FDA releases SFBC 483s, citing case histories, inadequate investigations and protocol violations.

South Florida Bioavailability Clinical International (SFBC), Miami, FL, Maitland, FL, District

South Florida Bioavailability Clinical International (SFBC), headquartered in Miami, FL, was cited by FDA in recent audits for improper filing of investigational records, case history errors and lack of proper informed consent. Also deficient were numerous violations of study protocol.

SFBC, a contract research organization and biopharmaceutics clinical facility, was audited at both its Miami and Ft. Myers, FL, cites by agency investigators Luz Collado, Keith Schwartz and Jennifer Menendez of FDA's Maitland, FL, District Office.

SFBC provides early- and late-stage clinical drug trials around the world. It has more than 30 offices in North America, Europe, South America and Asia.

SFBC made headlines earlier this year and in 2005 after allegations surfaced about lax FDA oversight, inadequate informed consent, conflicts of interest with Southern IRB and lack of professional credentials of some SFBC staff. The firm hired independent counsel to review the allegations and the resulting independent report, the company claimed, exonerated the firm of most of the allegations.

According to documents from the first inspection, SFBC's Miami facility was cited because "investigational records were not retained for a period of two years following approval of a drug's marketing application." For example, a copy of the CRF was not maintained on site for several study subjects.

Also, regarding protocol deviations, the firm failed "to randomly select and retain samples from the test and reference drug products in the bioequivalence study. Also, prior approval from the sponsor was not obtained for the use of concomitant therapy during a study, the 483 stated. For example, one subject received ibruprofen, another received miconazole nitrate and another received oxygen, which were not approved by the sponsor and these three subjects completed the study.

Further, there was no documentation showing that an acceptable undisclosed type of test within one year prior to the study entry was obtained for two subjects, "and there was no approval from the sponsor for this protocol deviation prior to the dosing of these subjects."

In the second inspection, conducted at the Ft. Myers site, SFBC was cited because it failed to prepare or maintain adequate and adequate case histories with respect to observations and data pertinent to the investigation and informed consent. "Source documentation for [undisclosed patients] detailing the time between their finishing breakfast and being dosed with study medication was not available during the inspection and apparently had been lost," the 483 noted.

In the same observation, the FDAer stated that case report forms for two other patients showed that they did not meet exclusion criteria yet were included in the study.

Next, the facility received a citation because three patients consented in March 2004 were not consented with the most recent approved and revised version of the informed consent, dated Jan. 27, 2004.

Further, investigational records "were not retained for a period of two years following approval of a drug's marketing application and discontinuance of the investigation and notification of FDA." Specifically, source documentation for two patients detailing the time between their finishing breakfast and being dosed with study medication was not available during the inspection and apparently had been lost.

In addition, the company "failed to ensure that an investigation was conducted in accordance with the general investigational plan and protocol specified in [undisclosed]." For example, one patient was included in the study even though the patient was not listed in source documentation and had apparently not been calculated as required by the protocol.

The firm responded: "We acknowledge the finding. Although a note to file was written to document the missing form, it was not written in the same timely fashion that the form was discovered to be missing. Additionally, although we realize the significance of the lost document, we feel strongly that the breakfasts were served on time as the dosing would have been delayed had there been any issue with the start and end time of the critical breakfast."

In the next inspection in Miami, SFBC was cited for "failure to randomly select and retain samples from the test and reference drug products used in this bioequivalence study performed."

In response, the company stated: "At the time of the initiation of this study, it was our understanding that this study was designed by the sponsor and conducted under control with our investigative site and two others, analytical lab site, an independent third party contract clinical trials organization for the selection, distribution and retention of all the samples for all the contracted investigative sites."

The firm also noted that a contracted coordinator was responsible for all aspects of the data management and analyses. Under the direction of the third party, they packaged and selected the test articles for and distributed the test articles to its clinical testing facility.

"In summary," the firm continued, "in view of the fact that at the time of the initiation that we were under the impression that the interpretation of the supposed conduct of this study met the letter and spirit of the 'Guidance for Industry: Handling and Retention of [undisclosed] Testing Samples.'"

In addition, SFBC was cited because "there is no source documentation to show that the subjects were dosed within [undisclosed number of days] after the completion of the [undisclosed] when administered the [undisclosed] in the fed condition as required by the protocol."

The company noted in response that it "conducted this study according to the 'Guidance for Industry Food Effect Bioavailability and Fed Bioequivalence Studies Guidelines set forth by the Department of Health and Human Services." All of the subjects in treatment C, the firm continued, were given the required meal an undisclosed number of days before dosing. Also, the dosing times were staggered to facilitate the collection of samples at the specified times post dose.

In the third inspection, the firm was written up because it failed to prepare or maintain accurate case histories with respect to observations and data pertinent to the investigation. For example, a discharge laboratory report dated July 27, 2003, for an undisclosed subject required a repeat test by the subinvestigator who reviewed the report and the laboratory tests were never repeated. "According to a note to file dated July 21, 2004, the subject was lost to follow up. However this subject was reported in the CRF as completing the study."

Also, the meal log for day 1 Dec. 6, 2004 shows that an undisclosed subject completed their meal at 21:40 and another undisclosed subject completed their meal at 21:48. However, on Dec. 6, it was reported in the CRF as 22:39 for the first subject and 22:58 for the second subject.

The firm could not be reached for comment.

Southern Florida Bioavailability Clinic International (SFBC), Miami, FL, 7/29-8/4/03, 7/20-23/04, 3/29-5/2/05, Doc. 115335, $25 plus retrieval.