The equivalence margin is the largest difference that is clinically acceptable between the test (or experimental) drug and the active control (or reference) drug. This paper discusses the scientific principles, along with the regulatory issues, that need to be addressed when determining the equivalence margin for the biosimilar product. The concept of assay sensitivity is introduced, and the ways to ensure assay sensitivity in the equivalence trial are emphasized. A hypothetical example is presented to show how an equivalence margin is determined. The regulatory agency should carefully assess if the equivalence margin of the biosimilar product was determined using a scientifically valid and clinically relevant approach, not subject to selection bias. This is important because the consumer risk of erroneously declaring equivalence when in fact it is not must be controlled conservatively low in the approval of any biosimilar products.
Dietary Sucrose ; Selection Bias

No abstract available.
Asthma*

We report a neonatal case of “intraluminal” pyloric duplication cyst, causing gastric obstruction after birth. Endoscopy revealed a submucosal cystic lesion approximately 15 mm in size arising from the anterior and inferior surfaces of the pylorus obliterating the pyloric canal. After laparotomy, intraoperative cholangiography was performed, which documented no communication between the cyst and the bilio-pancreatic duct. Gastrotomy was performed transversally over the antrum, and the cyst delivered through the incision. The cyst was incised, the upper part of the cyst wall removed, and a mucosectomy performed on the inner cyst wall of the lower part. The mucosa and muscle of the margin of the cyst were approximated. At follow up of 10 months, the patient is well without any sign of gastric obstruction.
Cholangiography ; Endoscopy ; Follow-Up Studies ; Humans ; Infant, Newborn ; Laparotomy ; Mucous Membrane ; Parturition ; Pylorus

Congenital complete atrioventricular heart block(CCAVB) is a rare disease of the newborn that carries significant mortality and has a heterogenous etiology. It may occur as a result of the presence of maternal autoantibodies that are transferred to the fetus and affect the fetal heart or be associated with a congenital structural abnormality of the heart. Infants with CCAVB are at risk of diminished cardiac output and the subsequent development of congestive heart failure. We report two cases of CCAVB in newborns treated with pacemaker implantation after birth. The first case revealed CCAVB with patent ductus arteriosus and anti- Ro(SS-A) antibody in both of the mother and the newborn. The second case was accompanied with mitral regurgitation and tricuspid regurgitation, but anti-Ro(SS-A) antibody was absent in both of the mother and the newborn. Pacemaker implantation was performed for both cases and the result was favorable. We concluded that our experience supports that the pacemaker implantation in the newborn is feasible and beneficial in the treatment of CCAVB.
Atrioventricular Block* ; Autoantibodies ; Cardiac Output ; Ductus Arteriosus, Patent ; Fetal Heart ; Fetus ; Heart ; Heart Failure ; Humans ; Infant ; Infant, Newborn ; Mitral Valve Insufficiency ; Mortality ; Mothers ; Parturition ; Rare Diseases ; Tricuspid Valve Insufficiency