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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Record of Telephone Conversation - GLASSIA, November 6, 2009

RECORD OF TELEPHONE CONVERSATION

Submission Type: BLA   

Submission ID: 125325/0   

Office: OBRR

Product: Alpha-1-Proteinase Inhibitor (Human)

Applicant: Kamada Ltd.

Telecon Date/Time: 06-Nov-2009 09:30 AM       

Initiated by FDA? Yes

Telephone Number:

Communication Categorie(s): 1. Information Request

Author: CHERIE WARD-PERALTA

Telecon Summary: Discuss PK data with Sponsor

FDA Participants: Cherie Ward-Peralta, Iftekhar Mahmood, Ewa Marszal

Non-FDA Participants: Ruth Wolfson, Ph.D. VP, Regulatory Affairs, Kamada
Pnina Strauss Manager, Clinical Trials and Intellectual Property
David Nakar, Ph.D. API-IV Regulatory Product Manager, Kamada
---(b)(6)--------- Clinical Development Associate, Kamada
---(b)(4)--------- ------(b)(4)------------------------------------------------
---(b)(4)--- ------(b)(4)------
---(b)(4)----------- ------(b)(4)------------------------------------------------------------
---(b)(4)--------------- ------(b)(4)----------------------------------------

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

Telecon Body:

FDA stated the half-life of Kamada-API based on 168 hours blood sampling scheme is too long.  Generally, the blood samples should be taken long enough so that at least 4 to 5 half-lives are covered.  This long half-life will have impact on the extrapolation of AUC from 0 to infinity (acceptable extrapolation is 20% of the total) which in turn will have impact on the clearance.  In your study, the extrapolation of AUC is more than 20%.  Please comment to resolve this issue.

Kamada agreed the effective half-life is less than the time from the first infusion to when the next infusion is administered, and believed the mathematics underlying MRT is flawed.

FDA suggested using the AUC from time 0-T to calculate clearance and caution within the patient labeling the product’s half-life is not accurate and not a useful parameter in the current context and a draft labeling suggestion will be provided on a later date.

FDA questioned if the analysis of PK data was based on baseline correction.  Please comment on differences between PK estimates obtained from baseline and without baseline corrected concentrations. 

Kamada stated the analysis of the PK data is based on a baseline correction due to presence of endogenous API.

FDA requested besides compartmental analysis has Kamada tried non-compartmental analysis.

Kamada stated the compartmental analysis was used for the exponential elimination rate, volume of distribution and the half-life.  AUC was derived by both compartmental and non-compartmental analyses, which showed close agreement.

FDA requested to provide the factor for conversion from µM to mg/mL.

Kamada agreed to provide the conversional calculation within their response to the meeting.

End of Call