Report of Telephone Conversation
Submission Type: BLA       Submission ID: STN#125512/0       Office: OBRR
Title/Product:
Antihemophilic Factor (Recombinant), Porcine Sequence [OBIZUR]
Applicant: Baxter Healhcare Corp.
Telecon Date/Time: August 22, 2014, 11:30 a.m. – 12:30 p.m.     FDA Initiated: Yes
Communication Category/Subject:
OTHER – To discuss the Chromogenic assay results for Drug Product testing
Telephone Number: 1-855-422-9837
FDA Participants:
Natalya Ananyeva, CBER/OBRR/DHRR/LH
Lokesh Bhattacharyya, CBER/OCBQ/DBSQC
Alexey Khrenov, CBER/OBRR/DHRR/LH
Timothy Lee, CBER/OBRR/DHRR/LH
Baxter Participants:
Mehrshid Alai, Senior Director Regulatory Affairs, Westlake Village
Erik Bjornson, Director Regulatory Affairs, Westlake Village
Iraj Daizadeh, Senior Manager Regulatory Affairs, Westlake Village
Kien Du, Manager Regulatory Affairs, Westlake Village
----(b)(4)-----------, Regulatory Affairs Specialist,(b)(4)
---(b)(4)---------, Associate Director Regulatory Affairs, (b)(4)
---(b)(4)------------, VP Quality, (b)(4)
---(b)(4)-----, Quality Control, (b)(4)
---(b)(4)---------------, VP Quality Compliance & Safety, (b)(4)
---(b)(4)-----, Director Quality – FQMR (b)(4)

Teleconference Discussion:
This teleconference was requested by the FDA during the August 19, 2014 Late-Cycle meeting for BLA 125512/0 to discuss discrepancies between Baxter’s and FDA’s test results from the Chromogenic Substrate (CS) Potency assay of OBIZUR identified by the DBSQC Reviewer. Baxter submitted a slide-deck (attached) in advance of the teleconference to clarify the issue. The slides discussion is as follows:
Slide 2:
Regarding three Process Validation batches, Baxter explained that the original results were obtained using the standard ---(b)(4)--------. For comparison, the FDA should use the results presented in the column “JoS” (Justification of Specification) as these data have been adjusted to the use of the commercial reference standard ---(b)(4)-------- which was provided to FDA for in-support testing. More accurate results for comparison are presented in the yellow column and were adjusted for ---(b)(4)-------- using a newly-calculated Correction Factor ---(b)(4)--
Slide 3:
Regarding two additional batches ---(b)(4)----------------- Baxter explained that the original results were obtained using the standard ---(b)(4)--------. For comparison, the FDA should use the results in the yellow column which were adjusted for the commercial standard –b(4)------ using the Correction Factor (b)(4).
Slide 4:
Regarding stability data, Baxter explained that the original data were obtained using the standard ---(b)(4)-------- and are presented in the white columns. For comparison, the FDA should use the values in the yellow columns that were adjusted to the standard ---(b)(4)----- using the Correction Factor. Stability studies were not performed on ---(b)(4)------------------.
Slide 5:
FDA inquired how the standard ---(b)(4)----- was qualified. Baxter explained that ---(b)(4)----- was qualified against the WHO 8th International Standard (IS) for human FVIII concentrate, and the Potency value was assigned based on the collaborative study of (b)(4) laboratories. FDA inquired whether the re-calculated Potency values (in the yellow columns) were verified experimentally using the ---(b)(4)----- reference standard. Baxter commented that they could not retrospectively verify their reference standards because the samples have aged. In the future, only the ---(b)(4)----- standard will be used.
FDA inquired why the Correction Factor (b)(4) is the same for ----------(b)(4)----------------------------- standards although their OSCA/CS ratios are different. Baxter explained that ---(b)(4)------ was qualified vs the WHO 8th IS in both the One-Stage Clotting (OSCA) and Chromogenic (CS) assays. -----(b)(4)-------- was qualified in the OSCA versus the WHO 8th IS but in the CS assay – versus ----(b)(4)--------. Therefore, it is more appropriate to calculate the Correction Factor based on the actual data from the CS assay, and not the OSCA/CS ratio; with this approach, the Correction Factors are the same for the two standards.
Slide 6:
FDA asked Baxter to share their experience with the Chromogenic assay in light of its sensitivity to the CS assay kit and standard. Baxter confirmed that they observed significant differences in results using different lots of CS assay kits, and specifically the FIXa reagent. This is typically observed when a plasma-derived standard is used and the differences are minimized when OBI-1 product is tested vs an OBI-1 reference standard. FDA acklowledged this phenomenon known in the hemophilia community.
Considering that the Drug Product (DP) will be labeled with the OSCA, FDA proposed to remove the Chromogenic assay from Specification as a lot release assay for Potency, and leave it “For-Information-Only”. Baxter agreed and indicated they will submit an amendment to formally remove the CS assay and the OSCA/CS ratio from Specification. FDA suggested that Baxter should continue monitoring DP using the CS assay as the information could be useful in the future. Baxter concurred.
END
