J&J Confide home HIV test kit fails GMPs for filter blood absorbency -- FDA warning letter.

J&J CONFIDE HIV HOME TEST KIT FAILS BLOOD ABSORBENCY TEST GMPs, FDA states in a warning letter sent to Johnson & Johnson's Direct Access Diagnostics company on May 28. FDA considers the home test kit adulterated in that it does not to conform to Good Manufacturing Practices for medical devices as pertains to the validation of blood tests; Confide also is considered misbranded because DAD did not submit information on the product required by the medical device reporting regs, FDA says; and the company is not collecting the required demographic information from Confide test kit users as mandated by the premarket approval application dated May 14, 1996. The warning letter was issued following postmarketing inspections of the company's manufacturing facility in Bridgewater, N.J. from March 24 through April 4.

FDA cites DAD for "failure to validate changes to the blood absorbency test utilized for incoming component testing and finished product testing." The standard established for testing by the National Committee for Clinical Laboratory Standards "requires the use of fresh, whole blood with a 55% hematocrit," FDA states. "Your firm is utilizing frozen and thawed blood with no addition of cryoprotective agents. Since hemolysis occurs when blood is frozen, the hematocrit would decrease as a result of the freeze/thaw storage process," the agency notes. "There is no documented evidence to substantiate this blood material is equivalent to 55% hematocrit fresh, whole blood for use in this significant testing method," the warning letter states.

Therefore, FDA is "concerned about the accuracy of any validation studies" for Confide "that included frozen/thawed blood performed to determine whether the filter paper" in the home test kit that receives the user's blood sample "is compromised by moisture, compression and/or contaminants," the warning letter states.

FDA notes that DAD's original pre-market approval application (PMA) and several amendments to the filing "committed to following NCCLS guidelines for performing the quality control blood absorbency testing of the filter paper," which the guidelines mandate must use fresh, whole blood. "While we note that subsequent to these commitments to use fresh, whole blood, you may have submitted information that indicated the use of frozen/thawed blood, you did not specifically highlight this change in methodology as required by" the regs for PMA amendments and supplements, the warning letter points out.

"Failure to establish and implement an adequate failure investigation program that would include an evaluation/review of device batch records for the home test kit, testing of retain[ed] samples and questioning the user on their collection experience and test card handling" also are cited by FDA as reasons for the warning letter.

With regard to misbranding, FDA says DAD "failed to submit" medical device reports to FDA "after receiving information which reasonably suggest that the Confide HIV Test Service may have reported false results to consumers on six occasions." The complaints came in by telephone between Sept. 16 and Jan. 15, FDA says.

DAD also failed to fulfill its obligations with regard to demographic data from the customer base. A company survey begun in February provides callers with an option to bypass the survey "completely," FDA notes. "As a result, the demographic information required by the conditions of approval of your PMA is not being collected for all callers as evidenced by the fact that only 19% of the positive [HIV-infected] subjects and 26% of the negative [HIV] subjects have participated in the optional demographic survey," FDA says. "Prior to change to an optional survey, 43% of the positive subjects participated in the counselor-initiated demographic survey," the agency points out.

DAD responded to FDA's inspection of its manufacturing facility and subsequent issuance of a FD-483 inspection report on May 7. The warning letter addresses two of the issues raised by DAD.

FDA "disagrees with the rationale that either fresh or frozen/thawed blood is suitable for testing the filter paper" used in the Confide test card. "NCCLS guidelines specifically state that fresh, whole blood with 55% hematocrit is used for absorbency testing," the warning letter states. "If you choose to use lysed blood," FDA says, "you need to validate this test and arrive at specifications for this material. An effective validation effort should include a `worst-case scenario' test designed to fail to meet specs if the filter paper is compromised," FDA notes.

The company's response to the FD-483 observation about the failing GMPs for the blood absorbency test "is not complete. Volume retention of the filter paper is an important quality feature," FDA notes. "Failure of filter paper to retain the minimal amount of blood used in testing, which cannot be visually determined, could possibly result in failure of the HIV test to detect antibodies," the agency states.

FDA acknowledges DAD's commitment to "retrospectively evaluate previously manufactured and released lots of test cards utilizing a...variation of the volumetric test." However, FDA says, "while this is appropriate for retrospective validation purposes, there is no commitment to perform a [quality control] test on each lot of finished product to determine if the volume retentive qualities of each finished product lot have been compromised."

DAD responded to FDA's warning letter on June 13, stating that it will comply with all of the agency's requests. DAD is in the process of switching to the use of fresh, whole blood instead of frozen, thawed blood in the blood absorbency paper tests. The company alternatively could have validated the tests using frozen, thawed blood, DAD noted. Additionally, the company has changed its medical device reporting practices, another issue in the warning letter, and has increased client participation in the consumer survey, offering 100% of clients the opportunity to participate in the voluntary survey, data from which are reported quarterly to FDA, the Centers for Disease Control & Prevention and state health departments.