	


Preclinical Study Request Response, October 23, 2013 - Hyqvia


 
From: Shah, Alpa
To: "Blackshere, Angela L"
Cc: Shields, Mark (Mark.Shields@fda.hhs.gov) 
Subject: Preclinical study Request; STN BL 125402

Date: Wednesday, October 23, 2013 8:47:00 AM

 

 

Hi Angela,

Following are the reviewers response for a preclinical study:

Thank you for informing us on your planned juvenile study in mice to look at the 
effect of life-long exposure to PH20 antibodies.  Absent a study protocol or 
design, it is not possible to comment on this study in detail.  It can only be 
noted that a juvenile animal study would usually (but not always) be limited in 
duration until the animals reach adulthood.  Given the potential for life-long 
exposure to the product, limiting the duration of the study would not provide 
adequate information on the effect of life-long exposure to anti-PH20 
antibodies. Baxter is requested to design a life-long study which, given the 
data from the preclinical studies outlined in your email, can be completed as a 
PMC.

Thanks. Alpa


From: Blackshere, Angela L
Sent: Thursday, October 10, 2013 1:53 PM 
To: 'Shields, Mark' 
Cc: 'Shah, Alpa' 
Subject: RE: Request Re: STN BL 125402

Dear Mark:

As a follow -up to my emails below, and FDA’s request for Baxter to provide our 
idea for a preclinical study to address FDA’s concern related to life-long 
exposure to anti-PH20 antibodies in an email for discussion, please regard the 
following:

Recent FDA communication indicates that toxicological data on life-long exposure 
to anti-PH20 antibodies is lacking and that an appropriate animal study 
conducted as a post-marketing commitment may be useful to address this concern. 
 In addition to the following, Baxter plans to address the life-long concern 
with appropriate labeling and risk mitigation measures:

Baxter has approached the life-long exposure question using a life stage 
approach and has already completed and submitted the following studies:
  A 39 week GLP toxicity study in adult monkeys (anti -rHuPH20 antibody exposure 
  for 3- 
  6 months) 
   
  EFD/PPND GLP toxicity and TK studies in mice (anti -rHuPH20 antibody exposure 
  from 
  GD15 through PND 60) 
   
  A GLP male fertility study to evaluate anti-rHuPH20 antibody effects in 
  rabbits (anti - rHuPH20 exposure from prior to mating through fertilization)
  A GLP female fertility and EFD study to evaluate anti-rHuPH20 antibody effects 
  in rabbits (anti -rHuPH20 exposure from prior to mating through weaning)

No adverse effects, including effects on fertility or neuronal development, have 
been associated with anti-rHuPH20 antibodies in any nonclinical study.  These 
findings are consistent with the absence of anti-rHuPH20 antibody associated 
effects in clinical investigation.

Baxter is completing a postnatal extension arm of the GLP female rabbit 
anti-rHuPH20 antibody fertility study.  Anti -rHuPH20 antibody exposure was 
measured before and during gestation and postnatal development, and no adverse 
effects have been attributed to antibody exposure.  The final report will be 
provided in December 2013.  In addition, Baxter proposes to conduct a new 
juvenile toxicity study with rHuPH20 in mouse to further investigate possible 
effects associated with exposure to anti-rHuPH20 antibodies in the developing 
animal.

With the results from the rabbit postnatal extension study and the proposed 
mouse juvenile study as a post-marketing commitment, Baxter believes that the 
possible toxicities of anti-PH20 antibodies during all life stages will have 
been adequately and appropriately addressed in nonclinical models.

Baxter would appreciate FDA input on the proposed juvenile study in mouse and 
requests an informal teleconference to discuss the study design and endpoints. 
 We welcome your input so that we can include this proposal as part of our 
response to the Complete Response Letter that will be submitted by 27 November 
2013.

Best regards, Angela 
*************************************

Angela Blackshere 
Sr. Director, Global Regulatory Affairs 
Baxter Healthcare Corporation, Baxter BioScience 
One Baxter Way 
Westlake Village, CA 91362 (805) 372-3050/Phone (805) 372-3052/Fax


From: Blackshere, Angela L
Sent: Friday, September 20, 2013 4:06 PM 
To: 'Shields, Mark' 
Cc: Shah, Alpa 
Subject: RE: Request Re: STN BL 125105

Thanks, Mark.  Baxter will send an email shortly. Regards,

Angela

************************************* Angela Blackshere 
Sr. Director, Global Regulatory Affairs 
Baxter Healthcare Corporation, Baxter BioScience 
One Baxter Way 
Westlake Village, CA 91362 (805) 372-3050/Phone (805) 372-3052/Fax


From: Shields, Mark [mailto:Mark.Shields@fda.hhs.gov] 
Sent: Thursday, September 19, 2013 11:04 AM 
To: Blackshere, Angela L 
Cc: Shah, Alpa 
Subject: RE: Request Re: STN BL 125105

Hi Angela,

We suggest you place your ideas into an email for discussion.

Thanks! Mark


From: Blackshere, Angela L [mailto:Angela_Blackshere@baxter.com] 
Sent: Friday, September 13, 2013 6:19 PM 
To: Shields, Mark 
Cc: Shah, Alpa 
Subject: Request Re: STN BL 125105

Dear Mark:

Baxter would like to schedule an informal teleconference with FDA’s Nonclinical 
Pharm/Tox review team to discuss technical details associated with a preclinical 
study to address FDA’s concern related to lifetime exposure to anti-PH20 
antibodies.  We have a few ideas and want to ensure the experiment design will 
adequately address FDA’s concern before we formally make our proposal in the 
submission to the Complete Response letter in November.  Please check the review 
team’s availability for a 30 minute teleconference for September 24-27, 2013.

Thanks and best regards, Angela 
*************************************

Angela Blackshere 
Sr. Director, Global Regulatory Affairs 
Baxter Healthcare Corporation, Baxter BioScience 
One Baxter Way 
Westlake Village, CA 91362 
(805) 372-3050/Phone 
(805) 372-3052/Fax

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