When this refrigerator-stable vaccine is reconstituted as directed, each 0.5 mL dose contains the following: a minimum of 1350 plaque forming units (PFU) of Oka/Merck varicella virus, approximately 18 mg of sucrose, 8.9 mg of hydrolyzed gelatin, 3.6 mg of urea, 2.3 mg of sodium chloride, 0.36 mg of monosodium L-glutamate, 0.33 mg of sodium phosphate basic, 57 mcg of potassium phosphate monobasic, 57 mcg of potassium chloride. Varicella virus vaccine live (Oka/Merck) is a lyophilized preparation. Preparation of experimental, refrigerator-stable varicella vaccine samples Thus, recombinant human gelatin, FG-5001, demonstrated a similar ability to stabilize the live attenuated VZV (Oka/Merck) in an experimental refrigerator-stable varicella vaccine when compared to the vaccine preparation formulated with a hydrolyzed porcine gelatin. Even more importantly, vaccine virus potency losses associated with a long-term storage under accelerated conditions at 15☌ for 12 months and real-time conditions at -15☌ and at 2–8☌ for 24 months were similar for both hydrolyzed porcine gelatin- and recombinant human gelatin-stabilized vaccines. VZV (Oka/Merck) potency change after a short-term stability study under accelerated conditions (37☌ for 7 days) was similar for both vaccine preparations. Moreover, the short-term, as well as long-term VZV (Oka/Merck) potency stability under accelerated and real-time storage conditions was evaluated in a comparative study. The stabilizing effect of FG-5001 on VZV (Oka/Merck) during vaccine lyophilization was assessed. VZV (Oka/Merck) was harvested in two formulations prepared with either a hydrolyzed porcine gelatin or FG-5001. In this study, FG-5001 was evaluated as a potential replacement for hydrolyzed porcine gelatin in an experimental refrigerator-stable varicella vaccine formulation. FG-5001 is a low molecular weight human sequence-based gelatin fragment (8.5 kDa) that can be used as a substitute for animal-derived material and has been shown to function as an effective alternative stabilizing ingredient in a live attenuated influenza vaccine. To support this goal, recombinant human gelatin, termed FG-5001, was obtained using a yeast expression system and a completely defined fermentation and purification process (FibroGen, Inc., South San Francisco, CA). The implementation of alternative, well-defined substitutes for biological materials of human or animal origin in vaccine formulations is a desirable trend in pharmaceutical industry. In contrast, use of non-hydrolyzed gelatin in vaccine formulations by Japanese vaccine makers in the past led to higher incidence of gelatin-specific immediate-type hypersensitivity reactions in vaccinated subjects in Japan. Currently, the incidence of anaphylactic reactions to the hydrolyzed porcine gelatin is very low (approximately 1 case per 2 million doses). Low molecular weight gelatin is less likely to stimulate gelatin-specific IgE than high molecular weight gelatin in vaccinated subjects. Hydrolysis converts high molecular weight gelatin (>100,000 Da) to low molecular weight gelatin (between 20 Da). The current manufacturing process of hydrolyzed porcine gelatin yields preparations which consist of a mixture of protein fragments of different sizes. In addition, hydrolyzed gelatin creates and maintains desirable structure/appearance of a lyophilized vaccine cake. It is believed that gelatin provides non-covalent and non-specific protective binding to the virus particles that enhances their stability. The exact mechanism of gelatin-mediated protection to the vaccine virus is unknown. Hydrolyzed porcine gelatin is a major protein/peptide-based component of the final formulation, as well as a component used in the processing of VZV (Oka/Merck) bulk intermediate. The refrigerator-stable varicella vaccine formulation contains stabilizers such as sucrose, hydrolyzed porcine gelatin, phosphate, glutamate, and urea, as well as a live attenuated varicella virus (Oka/Merck) and residual components of MRC-5 cells. The inherent lability of the live varicella virus (Oka/Merck) presents a formulation challenge in terms of stabilizing and preserving vaccine viability during manufacturing, storage and administration. Varicella virus vaccine live is a lyophilized preparation of live, attenuated VZV (Oka/Merck).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |