Navigating stormy waters: 10 years of operation of the European Union Regulatory Network Incident Management Plan for Medicines for Human Use.

PURPOSE: The article provides an overview of the European Union Incident Management plan (EU-IMP) and reviews its first 10 years of operation. It outlines its scope, objectives, triggers, principles, and components. METHODS: Records were extracted from the European Pharmacovigilance Issues Tracking Tool and a separate tracking system for the period August 20, 2009 to August 19, 2019. RESULTS: During the 10 years of observation, 78 incidents were reviewed by the Incident Review Network and addressed through routine measures. Their number has varied throughout the years with a significant decrease after 2012. Incidents mainly covered safety (56%) and quality (34%) issues or a combination thereof (5%). The majority (70%) were notified by EU regulators and involved centrally and nationally authorized product in similar proportions. A referral was recommended as the assessment pathway for 47% of the issues while lines-to-take were the most frequent communication measure (the sole measure in 65% cases). Forty-six per cent of the issues resulted in a variation, whereas 22% resulted in maintenance of the marketing authorization. CONCLUSION: The EU-IMP is underpinned by a robust regulatory framework with defined processes and clear roles and responsibilities and offers a platform to coordinate actions and communication at EU level, rapidly pool expertise, minimize duplications, and address public health incidents.

Supporting Innovation through Regulation and Science: Ireland as an Innovation Hub for Health Products.

New technologies and our ever-increasing knowledge provide an exciting potential to develop innovative health products that can address challenges such as chronic diseases and ultimately improve outcomes for patients. Ireland has a strategic focus on supporting innovation and offers an ideal environment for health product innovation. This is due to the expertise and experience that is available within the life sciences sector and an established national infrastructure which supports the translation of research into health products in a collaborative manner. The Health Products Regulatory Authority (HPRA) is committed to supporting innovation for health products. Anyone developing an innovative health product can obtain regulatory guidance via the HPRA's Innovation Office. Scientific advice and a product classification service are also available. The HPRA is actively engaging with innovators through an outreach programme to discuss how regulation can support innovation and to raise awareness of available supports. In order to facilitate the appropriate regulation of innovative therapies, the HPRA is performing horizon scanning to identify innovations at an early stage of development, so that proactive action can be taken to put in place any additional regulatory tools or develop any expertise required to regulate such products and provide safe and timely access for patients.

Modification of the solid-state nature of sulfathiazole and sulfathiazole sodium by spray drying.

Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water. Additionally, STNa was spray-dried from pure water. The physicochemical properties including the physical stability of the spray-dried powders were compared to the unprocessed materials. Spray drying of ST from either acetonic or ethanolic solutions with the spray drier operating in a closed cycle mode yielded crystalline powders. In contrast, the powders obtained from ethanolic solutions with the spray drier operating in an open cycle mode were amorphous. Amorphous ST crystallised to pure form I at ≤35 % relative humidity (RH) or to polymorphic mixtures at higher RH values. The usual crystal habit of form I is needle-like, but spherical particles of this polymorph were generated by spray drying. STNa solutions resulted in an amorphous material upon processing, regardless of the solvent and the spray drier configuration employed. Moisture induced crystallisation of amorphous STNa to a sesquihydrate, whilst crystallisation upon heating gave rise to a new anhydrous polymorph. This study indicated that control of processing and storage parameters can be exploited to produce drugs with a specific/desired solid-state nature.

Particle engineering of materials for oral inhalation by dry powder inhalers. II-Sodium cromoglicate.

Sodium cromoglicate is an antiasthmatic and antiallergenic drug used in inhalation therapy and commonly administered by a dry powder inhaler. In the present study we sought to examine the feasibility of producing nanoporous microparticles (NPMPs) of this hydrophilic material by adaptation of a spray drying process previously applied to hydrophobic drugs, and to examine the physicochemical and in vitro deposition properties of the spray dried particles in comparison to a commercial product. The storage stability of successfully prepared NPMPs was assessed under a number of conditions (4°C with dessicant, 25°C at 60% relative humidity and 25°C with dessicant). Spray dried sodium cromoglicate was amorphous in nature. NPMPs of sodium cromoglicate displayed superior aerodynamic properties resulting in improved in vitro drug deposition, as assessed by Andersen Cascade Impactor and twin impinger studies, in comparison to the commercial product, Intal. Deposition studies indicated that porosity and sphericity were important factors in improving deposition properties. The optimum solvent system for NPMP production was water:methanol:n-butyl acetate, as spherical NPMPs spray dried from this solvent system had a higher respirable fraction than non-spherical NPMPs of sodium cromoglicate (spray dried from methanol:n-butyl acetate), non-porous sodium cromoglicate (spray dried from water) and micronised sodium cromoglicate (Intal). While particle morphology was altered by storage at high humidity (60% RH) and in vitro deposition performance deteriorated, it was possible to maintain NPMP morphology and aerosolisation performance by storing the powder with dessicant.

Excipient-free nanoporous microparticles of budesonide for pulmonary delivery.

The aim of this study was to investigate the application of a spray-drying process for the production of nanoporous microparticles (NPMPs) to budesonide, and to characterise the particles produced in terms of their suitability for pulmonary delivery. Budesonide was spray dried with and without ammonium carbonate from ethanol/water or methanol/water solutions. The solid-state characteristics and micromeritic (particle size, density, surface area) properties of spray dried powders were assessed. In vitro deposition studies were performed to assess aerosol performance. The densities of the NPMPs were significantly lower and the surface areas significantly higher than for non-porous spray dried or micronised material. NPMPs of budesonide demonstrated improved aerosolisation properties compared to spray dried non-porous, micronised material and two budesonide commercial products. All spray dried materials were amorphous in nature. The glass transition temperature (approximately 90 degrees C) was sufficiently high to suggest good physical stability at room temperature. When stored at 25 degrees C/60% RH NPMPs showed a reduced tendency to recrystallise compared to the equivalent non-porous spray dried powder. The physical stability and amorphous nature of NPMPs was retained, under these storage conditions for at least one year and the in vitro aerosolisation properties were not affected by the storage conditions. Excipient-free porous microparticles, prepared by the novel process described, show good potential for drug delivery by oral inhalation with improved in vitro deposition properties compared to non-porous particles.