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lemma:
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entity:
  The Merging of Immunohematology Reference Lab s IRL Inventories Using Technology to Create Advanced Search


id: cord-010119-t1x9gknd
type: ORG
entity:
  Guidance for Industry Recommendations for Donor Screening Deferral and Product Management to Reduce the Risk of Transfusion Transmission of Zika Virus


id: cord-010119-t1x9gknd
type: CHEMICAL
entity:
  Cheryl Lobo 4 Michael Paul Busch 3 Susan L Stramer 2 and Jeffrey M Linnen 1 1 Grifols Diagnostic Solutions Inc 2 American Red Cross 3 Blood Systems Research Institute 4 New York Blood


# url

id: cord-253840-xudra8tp
domain: www.fda.gov
url:
  http://www.fda.gov/regulatory-information/searchfda-guidance-documents/meta-analyses-randomizedcontrolled-clinical-trials-evaluate-safety-human-drugs-orbiological


# bib

id: cord-001513-p7v5p036
title: A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus
author: Ekins, Sean
date: 2014-12-12
txt: ./txt/cord-001513-p7v5p036.txt
cache: ./cache/cord-001513-p7v5p036.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304229/
doi: 10.12688/f1000research.5741.2
summary:
  Common features pharmacophore for EBOV actives Two papers from 2013 described compounds active as inhibitors of different EBOV strains in vitro and in vivo, namely amodiaquine and chloroquine in one study 8 , clomiphene and toremifene in another 9 . These suggest that the receptor-ligand based approach results in a general similarity across the nine structures, likely indicating the similar binding mode and importance of features for interfering with this generally hydrophobic pocket for protein-protein interactions. In silico docking of molecules in VP35 structure Redocking the 4IBI ligand in the protein resulted in an RMSD of 3.02Å, which generally indicates the difficulty of predicting orientations for compounds binding in what is a relatively hydrophobic and shallow pocket ( Figure S1 ). Pharmacophores, receptor ligand models and docking data for FDA-approved drugs inhibiting the Ebola virus, 10.5256/f1000research.5741.d38449 35 .

abstract:
  We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.


id: cord-002626-jzwwses4
title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care
author: Kaul, Karen L.
date: 2017-07-16
txt: ./txt/cord-002626-jzwwses4.txt
cache: ./cache/cord-002626-jzwwses4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528950/
doi: 10.1177/2374289517708309
summary:
  Clinical laboratories have thus had to develop new assays or modified the existing FDA-approved ones to detect high-risk HPV genotypes in head and neck cancer specimens. The vast majority of reporting laboratories utilized LDPs. 57 KRAS and RAS family gene mutation analysis is also critical in the management of patients with non-small-cell lung cancer (NSCLC) and other tumors, 58 for which FDA approval of kits has not occurred; LDPs or off-label use of kits is required. 74, 75 The FDA approval of anti-EGFR therapies based on clinical trial outcomes data resulted in the need for clinical laboratories to test tumor tissue for the EGFR-sensitizing mutations in order for patients to be eligible for treatment. During those ground-breaking first 15 years of the targeted cancer therapy era, if the laboratory community had been prohibited from providing high-quality, standardized LDP-based testing under existing CLIA guidelines, the negative consequences to patient care in the past and the future would have been substantial.

abstract:
  An explosion of knowledge and technology is revolutionizing medicine and patient care. Novel testing must be brought to the clinic with safety and accuracy, but also in a timely and cost-effective manner, so that patients can benefit and laboratories can offer testing consistent with current guidelines. Under the oversight provided by the Clinical Laboratory Improvement Amendments, laboratories have been able to develop and optimize laboratory procedures for use in-house. Quality improvement programs, interlaboratory comparisons, and the ability of laboratories to adjust assays as needed to improve results, utilize new sample types, or incorporate new mutations, information, or technologies are positive aspects of Clinical Laboratory Improvement Amendments oversight of laboratory-developed procedures. Laboratories have a long history of successful service to patients operating under Clinical Laboratory Improvement Amendments. A series of detailed clinical examples illustrating the quality and positive impact of laboratory-developed procedures on patient care is provided. These examples also demonstrate how Clinical Laboratory Improvement Amendments oversight ensures accurate, reliable, and reproducible testing in clinical laboratories.


id: cord-003118-58ta20fg
author: Van Norman, Gail A.
date: 2018-06-25
txt: ./txt/cord-003118-58ta20fg.txt
cache: ./cache/cord-003118-58ta20fg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058931/
doi: 10.1016/j.jacbts.2018.02.001
summary:
  Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the "single-patient" investigational new drug [IND] application). Spurred by patient advocacy during the early days of the acquired immunodeficiency syndrome (AIDS) epidemic in the late 1980s, and facilitated by subsequent legislative efforts over the next 20 years, regulatory initiatives permit the FDA to release drugs for use in individual patients through expanded access (EA) INDs (4, 5) , in many cases allowing emergency treatment with nonapproved drugs within hours of application, and nonemergency treatment within an average of 4 days (6) . Releasing investigational new drugs to individual patients who are facing certain death or disability seems to be a relatively uncomplicated decision, but allowing EA to entire groups of patients for treatment with an investigational new drug presents more complex regulatory, logistical, and ethical challenges for scientists, commercial entities, and the FDA.

title:
  Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies

abstract:
  Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application). Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval. While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval. This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.


id: cord-010119-t1x9gknd
title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017
author: nan
date: 2017-09-04
txt: ./txt/cord-010119-t1x9gknd.txt
cache: ./cache/cord-010119-t1x9gknd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/
doi: 10.1111/trf.14286
abstract: nan
summary:
  Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip).


id: cord-014687-0am4l5ms
title: SPR 2012
author: nan
date: 2012-03-29
txt: ./txt/cord-014687-0am4l5ms.txt
cache: ./cache/cord-014687-0am4l5ms.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080092/
doi: 10.1007/s00247-012-2356-8
abstract: nan
summary:
  This presentation will focus on recent developments that have lead to a better understanding of the embryopathogenesis for fibropolycystic liver diseases (including choledochal cysts and Caroli disease), histopathological findings that have led to new classification systems for of pediatric vascular anomalies, technological advances and contrast agents in magnetic resonance imaging that are useful to characterize and limit the differential diagnosis of hepatic masses. Disclosure: Dr. Annapragada has indicated that he is a stock holder and consultant for Marval Biosciences Inc. Paper #: PA-067 Cardiovascular Image Quality Using a Nanoparticle CT Contrast Agent: Preliminary Studies in a Pig Model Rajesh Krishnamurthy, Radiology, Texas Children''s Hospital, rxkrishn@texaschildrens.org; Ketan Ghaghada, Prakash Masand, Abhay Divekar, Eric Hoffman, Ananth Annapragada Purpose or Case Report: Image quality in a separate study using a long circulating, liposomal-based nanoscale blood pool iodinated contrast agent (NCTX) suggests clinical utility in pediatrics, potentially reducing difficulties in contrast-CT of children with congenital heart disease (CHD) including the size of intravenous cannula, need for accurate timing, inability to simultaneously opacify multiple targets of interest (requiring repeated contrast administration and/or repeated imaging).


id: cord-016293-pyb00pt5
title: The flowering of the age of Biotechnology 1990–2000
author: Newell-McGloughlin, Martina
date: 2006
txt: ./txt/cord-016293-pyb00pt5.txt
cache: ./cache/cord-016293-pyb00pt5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120537/
doi: 10.1007/1-4020-5149-2_4
abstract: nan
summary:
  In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes.


id: cord-016640-pvlg3nkp
title: Technical and Clinical Niches for Point of Care Molecular Devices
author: Baron, Ellen Jo
date: 2012-04-05
txt: ./txt/cord-016640-pvlg3nkp.txt
cache: ./cache/cord-016640-pvlg3nkp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120995/
doi: 10.1007/978-1-4614-3970-7_33
summary:
  POCT infectious disease molecular assays may be developed to detect speci fi c • infections for which a rapid response is desirable. The most widely used molecular test at patient POC sites is the real-time PCR (RT-PCR) assay for detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) [ 2 ] . Another rapid molecular test has been FDA-cleared for multiplex detection of 15 respiratory viruses, including adenovirus, 2 coronavirus strains, 5 in fl uenza strains, human metapneumovirus, parain fl uenza virus types 1-4, RSV, and rhino-enterovirus, with a time-to-result of 1-1.5 h using a novel multiplex PCR and array detection format [ 14 ] . Although other PCR methods for virus detection and identi fi cation in respiratory secretions are available and show excellent sensitivities and speci fi cities, they are not candidates for POC tests due to their complexity, long performance time, or format that leads to inef fi ciencies when performing non-batch (such as stat) testing [ 14 ] .

abstract:
  A point of care (POC) device is one that is used outside of a central laboratory environment; generally near , or at the site of the patient/client. Point of care testing (POCT) varies from tests performed in physician’s office labs, or “satellite” or “stat” labs, to tests performed on tabletop instruments in a clinic area, to testing performed with hand-held instruments at the bedside. In peripheral lab settings, POCT may be performed by trained laboratory staff, but clinic and bedside POCT is frequently performed by staff who lack specialized laboratory training and whose primary job is something other than doing lab tests.


id: cord-017208-7oew461e
title: Regulatory Aspects in the Development of Gene Therapies
author: Aurigemma, Rosemarie
date: 2005
txt: ./txt/cord-017208-7oew461e.txt
cache: ./cache/cord-017208-7oew461e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121712/
doi: 10.1007/978-1-59259-785-7_29
summary:
  Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations.

abstract:
  Preclinical therapeutics development research is directed toward fulfilling two overlapping sets of goals. A set of scientific goals includes defining the best molecule or biologic construct for the task at hand, and proving the case for its development. The second set of goals addresses regulatory requirements necessary to introduce the agent into human subjects. In the case of “small molecule” drugs, in most cases the identity of the molecule and appropriate safety studies are straightforward. In contrast, the development of biologic agents, including gene therapies discussed here, presents distinct challenges. The nature of the “drug” may be an organism subject to mutation or selection of variants through recombination. Its properties may vary depending on the scale and method of its preparation, purification, and storage. How to test adequately for its safety prior to first introduction in humans may not be straightforward owing to intrinsic differences in response to the agent expected in humans as compared to animals.


id: cord-017413-ymo9h7wb
title: Selecting and Screening Donors
author: Nurudeen, Sahadat Kemi
date: 2012-10-19
txt: ./txt/cord-017413-ymo9h7wb.txt
cache: ./cache/cord-017413-ymo9h7wb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121967/
doi: 10.1007/978-1-4471-2392-7_4
summary:
  In these fi rst cases of donation, gametes were obtained primarily from women already undergoing Screening of egg donors is an intricate • and multifaceted process that includes obtaining informed consent; securing a detailed medical, genetic, psychosocial, and reproductive history; performing a thorough physical examination; and testing for speci fi c infectious diseases. Screening women interested in becoming oocyte donors is an intricate and multifaceted process that includes obtaining informed consent, taking a thorough medical history, performing a complete medical examination, testing for infectious diseases, providing a genetic screen, and evaluating the donor psychologically. The screening process has evolved since the introduction of oocyte donation with recommendations and evidence provided by the American Society for Reproductive Medicine (ASRM), the US Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and state health departments (Table 4 .1 ) [ 8, 9 ] .

abstract:
  Oocyte donation was originally established in 1983 as a treatment option for younger women with premature ovarian failure and for women with severe pelvic disease whose ovaries, as a result, were surgically inaccessible. The indications for donor oocyte in vitro fertilization (IVF) have now expanded to include not only women with hypergonadotropic hypogonadism but also those with advanced reproductive age, diminished ovarian reserve, significant genetic disease risk, poor oocyte or embryo quality, or multiple failures in prior attempts to conceive using conventional assisted reproductive technology (ART). Oocyte donation has also been recently used as an important source of material to promote the study of stem cell research. In these first cases of donation, gametes were obtained primarily from women already undergoing IVF who had excess oocytes at the time of retrieval. Today, most egg donors are not currently pursing infertility treatment themselves but are willing to donate their gametes for altruistic or commercial reasons. Since its initiation, oocyte donation services have spread throughout the USA and to many areas of the world. In the USA, 9,000–10,000 donor oocyte cycles occur annually. Though donor oocyte IVF is available throughout the USA, globally the practice of oocyte donation varies due to legal restrictions in many countries (Chap. 30).


id: cord-018566-dd5gw66t
title: The Political Economy of US Antibiotic Use in Animal Feed
author: Armbruster, Walter J.
date: 2018-05-30
txt: ./txt/cord-018566-dd5gw66t.txt
cache: ./cache/cord-018566-dd5gw66t.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123476/
doi: 10.1007/978-3-319-92138-9_15
summary:
  This chapter examines the evidence for antibiotic resistance in the United States and globally, the public health implications, and the impact of—and related industry and political responses to—antibiotic use in animal feed. The major stakeholders include pharmaceutical companies, production integrators, feed suppliers, farm groups, producers, restaurants, food retailers, the public, the medical community, the scientific community, government regulators and policy makers. In 1969, the United Kingdom''s (UK) Parliament received the Swann Report, which concluded that using antimicrobials at sub-therapeutic levels in food-producing animals created risks to human and animal health (Joint Committee on the use of Antibiotics in Animal Husbandry and Veterinary Medicine 1969). This scenario could be exacerbated to the extent FSIS approves additional international facilities, local regulations, and inspections as "equivalent to the United States." Future trade agreements will need to include provisions which address reduced use of medically important antibiotics in producing food animals.

abstract:
  This chapter examines the evidence for antibiotic resistance in the United States and globally, the public health implications, and the impact of—and related industry and political responses to—antibiotic use in animal feed. In 1969, the Swann Report in the United Kingdom noted a dramatic increase in antibiotic-resistant bacteria in food animals receiving low levels of antibiotics in their feed. While the Food and Drug Administration of the United States sought to control antibiotics in animal feed as far back as 1977, only in 2016 were such regulations fully implemented. The farm-level costs of such controls are estimated by the US Department of Agriculture’s Economic Research Service to be minimal, while the Centers for Disease Control and Prevention’s estimates of the public health costs of antibiotic resistance without implementing controls are $7 billion annually. The complex interactions which exist between economic interests, regulatory policy, and human and animal health are explored in this chapter.


id: cord-018770-uy76mc2j
title: Donor Evaluation for Hematopoietic Stem and Progenitor Cell Collection
author: Connelly-Smith, Laura S.
date: 2019-11-28
txt: ./txt/cord-018770-uy76mc2j.txt
cache: ./cache/cord-018770-uy76mc2j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123736/
doi: 10.1007/978-3-319-55131-9_4
summary:
  With the increasing incidence of hematopoietic allogeneic cell transplantation (allo-HCT), the importance of securing a cellular product, safely from a donor, and ensuring that the product is without additional risk to the recipient, continues to be of paramount importance. Various registries have developed HPC donor-screening questionnaires and their use recommended, to elicit medical history and to identify high-risk behaviors associated with risk of disease transmission (AABB n.d.-a; National Marrow Donor Program 2002) . One such questionnaire that is freely available is the hematopoietic progenitor cell (HPC), Apheresis and HPC, Marrow Donor History Questionnaire (DHQ) (Appendix 4.1) developed by the AABB Inter-organizational DHQ-HPC Task Force to provide establishments with a standardized tool to screen allogeneic HPC donors for communicable disease risk factors in accordance with requirements of the FDA, AABB, FACT, and the NMDP (AABB n.d.-a). Areas to be evaluated and documented during history and physical examination (H&P) of potential allogeneic/syngeneic donors of peripheral blood stem cells or marrow.

abstract:
  With the increasing incidence of hematopoietic allogeneic cell transplantation (allo-HCT), the importance of securing a cellular product, safely from a donor, and ensuring that the product is without additional risk to the recipient, continues to be of paramount importance. The evaluation of the donor’s medical eligibility and suitability is designed to identify and limit the risk of transmitting infectious, genetic, or neoplastic diseases to the recipient through the product. It also aims to ensure a maximum level of safety for the donor and informs them of the risks of donation. Several regulatory agencies, national and international registries, and accreditation bodies have facilitated the availability and safe provision of human cells, tissues, and cellular- and tissue-based products not only at local institutions but also through international exchange.


id: cord-022039-y0l943xg
title: Regulation and Testing of Vaccines
author: Gruber, Marion F.
date: 2017-07-17
txt: ./txt/cord-022039-y0l943xg.txt
cache: ./cache/cord-022039-y0l943xg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152379/
doi: 10.1016/b978-0-323-35761-6.00079-1
abstract: nan
summary:
  Section 901 of Title IX of the FDAAA authorizes the FDA to require certain postmarketing studies and clinical trials for prescription drug and biological products approved under the FDA should take action in response to such reports and whether the current pharmacovigilance plan is adequate. Critical information to be contained in the BLA include data derived from nonclinical laboratory and clinical studies that demonstrate that the manufactured product meets prescribed requirements for safety, purity, and potency. Following completion of IND studies demonstrating the safety and efficacy of the vaccine for a specific use and population the sponsor can submit a BLA to obtain a license for a new vaccine under section 351 of the PHS Act for commercial manufacture and distribution of the product.


id: cord-022053-idft1p6d
title: New Technologies for the Diagnosis of Infection
author: Pecora, Nicole
date: 2017-07-21
txt: ./txt/cord-022053-idft1p6d.txt
cache: ./cache/cord-022053-idft1p6d.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152403/
doi: 10.1016/b978-0-323-44585-6.00006-0
abstract: nan
summary:
  Organisms commonly identified this way include spirochetes, mycobacteria, DNA viruses, Aspergillus, Candida, and Toxoplasma, although special reference laboratories (e.g., The Infectious Disease Pathology Branch at the Centers for Disease Control and Prevention) have a wide range of antibodies for common to exotic pathogens for tissue confirmation. These include highly sensitive probes for use in direct specimens, to alternative amplification methods, rapid assays of single targets, and multiplexed systems that allow for the detection of many organisms in one assay. Application of RNA-ISH to Aspergillus and Candida in FFPE showed less sensitivity than real-time PCR with sequencing (gold standard), although some FISH-positive, PCRnegative cases with obvious fungal elements were seen, suggesting refinements of this technique may be valuable for rapid identification of these common organisms, especially if mucormycosis is in the differential. Comparative evaluation of the Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry systems for identification of yeasts of medical importance


id: cord-024833-e6vcf4un
title: Forum
author: nan
date: 2019-12-19
txt: ./txt/cord-024833-e6vcf4un.txt
cache: ./cache/cord-024833-e6vcf4un.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223806/
doi: 10.1007/s40290-019-00321-z
abstract: nan
summary:
  Approximately 80% of US hospitals rely on data and recommendations from the ECRI Institute to protect patients from unsafe practices and ineffective products, while the ISMP''s efforts to improve safety in patients have resulted in changes to clinical practice and public policy, including improvements in drug labelling, packaging, preparation and administration. The FDA has now announced the availability of a draft document entitled "Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff", which outlines the agency''s approach to timely postmarketing analyses of drugs and biologics, and "includes a high-level overview of tools, methods, and signal detection and evaluation activities, using varied data sources, for drug safety surveillance to provide a broader context and a general overview of our overarching effort and commitment in this area", says Woodcock. Analysis of spontaneous ADR reports to the European Medicine Agency''s EudraVigilance database has identified new safety signals for asthma drugs in paediatric patients, say authors of a study published in Drug Safety.


id: cord-026653-094bk0t0
author: Gülsen, Askin
date: 2020-06-24
txt: ./txt/cord-026653-094bk0t0.txt
cache: ./cache/cord-026653-094bk0t0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289641/
doi: 10.1007/s15007-020-2550-1
summary:
  This review will evaluate reports of allergic and substance-specific infusion reactions (IR), injection-site reactions (ISR), hypersensitivity reactions (HSR), urticaria, and anaphylaxis caused by BSs. The most common indications for the use of biologics in lung diseases are allergic and severe uncontrolled asthma. The Australian Public Assessment report and the FDA label did not observe an increase in the incidence of severe immunological and anaphylactic reactions related to the use of nintedanib [25, 26] . According to the recent BCCA Drug Manual, it was reported that HSR including anaphylaxis can develop in ≤ 1 % (severe < 1 %), IRs in 1 % (severe ≤ 1 %), and immune-mediated rash in 8-18 % ( severe ≤ 1 %) of patients [58] . The FDA''s 2019 label reported infusion-related reactions in 11-24 % of patients (placebo 7-18.0 %), acute urticaria in 1-2 %, acute HSRs in 1.5 %, pruritus in 4 %, and serious IRs and anaphylaxis in < 1 % [159] .

title:
  Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

abstract:
  Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). Conclusion: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future. Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events. Allergo J Int 2020; 29:97-125 https://doi.org/10.1007/s40629-020-00126-6


id: cord-033420-pjtyv0pv
title: The promise of direct-to-consumer COVID-19 testing: ethical and regulatory issues
author: Kalokairinou, Louiza
date: 2020-09-23
txt: ./txt/cord-033420-pjtyv0pv.txt
cache: ./cache/cord-033420-pjtyv0pv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543538/
doi: 10.1093/jlb/lsaa069
summary:
  Although the provision of DTC tests has potential benefits—such as expanding access to testing and reducing the risk of exposure for consumers and medical personnel—it also raises significant ethical and regulatory concerns. The second part discusses five primary issues for DTC COVID-19 tests: test accuracy; potential misinterpretation of results; misleading claims and other misinformation; privacy concerns; and fair allocation of scarce resources. The second part identifies five primary ethical and regulatory issues for DTC COVID-19 tests: uncertainty over the accuracy of test results; potential misinterpretation of test results by users; misleading product promotion and misinformation; privacy concerns; and fair allocation of scarce resources. We conclude with recommendations for regulators, companies, and other relevant stakeholders that can help ensure high-quality, accurate, and equitably distributed COVID-19 tests, and inform the ethical provision of DTC health tests during public health crises.

abstract:
  Widespread diagnostic and serological (antibody) testing is one key to mitigating the COVID-19 pandemic. While at first, the majority of COVID-19 diagnostic testing in the USA took place in healthcare settings, quickly a direct-to-consumer (DTC) testing market also emerged. In these DTC provision models, the test is initiated by a consumer and the sample collection occurs at home or in a commercial laboratory. Although the provision of DTC tests has potential benefits—such as expanding access to testing and reducing the risk of exposure for consumers and medical personnel—it also raises significant ethical and regulatory concerns. This article reviews these challenges and shows how they parallel and also diverge from prior concerns raised in the DTC health testing arena. The first part of this paper provides an overview of the landscape of diagnostic and serological tests for COVID-19, anticipating how provision models are likely to evolve in the future. The second part discusses five primary issues for DTC COVID-19 tests: test accuracy; potential misinterpretation of results; misleading claims and other misinformation; privacy concerns; and fair allocation of scarce resources. We conclude with recommendations for regulators and companies that aim to ensure ethically marketed DTC COVID-19 tests.


id: cord-253840-xudra8tp
title: Reflections of the Angiotensin Receptor Blocker Recall by the FDA and Repercussions on Healthcare
author: Gillette, Michael
date: 2020-04-21
txt: ./txt/cord-253840-xudra8tp.txt
cache: ./cache/cord-253840-xudra8tp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32318933/
doi: 10.1007/s10557-020-06976-0
summary:
  Over the preceding 12-24 months, healthcare providers have encountered an alarming number of recalls related to cardiovascular medications, particularly with angiotensin receptor blockers (ARBs). ARBs, such as valsartan and losartan, represent a class of medications that in randomized controlled clinical trials (RCTs) have been shown to reduce blood pressure (BP) in hypertensive patients and impart cardiovascular benefits in diabetic nephropathy, systolic heart failure, left ventricular dysfunction, and following stroke [1] [2] [3] [4] [5] [6] [7] [8] 10] . This is particularly important given the recent outbreak of the coronavirus disease 2019 (COVID19) and speculation that ACE-Is or ARBs could increase the risk of infection through upregulation of angiotensin converting enzyme-2 receptors (ACE2) thereby leading to inappropriate discontinuation by patients or providers [16] . Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial

abstract:
  PURPOSE: Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety profiles. METHODS: This report includes a review of data from all pertinent clinical and scientific sources including information from the FDA’s inspection documents and recall website. Additional information is provided on the specific bottles including all lot numbers, expiration dates, etc. RESULTS: The recalls/withdrawals are attributable to the presence of cancer-causing contaminants identified during the manufacturing process from drug manufacturers abroad. The root causes behind the recalls and subsequent shortage appear multifactorial, and stem to a certain extent from the outsourcing of medication manufacturing overseas and lack of quality checks and appropriate oversight. CONCLUSIONS: This inherent issue is not likely to resolve soon and has eroded the public trust of/in the healthcare system and the pharmaceutical industry. Patients and healthcare providers are significantly affected and should have a full understanding of the matter in order to guide appropriate response and actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10557-020-06976-0) contains supplementary material, which is available to authorized users.


id: cord-256852-lrz17bdx
title: Responding to the Pandemic of Falsified Medicines
author: Nayyar, Gaurvika M. L.
date: 2015-06-03
txt: ./txt/cord-256852-lrz17bdx.txt
cache: ./cache/cord-256852-lrz17bdx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.4269/ajtmh.14-0393
doi: 10.4269/ajtmh.14-0393
summary:
  15 The U.S. Institute of Medicine (IOM) has published a report "Countering the Problem of Falsified and Substandard Drugs." 16 The IOM recommendations to "stem the global trade" in such products are laudable in advising that the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology, and other U.S. and international pharmaceutical and financing agencies be more actively involved in setting standards and financing improvements; yet this report falls far short of making a strong call for standardized, agreed-upon quality assessment technologies; an international law convention; and a more activist, internationally recognized lead organization, all three of which are essential for stopping the many health threats of fake drugs.

abstract:
  Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals.


id: cord-268283-eja8fkwv
author: Iftikhar, Hafsa
date: 2020-06-09
txt: ./txt/cord-268283-eja8fkwv.txt
cache: ./cache/cord-268283-eja8fkwv.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0010482520302079
doi: 10.1016/j.compbiomed.2020.103848
summary:
  In this regard, several recent studies have been conducted using computational methods to screen libraries of approved drugs or drug-like molecules to identify potential inhibitors of different viral proteins, particularly, RdRp and 3CL-protease [13] [14] [15] [16] [17] . Here, we applied a computer aided drug discovery approach by targeting three important enzymes (RdRp, 3CL-protease and helicase) of SARS-CoV-2 and identified three FDA-approved drugs and three other drug-like molecules as potential therapeutics. In this study, we used a virtual screening based strategy to identify already approved drugs or drug-like molecules that can bind to any of the three key viral enzymes, 3CL-protease, RdRp and helicase, and potentially inhibit the function of these enzymes. In our studies we performed computational screening by targeting three important enzymes of SARS-CoV-2 including RdRp, 3CL-protease and helicase, to identify not only the already approved drugs for repurposing but also the drug candidates or lead structures that can be chemically modified to develop potential drugs.

title:
  Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach

abstract:
  The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.


id: cord-269194-b1wlr3t7
title: Chapter 5 Clinical Applications of Quantitative Real-Time PCR in Virology
author: Engstrom-Melnyk, Julia
date: 2015-12-31
txt: ./txt/cord-269194-b1wlr3t7.txt
cache: ./cache/cord-269194-b1wlr3t7.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0580951715000069
doi: 10.1016/bs.mim.2015.04.005
summary:
  Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. With the development and administration of newer drugs that target specific biological processes of HIV, routine and clinical monitoring of viral loads using a real-time quantitative PCR assay continues to be critical to predict treatment failure and early emergence of drug resistance mutations, within a timeframe that would increase subsequent treatment success.

abstract:
  Abstract Since the invention of the polymerase chain reaction (PCR) and discovery of Taq polymerase, PCR has become a staple in both research and clinical molecular laboratories. As clinical and diagnostic needs have evolved over the last few decades, demanding greater levels of sensitivity and accuracy, so too has PCR performance. Through optimisation, the present-day uses of real-time PCR and quantitative real-time PCR are enumerable. The technique, combined with adoption of automated processes and reduced sample volume requirements, makes it an ideal method in a broad range of clinical applications, especially in virology. Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. All of these serve vital roles in the continuum of care to enhance patient management. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats.


id: cord-269975-1ebmq7t8
title: Combating biothreat pathogens: ongoing efforts for countermeasure development and unique challenges
author: Duplantier, Allen J.
date: 2020-05-27
txt: ./txt/cord-269975-1ebmq7t8.txt
cache: ./cache/cord-269975-1ebmq7t8.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128184806000072
doi: 10.1016/b978-0-12-818480-6.00007-2
summary:
  None of the filoviruses or henipaviruses has any FDA-approved therapeutics or vaccines available for prevention or treatment of human disease, and while ribavirin is sometimes used to treat Lassa fever, it is not a terribly effective drug against this viral infection [28] . Many of the therapeutics that are in different stages of either preclinical or clinical development for select biothreat pathogens include small molecule antivirals (Tables 7.3 and 7.4), antibody (or antibody cocktails) against viruses or bacteria/virulence factors (Table 7 .5), and combination drug therapy (Table 7 .6). Although no FDA-approved HDT therapies are yet available for treating infectious diseases, we have summarized in this section the antimicrobial Primary screening of small molecule chemical libraries in the phenotypic HCI assay will identify compounds that inhibit pathogen infection as well as those that may contribute to cellular toxicity.

abstract:
  Research to discover and develop antibacterial and antiviral drugs with potent activity against pathogens of biothreat concern presents unique methodological and process-driven challenges. Herein, we review laboratory approaches for finding new antibodies, antibiotics, and antiviral molecules for pathogens of biothreat concern. Using high-throughput screening techniques, molecules that directly inhibit a pathogen’s entry, replication, or growth can be identified. Alternatively, molecules that target host proteins can be interesting targets for development when countering biothreat pathogens, due to the modulation of the host immune response or targeting proteins that interfere with the pathways required by the pathogen for replication. Monoclonal and cocktail antibody therapies approved by the Food and Drug Administration for countering anthrax and under development for treatment of Ebola virus infection are discussed. A comprehensive tabular review of current in vitro, in vivo, pharmacokinetic and efficacy datasets has been presented for biothreat pathogens of greatest concern. Finally, clinical trials and animal rule or traditional drug approval pathways are also reviewed. Opinions; interpretations; conclusions; and recommendations are those of the authors and are not necessarily endorsed by the US Army.


id: cord-273099-zkk5d6gd
title: Vaccine supply, demand, and policy: A primer
author: Muzumdar, Jagannath M.
date: 2016-01-01
txt: ./txt/cord-273099-zkk5d6gd.txt
cache: ./cache/cord-273099-zkk5d6gd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19589753/
doi: 10.1331/japha.2009.09007
summary:
  According to the authors, an integrated policy approach that preserves incentives for market entry and innovation in the vaccine industry while addressing parental vaccine concerns and increasing immunization funding and reimbursement for both providers and patients is needed. 2 Push strategies seek to address supply-side issues in the vaccine market by providing direct assistance to ease the burden of research, development, and production costs, whereas pull strategies are designed to manipulate demand for vaccines, thereby improving the likelihood of a return on investment by increasing the number of immunizations administered. The United Kingdom has taken a lead in promoting an International Financing Facility for Immunization (IFFIm) 69 IFFIm has raised more than $1 billion in capital markets to immunize poor children in developing nations against Reviews VACCINE POLICY vaccine-preventable diseases.

abstract:
  OBJECTIVE: To provide an overview of supply and demand issues in the vaccine industry and the policy options that have been implemented to resolve these issues. DATA SOURCES: Medline, Policy File, and International Pharmaceutical Abstracts were searched to locate academic journal articles. Other sources reviewed included texts on the topics of vaccine history and policy, government agency reports, and reports from independent think tanks. Keywords included vaccines, immunizations, supply, demand, and policy. STUDY SELECTION: Search criteria were limited to English language and human studies. Articles pertaining to vaccine demand, supply, and public policy were selected and reviewed for inclusion. DATA EXTRACTION: By the authors. DATA SYNTHESIS: Vaccines are biologic medications, therefore making their development and production more difficult and costly compared with “small-molecule” drugs. Research and development costs for vaccines can exceed $800 million, and development may require 10 years or more. Strict manufacturing regulations and facility upgrades add to these costs. Policy options to increase and stabilize the supply of vaccines include those aimed at increasing supply, such as government subsidies for basic vaccine research, liability protection for manufacturers, and fast-track approval for new vaccines. Options to increase vaccine demand include advance purchase commitments, government stockpiles, and government financing for select populations. CONCLUSION: High development costs and multiple barriers to entry have led to a decline in the number of vaccine manufacturers. Although a number of vaccine policies have met with mixed success in increasing the supply of and demand for vaccines, a variety of concerns remain, including developing vaccines for complex pathogens and increasing immunization rates with available vaccines. New policy innovations such as advance market commitments and Medicare Part D vaccine coverage have been implemented and may aid in resolving some of the problems in the vaccine industry.


id: cord-274061-ynqxgyw6
title: Blood system changes since recognition of transfusion‐associated AIDS
author: Epstein, Jay S.
date: 2013-10-17
txt: ./txt/cord-274061-ynqxgyw6.txt
cache: ./cache/cord-274061-ynqxgyw6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24032622/
doi: 10.1111/trf.12373
abstract: nan
summary:
  In a set of 14 recommendations directed primarily at federal agencies, the IOM called for a more responsive and integrated decision-making process including establishment of a Blood Safety Council reporting to a designated Blood Safety Director within HHS and a standing "expert panel" to assure communication of blood product risks and alternatives to their use both to care providers and to the public. Several possible strategies were presented, including deferral of blood donations by persons known to be at increased risk for AIDS and the use of surrogate tests to identify persons at increased risk of transmission, such as those with detectable antibody to hepatitis B core antigen (anti-HBc) or low CD4/CD8 T-cell ratios. The Transfusion Transmitted Virus Study, supported by the National Heart, Lung and Blood Institute, published a retrospective analysis of a prospective study that showed that alanine aminotransferase (ALT) testing of donors might effect a 30% reduction in TAH incidence.


id: cord-276414-kicu0tv5
author: Bahadur Gurung, Arun
date: 2020-06-10
txt: ./txt/cord-276414-kicu0tv5.txt
cache: ./cache/cord-276414-kicu0tv5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32837219/
doi: 10.1016/j.sjbs.2020.06.005
summary:
  Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. Interestingly, the antimigraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions.

title:
  In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors

abstract:
  Abstract Coronaviruses with the largest viral genomes are positive-sense RNA viruses associated with a history of global epidemics such as the severe respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and recently the coronavirus disease 2019 (COVID-19). There has been no vaccines or drugs available for the treatment of human coronavirus infections to date. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. We have used molecular docking approach and have successfully identified the best lead molecules for each enzyme target. Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. Hence both these lead molecules can be further taken for wet-lab experimentation studies before repurposing them as anti-coronaviral drug candidates.


id: cord-276460-nmugz0oh
title: Computer-Based Blood Donor Screening: A Status Report
author: Katz, Louis M.
date: 2007-01-31
txt: ./txt/cord-276460-nmugz0oh.txt
cache: ./cache/cord-276460-nmugz0oh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17174217/
doi: 10.1016/j.tmrv.2006.08.001
summary:
  Further enhancements of the basic CASI system include pictures illustrative of the content of the question; response inputs via touch screen; inclusion of back, help, and skip commands to improve accuracy and completeness of responses, staff review modules for assessment of completed DHQs, direct printing of the DHQ with provision for signatures, and electronic transfer of final interview data to other associated computer systems. In a similar study using essentially the same system at another regional blood center, Cumming et al 24 found that with a combination of FTFI and WSAQ, the rate of deferrals of first-time donors for high-risk behavior was 5.8 per 1000, whereas after installation of an AVT-CASI system the rate increased to 11.2 per 1000, a 93% increase. Cumming et al, 24 in their recent study at a regional blood center, found that in the first year after implementing an AVT-CASI system, the elicitation of information resulting in donor deferrals increased substantially.

abstract:
  There is a substantial literature suggesting that computer-assisted interviewing has advantages over face-to-face and written self-administration of interviews in venues eliciting sensitive information similar to that sought in blood donor history screening. We review some of the recent developments in blood donor history screening, the evidence suggesting that automated interviews should be useful, and the experience to date using computer interviews for blood donation. These data suggest that automated computer-assisted interviewing increases the elicitation of behaviors associated with the risk of transfusion-transmissible infection in donors, improves donor and staff satisfaction, and reduces errors and omissions that frequently accompany traditional interviewing methods. Food and Drug Administration–cleared systems for computer-assisted self-interview of blood donors are briefly described.


id: cord-278174-znc99yos
title: Managing recalls and withdrawals of blood components
author: Ramsey, Glenn
date: 2004-01-31
txt: ./txt/cord-278174-znc99yos.txt
cache: ./cache/cord-278174-znc99yos.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/14689376/
doi: 10.1016/j.tmrv.2003.10.005
summary:
  Abstract Donor centers are issuing a growing number of recalls and market withdrawals to hospital transfusion services about blood components. Using the FDA''s categories of donor center biological product deviations, we provide recommendations to consider for when to notify the recipient''s physician, after postdonation information is received about a previously transfused blood component. If a blood product has been transfused from a donor who should have been ineligible at the time of donation, then "we recommend that the establishments consider notifying the treating physician of those recipients about the post donation information, including whether the donor developed suspected SARS." Donors are deferred for 28 days after recovering from suspected SARS or for 14 days after exposure to a person with SARS or travel to SARS-risk areas.

abstract:
  Abstract Donor centers are issuing a growing number of recalls and market withdrawals to hospital transfusion services about blood components. More than 1 in 2,000 units were recalled in the late 1990s in the United States. The most common reason for these notices from donor centers is postdonation donor information. Most of these units had been transfused, and many present a “risk of a risk” (ie, a problem might have been present that might have affected the recipient). A few regulations and standards address recalls in general terms, but transfusion services generally have wide discretion in the management of specific common recall problems. The Food and Drug Administration (FDA) is now including posttransfusion evaluations in its guidelines for emerging infectious threats to the blood supply. We suggest that hospital transfusion services should have standard operating procedures for managing recalls and that the hospital transfusion committee and the quality management program should provide local input or oversight. Using the FDA’s categories of donor center biological product deviations, we provide recommendations to consider for when to notify the recipient’s physician, after postdonation information is received about a previously transfused blood component. More study of this important everyday issue in transfusion medicine is highly desirable.


id: cord-280040-xphxlaat
title: Disinfection and Sterilization in Health Care Facilities An Overview and Current Issues
author: Rutala, William A.
date: 2016-09-30
txt: ./txt/cord-280040-xphxlaat.txt
cache: ./cache/cord-280040-xphxlaat.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0891552016300228
doi: 10.1016/j.idc.2016.04.002
summary:
  [6] [7] [8] Because of noncompliance with recommended reprocessing procedures, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) issued a health advisory alerting health care providers and facilities about the public health need to properly maintain, clean, and disinfect and sterilize reusable medical devices in September 2015. There is excellent evidence in the scientific literature that environmental contamination plays an important role in the transmission of several key health care-associated pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycinresistant Enterococcus (VRE), Acinetobacter sp, norovirus, and Clostridium difficile. Comparison of ultraviolet irradiation versus hydrogen peroxide for room decontamination UV devices and HP systems have their own advantages and disadvantages ( Table 5) , 53 and there is now ample evidence that these no-touch systems can reduce environmental contamination with health care-associated pathogens and reduce HAIs. 84 However, each specific marketed system should be studied and its efficacy demonstrated before being introduced into health care facilities.

abstract:
  When properly used, disinfection and sterilization can ensure the safe use of invasive and noninvasive medical devices. The method of disinfection and sterilization depends on the intended use of the medical device: critical items (contact sterile tissue) must be sterilized before use; semicritical items (contact mucous membranes or nonintact skin) must be high-level disinfected; and noncritical items (contact intact skin) should receive low-level disinfection. Cleaning should always precede high-level disinfection and sterilization. Current disinfection and sterilization guidelines must be strictly followed.


id: cord-280571-ntgt5hy9
author: Ginocchio, Christine C.
date: 2011-05-01
txt: ./txt/cord-280571-ntgt5hy9.txt
cache: ./cache/cord-280571-ntgt5hy9.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/cid/cir046
doi: 10.1093/cid/cir046
summary:
  In addition to RADTs, there are U.S. Food and Drug Administration (FDA)-approved/cleared nonmolecular-based viral diagnostic methods with a more rapid time to result, compared with traditional viral tube culture, eg, direct fluorescent antibody (DFA) testing and rapid cell culture. Although these 8 viruses are responsible for a large number of respiratory tract infections, bocavirus, selected coronaviruses (229E, OC43, NL63, and HKU-1), parainfluenza 4, and rhinovirus are also important causes of respiratory disease and are generally only detected using NAATs. Because antiviral therapies are currently limited to the treatment of influenza A, influenza B, cytomegalovirus pneumonia, and varicella zoster virus pneumonia, it is often argued that the specific identification of other viruses is not relevant, because the information would not change patient management. With clinical integration of real-time polymerase chain reaction (PCR) and FDA-approved/cleared simple cartridge-based NAATs, laboratories of all sizes are now able to perform molecular diagnostic tests.

title:
  Strengths and Weaknesses of FDA-Approved/Cleared Diagnostic Devices for the Molecular Detection of Respiratory Pathogens

abstract:
  The rapid, sensitive, and specific identification of the microbial etiological characteristics of respiratory tract infections enhances the appropriate use of both antibiotics and antiviral agents and reduces the risk of nosocomial transmission. This article reviews the current nucleic acid amplification tests approved by the U.S. Food and Drug Administration (FDA) for the detection of respiratory pathogens. In addition, Emergency Use Authorization tests for the detection of 2009 influenza A H1N1 are discussed. The advantages and limitations of the current FDA-approved/cleared tests are reviewed.


id: cord-287758-da11ypiy
title: COVID-19 therapy: what weapons do we bring into battle?
author: Mônica Vitalino de Almeida, Sinara
date: 2020-09-10
txt: ./txt/cord-287758-da11ypiy.txt
cache: ./cache/cord-287758-da11ypiy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.bmc.2020.115757
doi: 10.1016/j.bmc.2020.115757
summary:
  The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell.

abstract:
  Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.


id: cord-288567-1nmk9qhr
title: Management of infantile hemangiomas during the COVID pandemic
author: Frieden, Ilona J.
date: 2020-05-16
txt: ./txt/cord-288567-1nmk9qhr.txt
cache: ./cache/cord-288567-1nmk9qhr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/pde.14196
doi: 10.1111/pde.14196
summary:
  The use of beta-blockers in the treatment of IH has revolutionized care, and recent American Academy of Pediatrics (AAP) clinical practice guidelines (CPG) emphasize that early therapeutic intervention is critical for complicated IH to prevent medical complications or permanent disfigurement. We give recommendations to help guide decisions about when telehealth may be an alternative to in-office visits, including initiation, dosage changes, and continued evaluation for those patients requiring treatment. [2] [3] [4] [5] [6] [7] [8] [9] Consensus recommendations prior to the FDA/EMA approval in 2014 included the following 10 : (a) screening for contraindications to propranolol, (b) performing or obtaining documentation of, a recent normal cardiovascular and pulmonary history and examination, (c) obtaining key historical data including poor feeding, dyspnea, tachypnea, diaphoresis, wheezing, heart murmur, or family history of heart block or arrhythmia, and (d) prolonged in-office monitoring.

abstract:
  The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.


id: cord-290895-tb0xald0
author: Indu, Purushothaman
date: 2020-10-26
txt: ./txt/cord-290895-tb0xald0.txt
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extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1876034120307127
doi: 10.1016/j.jiph.2020.10.015
summary:
  title: Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach Virtual screening was performed to find out the lead antiviral drug molecules against main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) using COVID-19 Docking Server. RESULTS: Out of 65 FDA approved small molecule antiviral drugs screened, Raltegravir showed highest interaction energy value of -9 kcal/mol against Mpro of SARS-CoV-2 and Indinavir, Tipranavir, and Pibrentasvir exhibited a binding energy value of ≥ -8 kcal/mol. In this study, FDA J o u r n a l P r e -p r o o f approved small molecule antiviral drugs were screened against protein targets of SARS-CoV-2 using a computational based approach. In our study, other screened antiviral drugs such as Indinavir, Tipranavir, and Pibrentasvir showed dock energy value more than -8 kcal/mol and these drugs might also serve as an inhibitors of Mpro target of SARS-CoV-2.

title:
  Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach

abstract:
  BACKGROUND: Outbreak of COVID-19 has been recognized as a global health concern since it causes high rates of morbidity and mortality. No specific antiviral drugs are available for the treatment of COVID-19 till date. Drug repurposing strategy helps to find out the drugs for COVID-19 treatment from existing FDA approved antiviral drugs. In this study, FDA approved small molecule antiviral drugs were repurposed against the major viral proteins of SARS-CoV-2. METHODS: The 3D structures of FDA approved small molecule antiviral drugs were retrieved from PubChem. Virtual screening was performed to find out the lead antiviral drug molecules against main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) using COVID-19 Docking Server. Furthermore, lead molecules were individually docked against protein targets using AutoDock 4.0.1 software and their drug-likeness and ADMET properties were evaluated. RESULTS: Out of 65 FDA approved small molecule antiviral drugs screened, Raltegravir showed highest interaction energy value of -9 kcal/mol against Mpro of SARS-CoV-2 and Indinavir, Tipranavir, and Pibrentasvir exhibited a binding energy value of ≥ -8 kcal/mol. Similarly Indinavir showed the highest binding energy of -11.5 kcal/mol against the target protein RdRp and Dolutegravir, Elbasvir, Tipranavir, Taltegravir, Grazoprevir, Daclatasvir, Glecaprevir, Ledipasvir, Pibrentasvir and Velpatasvir showed a binding energy value in range from -8 to -11.2 kcal/mol. The antiviral drugs Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine also exhibited good bioavailability and drug-likeness properties. CONCLUSION: This study suggests that the screened small molecule antiviral drugs Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine could serve as potential drugs for the treatment of COVID-19 with further validation studies.


id: cord-291626-lxa8pvt3
title: Monoclonal antibodies as anti-infective products: a promising future?
author: Pelfrene, E.
date: 2019-01-31
txt: ./txt/cord-291626-lxa8pvt3.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cmi.2018.04.024
doi: 10.1016/j.cmi.2018.04.024
summary:
  Additionally, the FDA recently licensed ibalizumab as a rescue therapy in heavily treatmentexperienced adults with multidrug-resistant HIV-1 infection and also previously approved raxibacumab (in 2012) and obiltoxaximab (in 2016), both intended for treatment of inhalational anthrax (in combination with appropriate antibacterial medicines) and for prophylaxis when alternative therapies are not available or are not appropriate [5e7] . François et al., ''Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in patients with severe pneumonia caused by Staphylococcus aureus: first in man trial,'' abstract 1992, paper presented at European Congress of Clinical Microbiology and Infectious Diseases 2017) [34, 38] . Compassionate use Benefits seriously ill patients who cannot be treated satisfactorily or cannot enrol in ongoing clinical trials Pertains to unauthorized medicinal products for chronically, seriously debilitating or life-threatening diseases, with no satisfactory treatment authorized in EU; targeted at a group of patients rather than individual; or undergoing centralized MAA or clinical trials EMA, European Medicines Agency; FDA, US Food and Drug Administration; HTA, health technology assessment bodies; MAA, marketing authorization application; SA, scientific advice.

abstract:
  Abstract Background The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. Aims This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. Sources A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. Content We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. Implications mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.


id: cord-294108-uvnh0s9r
author: Dube, Taru
date: 2020-10-25
txt: ./txt/cord-294108-uvnh0s9r.txt
cache: ./cache/cord-294108-uvnh0s9r.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/adtp.202000172
doi: 10.1002/adtp.202000172
summary:
  [2, [8] [9] [10] This article discusses SARS-CoV-2 nanostructure, the virus biology in connection to its epidemiology, clinical manifestations, and potential and future therapeutic options including repurposed drugs, vaccine/protein therapies, immune therapies, and nanotherapeutics. Mechanisms such as inhibition of viral enzymes (DNA and RNA polymerases, 3CL pro, TMPRSS2, reverse transcriptase, neuraminidase, endonucleases, and other proteases) or processes such as ACE2 cellular receptor inhibitors and endosomal acidification mediators prohibiting viral fusion; molecules interfering with glycosylation of the viral protein, viral assembly, new viral particle transport, and release, and immunomodulation of cytokine release can be potential targets in developing various antiviral drugs for the SARS-CoV-2. [85] A randomized, placebo-controlled, Phase IV clinical trial assessing the safety and efficacy of umifenovir as an adjuvant therapy to the combined therapeutic regimen of IFN 1a, lopinavir/ritonavir and hydroxychloroquine in moderate to severe COVID-19 patients (NCT04350684) is underway.

title:
  Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector

abstract:
  The deadly pandemic, coronavirus disease 2019 (COVID‐19), caused due to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has paralyzed the world. Although significant methodological advances have been made in the field of viral detection/diagnosis with 251 in vitro diagnostic tests receiving emergency use approval by the US‐FDA, little progress has been made in identifying curative or preventive therapies. This review discusses the current trends and potential future approaches for developing COVID‐19 therapeutics, including repurposed drugs, vaccine candidates, immune‐modulators, convalescent plasma therapy, and antiviral nanoparticles/nanovaccines/combinatorial nanotherapeutics to surmount the pandemic viral strain. Many potent therapeutic candidates emerging via drug‐repurposing could significantly reduce the cost and duration of anti‐COVID‐19 drug development. Gene/protein‐based vaccine candidates that could elicit both humoral and cell‐based immunity would be on the frontlines to prevent the disease. Many emerging nanotechnology‐based interventions will be critical in the fight against the deadly virus by facilitating early detection and enabling target oriented multidrug therapeutics. The therapeutic candidates discussed in this article include remdesivir, dexamethasone, hydroxychloroquine, favilavir, lopinavir/ritonavir, antibody therapeutics like gimsilumab and TJM2, anti‐viral nanoparticles, and nanoparticle‐based DNA and mRNA vaccines.


id: cord-299323-riotkgj4
author: Seo, Yurim
date: 2020-10-13
txt: ./txt/cord-299323-riotkgj4.txt
cache: ./cache/cord-299323-riotkgj4.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0264410X20312494
doi: 10.1016/j.vaccine.2020.09.067
summary:
  The key documents examined were the U.S. Food & Drug Administration''s (FDA) Package Inserts (PIs), U.S. Centers for Disease Control and Prevention''s (CDC) Vaccine Information Statements (VISs), and the European Medicines Agency''s (EMA) Summary of Product Characteristics (SmPCs) and Package Leaflets (PLs). Although efforts by the International Council for Harmonization (ICH) to harmonize technical requirements for registering drugs and biologics have produced a number of useful guidelines that are used around the world, such efforts have not been extended to the regulatory review process or product labeling [1] . This study compared vaccine prescribing information and patient information leaflet languages between FDA/Centers for Disease Control and Prevention (CDC) and EMA. The centralized route allows companies to submit a single Marketing Authorization Application (MAA) to EMA that leads to the product''s approval in all countries within the European Economic Area (i.e., the 27 member states of the EU plus Iceland, Liechtenstein and Norway).

title:
  Elements of Regulatory Dissonance: Examining FDA and EMA Product Labeling of New Vaccines (2006–2018)

abstract:
  With the ongoing globalization of the pharmaceutical industry, efforts to harmonize technical requirements of registering drugs and biologics, including vaccines, have produced a number of useful guidelines utilized around the world. However, such efforts have not been extended to the regulatory review process or product labeling. Prescribing information and patient information leaflet are two types of such product labeling documents. This study examined the differences in the languages of these documents between the United States (US) and European Union (EU). The key documents examined were the U.S. Food & Drug Administration’s (FDA) Package Inserts (PIs), U.S. Centers for Disease Control and Prevention’s (CDC) Vaccine Information Statements (VISs), and the European Medicines Agency’s (EMA) Summary of Product Characteristics (SmPCs) and Package Leaflets (PLs). Prescribing information and patient information leaflet languages were subsequently organized into ten and seven categories, respectively. Comparison of FDA PIs to EMA SmPCs showed little harmonization between the two regions, and CDC VISs to EMA PLs revealed even less.


id: cord-303865-vd3qr32o
title: Outsourcing facilities and their place in the U.S. drug supply chain
author: Gianturco, Stephanie L.
date: 2020-08-28
txt: ./txt/cord-303865-vd3qr32o.txt
cache: ./cache/cord-303865-vd3qr32o.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.japh.2020.07.021
doi: 10.1016/j.japh.2020.07.021
summary:
  Although it is preferable for providers to use Food and Drug Administration (FDA)eapproved, commercially available drug products, there are times when drug products need to be compounded to meet a patient-specific need. 4 FDA does not intend to take action against outsourcing facilities that compound drug products using bulk drug substances in category 1, in which information supports their clinical use or need, and FDA was unable to identify significant safety risks. Outsourcing facilities can provide hospitals and independent practices with ready-to-use sterile drug products because they can compound drug products on a larger scale and are not limited by the requirement of a patient-specific prescription. Challenges that limit the use of outsourcing facilities in the U.S. drug supply chain include a lack of a finalized 503B Bulks List, inconsistences in the inspection process, and lack of transparency in compliance status.

abstract:
  OBJECTIVE: The purpose of this commentary is to describe the ideal role of 503B outsourcing facilities in the U.S. drug supply chain. We also address the challenges that 503B outsourcing facilities are facing that limit their utilization and offer possible solutions. SUMMARY: Section 503B outsourcing facilities are emerging contributors in compounding owing to their ability to compound large quantities of medication without requiring patient-specific prescriptions. As such, they play a valuable role in the U.S. drug supply chain. The use of outsourcing facilities to compound ready-to-use drug products is gaining traction in hospitals and other health care systems. Outsourcing facilities help hospitals that are facing time and cost constraints owing to the evolving regulatory landscape around compounding. Although outsourcing facilities are assets to the drug supply chain, there are several challenges to their use. The lack of a finalized 503B Bulks List has led to outsourcing facilities being overly cautious in compounding products using bulk drug substances. In addition, the time between Food and Drug Administration (FDA) inspections is undefined, and a lack of follow-up information regarding concerns identified during an inspection may result in uncertainties about the current state of the outsourcing facility. CONCLUSIONS: Health care providers, outsourcing facilities, and FDA need to work together to ensure that patients are provided the drugs they need in a safe and effective way.


id: cord-304056-2bo0s0hz
title: Part I State of Play and Review of Major Cooperation Initiatives
author: Lezotre, Pierre-Louis
date: 2014-12-31
txt: ./txt/cord-304056-2bo0s0hz.txt
cache: ./cache/cord-304056-2bo0s0hz.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128000533000021
doi: 10.1016/b978-0-12-800053-3.00002-1
summary:
  ▸ To maintain a forum for a constructive dialogue between regulatory authorities and the pharmaceutical industry on the real and perceived differences in the technical requirements for product registration in the EU, US, and Japan in order to ensure a more timely introduction of new medicinal products, and their availability to patients; ▸ To contribute to the protection of public health from an international perspective (added upon revision in 2000); ▸ To monitor and update harmonized technical requirements leading to a greater mutual acceptance of research and development data; ▸ To avoid divergent future requirements through harmonization of selected topics needed as a result of therapeutic advances and the development of new technologies for the production of medicinal products; ▸ To facilitate the adoption of new or improved technical research and development approaches which update or replace current practices, where these permit a more economical use of human, animal, and material resources, without compromising safety; ▸ To facilitate the dissemination and communication of information on harmonized guidelines and their use such as to encourage the implementation and integration of common standards.

abstract:
  Abstract The basic principle of international cooperation is to establish bilateral and multilateral efforts to leverage the human, scientific and financial resources and the knowledge and experience of other key regulatory authorities to avoid duplication of efforts, to make activities more efficient and to allow the focussing of limited resources on higher-risk areas of concern. This increased cooperation between worldwide regulators has necessitated proactive deliberate efforts towards convergence/harmonisation of regulation, practices and requirements to eliminate or reduce differences. Cooperation and harmonisation of standards in the pharmaceutical domain are already a reality and have become increasingly important during recent decades, with a high level of commitment to these activities by all stakeholders. The worldwide Drug Regulatory Authorities (DRAs) have been working to end an isolationist attitude that cannot resolve current worldwide issues and challenges caused by an ever increasing globalisation. As a result, many cooperation and harmonisation initiatives have been established at the bilateral, regional and global levels as a response to the changing geo-economic-political situation. The spectrum of collaboration varies from simple informal technical cooperation to full integration of systems and regulations. Indeed, all these initiatives can be very different in scope (some are part of a broader harmonisation initiative), level of harmonisation (depending on the political support/commitment), organisation (well-structured versus simple discussion) or advancement (established process vs. pilot projects), but they all work towards convergence of requirements and/or practices. All these multiple worldwide cooperation and harmonisation programmes have evolved rapidly over the past decades. This book section provides the current status of this complex and broad phenomenon of cooperation, convergence and harmonisation in the pharmaceutical sector. It reviews all major global, regional and bilateral cooperation initiatives.


id: cord-308284-r546ypur
title: Navigating facilitated regulatory pathways during a disease X pandemic
author: Simpson, Shmona
date: 2020-10-23
txt: ./txt/cord-308284-r546ypur.txt
cache: ./cache/cord-308284-r546ypur.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33110630/
doi: 10.1038/s41541-020-00249-5
summary:
  Several potential regulatory scenarios may exist and co-exist during an epidemic: for example, (a) de-novo candidates requiring rapid development and regulatory assessment (b) de-novo products requiring assessment when the typical package of clinical efficacy data may not be available, (c) approval of de novo or repurposed products for "emergency" use only in specific populations (d) for compassionate use in specific (e.g., "named") individuals of an unauthorized medicine (e) conditional or accelerated authorization before the completion of efficacy studies or, (f) use of a licensed product outside of its approved use (e.g., for another indication, dosage regimen, or population). Conditional term-limited approval 22 FDA''s Expanded Access (EA) is a program designed for patients with an immediately life-threatening disease to access a product that has clinical trial data (putatively showing an acceptable benefit-risk profile)-but does not yet have marketing authorization.

abstract:
  In 2018, the Bill and Melinda Gates Foundation convened over thirty subject matter experts in clinical development, manufacturing, and regulatory assessment to determine how the development and approval of medical countermeasures could be accelerated in the event of Disease X. Disease X is the result of a presently unknown pathogen with epidemic or pandemic potential. A key opportunity to accelerate the scientific assessment and regulatory approval of medical countermeasures exists within efficient navigation of facilitated regulatory pathways. It was identified that not all stakeholders will be able to skillfully navigate the facilitated pathways offered by the various regulatory agencies during a public health emergency. To democratize this knowledge, we have written an overview of the facilitated approaches which have been developed and refined by Stringent Regulatory Authorities and the World Health Organization for the primary assessment of medical products. We discuss the conditions necessary for use of these approaches, scenarios in which certain pathways may be applicable, and the pros and cons of these approaches. We also address opportunities available to developers in, or developers who wish to access, low-income countries that may have nascent regulatory frameworks.


id: cord-317720-gbi11oxx
title: Implementation of an Emergency Use Authorization Test During an Impending National Crisis
author: Lefferts, Joel A.
date: 2020-05-14
txt: ./txt/cord-317720-gbi11oxx.txt
cache: ./cache/cord-317720-gbi11oxx.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1525157820303251?v=s5
doi: 10.1016/j.jmoldx.2020.05.001
summary:
  Concerned that the efforts of state laboratories would be further impacted by lack of resources, we began to identify sources -including the WHO, the CDC, and commercial vendors -of the required primers and probes for the reverse transcriptase polymerase chain reaction (RT-PCR) detection of the virus and placed orders for test reagents from potential suppliers. The document provided guidance for high complexity testing laboratories developing SARS-CoV-2 tests for submission for Emergency Use Authorization (EUA) status with respect to required validation experiments and reporting to the FDA. Initially laboratories were required to spike RNA transcripts into previously extracted nucleic acid from negative samples for the CDC assay to determine the limit of detection but this had its own challenges of not representing extraction of true clinical samples and issues with degradation were identified. Our plan included the production of enough contrived clinical specimens and control material to proceed with validation or verification of the multiple (laboratory-developed and CDC EUA) tests that we were evaluating.

abstract:
  Abstract The laboratory response to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may be termed heroic. From the identification of the novel coronavirus to implementation of routine laboratory testing around the world to the development of potential vaccines, laboratories have played a critical role in the efforts to curtail this pandemic. In this brief report, we review our own effort at a mid-sized, rural, academic medical center to implement a molecular test for the virus; and, we share insights and lessons learned from that process which might be helpful in similar situations in the future.


id: cord-322915-zrjx31ev
title: Microbial drug discovery: 80 years of progress
author: Demain, Arnold L
date: 2009-01-09
txt: ./txt/cord-322915-zrjx31ev.txt
cache: ./cache/cord-322915-zrjx31ev.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/ja.2008.16
doi: 10.1038/ja.2008.16
summary:
  Evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in 1991 were either natural products or their derivatives. In addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. 28 Among the novel class of antimicrobial agents used in treating resistance to Gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by Streptomyces roseosporus. 44 Other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. Considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past 15 years, with few new drug approvals.

abstract:
  Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.


id: cord-326922-bajpr5a2
author: Watson, C. James
date: 2020-11-02
txt: ./txt/cord-326922-bajpr5a2.txt
cache: ./cache/cord-326922-bajpr5a2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33140232/
doi: 10.1007/s13181-020-00814-3
summary:
  In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA''s Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] .

title:
  Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors

abstract:
  INTRODUCTION: Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. METHODS: We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration “Drug Alerts and Statements” repository. We categorized reports into errors of “contamination,” suprapotency,” and “subpotency.” Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. RESULTS: We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. DISCUSSION: Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. CONCLUSION: In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.


id: cord-328471-oz99upzz
title: SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp) – A drug repurposing study
author: Ahmad, Jamshaid
date: 2020-07-23
txt: ./txt/cord-328471-oz99upzz.txt
cache: ./cache/cord-328471-oz99upzz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.heliyon.2020.e04502
doi: 10.1016/j.heliyon.2020.e04502
summary:
  In this global health emergency, drug repurposing (or repositioning) is one of the fast track option that involves screening of existing FDA approved drugs for the identification of potential molecules that can disrupt the function of key proteins of the SARS-CoV-2 and can be used for treatment against COVID-19. Whereas, Demoxytocin showed ten H-bonds with both active site Asp760 and Asp761 and other key residues e.g. Trp617, Tyr619, Lys621, Ser682, Glu811, Lys621, Tyr619, Trp617, Ser682 and Glu811 with dock score -9.68kcal/mol and ligand efficiency of -0.142 (Supplementary Figure S3) . Colistin (polymyxin E, polypeptide antibiotics) showed most of the H-bonding with Lys551, Trp617, Tyr619, Asp618, Ser682, Asp684, Asn691, and both catalytic residues i.e. Asp760, Asp761, with a docking score of -9.24kcal/mol and ligand efficiency of -0.113 (Supplementary Figure S5) . Examorelin, Lypressin, Ornipressin, and Colistin are also common drugs in both form of RdRp. Only one H-bond with His810 and other non-covalent interactions were observed for Examorelin showed a docking score of -12.139 kcal/mol and ligand efficiency of -0.187.

abstract:
  The outbreak of SARS-CoV-2 in December 2019 in China subsequently lead to a pandemic. Lack of vaccine and specific anti-viral drugs started a global health disaster. For a sustained control and protection, development of potential anti-viral drugs is one of the targeted approach. Although, designing and developing a panel of new drugs molecules are always encouraged. However, in the current emergency, drug repurposing study is one of the most effective and fast track option. The crystal structure of a SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) RNA Dependent RNA Polymerase (RdRp) has recently been deciphered through X-ray crystallography. The single-chain of core RNA Dependent RNA Polymerase relies on virus-encoded cofactors nsp7 and two units of nsp8 for its optimum function. This study explored the FDA approved database of 7922 molecules and screened against the core polymerase along with cofactors. Here we report a panel of FDA approved drugs that show substantial interactions with key amino acid residues of the active site. Interestingly, some of the identified drugs (Ornipressin, Lypressin, Examorelin, Polymyxin B1) bind strongly within the binding pockets of both forms of RdRp. Besides, we found strong candidates for the complex form as well which include Nacortocin, Cistinexine, Cisatracurium (among others). These drugs have the potential to be considered while contriving therapeutic options.


id: cord-332038-icyut3xa
author: Pillaiyar, Thanigaimalai
date: 2020-04-02
txt: ./txt/cord-332038-icyut3xa.txt
cache: ./cache/cord-332038-icyut3xa.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0223523420302440?v=s5
doi: 10.1016/j.ejmech.2020.112275
summary:
  Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. While numerous studies suggest the potent anticancer activities of drug 20, the overall benefit is limited as it is associated with serious side effects including the gastrointestinal and renal toxicities. The recent phase 3 clinical trial studies using the occurrence of colorectal adenomas as a biomarker for cancer as a primary endpoint at 1 year after intervention revealed that metformin reduced both occurrence and number of adenomas/polyps in the patients at low dosage level. Out of the approved drugs, data for bexarotene have provided proof of concept as potential candidate for the treatment of Alzheimer''s disease as noted above, whereas acitretin (93, Figure 7) , which is known to penetrate tissues including brain may also be a promising candidate for AD [177] .

title:
  A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

abstract:
  Drug repurposing is a strategy consisting of finding new indications for already known marketed drugs used in various clinical settings or highly characterized compounds despite they can be failed drugs. Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. The success rate of drugs repurposing approach accounts for approximately 30% of new FDA approved drugs and vaccines in recent years. This review focuses on the status of drugs repurposing approach for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases. Efforts have been made to provide structural features and mode of actions of drugs.


id: cord-333732-dtfmcqh6
title: Legislating in the Time of a Pandemic: Window of Opportunity or Invitation for Recklessness?
author: Johnson, Walter G
date: 2020-06-15
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url: https://www.ncbi.nlm.nih.gov/pubmed/32959005/
doi: 10.1093/jlb/lsaa042
summary:
  24 However, the early enforcement decisions and lack of early engagement with industry had already discouraged many clinical laboratories from developing or seeking authorization for LDTs, 25 and the delayed availability of testing during the initial weeks of the pandemic significantly exacerbated the spread of the virus in the U.S. The U.S. legislative process for any given issue is characterized by static inertia interrupted by an occasional "policy window" opened by external changes or events that suddenly catapult a specific issue to the forefront of Congressional attention. Using the window of opportunity created by COVID-19, with the demonstrated urgency to reform emergency norms, to enact the comprehensive reform of diagnostics regulation provided by the VALID Act would therefore exemplify the type of crisis-based lawmaking that has been successful in the past to create much of our public health legislation.

abstract:
  The COVID-19 epidemic has been exacerbated by failures in diagnostic testing for the virus in the United States. In response to these problems, two bills have been introduced in Congress to not only reform emergency use of diagnostic tests, but to fundamentally reform diagnostics regulation in non-emergencies. There has been a long-standing recognition that current U.S. regulation of diagnostics is outdated and problematic, and the history of public health legislation is that emergencies and crises have been the primary motivating factor to break Congressional inertia and to implement new legislation. Thus, the COVID-19 may create a useful “window of opportunity” to pass much-needed legislative reform of diagnostic regulation in both emergency and non-emergency contexts. At the same time, rushing radical legislative changes, especially if they have not been subject to careful stakeholder engagement and Congressional deliberation in advance, is precarious and could result in reckless and disruptive changes. We review and apply the historical lessons of legislating in response to a crisis and conclude the one but not both of the pending legislative proposals may satisfy the criteria for an appropriate opportunistic change for diagnostics regulation.


id: cord-334847-lf1grybz
title: Regulatory Flexibility for COVID-19 Research
author: Lynch, Holly Fernandez
date: 2020-07-07
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url: https://doi.org/10.1093/jlb/lsaa057
doi: 10.1093/jlb/lsaa057
summary:
  Clinical research is critical to combatting COVID-19, but regulatory requirements for human subjects protection may sometimes pose a challenge in pandemic circumstances. Although regulators have offered some helpful guidance for research during the pandemic, we identify further compliance challenges regarding IRB review and approval, informed consent, emergency research, and research involving incarcerated people. Strict regulatory compliance may be challenging amidst a public health emergency, but participant protection and high-quality science remain essential.(1) In recognition of these considerations, FDA and the Office for Human Research Protections (OHRP) within the Department of Health and Human Services (HHS) have issued guidance on conducting research during the COVID-19 pandemic.(2) Although this guidance offers a helpful start, gaps remain and additional regulatory flexibility is warranted in some instances. To ensure that this research proceeds efficiently and ethically, we offer suggestions to proactively address regulatory compliance challenges regarding IRB review and approval, informed consent, and inclusion of vulnerable populations.

abstract:
  Clinical research is critical to combatting COVID-19, but regulatory requirements for human subjects protection may sometimes pose a challenge in pandemic circumstances. Although regulators have offered some helpful guidance for research during the pandemic, we identify further compliance challenges regarding IRB review and approval, informed consent, emergency research, and research involving incarcerated people. Our proposals for regulatory flexibility in these areas seek to satisfy the goals of protecting participants and promoting the development of high-quality evidence to improve patient care. These recommendations may have relevance beyond the COVID-19 pandemic to enhance the efficiency of research oversight and participant protection more broadly. Clinical research to understand, treat, and prevent COVID-19 is both crucial and highly regulated. Most intervention studies are subject to Food and Drug Administration (FDA) requirements and federally funded research with human subjects must follow requirements imposed by the Common Rule. Strict regulatory compliance may be challenging amidst a public health emergency, but participant protection and high-quality science remain essential.(1) In recognition of these considerations, FDA and the Office for Human Research Protections (OHRP) within the Department of Health and Human Services (HHS) have issued guidance on conducting research during the COVID-19 pandemic.(2) Although this guidance offers a helpful start, gaps remain and additional regulatory flexibility is warranted in some instances. COVID-19 research has been running at a remarkable pace,(3) challenging the capacity of both investigators and institutional review boards (IRBs). To ensure that this research proceeds efficiently and ethically, we offer suggestions to proactively address regulatory compliance challenges regarding IRB review and approval, informed consent, and inclusion of vulnerable populations.


id: cord-335776-e5wjsk8t
author: Costantino, Ryan C.
date: 2020-08-18
txt: ./txt/cord-335776-e5wjsk8t.txt
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url: https://www.sciencedirect.com/science/article/pii/S1544319120303435
doi: 10.1016/j.japh.2020.07.018
summary:
  Despite years of effort raising concerns about the USPSC, pharmacists and pharmacy technicians continue to spend a substantial amount of time and energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes related to low-quality medications. The U.S. pharmaceutical supply chain is complex, global, and goes beyond FDPs. The 2020 American Pharmacists Association House of Delegates has rightly asserted that "The quality and safety of pharmaceutical and other medical products and the global pharmaceutical and medical product supply chain are essential to the United States national security and public health." Pharmacy professionals on the front line engage with patients, identify medication-related issues, and engage in drug-procurement decisions. 1, 2 Over the past decades, the U.S. pharmaceutical supply chain (USPSC) has increasingly relied on international sources for pharmaceuticals and pharmacists continue to dedicate a sizable amount of energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes of low-quality medications.

title:
  The U.S. medicine chest: Understanding the U.S. pharmaceutical supply chain and the role of the pharmacist

abstract:
  The U.S. capacity to manufacture key essential medications has diminished. The U.S. pharmaceutical supply chain (USPSC) has diversified and now relies on international sources of active pharmaceutical ingredients and finished drug products (FDPs). Despite years of effort raising concerns about the USPSC, pharmacists and pharmacy technicians continue to spend a substantial amount of time and energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes related to low-quality medications. The extent of U.S. reliance on foreign sources of medications is largely unknown. Pharmacists do not have a reliable way to determine the country of origin (i.e., source), capacity, or geographic location of pharmaceutical manufacturers, limiting our ability to anticipate challenges or mitigate risks to our Nation’s drug supply. The U.S. Food and Drug Administration’s task of regulating quality and safety is challenging and will likely require additional safeguards and resources. In addition to pharmacists’ engagement, solutions will likely need to leverage a mix of policy, economic incentives, and expanded objective surveillance testing. The U.S. pharmaceutical supply chain is complex, global, and goes beyond FDPs. The 2020 American Pharmacists Association House of Delegates has rightly asserted that “The quality and safety of pharmaceutical and other medical products and the global pharmaceutical and medical product supply chain are essential to the United States national security and public health.” Pharmacy professionals on the front line engage with patients, identify medication-related issues, and engage in drug-procurement decisions. Pharmacists are essential to our nation’s overall health and must be engaged in the development and implementation of strategies to safeguard the USPSC.


id: cord-339122-7vvqtk84
title: Covid-19, Single-Sourced Diagnostic Tests, and Innovation Policy
author: Deb, Chaarushena
date: 2020-07-07
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url: https://www.ncbi.nlm.nih.gov/pubmed/32908672/
doi: 10.1093/jlb/lsaa053
summary:
  16 An appropriate model for diagnostic testing development, including innovation incentives, should go beyond simply discouraging test monopolies and promoting confirmatory testing, by also allowing for low R&D costs for test development and yielding fast delivery of high quality tests-preventing the errors highlighted in the Covid-19 testing response from occurring in both emergency and non-emergency situations. And thus any sort of incentive model that relies on granting market exclusivity -such as the traditional patent system, FDA approval exclusivity, or trade secret protection -raises the same sorts of issues, if on a smaller scale, as those grimly demonstrated by the failure of U.S. SARS-CoV-2 testing at the onset of the Covid-19 pandemic, which ultimately resulted in the loss of many lives. But for diagnostic tests which rely on confirmatory testing, innovative improvements, and robust access to supply, single-sourcing creates a host of serious problems.

abstract:
  The United States’ disastrous response to the onset of the Covid-19 pandemic has arisen in large part by an utter failure to provide adequate diagnostic tests for the presence of SARS-CoV-2. The Centers for Disease Control were the sole testing source authorized by the Food and Drug Administration, and when the CDC failed to provide reliable tests in sufficient volume, it took weeks for other providers to be approved and to ramp up testing. Revised policies should decrease the likelihood of sole-sourcing tests in pandemic contexts, which results in a fragile system. The pandemic sole-sourcing failure, however, not only accelerated the pandemic, but also provides lessons for innovation policy about diagnostic testing more generally. Sole-sourcing hurts clinical practice by limiting confirmatory testing and systemic robustness, whether in a pandemic or in regular practice. We thus argue against relying too heavily on exclusivity-creating patents as innovation incentive for diagnostic tests—including the proposed Coons-Tillis patent reform bill which would increase patentability for many such tests. Instead, we propose the use of reformed reimbursement to create better incentives for diagnostic test innovation. In both pandemics and elsewhere, single-sourcing creates too great a point of failure, but targeted innovation policy can help


id: cord-352579-ndcbmgfj
title: Pharmacogenomics of COVID-19 therapies
author: Takahashi, Takuto
date: 2020-08-18
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url: https://www.ncbi.nlm.nih.gov/pubmed/32864162/
doi: 10.1038/s41525-020-00143-y
summary:
  In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). Summary of clinical implications of pharmacogenomics for COVID19 We found evidence that several genetic variants may alter the pharmacokinetics of hydroxychloroquine, azithromycin, ribavirin, lopinavir/ritonavir and possibly tocilizumab, which hypothetically may affect clinical response and toxicity in the treatment of COVID-19. As previously described in this review, hydroxychloroquine, chloroquine and azithromycin can individually increase risk for QT prolongation, and those drugs have been used in combination in COVID-19 patients.

abstract:
  A new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB(®)) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β -1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.


id: cord-354445-lnvc7mmf
title: 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment
author: Lichtenstein, David
date: 2019-12-31
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url: https://www.sciencedirect.com/science/article/pii/B9780323415095000049
doi: 10.1016/b978-0-323-41509-5.00004-9
summary:
  Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. Salmonella is a serious primary pathogen, and Pseudomonas is ubiquitous in many water sources, and although both these pathogens have been associated most frequently with endoscopic transmission, they are both sensitive to multiple agents, including glutaraldehyde, and other HLDs. Transmission of bacterial pathogens from flexible endoscopes has been rare since the adoption of the current 2011 multisociety reprocessing guideline, 45, 160 with the exception of duodenoscope-related infections (discussed later). Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes

abstract:
  Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. This chapter presents the principles of flexible endoscope reprocessing along with a pragmatic approach to the judicious selection and proper reprocessing of endoscopic equipment, as well as guidance for prevention and management of infection transmission inclusive of newer sterilization (e.g., hydrogen peroxide vapor) and disinfection (e.g., improved hydrogen peroxide) technologies. It also provides an outline of the Quality Systems approach that is applicable to flexible endoscope reprocessing and the need for ongoing staff competency and audits of endoscope cleaning, disinfection, and storage practices. Furthermore, the most current regulatory, expert organization, and manufacturer's recommendations are reviewed.


