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Introduction Following the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV—0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV. Methods This was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types. Results Study enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks. Conclusion The study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793.

Objective: The present study compared the pharmacokinetics of two (1 mg) tacrolimus formulations (test (generic from Panacea) and reference (innovator from Astellas)) after a single-dose administration as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Materials and methods: This study was a randomized, open-label, balanced, two-treatment, two-period, two-sequences, singledose, truncated-area, crossover design with a washout period of 19 days between the phases. Healthy subjects aged 18-45 years (both inclusive) were included. Eligible subjects received a single oral dose of 5 × 1-mg capsule of tacrolimus either test or reference formulation. Blood samples were collected until 72.00 hours postdose, and peak concentration (C max) and area under the curve (AUC 0-72) were evaluated in whole blood using validated LC-MS/MS. Safety was also assessed in each period. Results: Of 56 subjects enrolled, 52 completed both study periods. The arithmetic mean (SD) C max for the reference and test formulations was 40.62 (11.30) and 46.20 (10.73) ng/mL, and AUC 0-72 was 348.34 (156.41) and 361.04 (158.71) ng×h/ mL, respectively. The geometric least square mean ratio (90% confidence interval (CI)) was 115.07% (90% CI: 109.81, 120.59) for C max and 103.78 (90% CI: 97.40, 110.58) for AUC 0-72 , which fell within the acceptance range as per EMA guidelines for narrow therapeutic index drugs (C max : 80.00-125.00%; AUC: 90.00-111.11%). No serious adverse event was observed. Conclusion: The generic tacrolimus was bioequivalent to the reference formulation, was well tolerated, and provides a well-acceptable alternative to the reference drug. Switching treatment to generic tacrolimus medication may reduce the cost and economic burden of treating transplanted patients. What is known about this subject-Tacrolimus, a narrow therapeutic index drug, is indicated for prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants due to its immunosuppressant property.-Generic versions of tacrolimus appear to be safe, and switching from brand-name tacrolimus is widely encouraged. What this study adds-A generic tacrolimus-containing product, developed by Panacea Biotec, was well tolerated and met the requirements of the European Medicine Agency guidelines for narrow therapeutic index drugs (NTID) in healthy subjects.-This generic version of tacrolimus could provide a well-accepted alternative to the reference drug.-This study is being published to increase transparency for these types of analyses and improve the confidence clinicians have regarding generic formulations of NTID medications.

CTRI/2014/12/005326 (registered with the Clinical Trial Registry of India (CTRI)).