Information Request Email, August 8, 2012 - Octaplas
From: Rana, Pratibha
Sent: Wednesday, August 08, 2012 7:53 AM
To: Ammons, Stanley; Rangetiner, Barbara
Subject: STN 125416/0 Information Request (8-9-2012)
Our Reference: STN 125416/0
Octapharma USA, Inc.
Attention: Stanley Ammons
Dear Mr. Ammons:
We are reviewing your December 22, 2011 biologics license application (BLA) for Pooled Plasma, Solvent Detergent Treated (Human). We are providing the following comments and request for additional information to continue our review:
1. Overall Serious AE Summary by Octaplas Product Category. FDA is looking for summary tables to characterize all serious adverse event reports for Octaplas (N=122) and OctaplasLG (N=8). Table 6 “Overview on Serious Case Reports Observed During the Post Marketing Period” is a summary of events related to Octaplas exposure. Please submit a similar table that separately analyzes Octaplas and OctaplasLG and evaluates the cases by relatedness to product exposure.
2. Conflicting TRALI Numbers. FDA notes that Table 6 reports zero TRALI reports (both related and unrelated to Octaplas exposure). However, in Table 20 “Number and Type of AEs Observed for OctaplasLG during the Post-Marketing Period (Irrespective of Causality)” on page 52 of Section 126.96.36.199., Octapharma reports 1 TRALI case. Moreover, FDA notes that in the Module 5.3.6, CIOMS II Line Listing of ICRs, Period 27-Oct-1989 to 31-Aug-2011, at least 5 TRALI cases with different causality assessments were recorded. Please reconcile the above findings with the statement that “It is worth noting that TRALI . . . has not been associated with the use of Octaplas or OctaplasLG during the entire post-marketing period.” on page 49 of Section 188.8.131.52.
3. Conflicting Fatal Report Numbers. On page 94 of “Section 5.3.6 Overall Safety Summary”, FDA notes that Octapharma describes 10 total fatal reports in the Overall Safety Evaluation. However, FDA notes 2 additional fatal reports that were classified as possibly related to Octaplas exposure (see Table below). Please reconcil e these numbers and identify all fatal cases.
Manufacturer Report Number
Adverse Event (MedDRA preferred term)
fibrinolysis, haemorrhage, coagulopathy
therapeutic response decreased, cardiac arrest
acute pulmonary oedema
hypotension, cardiac arrest
4. Targeted Reviews of Thromboembolism and (hyper)Fibrinolysis. Please submit targeted reviews of these 2 outcomes of interest to compare counts after Octaplas and OctaplasLG. FDA notes that in Table 19 in Section 184.108.40.206 on page 50, there are 7 reports of embolism, while Table 6 “Overview on Serious Case Reports Observed During the Post Marketing Period” reports only 4 total cases. Similarly, FDA notes 2 cases of fibrinolysis in Table 19, compared to 1 case of hyperfibrinolysis in Table 6.
Please submit your response to this information request as an amendment to this file by the date (to be discussed during today’s teleconference) referencing the date of this request.
The action due date for this file is October 22, 2012.
If you have any questions, please contact me.
Pratibha Rana, M.S.
Regulatory Project Manager
Division of Blood Applications
1401 Rockville Pike
Rockville, MD 20852
Office: (301) 827-6124
Fax: (301) 827-2857
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