CDER Consult Email, April 19, 2012 - Hyqvia




 
From:  Scott, Dorothy
Sent:  Thursday, April 19, 2012 7:12 PM
To: Reed, Jennifer; Shields, Mark
Subject: Sorry - here is the attachment - FW: Consult for CDER - CMC, HyQvia 
125402/0

Attachments:  HyQvia BLA-125402-S0 Baxter Consultative Review_final.doc


From: Luo, Shen  
Sent: Thursday, April 19, 2012 3:26 PM
To:  Scott, Dorothy
Cc: Lee, Kathy
Subject: RE: Consult for CDER - CMC, HyQvia 125402/0

 

Hi Dot, Attached please find our review memo containing answers to your question 
#1 and #2.
See


Division of Therapeutic Proteins
 Office of Biotechnology Products
 Office of Pharmaceutical Science
 Center for Drug Evaluation and Research 
 HFD-122

BLA-125402, Supplement 0

START DATE: March 28, 2012
 FINISH DATE: March 29, 2012
 REVISION DATE: April 13, 2012
 FROM: Shen Luo, Ph.D.
 THROUGH: Kathy Lee, M.S. 
 SUBJECT: CMC consultative review for CBER/DH, Dorothy Scott/Jennifer Reed
 SPONSOR: Baxter
 PRODUCT: HyQvia (API: hyaluronidase, rHuPh20, Hylenex® Recombinant from 
Halozyme Therapeutics, NDA 21-859) 
 INDICATION: Chronic subcutaneous administration of IGIV, 10% in patients with 
primary immunodeficiency diseases

This is a consultative review of CMC issues related to hyaluronidase 
manufacturing in the past two years. Hyaluronidase (rHuPh20) drug substance (DS) 
is a recombinant protein produced in CHO cells, manufactured at 
----(b)(4)-------. It is the API of Hylenex® recombinant (hyalurinidase human 
injection, Halozyme Therapeutics, NDA 21-859) manufactured at 
-----------------(b)(4)------------------.

Complete description of the request from CBER/DH: 
 (immunogenicity question #3 is not reviewed here thus not included).
   Is CDER aware of any ongoing CMC issues related to hyaluronidase 
  manufacturing, including presence of particulates or loss of stability?

  DTP Response:
   According to the sponsor's 2010 Annual Report (AR), a voluntary recall of all 
  distributed batches of HYLENEX was initiated on 20 May 2010 due to the 
  discovery of glass-like flake particles in 6 of (b)(4) vials of HYLENEX fill 
  lot number -(b)(4) (10/16/2009 released) at 6 months post filling during an 
  inspection of distributed and retention samples of HYLENEX (11 May 2010 Field 
  Office Alert Report). The particles were confirmed as glass flakes, and the 
  most probable cause had been established by the sponsor as a 
  --(b)(4)-------------------------------- quality of ---(b)(4)------ glass 
  vials in comparison to the (b)(4) vials used in the Hylenex registration 
  batches and the (b)(4) vials used in the clinical batches (supplement 11). As 
  of 11/15/2010, the recall was ongoing and HYLENEX had not been reintroduced 
  for sale. As part of the DP re-introduction plan, the sponsor 
  -----------------(b)(4)----------------------------------------------------------------o
  (supplement 11, approved 06/28/2011). However, based on the sponsor's 
  September 12, 2011 submission (General Correspondence), the reintroduction of 
  Hylenex is still pending. Please contact the sponsor regarding the current 
  status of reintroduction of Hylenex -----------------(b)(4)-------
   Can we obtain a bullet point list or paragraph summary of changes in the past 
  2 years to the rHuPh20 process?

DTP Response:
 
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------


Shen

Shen Luo, Ph.D.
Senior Staff Fellow

Laboratory of Biochemistry
Division of Therapeutic Proteins
Office of Biotechnology Products
FDA/CDER/OPS

8800 Rockville Pike
Bldg-29A, Room 2A-09, HFD-122
Bethesda, MD 20892
shen.luo@fda.hhs.gov
Phone: 301-827-1785
Fax: 301-480-3256
  


From: Scott, Dorothy  
Sent: Wednesday, March 14, 2012 12:02 PM
To: Lee, Kathy; Welschenbach, Marilyn A; Luo, Shen
Cc: Shacter, Emily; Reed, Jennifer; Struble, Evi
Subject: RE: Consult for CDER - CMC, HyQvia 125402/0

 

Dear Kathy, 

 For now it is fine to just let us know what you know about rHuPh20, with 
respect to the questions on the consult.  

Regarding immunogenicity, we found recently that anti-rHuPh20 antibodies bind to 
human testicular tissue and to mesenteric plexus and esophageal neurologic 
tissue.  We have a consult in with CDER's neurology and reproductive tox folks 
to obtain their assessment of potential consequences of this immunogenicity. 

However, if you have seen data that is unpublished which implies that there may 
be preclinical/clinical effects from anti-rHuPh20 antibodies in your products, 
we are very interested in knowing.   Likewise, "negative" data from 
preclinical/clinical studies is of interest.  Because the antibody levels are so 
high in a subset of patients, we are also interested in knowing whether they 
could affect the developing fetus, and have been discussing this with the 
reproductive toxicologist.

Thanks,

Dot


From: Lee, Kathy  
Sent  Wednesday, March 14, 2012 7:49 AM
To: Scott, Dorothy; Welschenbach, Marilyn A; Luo, Shen
Cc: Shacter, Emily
Subject:  FW: Consult for CDER - CMC, HyQvia 125402/0

 

Good Morning Dorothy,
 Shen Luo will be the reviewer for this consult. We are a bit confused on the 
timing of the requested review. Do you want us to look at the submission or do 
you just need information on the rHuPh20? Also when do you need the information?

I will forward this request to our immunogenicity review team to have them 
assign a reviewer for this consult.
 Thanks
 Kathy

Kathy Lee
 Associate Laboratory Chief, Lab of Biochemistry
 Division of Therapeutic Proteins/OBP/OPS/CDER/FDA
 301-594-6679
 P consider the environment before printing this e-mail


From: Welschenbach, Marilyn A 
Sent: Monday, March 05, 2012 9:02 AM
To: Rosenberg, Amy; Shacter, Emily
Cc: Lee, Kathy
Subject: FW: Consult for CDER - CMC, HyQvia 125402/0

For assignment by Emily Shacter.

Marilyn


From: Scott, Dorothy  
Sent: Monday, March 05, 2012 8:56 AM
To: Welschenbach, Marilyn A
Cc:  Reed, Jennifer
Subject:  Consult for CDER - CMC, HyQvia 125402/0

 

Dear Marilyn,

Thanks for your patience. Will you let us know which reviewer this goes to? We 
can send him/her some memos that are relevant to the consult.

Thanks,

Dot

 << File: 125402 0 HyQvia consult CDER CMC.pdf >>
 

    