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Background and aims: US tobacco companies owned leading US food companies from 1980 to 2001. We measured whether hyper‐palatable foods (HPF) were disproportionately developed in tobacco‐owned food companies, resulting in substantial tobacco‐related influence on the US food system. Design: The study involved a review of primary industry documents to identify food brands that were tobacco company‐owned. Data sets from the US Department of Agriculture were integrated to facilitate longitudinal analyses estimating the degree to which foods were formulated to be hyper‐palatable, based on tobacco ownership. Setting and cases: United States Department of Agriculture data sets were used to identify HPF foods that were (n = 105) and were not (n = 587) owned by US tobacco companies from 1988 to 2001. Measurements: A standardized definition from Fazzino et al. (2019) was used to identify HPF. HPF items were identified overall and by HPF group: fat and sodium HPF, fat and sugar HPF and carbohydrates and sodium HPF. Findings Tobacco‐owned foods were 29% more likely to be classified as fat and sodium HPF and 80% more likely to be classified as carbohydrate and sodium HPF than foods that were not tobacco‐owned between 1988 and 2001 (P‐values = 0.005–0.009). The availability of fat and sodium HPF (> 57%) and carbohydrate and sodium HPF (> 17%) was high in 2018 regardless of prior tobacco‐ownership status, suggesting widespread saturation into the food system. Conclusions: Tobacco companies appear to have selectively disseminated hyper‐palatable foods into the US food system between 1988 and 2001. [ABSTRACT FROM AUTHOR]

Oligonucleotide drug products commercially approved in the US and the EU are reviewed. A total of 20 products that includes 1 aptamer, 12 antisense oligonucleotides (ASOs), 6 small interfering ribonucleic acids (siRNAs), and 1 mixture of single-stranded and double-stranded polydeoxyribonucleotides have been identified. A typical oligonucleotide formulation is composed of an oligonucleotide with buffering agent(s), pH adjusting agents, and a tonicity adjusting agent. All the products are presented as 2.1 - 200 mg/mL solutions at pH between 6 and 8.7. Majority of the products are approved for intravenous (IV) and subcutaneous (SC) routes, with two for intravitreal (IVT), two for intrathecal (IT), and one for intramuscular (IM) routes. The primary packaging includes vials and prefilled syringes (PFS). Products approved for IV and IT administration routes and requiring >1.5 mL dose volumes are supplied in vials, while those approved for SC, IM, and IVT and requiring ≤1.5 mL dose volume are supplied in PFS. Based on the compiled dataset, we propose a generalized starting point for an oligonucleotide formulation during early phase development for IV, SC, and IT administration routes. Overall, we believe this harmonized evaluation and understanding of various oligonucleotide drug product attributes will help derive platform generalizations and allows for accelerated early phase development for first-in-human studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Humira® (adalimumab) by AbbVie has been the top-selling biologic drug product for the last few years – reaching nearly $20 billion in annual sales in 2018. Upon the October 2018 release of four adalimumab biosimilars into the European market, those sales began to shrink. By the end of 2019, the annual sales of Humira®, albeit still high, dipped closer to $19 billion as nearly 35% of European patients had been switched from Humira® to a biosimilar. Diminishing sales are expected to continue as the adoption of adalimumab biosimilars increases in Europe and Humira®'s patent protection is lost in the United States come 2023. In this review we discuss how impactful the availability of biosimilars has been to the European adalimumab market approximately two years after their release. We further analyze the marketed biosimilars with regards to differences in their formulation, delivery devices, biological activity, physicochemical properties, clinical trials data, and current financial foothold. More importantly, though, we highlight how "similar" these biosimilars are to Humira®. In doing so, we seek to educate the public on what they may be able to expect once adalimumab biosimilars enter the United States market in 2023. [ABSTRACT FROM AUTHOR]

In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop "Mechanisms and Barriers in Nanomedicine" in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, and students to trigger ideas and concepts to move the field forward.

With the remarkably strong growth of the biopharmaceutical market, an increasing demand for self-administration and rising competitions attract substantial interest to the biologic-device combination products. The ease-of-use of biologic-device combination products can minimize dosing error, improve patient compliance and add value to the life-cycle management of biological products. As listed in the purple book issued by the U.S. Food and Drug Administration (FDA), a total of 98 brand biologic-device combination products have been approved with Biologic License Application from January 2000 to August 2023, where this review mainly focused on 63 products containing neither insulin nor vaccine. Prefilled syringes (PFS) and autoinjectors are the most widely adopted devices, whereas innovative modifications like needle safety guard and dual-chamber design and novel devices like on-body injector also emerged as promising presentations. All 16 insulin products employ pen injectors, while all 19 vaccine products are delivered by a PFS. This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. In addition, challenges and opportunities associated with biologic-device compatibility, regulatory complexity, and smart connected devices are also discussed. It is believed that evolving technologies will definitely move the boundaries of biologic-device combination product development even further., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Abstract Oral pediatric formulations are either ready-to-use or require manipulation and multiuse or single-use. Strong encouragement for preservative-free pediatric formulations has resulted in fewer multiuse solutions or suspensions in favor of single-use solid oral dosage forms. This updated review covering new pediatric formulations marketed in the United States of America, Europe, and Japan spanning the years 2007 to mid-2018 identified 16 types of pediatric oral formulations of which 7 are ready-to-use and 9 require manipulation, and 51 total new pediatric oral formulations of which 21 are ready-to-use and 30 require manipulation. Ready-to-use formulations include oral solution, oral suspension, oral soluble film, tablet, scored tablets, orally disintegrating tablet, chewable tablet, and mini-tablets. Formulations requiring manipulation include sprinkle capsule, powder for oral solution, powder for oral suspension, granules for oral suspension, oral powder, oral granules, tablet, dispersible tablet, dispersible scored tablet, tablet for oral suspension, and mini-tablets (oral granules). Significant advances in packaging technology include filling mini-tablets, granules, or powders into sachets, stick packets, blisters, and 2-piece capsules. The future of pediatric oral formulations will increasingly be with user-friendly, preservative-free, taste-masked formulations including multiparticulate single-use solid dosage forms including mini-tablets, orally disintegrating tablets, and sprinkle capsules with or without a specialized package configuration. [ABSTRACT FROM AUTHOR]

E-cigarettes are gaining popularity in the U.S. as well as in other global markets. Currently, limited published analytical data characterizing e-cigarette formulations (e-liquids) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to analytically characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addition, nicotine-related chemicals have been previously reported as potential e-cigarette formulation impurities. This study determined e-liquid formulation impurities and potentially harmful chemicals in aerosols of select commercial MarkTen ® e-cigarettes manufactured by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chemicals was also estimated. E-cigarettes were machine puffed (4-s duration, 55-mL volume, 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels observed in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chemicals detected in the aerosols were determined to be below published occupational exposure limits. [ABSTRACT FROM AUTHOR]

The Department of Defense ( Do D)-United States Food and Drug Administration ( FDA) shelf-life extension program ( SLEP) was established in 1986 through an intra-agency agreement between the Do D and the FDA to extend the shelf life of product nearing expiry. During the early stages of development, special attention was paid to program operation, labeling requirements, and the cost benefits associated with this program. In addition to the substantial cost benefits, the program also provides the FDA's Center for Drug Evaluation and Research with significant scientific understanding and pharmaceutical resource. As a result of this unique resource, numerous regulatory research opportunities to improve public health present themselves from this distinctive scientific database, which includes examples of products shelf life, their long-term stability issues, and various physical and chemical tests to identify such failures. The database also serves as a scientific resource for mechanistic understanding and identification of test failures leading to the development of new formulations or more robust packaging. It has been recognized that SLEP is very important in maintaining both national security and public welfare by confirming that the stockpiled pharmaceutical products meet quality standards after the 'expiration date' assigned by the sponsor. SLEP research is an example of regulatory science that is needed to best ensure product performance past the original shelf life. The objective of this article is to provide a brief history and background and most importantly the public health benefits of the SLEP. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1331-1336, 2014 [ABSTRACT FROM AUTHOR]

Background: Biological control (i.e., biocontrol) can be defined as the use of microbial inoculants with a direct and purposeful manipulation of natural enemies, potentially replacing harmful pesticides, to control pests, plant pathogens, and weeds. This study concerns patent analysis of biocontrol agent-based formulations. This form of patent analysis encapsulates information that could be used as a reference by researchers in the fields of agriculture and plants, as well as those interested, especially in biocontrol agents for agriculture., Methods: The state has been reviewed by introducing what has been patented concerning Biocontrol Agents (BCAs). Four patent databases have been used, and different keywords and related terms to BCAs were used, and patents were searched according to title, abstract, and claims. The search was then filtered regarding publication year, patent families, patent classifications, inventors, applicants, owners, and jurisdictions., Results: During a search, 2371 patent documents were found between 1982 and 2021. The United States was ranked first with 694 patent documents. 2015 was the year with the maximum number of patent documents (278). The patent classification codes reveal that most inventions are intended for biocides, pest repellants or attractants, or plant growth regulators containing or obtained from microorganisms, viruses, microbial fungi, etc. Moreover, they are also intended for biocidal, pest repellant, pest attractant, or plant growth regulatory activities of chemical compounds or preparations, such as fungicides, athropodicides, and nematocides, which are concentrated in most patents., Conclusion: The knowledge clusters and expert driving factors of this patent analysis indicate that the research and development based on the formulation of biocontrol agents are concentrated in most patents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Highlights: [•] CYD-TDV is a tetravalent candidate dengue vaccine. [•] Immune response is imbalanced with a reduced dose of serotype 4 antigen. [•] Our results support development of CYD-TDV 5555 as opposed to other formulations. [Copyright &y& Elsevier]

The powers to formulate foreign policy had been divided between the president and the Congress with an object to achieve continuity, coherence, and consistency in foreign policy. Both have opportunity to change features of foreign policy, to approach complete process and to execute and implementation of foreign policy. The formation of US foreign policy is more difficult and complex, and the support of these two branches is required for the making of strong and effective foreign policy. Check and balance is the key feature of relations between the President and Congress. This is the most important feature of the US political system in order to prevent the one organ of Government to become so powerful to impose its hegemony and the domination over the other. The dispersal of power over foreign policy puts a heavy premium on consultation, coordination, and cooperation by these two important organs of US Government. [ABSTRACT FROM AUTHOR]

Abstract: Background: We sought to estimate the prevalence of types of combined oral contraceptives (COCs) used among US women. Study Design: We analyzed interview-collected data from 12,279 women aged 15–44 years participating in the National Survey of Family Growth, 2006–2010. Analyses focused on COC use overall, by pill type, across sociodemographics and health factors. Results: The prevalence of current COC use (88 different brands) was 17%. The majority of COC users used earlier-formulation COCs: ≥30 mcg (67%) versus <30 mcg estrogen (33%), monophasic (67%) versus multiphasic (33%) dosages and traditional 21/7 (88%) versus extended/other cycle regimens (12%) regimens. Norgestimate (32%) and norethindrone (20%) were the most commonly used progestins. Sociodemographic, gynecological and health risk factors were associated with type of COC use. Conclusion: Further investigation of specific COC use and of the factors associated with types of pills used among US women at the population level is needed. [Copyright &y& Elsevier]

Papers and patents that deal with polymorphism and solvatomorphism have been summarized in an annual review. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2008. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3648–3664, 2010 [ABSTRACT FROM AUTHOR]

In 1989, Manning, Patel, and Borchardt wrote a review of protein stability (Manning et al., Pharm. Res. 6:903–918, ), which has been widely referenced ever since. At the time, recombinant protein therapy was still in its infancy. This review summarizes the advances that have been made since then regarding protein stabilization and formulation. In addition to a discussion of the current understanding of chemical and physical instability, sections are included on stabilization in aqueous solution and the dried state, the use of chemical modification and mutagenesis to improve stability, and the interrelationship between chemical and physical instability. [ABSTRACT FROM AUTHOR]

Recombinant protein pharmaceuticals may bear some risks and undesirable side effects, such as the appearance of immunogenic reactions. The increased incidence of antibody-mediated pure red cell aplasia (PRCA) outside the United States after administration of a human serum albumin (HSA)-free EPREX® (recombinant human erythropoietin alpha) formulation was explained with the generation of rubber stopper related leachables, possibly acting as immunogenic adjuvants. In our study, we have investigated the potential of extractable and leachable preparations of three different pharmaceutical relevant stoppers to generate a “danger signal” in a dendritic cell assay. Furthermore, the investigated extractable and leachable preparations were characterized by NMR and a micelle-based polysorbate quantification method. In summary, we could demonstrate that stopper extractables, either generated by extraction or by leaching conditions, were not acting as danger signals for dendritic cells. Instead we identified degradation products of polysorbate 80, oleic acid and follow-up products, occur only under very accelerated conditions (100°C for 4 days) as a potential stimulator for these immune cells. As this degradation did not occur at real-time, the authors however do not consider their finding to be linked to any direct safety implications of polysorbate-containing formulations in clinical practice. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3548–3561, 2009 [ABSTRACT FROM AUTHOR]

This article examines a discussion among US Federal Trade Commission attorneys concerning a passage in a draft memo. The focus is primarily on the expression we think it's bad public policy, which is a reformulation, and a generalization, of what is said in the draft. I propose certain techniques of studying generalization, based in earlier work by Charles Frake and by Harvey Sacks. A close analysis of transcribed talk is combined with semantic/taxonomic considerations and related to ethnographic setting. A central finding is that generalization must be understood not only within its local context of talk but also within wider discursive contexts. The formulation is fitted to an argument, which is in turn fitted to a broader controversy in the agency. The analytic techniques employed in this essay should have broad applicability in studies of how participants formulate their utterances. [ABSTRACT FROM AUTHOR]

Complex generics are generic versions of drug products that generally have complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, are complex drug-device combination products, or have other characteristics that can make it complex to demonstrate bioequivalence or to develop as generics. These complex products (i.e. complex generics) are an important element of the United States (U.S.) Food and Drug Administration's (FDA's) Generic Drug User Fee Amendments (GDUFA) II Commitment Letter. The Center for Research on Complex Generics (CRCG) was formed by a grant from the FDA to address challenges associated with the development of complex generics. To understand these challenges, the CRCG conducted a "Survey of Scientific Challenges in the Development of Complex Generics". The three main areas of questioning were directed toward which (types of) complex products, which methods of analysis to support a demonstration of bioequivalence, and which educational topics the CRCG should prioritize. The survey was open to the public on a website maintained by the CRCG. Regarding complex products, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and inhalation and nasal products. Regarding methods of analysis, the top three selections were locally-acting physiologically-based pharmacokinetic modeling; oral absorption models and bioequivalence; and data analytics and machine learning. Regarding educational topics, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and data analytics, including quantitative methods and modeling & simulation. These survey results will help prioritize the CRCG's initial research and educational initiatives., (© 2021. The Author(s).)

Purpose: To educate healthcare professionals regarding the risks of manipulating drug products formulated via nanocrystal or amorphous solid dispersion technologies., Summary: Recent pharmaceutics innovations such as nanocrystals and amorphous solid dispersions have been used successfully to improve oral bioavailability of drugs. Over 30 drug products based on these technologies have been approved by the Food and Drug Administration, and more are in the development pipeline. While these products are similar in appearance to traditional tablets or capsules, they should not be crushed or suspended in liquid vehicles. Such manipulations can compromise the integrity of the formulation and subsequently alter the oral bioavailability. It is alarming that the majority of these products are not included in the Institute for Safe Medication Practices (ISMP) "Do Not Crush" list. A summary drug table is presented in this article to provide accurate information for pharmacists and other healthcare providers., Conclusion: Novel formulations of tablets and capsules are being used to increase the oral bioavailability of certain drugs. Crushing these products can significantly alter product performance and clinical outcomes. We encourage ISMP to add these drug products to the Do Not Crush list due to wide use of this list throughout healthcare. In the meantime, pharmacists should be mindful of the new formulation technologies and advocate for the proper use of these drug products., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). This review also provides an in-depth analysis of dosage forms and administration routes for delivering peptide therapeutics, including injectables, oral dosage forms, and other routes of administration. We discuss the function of excipients in parenteral formulations in detail, since most peptide therapeutics are parenterally administered. We provide case studies of alternate delivery routes and dosage forms. Based on our analysis, therapeutic peptides administered as injectables remain the most commonly used dosage forms, particularly in the form of subcutaneous, intravenous, or intramuscular injections. In addition, therapeutic peptides are formulated to achieve prolonged release, often through the use of polymer carriers. The limited number of oral therapeutic peptide products and their poor absorption and subsequent low bioavailability indicate a need for new technologies to broaden the formulation design space. Therapeutic peptide products may also be delivered through other administration routes, including intranasal, implant, and sublingual routes. Therefore, an in-depth understanding of how therapeutic peptides are now formulated and administered is essential to improve peptide delivery, improve patient compliance, and reduce the healthcare burden for these crucial therapeutic agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Treatments are needed to address the growing prevalence of Alzheimer's disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes., Methods: We assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020., Results: We identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov., Conclusions: Drug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.

Extemporaneous compounding is a means to tailor a medication to an individual patient's needs and may be required when no commercial product exists to meet that need. Compounded products range from buffered lidocaine to topical creams and ointments. Recent heightened regulations have made compounding more challenging for dermatologists and prompted this review of regulations, liability, and safety related to compounding. With this information, providers may minimize liability and maximize safety while caring for their patients., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pharmacopeial quality standards for medicines are associated with ensuring quality, but they can also facilitate innovation and competition in pharmaceutical markets. Unpublished data suggest that pharmacopeial quality standards, while not associated with increasing the likelihood of a first generic entrant in the market, are associated with increasing the overall number of generic entrants. This commentary describes an online survey of finished-dose generic drug manufacturers in the United States and India that explores whether using pharmacopeial documentary standards and physical reference standards (RSs) such as those developed by the US Pharmacopeial Convention, accelerate generic drug development and reduce the duration, cost, and risk involved in bringing generic drugs to the US market. The survey provides new evidence that using pharmacopeial documentary standards and physical RSs (1) saves generic drug companies 19% of the time spent on generic product development overall and 31% of time spent on analytical method development and (2) provides clear guidance on quality, thereby reducing the perceived risk of Abbreviated New Drug Application rejection by the US Food and Drug Administration. Ninety percent of respondents agreed that the use of pharmacopeial documentary standards accelerated product development compared with 85% for physical RSs; and 92% of respondents agreed that the use of documentary standards and physical RSs reduced the risk that their Abbreviated New Drug Application would be rejected. Owing to the relatively small sample size of the survey, the results should be viewed as entirely directional for use in trends analysis on the finished-dose generic pharmaceutical industry. The margin of error for all results is 8%-14% at a 95% confidence interval., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Introduction: Prescription opioid abuse is now an epidemic that has forced the government and industries to take initiatives. These include developing abuse-deterrent formulations (ADFs), issuing regulatory guidances and allocating massive budgets to ensure the safety and effectiveness of these medications. Areas covered: This review covers the regulatory guidance on evaluation and labeling of the branded and generic ADFs. It also includes the relevant patents and technologies, the in-vitro, in-vivo, the post-marketing data, the FDA reviews, and the products' labeling of the FDA-approved products with abuse-deterrent features. Expert opinion: Despite the development of a dozen products with abuse-deterrent features, most of these technologies rely on the same deterrent agent, making it easier for abusers to focus their manipulation efforts and share their experience to defeat the technology. Further advancement in the field requires developing more robust, more diverse, safer, and affordable deterrent technologies for the extended- and immediate-release opioid products. Moreover, advances in the reporting of the post-market results, issuance of policies in support of the ADFs, and concurrent monitoring of the illicit opioid market are other considerations that can further help in confronting the epidemic.

Daptomycin is a cyclic lipopeptide antibacterial agent with potent bactericidal activity against a broad range of Gram-positive organisms. In 2003, daptomycin for injection received approval from the US Food and Drug Administration (FDA) for the treatment of patients with complicated skin and skin structure infections (cSSSIs); in 2006, it was approved for the treatment of patients with Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis caused by methicillin-susceptible and methicillin-resistant isolates. In 2016, the FDA approved a new formulation of daptomycin for injection (daptomycin RF) for the same indications. The efficacy and safety of daptomycin for injection have been established in pivotal clinical trials, and the findings of nonclinical studies indicate that both formulations of daptomycin for injection are equivalent. Herein we refer to the new daptomycin formulation as daptomycin RF to distinguish it from the original formulation. Daptomycin RF provides clinicians and clinical pharmacists with a product that offers improved stability and more rapid, in-vial reconstitution with either sterile or bacteriostatic water for injection, while maintaining the same antibacterial coverage. Here we discuss the rationale for and the potential value of daptomycin RF, and briefly review the similarities and differences between the original formulation of daptomycin and daptomycin RF., Competing Interests: Disclosure All authors are employees of Merck & Co., Inc., Kenilworth, NJ, USA. The authors report no other conflicts of interest in this work.

Purpose: Multiregional clinical trials (MRCT) are a standard strategy used to improve global drug approval efficiency and the feasibility of clinical trials. Japan is the world's third largest drug market with a unique health care system, making it a key inclusion as an operational region for MRCT (MRCT-JP) for global drug development. We aimed to identify the factors required for efficient drug development by comprehensively reviewing the clinical trials of drugs approved in Japan to identify the factors associated with whether or not MRCT-JP is implemented., Methods: We surveyed the review reports and summaries of application data published by the Pharmaceuticals and Medical Devices Agency. We identified drugs for which the clinical trial data package included MRCT-JP and selected the same number of drugs for which the clinical trial data package did not include MRCT-JP from the most recent survey period for comparison. We also examined other publication information, in addition to the review reports, as necessary. The influence of each explanatory variable was analyzed by logistic regression analysis, with whether or not MRCT-JP was implemented as the explanatory variable. Statistical significance was set at 5%., Findings: In the survey period up to September 2017, 165 drugs developed with MRCT-JP were approved for manufacture and sale in Japan. "Respiratory system," "inhalation," "biological drug," and "under review" evaluation status for the United States, European Union, and other areas, "approved" evaluation status for the United States, "new ingredients," "priority review," "non-Japanese firm," and "Top 1-10" and "Top 11-20" drug sales rankings for pharmaceutical companies were identified as potential factors leading to the implementation of MRCT-JP. In contrast, "general anti-infectives for systemic use," "various," "external," "chemical compound," "unsubmitted" evaluation status for both the United States and European Union, and "Top 51+" drug sales rankings were potential factors for not implementing MRCT-JP., Implications: Therapeutic classification and agent type, in addition to capital type and United States and European Union evaluation status suggested by a previous study, were associated with implementing MRCT-JP. It is important to determine the best way to utilize MRCT-JP to maximize the value of products. Our findings were based on successful cases and may therefore be helpful for designing clinical development plans. Appropriate use of MRCT-JP will improve productivity in the pharmaceutical industry., (Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.)

The garlic (Allium sativa L.) bulb has been used as a food and condiment for centuries throughout the entire world and in Egypt for perhaps 5000 years. Since the passage of the Dietary Supplement Health and Education Act (DSHEA) of 1994 by the U.S. Congress, it has been claimed that garlic dietary supplements possess health benefits. Support for this claim is not the primary objective of this publication. The primary objective of this article is to demonstrate that the prediction of a potential health benefit(s) from garlic is largely dependent on the process used to produce a product. [ABSTRACT FROM AUTHOR]

Objectives: To estimate and compare the risk of emergent bradycardia associated with starting immediate-release (IR) and slow-release (SR) formulations of metoprolol., Design: Retrospective analysis of administrative claims data., Data Source: State of California Medicaid program (Medi-Cal) claims database., Patients: A total of 31,574 adults beginning metoprolol between May 1, 2004, and November 1, 2009, without a pharmacy claim for a β blocker within the previous 6 months of metoprolol initiation; patients with a primary or secondary diagnosis of symptomatic bradycardia, pacemaker, or implantable cardioverter-defibrillator placement before metoprolol initiation were excluded., Measurements and Main Results: The study outcome was the time to first occurrence of emergent bradycardia, measured at an emergency department visit or hospitalization due to diagnosis of symptomatic bradycardia, after metoprolol initiation. We calculated the incidence and compared the risk of emergent bradycardia by using a proportional hazards model that included the metoprolol formulation with adjustment for total daily metoprolol dose and the use of other drugs as time-varying covariates, as well as demographics and comorbidities. Among 31,574 patients starting metoprolol, 18,516 (58.6%) used the IR formulation. The incidence of emergent bradycardia was 19.1/1000 person-years overall but was nearly twice as common in patients using the IR versus the SR formulation (24.1/1000 person-yrs in the IR group versus 12.9/1000 person-yrs in the SR group, unadjusted hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.28-2.56). Adjustment for other drugs also associated with symptomatic bradycardia (cytochrome P450 2D6 inhibitors, class I or III antiarrhythmics, and atrioventricular node-blocking agents), metoprolol dose, and other participant characteristics somewhat attenuated the association (adjusted HR 1.48, 95% CI 1.03-2.13)., Conclusion: The risk of emergent bradycardia associated with metoprolol initiation was higher with the IR formulation than the SR formulation, although the absolute risk was low., (© 2013 Pharmacotherapy Publications, Inc.)

In the 5-year cycle that characterizes a continuous improvement of the US Pharmacopeial (USP) Convention, the Council of the Convention's Section on Global Public Health worked with USP's staff to assess USP's international contributions to date and to consider opportunities for expanding activities that help to ensure good healthcare around the globe.1 This article reviews USP's process and product standards that are used worldwide to ensure the quality of medicines and dietary supplements and to help mitigate the burden of counterfeit and substandard ingredients and products. The article also reviews USP's international programs during the past 5-year cycle, along with continuing and planned international activities., (Copyright © 2010 Wiley-Liss, Inc.)