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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Review of Responses to CMC Issues for BN080041 - Intersol

Review of Responses to CMC Issues for BN080041

FDA questions to the sponsor (Feb. 11, 2009)

  1. Provide a list of batches of your drug product (Intersol Platelet Additive Solution) used in pre-clinical and clinical studies along with release test results and stability test results (if available).
  2. Provide justification with data for your proposed specifications of Intersol Platelet Additive Solution at release and during stability. 

Sponsor Response (Feb. 20, 2009)

The specifications for solution component concentrations are based on the product design, the capability of the process, and on the stability behavior of the product.

Product Limit:

Fenwal defines the Product Limit as a specification that must be met at all times over the full expiration period of the product (sometimes called the stability limit). Fenwal has been manufacturing blood anticoagulant and blood additive solutions in a variety of presentations for many years. An historically acceptable range in terms of process capability for the Product Limit has been --(b)(4)-- of the label concentrations for the various sugar and salt formulation compponents. One can point to some deviations to this in other product applications as a result of specific stability characteristics. ----------------------------------(b)(4)-----------------------------------------------------------------------------------------. In developing the InterSol platelet additive solutions, Fenwal has applied this same ---(b)(4)--  Product Limit range to the solution formulation component concentrations.

The target, gravimetric, formulation amounts of the solution formulation components are presented as (b)(4) of the label concentration amounts. This is intentional and provides additional support for the product shelf life in a solution product that ------------------------------------------------------------------------------------(b)(4)-----------------------------------------------.

The shelf life controlling parameter for InterSol platelet additive solution in PL 2411 plastic container is-- (b)(4)--.-- (b)(4)--- is monitored by--- (b)(4)---  testing of the product and this has been found to be an accurate predictor of the stability behavior of the product. The container is designed to allow up to--- (b)(4)------  during long term storage of the 500 mL product.

There are also various batch stability data in the response.

Evaluation:

According to the firm the concentration ranges for various salts are set as ---(b)(4)--- of label concentration based on historic precedents and similar products with USP monograph.  This is acceptable. 

The firm did not address the two leachable compound acceptance criteria in the stability specification.  This needs to be followed up.

As for the --(b)(4)--  during stability issue here is our current thinking:

We normally only require firms to set acceptance criteria for the attributes in the product specification that affect safety, efficacy and quality.  Sometimes firms have tighter internal standard for quality control purpose and we do not hold that against them.  From my understanding of the intended purpose of this solution the salt concentrations are the attributes that will affect the quality of this drug.  Therefore the salt concentrations should be within specification limits during stability.  --(b)(4)-- will affect the --(b)(4)----------------------- in the bag which is not part of the specification.  If --(b)(4)-- in the bag is important to the performance of the drug then we should make this as part of the specification.  Please also note that --(b)(4)-- limit is tighter than the -(b)(4)- concentration limits.