Filing Meeting Summary, May 31, 2013 - Ruconest

DEPARTMENT OF HEALTH & HUMAN SERVICES
 Public Health Service

Food and Drug Administration
 1401 Rockville Pike
 Rockville, MD 20852-1448

Filing Meeting Summary 
Date: May 31, 2013 Time: 1:00 – 2:00 PM 
From: Elena Karnaukhova, CBER/OBRR/DH, HFM-380 
To: STN 125495/0 
Subject: Filing Meeting for Pharming’s Recombinant C1 Esterase Inhibitor (Human) 
 _____________________________________________________________________________

CBER Participants: 
 Basil Golding
 Chazin Howard
 Mahmood Farshid 
 Nisha Jain
 Charles Maplethorpe
 Iftekhar Mahmood 
 Laura Polakowski 
 Yukun (Abigail) Luo
 Renee Rees
 Iliana Valencia 
 Elena Karnaukhova
 Vasantha Kumar - by phone 
 Anthony Hawkins - by phone
 Felice D’Agnillo - by phone
 Paul Buehler - by phone
 Dominador Manalo - by phone
 Lokesh Bhattacharyya - by phone
 Todd Mollan - by phone
 Jin Baek – by phone
 Nancy Waites - by phone 
 Rabia Ballica - by phone 
 Alpita Popat - by phone
 John Dennis - by phone
 Manette Niu- by phone
 Kelly Lewis - by phone
 Catherine Poole – by phone
 Cheryl Hulme – by phone

Discussion:

From the standpoint of CMC, Facility, Product, Quality control, Animal husbandry, BIMO, Epidemiology, Labeling, Biostatistics, Pharm/Tox, and Clinical pharmacology, this submission is recommended for filing.

Dr. Maplethorpe provided a strong evidence of the major flaw in clinical content of this submission, i.e. the failure to demonstrate efficacy in pivotal study 1310 in the US and the failure to demonstrate efficacy for female subjects in pivotal study 1310, and recommended a RTF decision for this BLA on the basis of its scientific incompleteness (SOPP 8404).

The participants discussed the clinical data presented in Table 15 and agreed that clinical issues seem to be substantive, cannot be resolved during the review cycle, as an additional clinical trial is required, and a CR letter appears likely.

Dr. Jain indicated that in the November 30, 2012, pre-BLA meeting briefing package Pharming did not inform CBER of the failure to demonstrate efficacy for subjects enrolled at US sites in pivotal study 1310, and did not inform CBER of the failure to demonstrate efficacy for female subjects in pivotal study 1310.

Dr. Karnaukhova emphasized that since the pivotal study 1310 in the US (recommended by CBER in 2011 with regards to RTF for BLA-(b)(4)-) did not demonstrate efficacy, this BLA is in the same state as it was at the time of RTF letter in February 2011, and therefore, FDA has to be consistent with earlier issued RTF decision. Filing this BLA while a CR letter and recommendation for additional clinical studies are likely, not only indicates inconsistency in the FDA decisions, but projects a criticism for a prolonged time of review and indicates a very significant waste of FDA resources (DH, DMPQ, APLB, DVM, DBSQC and BIMO) including several inspections, BPAC, etc. that will be unnecessarily dedicated to the review of this BLA at this time.

The review committee agreed with Dr. Maplethorpe that clinical issues in pivotal study 1310 are serious and substantive. However, the opinions were split on whether this is a filing issue or review issue, and how SOPP 8404 must be interpreted in this case.

Dr. Golding said that this is a review issue, and BLA 125495 must be filed.

The filing decision has been further discussed with Dr. Michaud during CRB meeting and telecon on June 4, 2013.

The reviewers will send additional deficiency items to the RPM and the Chair by June 10, 2013 for inclusion in the action letter.

Nannette Cagungun will inform the review committee about Review Management’s decision regarding OBRR’s recommendation.

The meeting ended.
