Use of Hexyon/Hexacima/Hexaxim in preterm infants in Europe

Background Worldwide 13 million babies born prematurely every year have increased susceptibility to infection and require adequate immunization. Hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b are standard of care in pediatric vaccination and are particularly important for preterm infants. Hexyon® is registered in Europe since April 2013. Methods Considering birth data from official national databases and only countries with periods of exclusive use of Hexyon from 2013-19, we estimated the total number of preterm infants (<37weeks GA) vaccinated with Hexyon. Results Since registration, Hexyon has been used in 23 European countries and exclusively used in the following: Austria, Feb-2017 to present; Belgium, Jul-2014 (Flanders)/Sep-2015 (Overall) to present; Bulgaria, Nov-2014 to Dec-2016; Croatia, Jan-2016 to present; Denmark, Feb-2016 to Apr-2017; Italy, Apr-2016 to present, exclusivity based on Regions; Macedonia, Oct-2015 to present; Norway, Feb-2017 to present; Romania, Apr-2015 to Dec-2017. The estimated total number of preterm infants during these periods of exclusive use is 183 000. Assuming 90% vaccination coverage, ∼164 700 preterm infants received at least 1 dose of this vaccine. From the analysis of the post-marketing safety data available to date, no new risk has been identified in preterm infants. Conclusions Hexyon has become a standard for hexavalent immunization in infants, regardless of the gestational age at birth. More than 90 million doses have been administered worldwide, including the estimated 164 000 preterm infants in the 9 European countries considered here. The EU Marketing Authorization granted in 2013 with no contraindication for use in preterm infants, was renewed in 2018 and the black triangle was removed confirming that the safety of Hexyon is well established. The marketing authorization holder continues to support evidence generation for use in preterm infants. Key messages Hexyon/Hexacima/Hexaxim has become a standard for hexavalent immunization in infants including for preterm infants (<37weeks GA); around 164 000 preterm infants in 9 European countries received it. The safety of Hexyon/Hexacima/Hexaxim is well established, no new risk has been identified in preterm infants from the analysis of the post-marketing safety data available to date.

The Challenges to be a Regulatory Affair Associate: Day-To-Day Questions on How to Reach Consensus between Manufacturers of Pharmaceutical Products and Government Regulatory Authorities

The modern pharmaceutical industry is one of the main branches in the healthcare segment and is considered to be the most highly regulated industries worldwide. The regulation is provided by a specialist, named Regulatory Affairs Manager (syn.: Regulatory Affairs Executive or Regulatory Affairs Associate), involved in authorization process of pharmaceutical products. When person graduates from University with medical, pharmaceutical or even chemical diploma, he/she never thinks about professional career as a Regulatory Affairs Manager, because this specialty is new, about 40 years old. What is a Regulatory Affairs Associate’s duty? One category-Regulatory Affairs Associate inside the manufacturing office, whose duty is to prepare registration dossier based on the process of artworks and Patient Information Leaflet preparation, prior to completing Common Technical Document (CTD) format dossier; other category (national regulatory affairs Associate)-are those who are ensuring mediation between Manufacturer and Government Regulatory Authorities. Regardless of differences of each Government requirement for dossier registration, the main task of each Regulatory Affairs Associate is to prepare Dossier for submission which will pass successful registration. For this purpose, the National Regulatory Affairs Associate should ensure that manufacturer/Marketing Authorization Holder (MAH)’s dossier is complete and in line with different documentation requirements, following the national requirements and in case such requirement don’t exist-with the guidelines of the World Health Organization (WHO) and International Council for Harmonization (ICH). On the other hand, National Regulatory Affairs Associate is working with National Regulatory Affairs officers to correct and align deficiencies in documentation in accordance with the National requirements. Each drug as a living organism (innovative drugs even have birthdays), which is subject to many changes reflected in the registration dossier: whether in its pharmaceutical part (composition, production process, stability etc.,) or pharmacological (therapeutic indications, side effects and others), as a consequence the Regulatory Affairs Manager is constantly involved in registration of an infinite number of Variations. The main goal of Regulatory structures-both governmental and private-is to ensure the safety, quality and efficacy of medicines.

Status Analysis on the Marketing Authorization Holder of China's Drugs

We analyze the basic situation of Marketing Authorization Holder (MAH) of drugs in China. Mathematical analysis was carried out on the approval time, product category, dosage form, listing permit holder and production unit of 3239 MAH of drugs in China as of July 31, 2019. We found the following results. The approval time for MAH of drugs was concentrated in 2015, mainly based on chemicals, and the dosage forms were mostly tablets and injections. Furthermore, the number of MAH of drugs varies greatly among different provinces, and the number of Hebei, Guangdong, and Jiangsu ranks in the top three. Thirdly, there are time differences, variety types and geographical differences in the MAH of drugs. This is the application for examination and approval after the full implementation of the MAH of drugs system, and the patent and intellectual property protection in the process of entrusted production technology transfer. The research provides reference for enterprise declaration and regulatory approval management after the full implementation of the MAH system in China.

Safety of SGLT2 Inhibitors in Patients with Diabetes Mellitus

Background:Recently, Food and Drug Administration (FDA) has approved sodium/ glucose co-transporter 2 (SGLT2) inhibitors for the treatment of diabetes mellitus. However, regarding adverse drug reactions (ADRs) of SGLT2 inhibitors in large group of population, very less information is available. Thus, we have tried to find out the risk profile of SGLT2 inhibitors. Materials and Methods: A total of 1,042 studies have been published from Nov. 2012-Nov. 2017 regarding SGLT2 inhibitors. After inclusion and exclusion criteria, 27 studies have been selected for the analysis of risk. Results and Discussion:The emerging evidence indicates various adverse drug reactions such as foot and toe amputation, cancer, diabetic ketoacidosis, bone fracture risk and urinary as well as mycotic genital infection. The causality assessment has shown a correlation between SGLT2 inhibitors and diabetic ketoacidosis and urinary tract infection. Conclusion:In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RA) should monitor various adverse drug reactions such as diabetic ketoacidosis and urinary tract infection with the use of SGLT2 inhibitor.