10 years EU regulation of pediatric medicines – impact on cardiovascular drug formulations

Abstract

Child-appropriate drug formulations are mandatory for an efficient and safe drug therapy in children. Since the implementation of supportive legislations development of novel drug formulations has significantly been enforced despite the fact that children are a heterogeneous group of patients with varying needs according to age, maturation and disease. Areas covered: In this review, recent advances and current strategies are evaluated how to overcome the specific hurdles in pediatric drug development. For cardiovascular diseases as an example, EMA's decisions on pediatric investigation plans (PIPs) have been evaluated. New developments with innovative platform technologies such as mini-tablets and orodispersible preparations have been identified indicating a clear shift from liquid preparations to small-sized solid (multiparticulate) or orodispersible dosage forms. Reasons for this shift of paradigm are discussed. Expert opinion: Innovative platform technologies for solid drug dosage forms such as mini-tablets, orodispersible tablets or film preparations will continue to conquer the pharmaceutical market. Still, there are some major issues to be resolved, e.g. how to ensure quality of the new dosage forms and dose accuracy in flexible dosing, but the governmental incentives will continue to accelerate development of pediatric medicines and will bridge the still existing gaps in the near future.

Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics

“…One of the most interesting and innovative therapeutic areas concerns cardiovascular drugs for children. Pharmaceutical companies had submitted 55 PIPs in the area of cardiovascular drugs by the end of January 2017 . Of these PIPs, 81.8% are dosage forms intended for oral use, whereas only 18.2% use the parenteral route of administration .…”

“…Pharmaceutical companies had submitted 55 PIPs in the area of cardiovascular drugs by the end of January 2017 . Of these PIPs, 81.8% are dosage forms intended for oral use, whereas only 18.2% use the parenteral route of administration . Further routes of administration for the pediatric population are rectal, cutaneous, nasal, conjunctival application, and inhalation.…”

“…Pharmaceutical companies had submitted 55 PIPs in the area of cardiovascular drugs by the end of January 2017. 14…”

Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults

“…1 Enalapril is an angiotensin-converting enzyme inhibitor commonly used for cardiac failure in children of all ages including the age group under 1 year of age, although it is not labeled for any condition in patients <20 kg in European countries. 1 Enalapril is an angiotensin-converting enzyme inhibitor commonly used for cardiac failure in children of all ages including the age group under 1 year of age, although it is not labeled for any condition in patients <20 kg in European countries.…”

“…The European Medicines Agency (EMA) Paediatric Committee has prioritized the unmet needs for the cardiovascular off-patent drugs in the European pediatric population. 1 Enalapril is an angiotensin-converting enzyme inhibitor commonly used for cardiac failure in children of all ages including the age group under 1 year of age, although it is not labeled for any condition in patients <20 kg in European countries. [2][3][4][5] The pharmacopoeial form of enalapril is its maleate salt.…”