Clinical data required for the approval of pediatric pharmaceuticals in Japan

BMC Pediatrics

Table 7 Utilization of Japanese studies in both adults and/or older children (N = 100)

	Discussion of extrapolation due to similarities in PK		Discussion of extrapolation due to similarities in PK/PD		Discussion of extrapolation due to similarities in ethnic factors		Discussion of extrapolation due to similarities in efficacy and safety		Total
Number of products with extrapolation discussions	63	63.0%	10	10.0%	64	64.0%	62	62.0%	100	100.0%
Predictions using population analysis models	28	28.0%
Visual comparisons of PK parameters	41	41.0%
Predictions from non-Japanese children	41	41.0%	4	4.0%	26	26.0%	24	24.0%	61	61.0%
Predictions from Japanese adults and/or older children	43	43.0%	6	6.0%	52	52.0%	53	53.0%	100	100.0%
Predictions from other populations^a	0	0.0%	2	2.0%	0	0.0%	0	0.0%	0	0.0%
No extrapolation discussions	37	37.0%	90	90.0%	36	36.0%	38	38.0%	0	0.0%

^aFor two products, similarities with non-pediatric populations were discussed. The first case was oblizumab, which added the indication of seasonal allergies, including in children, to already approved bronchial asthma. Population pharmacokinetic and clinical pharmacology studies demonstrated that serum IgE levels and body weight influenced pharmacokinetics and clinical pharmacology, whereas race, age, and disease-related effects had no significant impact. The mean serum-free IgE level was below the target of 25 ng/mL expected to be effective. Hence, the same dosage regimen for bronchial asthma was established for seasonal allergies. The other case was rituximab, approved for the treatment of organ transplant rejection, including in children. This product has already been approved for preventing organ transplant rejection. Given that rituximab reduces B-cell counts in target organs and the disappearance or decrease of DSA (Donner-specific antibody) and anti-HLA antibodies, the PMDA considered that the same pharmacokinetics profile could be achieved for this indication as in the previously approved indications
PD pharmacodynamics, PK pharmacokinetics, PMDA Pharmaceuticals and Medical Devices Agency

ISSN: 1471-2431