Current Status of Pediatric Labeling in China and the Near Future Efforts Needed for the Country

Background: Children are recognized as therapeutic orphan in many parts of the world, one expression of this is the lack of adequate pediatric labeling information. Some researches have been done to investigate the pediatric labeling condition in the U.S. and other countries, but no national studies had been carried out in China. This survey was conducted aiming to inquire the current situation of pediatric labeling in China.Methods: We investigated 6020 child-applied medicines from 15 representative Chinese hospitals, and analyzed the information according to the dosage forms, therapeutic category, and label information integrity.Results: Among all these medicines, only 238 (3.95%) are pediatric products, the rest are adult formulations with an extended use in children. The major pediatric formulations were injection (45.95%), tablet (23.69%) and capsule (4.93%), respectively. Alimentary tract/ metabolism medicine (24.70%) and infections medicines (20.60%) had the most species . In prescription drugs, only 210 of 5187 (4%) medicines had adequate pediatric labeling information. The main cause of this deficiency was lack of evidence derived from pediatric clinical trials. Conclusion: The dilemma of therapeutic orphan requires significant attention. Inadequate labeling information and lack of pediatric clinical trials were two prominent issues in China. It calls for more efforts from pharmaceutical industries, regulatory agencies, and legislature in China to collaborate and find solution to improve the situation.<br/

Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex

Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS) protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP)6 peptide conjugated to an outer membrane protein complex (OMPC) derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP)6-OMPC, with or without Iscomatrix&#169; as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb). Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had &gt; 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP)6-OMPC/MAA formulated with Iscomatrix&#169; developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP)6-OMPC/MAA+ Iscomatrix&#169; at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasite