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Q&A With Dr. Aryeh Shander: Room Temperature Formulation of rVIIa

What are the clinical advantages of a room temperature formulation of recombinant factor VIIa for perioperative use?

A major clinical advantage of the new formulation is that it does not need to be brought to room temperature before use; with temperature stability (from 36°F-77°F), specialized refrigerated storage is not necessary for the product. Both formulations yield the same product when reconstituted and share the same uses. Another advantage is that an external circumstance such as a power outage will not affect product quality. Finally, in terms of storage, the new formulation can be made available to all healthcare facilities, including those with limited refrigeration space.

The original formulation is reconstituted with sterile water for injection; Petersson and colleagues report that the new formulation is reconstituted with a histidine-containing solvent. How will you advise your colleagues about proper reconstitution?

Both products are formulated as dry powders for injection, available in pack sizes or single doses ranging from 1 mg to 5 mg, and both products have to be reconstituted before use. The original formulation is reconstituted with sterile water for injection, whereas the new formulation is reconstituted with a dedicated solvent containing histidine. It is being called histidine solvent. These solvents of appropriate volumes are supplied with each product (with the exception of the original formulation in the United States, Canada, and Australia). Although the new formulation of recombinant factor VIIa (rVIIa) is expected to replace the original formulation, there will be a transition period during which both products will be available in the markets. At that time, despite color coding of the products and solvents, accidental inappropriate reconstitution may occur.

Petersson and colleagues studied such a scenario, and their experiment revealed no changes in rVIIa derivatives, concentration, or pH for either formulation during storage under the conditions investigated. Thus, reconstitution of the new formulation with double or half the appropriate volume of histidine solvent did not appear to adversely affect stability of rVIIa, nor did reconstitution in a double volume of saline or dilution of the correctly reconstituted formulation with an equal volume of saline. Biologic potency was measured for all reconstituted solutions for all time points and was found to meet and remain within expected levels.

However, during this in vitro experiment, Petersson and colleagues noted that when reconstitution was performed in an incorrect volume of solvent or the correctly reconstituted formulations were inappropriately pooled, concentrations of the active substance differed from those stated on the product labeling (1.0 mg/mL for the new formulation, 0.6 mg/mL for the original formulation). Since the dose of rVIIa is calculated according to body weight (in ug/kg) for both formulations, and the required volume of solution for injection is dependent on the concentration of rVIIa in the reconstituted product, healthcare providers and caregivers must pay careful attention to the concentration of the reconstituted product and must be aware of the importance of reconstitution in the correct volume of solvent and the difference in concentrations of the two products.

Which clinicians (eg, surgeons, hematologists, pharmacists, blood bankers) should be included in education about the new formulation?

Aside from the above-mentioned personnel, anyone involved in handling and administration of the new product, including residents, fellows, nursing staff, and outpatients and their caregivers, should be educated about the new formulation.

Do you foresee a rapid transition at your institution from the original formulation to the new formulation? If so, why?

I do see our institution rapidly transitioning to this new formulation, as it does not need to be brought to room temperature before use and it does not require specialized refrigerated storage.

Wrap-up

For more information about the room temperature formulation of rVIIa, please click here.




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