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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Mid-Cycle Review Meeting Minutes, October 19, 2009 - Spherusol

BLA 125354/0  
Mid-Cycle Review Meeting Minutes
October 19, 2009 1:00 PM WOC 1 CR 300 N

 
Attendees: Bridgewater, Jennifer (by phone), Campbell, Karen M. (by phone), Cowley, Siobhan, Daugherty, Jon, Hawkins, Anthony, Jingyee, Kou, Miller, Catherine (by phone), Morris, Sheldon, Mosquera, Alexis, Wieland, Holly, Wise, Bob, Zinderman, Craig (by phone).
 
Purpose: The purpose of the meeting was to obtain a status update from the review team and determine if there were any issues that might delay the progress of this review.
 
Brief Recent History: The sponsor was sent a Deficiencies Identified (DI) letter on August 4, 2009. The sponsor responded to the DI letter in Amendment 2, submitted to FDA on October 8, 2009. Amendment 2 had technical problems related to the electronic submission and Amendment 2 was voided. Amendment 3 was submitted on October 15, 2009.
 
Current Status: Members of the review team are actively working on the review and had some preliminary comments for an Information Request (IR) letter. Review team members will continue their reviews and provide the Committee Chair with letter-ready IR comments by COB November 16, 2009. Tentative plans are to issue the IR letter by COB on November 23, 2009. 
 
BLA Check List Items Discussed:

  1. Advisory Committee: Not needed.
 
  1. PREA: Not necessary for products with Orphan Drug Designation.
 
  1. Lot Release protocol: Firm must have a lot release protocol (blank) submitted to the file that provides the format for all future lots that will be released and this was submitted in their last amendment. DBPAP and DMPQ will ensure that the lot release protocol is acceptable. Firm also needs to submit completed lot release protocols for all lots submitted in support of the application. DBPAP will communicate with the sponsor re: submitting completed lot release protocols for lots in support of this BLA.
 
  1. Product Testing Plan: Currently in draft form.
 
  1. Lot Release Testing: Based on past history with prior product, most tests for current product are probably not needed. Review of lots in support will primarily be paper review of Lot Release protocols; however, sterility and phenol content will need to be confirmed by actual testing. Submission contains three (3) consistency lots dated 2003, -----------------(b)(4)-----------------. Expiration dates for lots is not currently known and will need to be determined. OVRR has found with other vaccine products that approximately 18 months expiry remaining post-approval is most useful for firms and practitioners. Firm may need to formulate a new launch lot if remaining dating post approval is not sufficient (not less than 12 months). Product appears to be stable for ---(b)(4)---. If the product is approved on the first action due date, then use of the launch lot should be acceptable. If licensure is delayed, then use of the launch lot could be problematic.
 
  1. Lot Release Clearance: Deferred until 2010.
 
  1. BiMo: Sites selected and inspections scheduled. Anticipated completion date November 27, 2009.
 
  1. Prelicensure Facility Inspection: DMPQ reported that a facility inspection is not needed and will write an inspection waiver memo.
 
  1. Compliance Check: Deferred until 2010.
 
  1. Environmental Assessment: DMPQ will verify that sponsor is requesting categorical exclusion.
 
  1. Proprietary Name Review: Initial name submission CR’ed. Amendment 3 sufficiently addressed concerns and review clock was restarted.
 
  1. Draft Reviews due at Mid-Cycle: See paragraphs 3 and 4 above.
 
Other Review Items Discussed:
 
  1. The clinical relevance of the proposed indication continues to be a subject of discussion. It was noted that in this submission in regards to pharmacovigilance (PCV), the sponsor stated that his active surveillance plan contains a plan to “establish a reporting system …regarding the following items of interest: intended use of the product…” (See page 46 of the PCV Plan.)

    There were questions raised about false positive and false negative results, and also about true positives and true negatives. What should the health care practitioner do with these results since this product is not indicated for diagnostic use? What should the patient do with the information? The review team was in agreement that additional guidance from upper management is needed for this issue.
  2. A preliminary review by OBE has identified potential limitations of the previously conducted clinical studies as regards to their capability to detect co-morbidities, concomitant medications, or other factors that could lead to adverse events, and questioned whether the design, size (300 patients) and stated purpose of the proposed surveillance activity would sufficiently address these concerns.

    One possible approach for this product may be relicensure. This option will be further explored by the team.
 
  1. A preliminary review identified clinical and product issues. DMPQ review will be completed in about 3 weeks. The clinical review is ongoing, with approximately 20 clinical issues identified to date.
 
  1. Possible statistical issues were identified. OBE agreed to evaluate the statistics included for the animal studies to make a recommendation.
 
  1. The review team will seek supervisory guidance for additional action if the sponsor’s responses to the IR letter are inadequate.
 
Action items/deadlines:

Reviewers to send Chair “letter-ready” IR comments by COB 11-16-2009.
 
OVRR to issue IR letter by COB 11-23-2009.
 
BiMo inspectors to complete inspections by COB 11-27-2009 (estimate).
 
Regulatory Coordinator(s) to set up meeting for clinical reviewers and upper management ASAP.
 
Chair to schedule monthly review team meetings until action due date.
 
OBE to make recommendation about the need for assignment of a non-clinical statistical reviewer.
 
Chair to send OVRR Director weekly status updates until action due date.