Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Apr 2016
Biosimilars: A consideration of the regulations in the United States and European union.
Biosimilars are defined as biological products that are highly similar to a reference product, notwithstanding minor differences in clinically inactive components. Biosimilars show no clinically meaningful differences in safety, purity, and potency of the product in comparison to the reference product. With the ever looming patent expiry of some major high cost biologics, biosimilar production is becoming ever more lucrative to companies. ⋯ The current Food and Drug Administration (FDA) and European Medicines Agency's (EMA) guidance documents for biosimilars were reviewed revealing a need for further clarifications, as well as specifically addressing Celltrion's and Sandoz's application for approval for the biosimilars infliximab and filgrastim, respectively. Currently, the FDA and EMA focus on comparability in terms of the clinical, pharmacokinetic (PK)/pharmacodynamic (PD), preclinical, biological activity, and physiochemical characterization results, as well as requiring a robust and consistent manufacturing process. Both the EU and US have prepared guidance documents for biosimilars that will result in biotherapeutics that are as safe and efficacious as the innovator product but the necessity exists to globally harmonize international nonproprietary naming nomenclature and clarify how the concept of pharmacovigilance, extrapolation, and interchangeability will be handled and regulated in the future.
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Regul. Toxicol. Pharmacol. · Apr 2016
Comparative StudyTobacco-specific N-nitrosamines NNN and NNK levels in cigarette brands between 2000 and 2014.
The evolution of the levels of tobacco-specific N-nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mainstream (MS) cigarette smoke is investigated based on smoke and tobacco chemistry data of cigarette brands sold by Philip Morris International (PMI) between 2000 and 2014. A total of 315 cigarette samples representing a wide range of product and design characteristics manufactured by PMI between 2008 and 2014 were analyzed and compared to a previously published dataset of PMI brands manufactured in 2000. The data indicate that there is a substantial reduction of NNN and NNK levels in tobacco fillers and MS cigarette smoke per mg of tar and per mg of nicotine using Health Canada Intense (HCI) machine-smoking regime. This observed reduction in NNN and NNK levels in MS cigarette smoke is also supported by the downward trend observed on NNN and NNK levels in USA flue-cured Virginia and Burley tobacco lots from 2000 to 2014 crops, reflecting effectiveness of measures taken on curing and agricultural practices designed to minimize TSNA formation in tobacco.