October 3, 2006
Our STN: BL 125113/0
Attn: Leanne Kiviharju
10210 Genetic Center Drive
San Diego, California 92121
Dear Ms. Kiviharju:
We have approved your biologics license application for PROCLEIX® ULTRIO® Assay effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, PROCLEIX® ULTRIO® Assay under your existing Department of Health and Human Services U.S. License No. 1592. The PROCLEIX® ULTRIO® Assay is a qualitative in vitro nucleic acid assay system to screen for human immunodeficiency virus type 1 (HIV-1) RNA and hepatitis C virus (HCV) RNA in plasma and serum specimens from individual human donors, including donors of whole blood and blood components, source plasma and other living donors. It is also intended for use in testing plasma and serum specimens to screen organ donors when specimens are obtained while the donor's heart is still beating, and in testing blood specimens from cadaveric (non-heart-beating) donors. The assay is not intended for use on cord blood specimens.
The assay is intended for use in testing individual samples from living donors of whole blood, blood components, or source plasma, other living donors and heart-beating organ donors, and for testing individual blood specimens from cadaveric (non-heart-beating) donors. It is also intended for use in testing pools of human plasma comprised of equal aliquots of not more than 16 individual donations from donors of whole blood, blood components, or source plasma. This assay is intended to be used in conjunction with licensed tests for detecting antibodies to HIV-1 and HCV.
The PROCLEIX® ULTRIO® Assay is not intended for use to screen donor specimens for HBV DNA. The assay detects HBV DNA in HBV seroconversion panel specimens that are negative for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc). The assay also detects HBV DNA in donor specimens that are positive for HBsAg and/or anti-HBc. However, detection of HBV DNA in donations negative for both HBsAg and anti-HBc has not been demonstrated in the donor setting.
This assay is not intended for use as an aid in diagnosis of infection with HIV-1, HCV or HBV.
Under this authorization, you are approved to manufacture PROCLEIX® ULTRIO® Assay at your facilities in San Diego, California. You may label your product with the proprietary name PROCLEIX® ULTRIO® Assay.
Please submit final container samples of the product and each kit component in final containers together with protocols showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research (CBER). FDA will be performing lot release testing on PROCLEIX® ULTRIO® Assay kits for HIV-1 and HCV. Prior to marketing, the kits must pass the lot-release standards for these two markers. FDA will also be testing the PROCLEIX® ULTRIO® Assay kits with the HBV lot release panel. However, HBV panel testing will be for information purposes only and will not be used to determine suitability for lot release.
You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in the manufacturing, testing, packaging or labeling of PROCLEIX® ULTRIO® Assay, or in the manufacturing facilities.
We acknowledge your written commitment as described in your letter of August 23, 2006 to perform a postmarketing study to demonstrate detection of window period donations ("serologically-confirmed NAT yield cases") for HBV infection in individual donor samples (IDS) and pools (up to 16 donations) with the PROCLEIX® ULTRIO® Assay. Serologically-confirmed NAT yield cases are defined as donors who have 1) PROCLEIX® ULTRIO® Assay reactive, PROCLEIX® HBV Discriminatory (dHBV) Assay reactive, HBsAg negative, and anti-HBc negative results at index, and 2) HBsAg, anti-HBc, and/or anti-HBs seropositive results at follow-up.
We request that you submit clinical protocols to your IND, with a cross-reference letter to this biologics license application (BLA), STN BL 125113/0. Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA, STN BL 125113/0 Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:
- Postmarketing Study Protocol
- Postmarketing Study Final Report
- Postmarketing Study Correspondence
- Annual Report on Postmarketing Studies
For each postmarketing study subject to the reporting requirements of 21 CFR 601.70, you must describe the status in an annual report on postmarketing studies for this product. The status report for each study should include:
- information to identify and describe the postmarketing commitment,
- the original schedule for the commitment,
- the status of the commitment (i.e. pending, ongoing, delayed, terminated, or submitted), and
- an explanation of the status including, for clinical studies, the patient accrual rate (i.e. number enrolled to date and the total planned enrollment).
As described in 21 CFR 601.70(e), we may publicly disclose information regarding these postmarketing studies on our Web site (http://www.fda.gov/cder/pmc/default.htm). Please refer to the April 2001 Draft Guidance for Industry: Reports on the Status of Postmarketing Studies - Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997 (see http://www.fda.gov/cber/gdlns/post040401.htm) for further information.
Submit adverse experience reports in accordance with the Medical Device Reporting requirements for medical devices (21 CFR 803) as required by (21 CFR 600.81(k)(2)). Since your product is characterized as a device as well as a biological, submit these reports to the MedWatch System using MedWatch Reporting Form 3500A. Required reports should be submitted to the Food and Drug Administration, Center for Devices and Radiological Health, Medical Device Reporting, PO Box 3002, Rockville, Maryland 20847-3002.
You must submit reports of biological product deviations under 21 CFR 600.14. You promptly should identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.
Please submit all final printed labeling at the time of use and include implementation information on FDA Form 356h and FDA Form 2567 as appropriate. Please provide a PDF-format electronic copy as well as original paper copies (ten for circulars and five for other labels). In addition, you may wish to submit two draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Two copies of final printed advertising and promotional labeling should be submitted at the time of initial dissemination, accompanied by a FDA Form 2253.
All promotional claims must be consistent with and not contrary to approved labeling. You should not make a comparative promotional claim or claim of superiority over other products unless you have submitted data to support such claims to us and had them approved.
Jay S. Epstein, M.D.
Office of Blood
Research and Review
Center for Biologics
Evaluation and Research