Record of Telephone Conversation, August 8, 2013 - RAGWITEK

Submission Type: BLA Submission ID: 125478/0 Office: OVRR
 Product:
 Short Ragweed Pollen Allergen Extract
 Applicant:
 Merck Sharp & Dohme Corp.
 Telecon Date/Time: 08-Aug-2013 10:00 AM Initiated by FDA? Yes
 Telephone Number: 
 Communication Categorie(s):
 1. Advice
 Author: KATIE RIVERS

Telecon Summary:
 CBER sent an information request regarding —b(4)-------------------------- testing to the sponsor on June 18, 2013. Merck responded in amendment 6 on July 19, 2013. The purpose of this telecon is to discuss Merck’s reply and the need for b(4) testing on the final drug product.

FDA Participants: 
 Jay Slater
 Jennifer Bridgewater
 Taruna Khurana
 Ed Patten
 Paul Richman
 Julie Vaillancourt
 Jon Daugherty
 Rana Chattopadhyay
 Colleen Sweeney
 Elizabeth Valenti
 Katie Rivers

Non-FDA Participants:
Merck
 Scott Greenfeder
 Pat Valan
 Jin Xu
 Mirko Bollen
 Susan Scully
 Lin Li

ALK-abello, DK
 Lotte Jensen
 Annette Römmelmayer Lundegaard
 Rikke Mørkeberg

Catalent, UK
 Ralph Gosden
 Rosie McLaughlin

Telecon Body: 
 CBER stated that they have reviewed Merck’s response to the June 18, 2013, information request and consulted internally with CDER experts and high-level management. The proposed use of –b(4)-----------------------to test for –b(4)----------------------- is not sufficient; --b(4)------------------- Testing is required according to –b(4)-----------

CBER explained that the justification for use of a b(4) test, as proposed with a –b(4)------------------------------------, was not sufficient. There is not enough evidence to confirm that the product is a true solution prior to –b(4)------, and testing b(4) on the product in the final blister pack is not sufficient to show –b(4)----------------. Although the flow diagram explains the manufacturing process, there are multiple stages throughout manufacture where the –b(4)--------------------- may occur. The drug product has been analyzed only using the b(4) test which, considering the nature of the product, is why the data may appear acceptable. However, the product will not be considered in compliance if b(4) testing is not performed.

CBER requested that the sponsor implement a b(4) test and stated that there are currently acceptable methods available to meet this requirement. CBER noted that the b(4) value in –b(4)------ may not work exactly for these types of products and that therefore it may be acceptable to broaden the b(4) values to meet the needs of this product. CBER is also open to discussion regarding the –b(4)----- values. CBER asked if there is available European data for b(4) testing on GRASTEK. Merck stated that there is not a procedure in place for determining b(4) and therefore data are not available.

CBER requested that due to limited time frames, Merck get started working on implementing a procedure for b(4) testing as soon as possible. Merck thanked CBER for making their position and perspective clear, and questioned whether the b(4) test needs to be in place for testing of the launch batches. CBER expressed concern about this question; since the b(4) test can be performed using an assay that is already in place, Merck should be able to have a b(4) testing protocol approved before launch batches are due to be released. A new assay does not need to be developed and a large amount of launch lot product will not need to be sacrificed. CBER anticipates that implementing a procedure for b(4) testing will take weeks, while final lot release testing will not take place for months.

CBER asked if any b(4) testing has been previously performed and Merck responded that they have not completed any b(4) testing due to previous guidance that it was not required; however, they can implement the b(4) test. Merck questioned whether the -b(4)--, proposed for b(4) testing, could be used for b(4) testing. CBER responded that this approach seems reasonable and asked that Merck send a proposal to CBER for review. CBER advised Merck to look at their data for appropriate measures of components in the assay. CBER stated that Merck has two options, test for either allergenicity or allergen content. Both the –b(4)-- and the –b(4)--should be considered for b(4) testing; however, the –b(4)-- requires reference material and this may be an issue.

Merck stated that they plan to manufacture the launch lots beginning in September.
 CBER stated that multiple CMC information requests (IRs) are forthcoming, as appropriate at this point in the review cycle. Additional IRs may be sent by the facilities reviewer. CBER clarified that these requests may impact manufacturing actions. Merck stated that this timeframe is due to production of lots needed for CBER lot release. CBER encouraged the sponsor not to rush production because changes to manufacturing may be needed based on the IRs that CBER sends to Merck.

CBER noted that the need for b(4) testing will most likely also apply to the –b(4)--------------------------------------------------------------------------------, but a formal review has not yet been completed.

Merck stated that they understand the requirement for b(4) testing and will move forward and provide a proposal.

We thanked each other and the call ended.
