	

Teleconference Memorandum: 483 Responses - Provenge, April 4, 2007


 
DEPARTMENT OF HEALTH AND HUMAN SERVICES
 


TELECONFERENCE MEMORANDUM                                                        
                          Public Health Service
                                                                                 
                                             Food and Drug Administration
                                                                                 
                                             Center for Biologics Evaluation and 
Research
 

 

Date\Time: April 4, 2007

CBER Representatives: Keith Wonnacott, Thomas Finn, Gang Wang, Mary Padgett

Sponsor’s Representative: Elizabeth Smith, Karen Krstulich, Connie Spooner, 
Heidi Hagen, Mike Poor, Mary Coon, Helen Kim, Dave Urdal, Mike Covington, Cyril 
Possa, Michael Curry, Ann Fairchild, Mark Frohlich, Lianng Yuh, Jamie Morrison

STN : 125197/0

Subject: 483 Responses

Discussion:

Observation #1

As we stated in our previous telecon the validation plan for (b)(4) lots, when 
submitted to the FDA would constitute a major amendment and extend the clock 3 
months from the action deadline. You had asked if we were willing to consider a 
license based on the existing 3 lot validation and could this be handled as a 
minor amendment. As indicated previously we are willing to consider a license 
based on validation data that currently exists. We would like to come to an 
agreement on what that licensing scheme would include.

We have a proposal, but we would first like to know if you want to make a 
proposal before we offer ours.

Dendreon

Concerning a license based on the 3 lot validation, we would propose that you be 
able to operate (b)(4) workstations (b)(4) in module (b)(4) for commercial 
manufacturing. We would allow the use of module (b)(4) for clinical 
manufacturing. We think this would be an advantage to both of us in that:
  You can complete enrollment in your clinical trial
  We do not need to worry about clinical manufacturing validation at this time
  It allows greater experience with logistical management and QC through-pu

Questions we have concerning this approach are:
  Does Dendreon agree that this is an agreeable solution?
  How many lots would this allow for commercial manufacture on a daily, weekly, 
  and monthly basis? What are your intentions for scheduling ((b)(4) etc)? 
  Maximum number of lots for one workstation in one day?
  How will Day b(4) manufacturing play into this scheme?

Dendreon generally agreed to this proposal, but requested hat they have the 
option of campaigning the commercial production through module (b)(4) in the 
event that module (b)(4) is closed for maintenance. They said they would submit 
their projections for demand and manufacturing capacity based on this scheme 
later in the week in an email.

We informed them that being able to switch commercial manufacturing to the 
(b)(4) module seemed problematic, but that we would look into it and let them 
know.

Observation #2
Response was adequate.

Observation #3

Concerning the tracking of samples in the QC lab. We would like to request the 
following information and clarifications:
  Where and how will the (b)(4) system be used in the QC lab?
  Where will bar code readers be located and what will be their purpose in the 
  QC lab?
  How will the barcode system be validated and what is the potential for 
  submitting that data quickly?

Dendreon said that (b)(4) will not be involved in the QC lab and that the 
barcode readers are simply for linking the sample with the data at the work 
station in the QC lab.

We informed them that this was not clear in the submission and that after they 
provided the additional data in the bullets below that we may have additional 
comment.
  Please submit the revised SOP 10400
  Please submit the new form 60331
  Please submit copies of all labels that will be used in the QC lab and an 
  explanation of how they will be used
  Please clarify if test tube racks can hold multiple samples and if there is 
  any plan to label racks
  Please confirm that both multi-well plates and the accompanying plate layout 
  that will be printed will both contain similar labeling

Observation #4
Concerning your ability to ensure proper production management and timing we 
have the following comments:
  Please establish time limits for individual process steps during manufacturing
  Please describe procedures for avoiding a bottleneck at critical equipment in 
  the QC lab. (i.e. alternative workstations for (b)(4) analysis, secondary 
  equipment in case of equipment failure for equipment that is not duplicated)
  Please establish time limits for sample holding in the QC lab and provide 
  justification for holding conditions
  Please discuss the potential bottleneck in the pass-through areas. Please 
  discuss the ability to transfer information electronically.
  Please describe the mechanisms for managing logistical oversight, particularly 
  in regard to sample processing in the QC lab.

Dendreon commented that they hoped to go to an electronic batch record in the 
future, but that they do not have a plan in place right now to transfer 
information electronically. They also agreed to submit the requested 
information.

Observation #5
Please provide a copy of the revised SOPs.

Dendreon agreed.

Observation #6
Please provide a copy of the revised SOPs.

Dendreon agreed.

 Observation #7
Response is adequate.

 Observation #8
Response is adequate.

 Observation #9
Response is adequate.

OCTGT:IOD:Wonnacott:4/4/07
(N:/IOD/Tull/125197/tcons/040407_cmc.doc)
 

   
 