Major Amendment 16 - GLASSIA, March 15, 2010

Date: 3/15/10

To: To File STN 125325/0

From: Ewa Marszal, PhD; CBER/OBRR/DH/LPD, HFM-345, 301-402-4368

Through: Dorothy Scott, MD; CBER/OBRR/DH/LPD, HFM-345, 301-827-3016
Basil Golding, MD; CBER/OBRR/DH, HFM-300, 301-496-4396

CC: Cherie Ward-Peralta, RPM; CBER/OBRR/DBA/RPMB, HFM-380, 301-827-9170

Applicant: Kamada

Product: Alpha-1-Proteinase Inhibitor (Human)

Proposed names: GLASSIA

Subject: Major amendment – Amendment 16

• Recommendation: Review cycle extension.  The submitted information in 125325/amendment 16 contains a substantial amount of new manufacturing or facility information not previously submitted to, or reviewed by, the agency.  According to CBER SOPP 8402, this submission constitutes a major amendment. 
  Amendment 16 dated 3/11/10, contains new information resulting from a change in the manufacturing process implemented recently due to equipment malfunction and               --(b)(4)-- yields resulting from process optimization and the use of --------(b)(4)---------    ------------------------------- then that used in the early full scale manufacturing runs. The following information is submitted:
• Validation of ----(b)(4)---- at the -----(b)(4)---- step supported with the following reports (final container lots reported in the original submission were manufactured using only ----(b)(4)---):
  - Summary of Mixing Validation for Vessel -(b)(4)- for the AAT Product (Rep-VL-100332-PQ)
  - Conformance Report: AAT ----(b)(4)---- Process Using a Combination of -(b)(4)- ---------- in Vessel -(b)(4)- (Rep-VL-100339-PV)
• Validation of the -----------------(b)(4)--------------------- supported with  the following validation protocols and reports:
  - Summary of Alpha-1 Antitrypsin (AAT) Uniformity of Filling Validation (Rep-VL-07704-PV/A2)
  - Protocol for the Validation of ----------------(b)(4)------------------ for the -(b)(4)-    ------------ of API (Alpha 1 Proteinase Inhibitor) Viability Study (VL-100291-PQ)
  - Report: Validation of ----------------(b)(4)----------------- for the -------(b)(4)------ of API (Alpha 1 Proteinase Inhibitor) Viability Study (Rep-VL-100291-PQ)
  - Protocol for the Validation of ----------------(b)(4)------------------ for the -(b)(4)------------- of API Bacterial Challenge Study (VL-100293-PQ)
  - Report for the Validation of -----------------(b)(4)----------------- for the --(b)(4)------------- of API (Alpha 1 Proteinase Inhibitor) Bacterial Challenge Study (Rep-VL-100293-PQ)
  - Risk assessment for -----------(b)(4)------------ API Drug Product Formulation Lot  --------------(b)(4)------------- (RM-017)
• Updated list of process quality attributes based on the agreements reached during the inspection.
• Modification of ---(b)(4)-- reporting requirement at the critical steps to agree with the accuracy level of the ---(b)(4)---.

Also, BLA chapters 3.2.S.2.2, 3.2.S.2.4, 3.2.P.3.2, 3.2.P.3.4, 3.2.P.3.5 and 3.2.P.8, which were updated due to the modifications listed above, and the revised Attachment 43-1 of Amendment 14 are included.

This submission qualifies as a major amendment and, thus, the review cycle should be extended by 3 months.