• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

  • Print
  • Share
  • E-mail

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)