, the footnotes (a through e) that are presented in the sheet apply only to the table titled, "Reactivity of the ABBOTT PRISM HBsAg Assay in Selected Populations with HBV Infection and at Increased Risk for HBV Infection", as noted in Table V of the PI. On the other hand, the footnotes (a through d) from Table IV of the PI (titled "Reactivity of the ABBOTT PRISM HBsAg Assay in Whole Blood and Plasmapheresis Donors, in Specimens from Individuals with Medical Conditions Unrelated to HBV Infection, and in Specimens Containing Potentially Interfering Substances") are omitted from the same table which appears in the product information sheet and would provide important contextual information for interpreting this table.
Failure to Provide Adequate Directions for Use
It appears that the product information sheets and launch presentation were disseminated without a PI. The failure to disseminate these materials with the PI render your product misbranded in violation of the Act. See 21 U.S.C. §352(f)(1); cf. 21 C.F.R. 801.119 and 809.10(b).
Further, the webpages for ABBOTT PRISM HBcore continue to disseminate the October 2005 outdated version of the PI under the heading "ABBOTT PRISM Package Inserts" under the "Package Inserts" webpage. We note that the revised PI, dated January 2006, (updated Name and Intended Use section) is posted on the website, albeit under "Customer Communications." See 21 U.S.C. §352(f)(1); cf. 21 C.F.R. 809.10(b)(15).
Conclusion and Requested Actions
For the reasons discussed above, the product information sheets, launch presentation, and webpages found at www.abbottdiagnostics.com cause the ABBOTT PRISM HBsAg and ABBOTT PRISM HBcore to be misbranded in violation of the Act. See 21 U.S.C. §§321(n) and 352(a) and (f)(1) and (2); cf. 21 C.F.R. 801.119 and 809.10(b)(5)(ii), (12), and (15).
We request that Abbott Laboratories immediately cease the dissemination of violative promotional materials for ABBOTT PRISM HBsAg and ABBOTT PRISM HBcore such as those described above. Please submit a written response within ten (10) business days of the date of this letter, stating whether you intend to comply with this request, listing all violative promotional materials for ABBOTT PRISM HBsAg and ABBOTT PRISM HBcore such as those described above, and explaining your plan for discontinuing use of such materials.
Please direct your response to the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-602, 1401 Rockville Pike, Rockville, Maryland 20852-1448, facsimile 301-827-3528. In all future correspondence regarding this matter, please refer to the BLA/STN numbers. We remind you that only written communications are considered official.
The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for ABBOTT PRISM HBsAg and ABBOTT PRISM HBcore comply with each applicable requirement of the Act and FDA implementing regulations.
----- signature -----
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research