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Vaccines, Blood & Biologics

Record of Telephone Conversation, June 30, 2011 - MenHibrix


Submission Type: BLA    Submission ID: 125363/0    Office: OVRR
Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine
GlaxoSmithKline Biologicals
Telecon Date/Time: 30-Jun-2011 01:00 PM        Initiated by FDA? Yes
Telephone Number: ---b(4)----------------------
Communication Categorie(s):
Telecon Summary:
DMPQ Discussion of CR Letter Item 86 with GSK
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Telecon Body:
CBER and GSK representatives met to discuss the IR sent on June 23, 2011.
1.      We do not agree with your proposal to submit the data on manually inspected lots of diluent as a Post Marketing Commitment. Please describe the procedure that will be used to perform the 100% manual inspection of the diluent and show in detail how your ---b(4)---------------------------------------- is related to the process. Also, please submit data for the first lot using the 100% manual inspection of filled lots of diluent as an amendment to the file.
CBER stressed that the current plan for inspection (as found in GSK's CR response) was unacceptable to do post licensure (PMC), but would be required to be completed pre-approval. GSK understood CBER’s concerns. GSK explained that their protocol was for 100% of all diluent samples to be inspected using their –b(4)--------------------------------------------------- instrument followed by a –b(4)---------------------------------. GSK indicated that ALL samples rejected by the –b(4)--------- were discarded.  Sean Byrd stressed that the –b(4)--------- was not qualified. GSK understood and indicated that they will qualify their                        --b(4)-------------- CBER reiterated that a detailed diluent inspection protocol describing how the –b(4)--------- is used in combination with a –b(4)--------------------------. GSK indicated that they would need at least 2 weeks to communicate with their Belgium plant. Joe Temenak stressed that this material was important given the short, 6 month review time period. GSK understood. GSK also indicated that they had submitted a CBE-30 for a fully automated inspection using a ---b(4)------------ instrument which may be used in the future for MenHibrix.
2.   It is noted you use the AQL to either accept or reject a lot. The AQL is the “Manufacturer’s Risk” of rejecting a good lot; i.e. it is a business risk. Please define and submit your Reject Quality Level as the Lot Tolerance Percent Defect (LTPD) as it is the “consumer’s risk” of accepting a lot that is defective. Also, please submit the Operating Characteristic (OC) Curve; i.e. the plot of the percent defectives versus the corresponding probabilities of acceptance. In addition, please provide a justification for the current LTPD levels associated with critical and major defects.
GSK understood and indicated that they would submit a response as an amendment to the BLA. GSK indicated that getting this information may take over 2 weeks to submit. 
3.   Please provide your rationale for the AQL of Critical Defects as –b(4)- when it should be “accept on b(4), reject on b(4)
GSK agreed and indicated that they will be implementing these criteria. GSK will submit a new AQL of Critical Defects as an amendment to the BLA.
4.   We find the following statement confusing: “The current –b(4)-------------------------------- program will be completed with an additional step of –b(4)---------------------------------------- to identify and remove defective containers prior to AQL inspection and release.” Please clarify if defects rejected by the b(4) remain part of the follow-up ----b(4)--------------------------
Answered in Item 1 discussion
5.   Please note that the b(4) is not considered a qualified piece of equipment and no decisions on lot disposition should be made based on information collected by the b(4)-. Once qualified, the data must be submitted as a CBE with data from product inspections and an indication that it will be used on diluent. However, if the b(4) is used only for the diluent and not reconstituted product, you may report your qualification as an annual report. Please comment.
Answered in Item 1 discussion
6.   Please provide your rationale for why liquid within the plunger stopper is considered a minor defect. Such fluid may be indicative of a container-closure integrity breach. Furthermore, if the diluent is –b(4)-------------------, this liquid could be an indication of a problem in the sterilization parameters/conditions. Please note that during shipment these plunger stoppers do move, and may contaminate the sterile region of the barrel. Please comment.
GSK understood and agreed to submit their rationale as an Amendment to the BLA
7.   Please provide your rationale for why –b(4)----- particles visible to the naked eye are considered a minor defect. ---------b(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
GSK agreed to submit their rationale as an amendment to the BLA. Deborah Trout stressed that “minor defects” are generally cosmetic. Any particles in solution should be considered a major defect and a reason to reject a sample. GSK understood and indicated that the discrepancy may be due in part to language translation from their Belgium site.  GSK also indicated that the diluent –b(4)----- used are purchased –b(4)------------------------------- by GSK at their facilities.
  1. Please describe “needle protection damaged” and provide your rationale for why it is considered a minor defect.
GSK indicated that this item was not intended for Menhibrix. It was language from a protocol used in the production of their Flu vaccines. GSK agreed to submit updated language to the BLA.

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