Hemolysis Reports - VARIZIG, September 26, 2012	

From: Winiecki, Scott
Sent: Thursday, September 27, 2012 9:02 AM
To: Virata, Maria Luisa
Subject: RE: Any hemolysis reports for intramuscular immune globulin products?
Liza,
David Menschik repeated the search with his more extensive list - he found no cases.
Scott

_____________________________________________ 
From: Virata, Maria Luisa 
Sent: Wednesday, September 26, 2012 4:04 PM
To: Winiecki, Scott
Cc: Zhang, Pei 
Subject: RE: Any hemolysis reports for intramuscular immune globulin products?

Wow, I appreciate your quick response, Scott! Thanks for checking the database. And please thank Jane Woo for the anti-D product data. David Menschik is actually assigned to this particular BLA as our Epidemiological Reviewer. Yes, we would be interested to see if he finds more hemolysis cases among the hyperimmune IG products.

It appears that setting an –b(4)- spec for this lyophilized, intramuscular VZIG product will be for precautionary measures (as you pointed out re: few or zero cases of hemolysis).

Cheers,
Liza

_____________________________________________ 
From: Winiecki, Scott 
Sent: Wednesday, September 26, 2012 3:49 PM
To: Virata, Maria Luisa
Subject: RE: Any hemolysis reports for intramuscular immune globulin products?

I have some answers for you. Keep in mind that few or zero cases only means that we don't have any reports. This should not be interpreted as hemolysis doesn't happen; only that it hasn't been reported (or is reported infrequently).

We recently changed systems, so it may be possible that cases reported since about 1Sep2012 may not yet be entered into the database. (There is a backlog of cases waiting to be entered into the system).

I searched by either the product name or a list of names (the trade name plus common variants) and used the Standard MedDRA Query (SMQ) Haemolytic disorders. For the WinRho attachment, we did not attempt to eliminate duplicates, etc.

1) Have you seen any hemolysis reports for Immune Globulin (Human) and hyperimmune IG products that are administered intramuscularly? Some products in that category are:

Grifols (formerly Talecris) GamaSTAN (formerly BayGam) No reports of hemolysis
Grifols (Talecris) HyperHEP B S/D None
Grifols (Talecris) HyperRAB S/D None
Grifols (Talecris) HyperTET S/D None
Grifols (Talecris) HyperRHO S/D None.

2) Have you seen any hemolysis reports with Cangene's other products?

CNJ-016 (Vaccinia Immune Globulin Intravenous) None
WinRho SDF - also administered intravenously None. There are 5 reports (see attached spread sheet - lines 320, 321, 325, 332, 344 explicitly state S/D) for WinRho S/D
HepaGam B - administered both intramuscularly and intravenously None

The only products with large numbers of reports are the anti-Ds. Jane Woo made a spreadsheet. There are approx 340 cases for all the anti-D products and the Haemolytic D/O SMQ (but only the 5 above are listed as WinRho S/D, none as "SDF").

I actually only cover the non-specific Igs. The hyper-immunes are covered by David Menschik (--b(6)----------------------- and I am covering). Jane Woo covers the anti-D products. I will have David repeat the searches for his products tomorrow (as he most likely has an extensive list of common variants names and I searched only by Trade name). This may turn up a few cases, but I doubt there will be many.

Please let me know if we can be of further assistance.
Thanks,
Scott

 

 

<< File: rho_hemolysis_26SEP12 (2).xls >>

 

 

_____________________________________________ 
From: Virata, Maria Luisa 
Sent: Wednesday, September 26, 2012 12:56 PM
To: Winiecki, Scott
Subject: Any hemolysis reports for intramuscular immune globulin products?

Hi Scott,
I'm reviewing this Original BLA from Cangene on their Varicella zoster immune globulin product and saw that they did not set an –b(4)-- specification.

Was wondering if we should really require them to set an –b(4)-- spec (they do have –b(4)---------------------------specs). If it's not too much trouble for you to check our AERS database, I have the following queries:

1) Have you seen any hemolysis reports for Immune Globulin (Human) and hyperimmune IG products that are administered intramuscularly? Some products in that category are:

Grifols (formerly Talecris) GamaSTAN (formerly BayGam) 
Grifols (Talecris) HyperHEP B S/D
Grifols (Talecris) HyperRAB S/D
Grifols (Talecris) HyperTET S/D
Grifols (Talecris) HyperRHO S/D

2) Have you seen any hemolysis reports with Cangene's other products?

CNJ-016 (Vaccinia Immune Globulin Intravenous)
WinRho SDF - also administered intravenously
HepaGam B - administered both intramuscularly and intravenously

Any info you can find would be appreciated. We have Midcycle Meetings scheduled tomorrow (internally among CMC reviewers) and on Monday (with the other reviewers).

Thanks,
Liza

Maria Luisa Virata-Theimer, Ph.D.
Division of Hematology | Office of Blood Research and Review 
FDA | Center for Biologics Evaluation and Research
NIH Bldg 29, Room 304 | HFM-345 | Bethesda, MD 20892
Office 301-402-4637 | Fax 301-402-2780 
MariaLuisa.Virata@fda.hhs.gov
