Purpose: The objective of the study is to evaluate the overall risk on the process transferability of a poorly flowing blend between two 10 Cu.ft V blenders manufactured by the different vendors.
Methods: To evaluate the risk during the process transferability between 10 cu.ft blenders from
Vendor A to Vendor B, the volume and height aspect ratios of different size blenders 5 and 10 cu.ft manufactured by vendor A, and 3 cu.ft V Blender manufactured by vendor B were compared against respective blend uniformity results obtained during the previous runs (drug load in blend: approx. 37%). The volume and height aspect ratios studied were: Working capacity to Total capacity of blender (WC/TC, Volume), Leg Diameter to Mid-top ratio (LD/MT, Height) and Mid-top to Mid-Bottom ratio (MT/MB, Height) (see Figure 1), Fill Volume, Bulk Density of blend and Number of Revolutions maintained during each run were compared against proposed 10 cu.ft V- blender dimensions (Vendor B) followed by the blend uniformity results.
The calculated WC/TC, LD/MT and MT/MB ratios obtained for 5 and 10 cu.ft (Vendor A) and
3 cu.ft ( Vendor B), were between 0.60 to 0.63, 0.66 to 1.1 and 0.6 to 1.1 (see Table 1), respectively has no impact on the Blend uniformity results obtained (Assay 98-99%, RSD: 0.7-2.2%). Similarly, the fill volume of blend studied was maintained between 30-33%, Bulk Density of the blend was 0.55-0.58 g/cc, blend revolutions were 416 (5 and 10 cu.ft) and 484 revolutions (3 cu.ft) and have no effect on achieving successful blend uniformity results within the blenders studied (see Table 2). The calculated WC/TC, LD/MT and MT/MB ratios obtained for 10 cu.ft V-Blender (Vendor B) to be used during the transfer were 0.58, 1.1, and 0.8, respectively and these ratios were either close or within the range obtained for other blender sizes studied either from Vendor A or B to expect successful process transfer to the new blender (Vendor B). The blend uniformity (BU) results obtained from the new blender (Vendor B) were well within the acceptable specifications with tight RSD which provide a high degree of assurance to transfer from one vendor to the other vendor blender with minimal risk to the product studied.
The proposed study demonstrated the dimensional differences between the blenders, manufactured by different vendors, are common but the overall risk involved in transferability between blender manufacturers can be mitigated with proper understanding of blender design specifications, comparison of various process parameters and review of blend uniformity data available from previous studies. This will aid in reducing the overall costs associated with the process scale up and eliminate the need for performing additional time consuming mixing studies prior to process transfer.