Marketing authorisations for unmet medical needs: A critical appraisal of regulatory pathways in the European Union.

For unmet medical needs, the European Union has established fast-track regulatory pathways for ensuring patients' access to essential treatments. It is the case of the Conditional Marketing Authorisation (CMA) and the Authorisation under "Exceptional Circumstances" (EXC), which can be granted even if the clinical part of a medicinal product's dossier is not yet complete. The article aims to discuss the peculiarity of such regulatory pathways and assess the impact of their application on products' market access and penetration.

Medicinal products meet medical devices: Classification and nomenclature issues arising from their combined use.

When a medicinal product (MP) and a medical device (MD) are combined, their correct classification implies discrimination among different possible scenarios, based on the nature of the combination and the principal mechanism of action. In the European Union (EU), stakeholders deal with a lack of harmonization, which can represent an obstacle toward the development of these products, and a complex nomenclature, emerging from two divergent regulatory philosophies (i.e.

Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy?

Rituximab is a chimeric anti-CD20 monoclonal antibody. It acts mainly through complement-dependent cytotoxicity on B cells expressing the CD20 marker. In this review, we analyse the efficacy and possible pitfalls of rituximab to treat nephrotic syndromes by taking into account pharmacological considerations and CD19 marker testing utility.

Rationalizing the Design of Hyaluronic Acid-Decorated Liposomes for Targeting Epidermal Layers: A Combination of Molecular Dynamics and Experimental Evidence.

This work provides information on the features of low molecular weight hyaluronic acid (HA)-decorated liposomes to target resveratrol (RSV) in the skin. Deformable liposomes were made of soy-phosphatidylcholine with Tween 80 as the fluidizing agent. For HA conjugation, three different phosphoethanolamines were tested: 1,2-dipalmitoyl--glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl--glycero-3-phosphoethanolamine (DMPE), and 1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE).

Community Pharmacist's Role in Detecting Low Back Pain, and Patient Attitudes-A Cross-Sectional Observational Study in Italian Community Pharmacies.

Background: Low back pain (LBP) is one of the most frequent diseases for which patients seek advice in a community pharmacy. The study aimed to evaluate the feasibility of the administration by community pharmacists of questionnaires to assess the LBP intensity and disability degree in patients entering community pharmacies and the attitudes they have toward pain management by pharmacological and non-pharmacological strategies.

Methods: An explorative, cross-sectional, observational, and quantitative study was performed.

Old active ingredients in new medicinal products: is the regulatory path coherent with patients' expectations?

The rising costs of new medicinal products are a challenge to the economic sustainability of national healthcare systems in ensuring patients' access to therapies. European Union (EU) and US legislators have provided regulatory pathways aimed at simplifying Marketing Authorization (MA) applications for new medicinal products in cases when safety and efficacy profiles can be derived from the data of already-marketed products. In this review, we discuss the different regulatory pathways towards the MA of new medicinal products containing old drug substances and intended to improve the therapeutic value of a treatment, to obtain a new therapeutic indication (drug repositioning), or to ensure the same therapeutic value of a reference product at lower costs.

Regulatory aspects and quality controls of polymer-based parenteral long-acting drug products: the challenge of approving copies.

To assure the safety and the efficacy of a medicinal product, quality and batch-to-batch reproducibility need to be guaranteed. In the case of parenteral long-acting products, the European Union (EU) and US Regulatory Authorities provide different indications, from the classification to the in vitro release assays related to such products. Despite their relevance, there are few in vitro experimental set-ups enabling researchers to discriminate among products with different in vivo behaviors.

Glatiramer acetate: A complex drug beyond biologics.

Complex drugs may be either biological, if the active ingredients are derived from a biological source, or non-biological, if obtained by chemical synthesis. In both cases, their quality depends considerably on the manufacturing process. In the case of Non Biological Complex Drugs (NBCDs), complexity may arise either from the active substance, as in the case of glatiramer acetate, or from other sources, such as the formulation, as in the case of liposomes.

The safety of tattoo inks: Possible options for a common regulatory framework.

Tattoo prevalence has been increasing in the last 25 years, but specific regulations on tattoo inks are still missing. In the European Union, no supranational regulation is available and only few national provisions cover them. In the United States, tattoo inks are classified as cosmetics but are not approved for injection into the dermis.

Do laws impact opioids consumption? A breakpoint analysis based on Italian sales data.

Purpose: In Italy, where the adoption of opioid analgesics in pain management has been historically poor, an increase in opioids consumption occurred between 2000 and 2015. The aim of this study is to assess, through specific time series analyses for trend changes, the impact of different intervening factors - such as the availability of new drugs, the observance of clinical guidelines, changes in prescription regulations, and in reimbursement policies - on opioids sales to community pharmacies in Italy, focusing on the time period 2000-2010.

Materials And Methods: Five opioids were considered: codeine, tramadol, buprenorphine, morphine, and fentanyl.

Copies of nonbiological complex drugs: generic, hybrid or biosimilar?

The experience gained with biosimilars has made it clear that copies of complex drugs are more challenging to produce and put on the market than generics. In the case of so-called nonbiological complex drugs (NBCDs), the complexity can arise either from a complex active substance or by other factors, such as formulation or route of delivery. Regulatory policies in the USA and the EU for the marketing of NBCD copies are reviewed, using glatiramer acetate copies as a case study.

Biosimilar switching and related medical liability.

Unlike generics, biosimilars are similar, but not equivalent, to the reference biological medicinal product. Therefore, if a patient experiences an adverse event, or a loss of efficacy, when transitioned to a biosimilar, the distribution of medical liability will be different from the case of both the originator and generics. Moreover, the case of naïve patients is different from that of non-naïve patients.

Poly(methyl methacrylate) salt as film forming material to design orodispersible films.

This work aims to evaluate the possible use of a poly(sodium methacrylate, methyl methacrylate) (NaPMM) plasticized by PEG400 in the design of orodispersible films (ODF). Placebo ODF prepared by solvent casting were intended to study the impact of the polymer/plasticizer ratio and residual moisture on disintegration time, stickiness and mechanical properties. The drug loading capacity was assessed using ketoprofen and paracetamol.

Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil Preparations.

Recently, an increasing number of pharmacists had to supply medicinal products based on L. (Cannabaceae), prescribed by physicians to individual patients. Cannabis olive oil preparation is the first choice as a concentrated extract of cannabinoids, even though standardized operative conditions for obtaining it are still not available.

Simulation data for an estimation of the maximum theoretical value and confidence interval for the correlation coefficient.

The data presented in this article are related to the article titled "Molecular Dynamics as a tool for in silico screening of skin permeability" (Rocco et al., 2017) [1]. Knowledge of the confidence interval and maximum theoretical value of the correlation coefficient can prove useful to estimate the reliability of developed predictive models, in particular when there is great variability in compiled experimental datasets.

Molecular Dynamics as a tool for in silico screening of skin permeability.

Prediction of skin permeability can have manifold applications ranging from drug delivery to toxicity prediction. Along with the semi-empirical or mechanistic models proposed in the last decades, Molecular Dynamics simulations have recently become a fruitful tool for investigating membrane permeability, in particular as they allow the involved mechanisms to be modelled at a molecular level. Despite their significant structural complexity, Molecular Dynamics simulations can also be utilized to study permeation through the lipid matrix that characterizes the stratum corneum.

Risk management of in-hospital administration of anticancer drugs: impact of Raccomandazione 14 from the Italian Ministry of Health.

Purpose: The different stages of antineoplastic agent management build up a complex process, from supply to prescription, preparation, and administration. All steps in this process must be carefully monitored in order to control/reduce the risk of errors that can impact on patient safety. This work overviews the prevention of medication errors in oncology, including regulatory and legislative frameworks with specific reference to the Raccomandazione 14 (Recommendation 14) issued by the Italian Ministry of Health.

Topical Treatment of Infantile Haemangiomas: A Comparative Study on the Selection of a Semi-Solid Vehicle.

Background/aim: Topical β-blockers have recently been proposed as a valid alternative to oral drugs for treating cutaneous infantile haemangiomas, but clinical results in the literature are inconsistent due to the empirical choice of topical preparations. The current investigation aimed to rationalize the selection of a semi-solid vehicle for a locally applied drug product containing 1% w/w propranolol hydrochloride (PR-Cl).

Methods: A hydrophobic ointment of PR-Cl, two lipophilic creams, and a hydrophilic cream were prepared.

Acceptability of robotic manipulators in shared working environments through human-like redundancy resolution.

Next generation robotic manipulators are expected to resemble a human-like behavior at kinematic level, in order to reach the same level of dexterity of humans in operations like assembly of small pieces. These manipulators are also expected to share the same working environments with humans without artificial barriers. In this work we conjecture that making robots not only kinematically similar but also able to move and act in the same way as humans do, might facilitate their social acceptance.

The regulatory framework of biosimilars in the European Union.

In the European Union (EU), the regulatory policy for biosimilars has enabled different biosimilar products to be marketed through an abridged application, which allows the applicant to submit a reduced dossier. Nevertheless, some manufacturers of biological products that share some characteristics with copies have opted for a full application; therefore, the number and extent of clinical studies required in these cases is increased. Here, we focus on a comparison of recombinant human erythropoietin medicinal products.

Biosimilars and regulatory authorities.

The patent expirations for many biotechnological medicines have prompted the development of copies of biological medicinal products. Unlike generics, biosimilars are similar but not identical to their reference product, because their chemical characteristics are directly related to the manufacturing process which cannot be precisely duplicated. The regulatory policy for biosimilars is complex and in Europe it is regulated mainly by guidelines issued by the European Medicines Agency (EMEA); additional product-class specific guidelines have been developed as in the case of recombinant human erythropoietin (rHuEPO).

Metallothionein-I-II expression in young and adult bovine pineal gland.

Aging is characterized, among other features, by an increased concentration of metal ions in the brain that may contribute to a greater increase in free radicals production. The present paper reports data regarding the concentration of some relevant metal ions (Cu, Fe, Mn, Zn), as well as the immunopositivity of metallothionein-I-II and GFAP in the bovine pineal gland with respect to animal aging. The pineal gland of young bovines displays several immunoreactive metallothionein-I-II positive elements in the parenchyma, whose number decreases with age.