Requirements For Drug Approval Research Articles

Medicines development in the Asia Pacific region

The Asia Pacific region is an extremely diverse region, characterized by heterogeneity from a number of aspects, including culture, religion, economics, landscapes, and languages. This also applies to the standard of medical care and the regulatory requirements for approval of drugs in the region. Developed economies such as Japan and Australia have requirements which are not dissimilar to those of the EU and USA, but still have their own unique requirements. The developing economies all have their own requirements. In the ASEAN region there is harmonization of the dossier format, but each country still has local requirements. The region has seen significant growth in clinical trial activity, both to satisfy local registration and safety requirements and to help accelerate global trial patient recruitment. There is a clear need for training in all aspects of medical, regulatory, clinical and safety aspects of medicines development, which is being addressed through several organizations and at different locations in the region.

Clinical trials of novel psychotropic agents: some caveats.

Clinical trials of novel psychotropic agents: some caveats.

Concepts and applications of pharmacokinetic parameters: A guide for the classroom

Context: Pharmacokinetic studies play a fundamental role in making informed decisions during the drug development stage and fulfilling regulatory agencies' requirements for drug approval. Disposition profiles of plasma drug concentrations over time can be characterized by using non-compartmental analysis, compartmental and physiological-based modeling. These models allow us to determine the pharmacokinetic parameters that best describe the absorption, distribution, metabolism, and excretion (ADME) processes. Aims: To develop a conceptual and practical guide for the classroom on the most relevant pharmacokinetic parameters and their applications. Results: The apparent volume of distribution (Vd), systemic drug clearance (CL), bioavailability (F) and elimination half-life (t1/2) are among the most relevant pharmacokinetic parameters discussed in this article. The Vd describes the relationship at equilibrium between the amount of drug in the body and its plasma concentrations after distribution, used to calculate the initial dose to reach the target drug concentration. The CL describes the relationship between plasma drug concentrations and the rate of elimination from the body, allowing calculation of a maintenance dosing rate to maintain an average target concentration at steady-state. The t1/2 is the time required to halve the plasma drug concentration, whereas F is critical to understand the biological performance of the drug formulation. Conclusions: In this teacher's topic text, we emphasize the importance of these parameters for optimizing strategies of model-informed dose individualization. Indeed, they are crucial for predicting systemic drug exposures and how long the drug will last in the body, as well as time to steady state after multiple-dosing regimens.

Essential list of medicinal products for rare diseases: recommendations from the IRDiRC Rare Disease Treatment Access Working Group

BackgroundTreatments are often unavailable for rare disease patients, especially in low-and-middle-income countries. Reasons for this include lack of financial support for therapies and onerous regulatory requirements for approval of drugs. Other barriers include lack of reimbursement, administrative infrastructure, and knowledge about diagnosis and drug treatment options. The International Rare Diseases Research Consortium set up the Rare Disease Treatment Access Working Group with the first objective to develop an essential list of medicinal products for rare diseases.ResultsThe Working Group extracted 204 drugs for rare diseases in the FDA, EMA databases and/or China’s NMPA databases with approval and/or marketing authorization. The drugs were organized in seven disease categories: metabolic, neurologic, hematologic, anti-inflammatory, endocrine, pulmonary, and immunologic, plus a miscellaneous category.ConclusionsThe proposed list of essential medicinal products for rare diseases is intended to initiate discussion and collaboration among patient advocacy groups, health care providers, industry and government agencies to enhance access to appropriate medicines for all rare disease patients throughout the world.

PP077 Intravitreal Corticosteroids In Macular Edema: Quality Of The Evidence

INTRODUCTION:Treatment options for macular edema include intravitreal corticosteroids (1). Traditionally, an injectable suspension of triamcinolone acetonide (TA) had been employed off-label (2); in recent years, authorities have approved sustained-release drug delivery systems (DDSs) for corticosteroids (3). Considering the hypothesis that the use of these drugs is based on widely variable evidence in terms of methodological quality and robustness, the purpose of this analysis is to compare the quality of the evidence on efficacy and safety of three different formulations of intravitreal corticosteroids: the dexamethasone (DEX) implant, the fluocinolone acetonide (FA) implant, and the preservative-free injectable suspensions of TA, in the management of two retinal pathologies: diabetic macular edema (DME) and macular edema secondary to retinal vein occlusion (RVO).METHODS:A search of clinical trials on MEDLINE from 1 January 2000 to 16 December 2015 was performed. Studies were included in the analysis if they met the following criteria: (i) related to at least one of the preparations of interest in patients with DME or macular edema secondary to RVO; (ii) included a control group treated with placebo, observation, sham procedures or conventional treatments; and (iii) included visual acuity, retinal thickness and/or safety parameters as outcomes. Results were summarized in a narrative manner.RESULTS:Twenty-five publications from nineteen RCTs were included. We observed increased attention of researchers towards TA compared to DEX and FA; however, studies for TA are less robust. Scientific publications related to DEX and FA implants are of higher quality, especially in terms of randomization and masking procedures.CONCLUSIONS:Even though each of the three considered corticosteroid-containing medicines are approved for marketing and included in clinical guidelines for treatment of macular edema, a high degree of heterogeneity in terms of quality of evidence has been noticed among them. This observation underlines the need to review the requirements for drug approval and their inclusion in clinical recommendations, as well as the importance of post-markeing monitoring to generate new evidence.

Regulatory Considerations for the Approval of Drugs Against Histomoniasis (Blackhead Disease) in Turkeys, Chickens, and Game Birds in the United States.

Histomoniasis, commonly referred to as blackhead disease, is a serious threat to the turkey and game bird industries worldwide, and it is having an increasingly negative impact on the chicken industry as well. The Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM), charged with the approval and regulation of new animal drugs in the United States, understands the rising need for the availability of therapeutic options against histomoniasis. CVM has actively engaged in discussions with the poultry industry, academic institutions, and animal health companies regarding the current status of histomoniasis in the United States and varied success of past and current management, prophylactic, and therapeutic interventions that have been used against the disease. As effective options against the disease are severely limited, CVM encourages the poultry industry, academic institutions, and animal health companies to work together to research and develop viable management, prophylactic, and therapeutic strategies, such as litter management, deworming programs, vaccines or other biologics, novel technologies, and animal drugs. CVM also recognizes the potential challenges that the poultry industry, academic institutions, and animal health companies may encounter while working towards the approval of safe and effective drug products for the treatment and control of histomoniasis. With that recognition, CVM encourages interested parties to begin discussions with CVM early in order to align research of the drug product against histomoniasis with the drug approval requirements, such that it leads to the approval of a new animal drug in an efficient and expedient manner. This article provides information about the FDA's regulatory process for the approval of new animal drugs in the United States, with especial emphasis on drug products for the treatment and control of histomoniasis in turkeys, chickens, and game birds.

Medicines development in the Asia Pacific region

The Asia Pacific region is an extremely diverse region, characterized by heterogeneity from a number of aspects, including culture, religion, economics, landscapes, and languages. This also applies to the standard of medical care and the regulatory requirements for approval of drugs in the region. Developed economies such as Japan and Australia have requirements which are not dissimilar to those of the EU and USA, but still have their own unique requirements. The developing economies all have their own requirements. In the ASEAN region there is harmonization of the dossier format, but each country still has local requirements. The region has seen significant growth in clinical trial activity, both to satisfy local registration and safety requirements and to help accelerate global trial patient recruitment. There is a clear need for training in all aspects of medical, regulatory, clinical and safety aspects of medicines development, which is being addressed through several organizations and at different locations in the region.

FDA special designations: Impact on drug development

CDER and CBER must always maintain a balance between thoroughness and speed regarding drug approval requirements and timelines. Requiring more study data than necessary and spending too much time completing the review of an NDA or BLA will delay access to a drug that could prove bene cial to patients. Alternatively, pushing a drug through the approval process too quickly increases the risk that the drug may not be as safe or effective as it originally appeared to be.

Study design considerations: conducting global clinical trials in early Alzheimer's disease.

An increasing number of Alzheimer's disease (AD) clinical trials are being conducted in countries in which such trials have infrequently, if ever, been conducted. The infrastructure for conducting trials in many of these regions is not well developed, leading to particular challenges in collection of biomarkers, which are becoming increasingly important in trials in early AD. Linguistic and cultural differences make scale translation, adaptation, validation and implementation across countries and regions difficult. In addition, multiple translations and versions of scales and differences in their administration increase variability and thus decrease the chance of detecting a signal. These issues are magnified in trials in early AD, where detecting subtle neuropsychological deficits is even more challenging. Two additional significant factors for global AD research include: 1) Differing regulatory authority requirements resulting in the need for repeat studies to satisfy diverse regulatory requirements in different parts of the world; and 2) reimbursement and access may be limited due to different data requirements for country specific economic evaluations. While standardization of biochemical assays and neuroimaging protocols have recently been undertaken, there remains a pressing need for standardization of clinical measures (including translation, linguistic and cultural validation and administration). In addition, a global consensus on regulatory requirements for approval of drugs for the treatment of early AD and identification of universally accepted variables from a cost-effectiveness or value perspective would have significant impact on advancing drug development in early AD.

Pharmaceutical Probiotics for the Treatment of Anaerobic and Other Infections

Pharmaceutical probiotics have been used as alternative treatments or preventative therapies for a variety of clinical diseases. The overuse of antibiotics and emergence of multiple-antibiotic resistant pathogens has refocused clinical attention on the field of probiotics. Anaerobic infections which seem to respond well to probiotics are infections which involve the disruption of normal microbial flora. Gastrointestinal infections (travelers' diarrhea, antibiotic-associated diarrhea,Clostridium difficiledisease, rotavirus diarrhea) have been studied using the following pharmaceutical probiotics:Saccharomyces boulardii, Lactobacillus caseiGG,Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium bifidum, Streptococcus thermophilusandEnterococcus faecium. Vaginitis has been experimentally studied usingL. acidophilusandL. caseiGG. The efficacy, safety and mechanisms of action of these various probiotics are reviewed. Requirements for drug approval are similar for biologic probiotics and new drug entities and these requirements involve preclinical tolerability studies, pharmacokinetic studies and large, well-controlled blinded clinical trials.

Progress in International Harmonization of Drug Approval Requirements

Progress in International Harmonization of Drug Approval Requirements