Combination vaccine composition comprising reduced dose inactivated poliovirus and method for preparing the same

A process of manufacturing a fully liquid multi-dose immunogenic composition wherein 0.5 ml of the composition comprises:

• (i) a diphtheria toxoid, (D) in an amount of 10 Lf to 25 Lf, adsorbed onto aluminium salt having percentage adsorption of at least 50%;
• (ii) a tetanus toxoid, (T) in an amount of 2 Lf to 10 Lf, adsorbed onto aluminium salt having percentage adsorption of at least 40%;
• (iii) an inactivated whole cell pertussis, (wP) containing inactivated Bordetella pertussis strains 134, 509, 25525 and 6229 in a ratio of 1:1:0.25:0.25, in an amount of 12 IOU to 16 IOU;
• (iv) a hepatitis B virus surface antigen, (HBsAg) in an amount of 7 μg to 15 μg, adsorbed onto aluminium salt having percentage adsorption of at least 50%;
• (v) a Haemophilus influenzae type b antigen, (Hib) in an amount of 7 μg to 13 μg;
• (vi) an inactivated polio virus antigen, (IPV) containing IPV Type 1 in an amount of 1 -25 DU, IPV Type 2 in an amount of 1-10 DU or IPV Type 3 in an amount of 1-20 DU;
• and
• (vii) total aluminium adjuvant content (A13+) in a range of 0.1 mg to 0.6 mg;
• and
• (viii) preservative as 2-phenoxyethanol in an amount of 1-6 mg (v/v);
• methylparaben in an amount of 0.1-1.5 mg (w/v) and propylparaben in an amount of 0.05-0.2 mg (w/v);
• or
• 2-phenoxyethanol in an amount of 1-6 mg (v/v) and methylparaben in an amount of 0.1-1.5 mg (w/v);
• or
• 2-phenoxyethanol in an amount of 1-6 mg (v/v) and propylparaben in an amount of 0.05-0.2 mg (w/v);
• the process comprising the steps of:
• a). Addition of 80% of total Normal saline (NaCl) in a blending vessel/container;
• b). Addition of Component-I comprising Diphtheria Toxoid in a blending vessel/container;
• c). Addition of Component-II comprising Tetanus Toxoid to Component-I of Step-b) with agitation at room temperature;
• d). Addition of Component-III comprising inactivated whole cell pertussis antigen to a mixture obtained in Step-c) with agitation at room temperature;
• e). Addition of Component-IV comprising Hepatitis B surface Antigen to mixture obtained in Step-d) at room temperature;
• f). Addition of Component-V comprising Hib Antigen to the mixture obtained in Step-e) at 6-16° C. .;
• g). Addition of Component-VI comprising IPV antigen to the mixture obtained in Step-f) at 6-16° C. .;
• h). Addition of a preservative combination selected from:
• 2-Phenoxyethanol in an amount of 1 to 6 mg per 0.5 ml (v/v) and methylparaben in an amount of 0.1-1.5 mg per 0.5 ml (w/v);
• or
• 2-Phenoxyethanol in an amount of 1 to 6 mg per 0.5 ml (v/v) and propylparaben in an amount of 0.05-0.2 mg per 0.5 ml (w/v);
• or
• 2-Phenoxyethanol in an amount of 1 to 6 mg per 0.5 ml (v/v), methylparaben in an amount of 0.1-1.5 mg per 0.5 ml (w/v) and propylparaben in an amount of 0.05-0.2 mg per 0.5 ml (w/v);
• i). Adjusting pH of the mixture obtained in Step-h) to 6.0 to 7.0 with Sodium Hydroxide/Sodium Carbonate;
• and
• j). Adding remaining 20% total normal saline (NaCl) to make up a volume with agitation.