Minutes of Meeting, October 18, 2010 - Spherusol
Coccidioides immitis Spherule-Derived Skin Test Antigen
Detection of delayed type hypersensitivity following exposure to C. immitis
Allermed Laboratories, Inc
Review Team Meeting
October 18, 2010, 2:30 PM
Conference Room 308 S
Holly Wieland, RPM
| CBER Attendees (10):|| |
Deborah Trout (via call-in)Holly Wieland
Purpose of Meeting
- To discuss the status of the September 15, 2010, resubmission and determine if the submission is complete enough for review.
- To determine a plan for working with the sponsor to resolve any outstanding issues with the proposed indication.
Background (by dates and selected to address the proposed indication issue only)
March 26, 2010, CBER sent the sponsor a Complete Response (CR) Letter. CBER raised several issues, one being an issue with the proposed indication. CBER stated in the CR Letter “In letters for IND -(b)(4)-, dated June 21, and November 18, 2004, we requested that you specify the proposed clinical indication that would be supported by the studies which you have now completed. You have proposed that the product, Spherusol, should be used for "the detection of delayed type hypersensitivity following exposure to C. immitis", but you have not provided any description of how this information will be used in a clinical setting. Without this description, we are unable to assess the risks and/or benefits of the use of this product. If this information is not available or is not sufficient to support a labeled indication for this product, further discussion and clinical studies may be necessary. Please provide in your response the proposed clinical use of the candidate product and data to support this clinical use. Of particular interest will be your explanation of how the "detection of delayed type hypersensitivity to C. immitis" will inform the clinical management of patients tested using your product.”
June 8, 2010, the sponsor responded with an amendment to the BLA, with a modification to the proposed indication to state “Spherusol is indicated for use as a skin test antigen to detect cellular hypersensitivity to C.immitis. A positive delayed-type skin test to Spherusol can be indicative of past or present infection with C.immitis.”
August 26, 2010, CBER sent the sponsor an Incomplete Response (IR) Letter. CBER stated in the IR Letter “We note that detection of delayed type hypersensitivity during a “present” or active/current infection was not previously evaluated in studies conducted under the IND, and you did not address detection during active/current infection in the original BLA submission. You have provided Case Report Forms for seven subjects that are described as having a current infection with C. immitis to support the use of Spherusol as an agent to detect cellular hypersensitivity to C. immitis in active disease. However, the diagnostic criteria for active coccidioidal disease were not pre-specified in the IND studies. It appears that diagnostic criteria for active disease were set in a post hoc determination by study investigators. According to these criteria, subjects receiving anti-fungal therapy would be classified as having active disease regardless of symptoms....”
September 15, 2010, the sponsor responded with an amendment to the BLA, with the following statement: “Spherusol is indicated for use as a skin test antigen to detect cellular hypersensitivity to C.immitis.”
The review team determined that an outstanding issue remained with the proposed indication in that without a more clear description of how the product would be used, it was not possible to evaluate the safety and/or effectiveness of the product. The review team agreed to encourage the sponsor to request a meeting with CBER and bring consultants or others who may be helpful in resolving this issue.