RE: BLA 125478 pediatric plan Email, February 26, 2014 - Ragwitek

From: Valenti, Elizabeth
Sent: Wednesday, February 26, 2014 8:57 AM
To: Greenfeder, Scott
Cc: Rivers, Katie; Valenti, Elizabeth
Subject: RE: BLA 125478 pediatric plan
 Dear Scott,
 Per PREA (http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM077853.pdf), SECTION 505B(a)(2)(B)(i): “IN GENERAL. – If the course of disease and the effects of the drug are similar in adults and pediatric patients, the Secretary may conclude that pediatric effectiveness can be extrapolated from adequate and well controlled studies in adults, usually supplemented with other information obtained in pediatric patients, such as pharmacokinetic studies.” And, PREA, SEC. 505B(a)(2)(B)(ii): “EXTRAPOLATION BETWEEN AGE GROUPS. – A study may not be needed in each pediatric age group if data from one age group can be extrapolated to another age group.”
At the current time we do not have the sufficient experience with Ragwitek to comment on the feasibility of extrapolating effectiveness from adult to pediatric patients. With regard to other SLIT products in development, a discussion of the feasibility of extrapolation from older to younger patients and additional data that might inform the discussion should be held under the IND for the product under development.
 Betsy
Elizabeth J. Valenti, MPH, RAC (U.S.), REHS/RS
 LCDR, USPHS
 Regulatory Project Manager
 FDA/CBER/OVRR/DVRPA
 1401 Rockville Pike
 Mailstop HFM-481
 Rockville, MD 20852
 (301) 796-2640
elizabeth.valenti@fda.hhs.gov 
 THIS MESSAGE IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS ADDRESSED AND MAY CONTAIN INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER LAW. If you are not the addressee, or a person authorized to deliver the document to the addressee, you are hereby notified that any review, disclosure, dissemination, copying, or other action based on the content of this communication is not authorized. If you have received this document in error, please immediately notify the sender immediately by e-mail or phone.


From: Greenfeder, Scott [mailto:scott.greenfeder@merck.com]
Sent: Tuesday, February 25, 2014 3:37 PM
To: Valenti, Elizabeth
Cc: Rivers, Katie
Subject: RE: BLA 125478 pediatric plan
 Betsy,
 With regard to the comment below that CBER does not currently consider that it is feasible to extrapolate effectiveness of Ragwitek from adults to pediatric patients, we are wondering if it would be possible to get elaboration of the reasons why CBER has this position. We would like to have a discourse on this in the future and understand if there is additional research or studies that we may conduct moving forward that would augment the science.
 Many thanks,
 Regards, 
 Scott 
Scott Greenfeder, Ph.D.
 Director and Liaison
 Global Regulatory Affairs
 T: +1 732-594-1021
 Fax: +1 732-594-1030
scott.greenfeder@merck.com
 Merck Research Labs
 126 East Lincoln Ave.
 MS RY33-204
 Rahway, NJ 07065
www.merck.com


 From: Valenti, Elizabeth [mailto:Elizabeth.Valenti@fda.hhs.gov]
Sent: Tuesday, February 25, 2014 2:11 PM
To: Greenfeder, Scott
Cc: Rivers, Katie; Valenti, Elizabeth
Subject: RE: BLA 125478 pediatric plan
 Dear Scott,
 Once we receive revisions to your pediatric study plan synopsis including a timeline for completion of the deferred studies it will be reviewed and discussed internally. After agreement with your plan and the synopsis we will submit the plan to the Pediatric Review Committee (PeRC) for consultation. The deferred studies, which you will outline in your pediatric study plan, will be required post marketing studies.
 Regarding extrapolation, CBER does not currently consider that it is feasible to extrapolate effectiveness of Ragwitek from adults to pediatric patients.
 Thank you, Betsy
Elizabeth J. Valenti, MPH, RAC (U.S.), REHS/RS
 LCDR, USPHS
 Regulatory Project Manager
 FDA/CBER/OVRR/DVRPA
 1401 Rockville Pike
 Mailstop HFM-481
 Rockville, MD 20852
 (301) 796-2640
elizabeth.valenti@fda.hhs.gov 
 THIS MESSAGE IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS ADDRESSED AND MAY CONTAIN INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER LAW. If you are not the addressee, or a person authorized to deliver the document to the addressee, you are hereby notified that any review, disclosure, dissemination, copying, or other action based on the content of this communication is not authorized. If you have received this document in error, please immediately notify the sender immediately by e-mail or phone.


 From: Greenfeder, Scott [mailto:scott.greenfeder@merck.com]
Sent: Monday, February 24, 2014 4:08 PM
To: Rivers, Katie; Valenti, Elizabeth
Subject: BLA 125478 pediatric plan
 Katie, Betsy,
 As I indicated earlier today, we are finalizing our internal discussions and will be responding to you tomorrow regarding the IR from last week.
 I have the following question which will help me prepare the team.
1.Can you help me understand the expected path for the pediatric plan once we respond? For example, when would you expect us to submit a revised plan? Also, what groups within FDA will be involved in providing feedback on the PSP?

Also, out of curiosity, in the discussions that you have had within the Division regarding the PSP, has there been any discussion of extrapolation of efficacy from adults to children, particularly given the mode of action and the precedence from SCIT?
 Regards,
 Scott
Scott Greenfeder, Ph.D.
Director and Liaison
 Global Regulatory Affairs
 T: +1 732-594-1021 
 Fax: +1 732-594-1030
scott.greenfeder@merck.com
 Merck Research Labs
 126 East Lincoln Ave.
 MS RY33-204
 Rahway, NJ 07065 
www.merck.com
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