Modeling supply chain network traffic

What’s the Latest on Acrylamide?

FDA's role in anesthetic drug development.

The use of histone deacetylase (HDAC) inhibitors to sensitize patients to cancer therapies, particularly patients with hormonally positive breast cancer with resistance to drugs like tamoxifen, were among the advances discussed in November at the Molecular Targets and Cancer Therapeutics Conference, sponsored by the American Association for Cancer Research (AACR). In a randomized controlled phase 2 study of metastatic breast cancer patients, for instance, postmenopausal women with positive disease achieved double the progression-free survival with use of entinostat combined with exemestane versus exemestane alone, Researchers examined blood samples in a subset analysis of 49 patients to evaluate whether changes in circulating blood cells reflected the activity of the HDAC inhibitor and found that biological activity of the drug, which could be associated with clinical benefit, was apparent as soon as 8 days after administration. Entinostat is the first drug for metastatic breast cancer to show that clinical outcome can be predicted shortly after administration.1 More than 750 abstracts in oral and poster sessions were presented at the AACR Molecular Targets meeting. Abstracts delved into subjects such as the molecular drivers of metastasis, immunotherapy, cancer stem cells, tumor metabolism and epigenetics, and drug development for targeted therapies. In one of the most highlighted studies of the meeting, researchers reported that amplification of anaplastic lymphoma kinase (ALK), which has been reported in other cancers such as non-small cell lung cancers, may be a primary driver of the rapid metastasis experienced by patients with inflammatory breast cancer. If validated, the use of anaplastic lymphoma kinase (ALK) inhibitors may be a new treatment approach for patients with this lethal form of breast cancer, says Kenneth Anderson, MD, co-chair of the meeting and editor-in-chief of Clinical Cancer Research.2 Other studies explored the subject of antifolate resistance in non-small cell lung cancer and how best to predict such resistance. In one study, researchers treated human NSCLC cell lines (KRAS wild type, KRAS mutant nonamplified, and KRAS mutant amplified) with the antifolates methotrexate or pemetrexed. Results showed that KRAS wild-type and KRAS mutant amplified cells were relatively resistant to antifolate treatment. In contrast, antifolates inhibited growth in KRAS mutant nonamplified cell lines. The researchers also reported dramatic and prolonged responses to pemetrexed therapy in patients with KRAS mutant NSCLC. Thus, it's important for oncologists to test for KRAS mutation as well as KRAS amplification in order to assess the potential efficacy of antifolates, the researchers concluded.3 “Many of the studies presented here show the power of mechanistic-based science to elucidate new diagnostic biomarkers or targeted treatment options with either a single agent or combined therapy,” says Dr. Anderson. The U.S. Food and Drug Administration (FDA) is funding centers at the University of Maryland and Georgetown University aimed at improved review of the safety and efficacy of drugs and medical products. The Centers of Excellence in Regulatory Science and Innovation (CERSI) were each funded with a $1 million grant and may receive more funds over the next 3 years. It currently costs $1 billion and takes about 10 years to develop a new drug, according to James Polli, PhD, the Shangraw/Noxell Endowed Chair in pharmaceutical sciences at the University of Maryland and co-principal investigator for the University of Maryland CERSI. “We plan to sponsor educational lectures and daylong events that will feature the best academic scientists and provide FDA reviewers with a broad exposure to current research,” he says. According to Dr. Polli, FDA reviewers need improved training in preclinical science. “When regulators can ensure that the science is better for products such as predictive tests, there will be less need for oversight and more opportunities for accurate risk evaluation,” he says. Instructors at the University of Maryland will train FDA reviewers in how to use clinical data to assess the possible side effects of new drugs and drug-drug interactions. “The problem the FDA faces is that it's often hard for reviewers to get additional training in new research since their time is limited and so are the resources of the FDA,” Dr. Pollli says. The Georgetown CERSI will be working on one project to assess ways to use bioinformatics to enhance medical product development and another to examine data sharing. “The FDA has access to vast amounts of data that can be mined to answer important biomedical and public health questions but it's important to determine how data can best be utilized while protecting the intellectual property rights of pharmaceutical companies and stakeholders such as researchers, universities, and the public,” says Ira Shoulson, MD, professor of neurology, pharmacology, and human science at Georgetown and the university's CERSI principal investigator and director. The U.S. Department of Defense has awarded Boston University Medical School a $13.6 million grant to lead 2 multi-site studies aimed at finding ways to detect lung cancer noninvasively and to distinguish those smokers at highest risk for developing lung tumors. Although the National Lung Screening Trial showed that there were fewer fatalities among smokers and former smokers screened with low dose helical CT, using such screening for all smokers is cost-prohibitive, says Avrum Spira, MD, a pulmonary and critical care physician at Boston University Medical Center, who is leading the Department of Defense lung cancer research effort. Only 10 to 20% of smokers and former smokers actually develop lung cancer, leading researchers to ask which smokers and former smokers should receive imaging tests, particularly expensive ones, such as CT scans. To help answer this question, Boston University researchers will collaborate with military hospitals and Veteran's Affairs medical centers to investigate lung cancer risk among a large number of patients. The consortium for the lung cancer studies, called the Detecting Early Lung Cancer Among Military Personnel (DECAMP) Consortium, is the largest consortium of researchers in the U.S. dedicated to identifying noninvasive ways to detect early-stage lung cancer. Lung cancer is of special concern to the Department of Defense because military and military veterans have higher rates of smoking than the national average. They're also exposed to toxins during military action that can put them at elevated risk for lung cancer, Dr. Spira says. Researchers will investigate ways that molecular biomarkers, both genomic and proteomic, could be used to predict risk of lung cancer and to distinguish between smokers and former smokers with benign nodules in the lung versus patients with cancerous ones. In the first study, 500 military personnel with suspect lung nodules will undergo blood tests and bronchoscopy for samples that might yield molecular clues to the presence of cancer in the lungs versus those that might indicate benign nodules, and then will be followed until biopsy is completed. “One of the exciting aspects of this research is that although the cells we'll be collecting are far away from the lung, they are all bathed in the toxins in cigarette smoke that eventually cause genetic and genomic alterations as well as lung cancer,” Dr. Spira says. “Epithelial cells derived from bronchoscopy might act like a canary in a cold mine, telling you about the presence of lung cancer,” Dr. Spira said. In a second study, researchers will follow 1,000 smokers and former smokers at high risk for development of lung cancer because of the amount of cigarettes they smoked or the duration of their smoking habit. Presence of lung nodules or lung cancer will be assessed over a 5-year period. “If we can find molecular markers that cause smokers to be at elevated risk for lung cancer, then we can follow them more closely with imaging studies, and find cancer at an earlier stage. And we could potentially offer them treatment that might prevent lung cancer,” Dr. Spira said. A number of compounds to prevent lung cancer are now being tested in early clinical trials, including the prostacyclin, iloprost. Research advances in sequencing technologies that make it possible to scan entire human genomes more cost-effectively are fueling a research initiative by the National Institute of Neurological Disorders and Stroke (NINDS). Duke's Center for Human Genome Variation won the first grant in the NINDS initiative, called the Center Without Walls on Human Genetics. The Center will be using the $25 million grant, awarded over the course of 5 years, to sequence and analyze the entire genomes of 4,000 epilepsy patients. “Improved understanding of the genetic basis of epilepsy will shed light on the underlying pathophysiology that leads to epilepsy disorders,” says Erin Heinzen, PhD, co-principal investigator and assistant professor in Duke's Center for Human Genome Variation. “This knowledge will likely lead to the development of medications or treatments that can specifically treat the cause of seizures in patients,” Dr. Heinzen says. Although Duke will be leading the effort, investigators from other universities in the United States, Canada, and Australia will be contributing genomic and detailed clinical information on patients with epilepsy. Genetic studies of epilepsy indicate that many different genes are disrupted in order to cause the condition. “This high level of heterogeneity means that we will likely need very large sample sizes to identify epilepsy susceptibility genes, which can only be obtained by collaborating with other institutions studying epilepsy,” Dr. Heinzen says. When exactly might this research work affect treatment?“The timing of how long it may take for gene discoveries to be translated into clinically useful information or drug therapies is uncertain,” Dr. Heinzen says. “But it's clear that gene discovery will improve our understanding of epilepsy and over time this will improve patient care.” CTS

Patient-individual 3D-printing of drugs within a machine-learning-assisted closed-loop medication management – Design and first results of a feasibility study

Electronic resource planning (ERP) software is a valuable tool for optimizing business processes. The primary purpose of these packages is to improve information exchanges throughout organizations. The modular design of Electronic Resource Planning software allows companies to tailor it to their particular business practices.Many factors must be considered when choosing an Electronic Resource Planning package such as return on investment calculations, training, management support, and the current IT infrastructure. Omitting any of these considerations can increase costs and waste valuable company time.Electronic Resource Planning packages may be purchased outright or one module at a time. Leasing options are also available which offer Internet-based ERP. This represents the latest trend in Electronic Resource Planning computing; however, security issues may outweigh the benefits associated with this method.An ERP package must be properly implemented and maintained. The preferred method of implementation is a step-by-step approach as opposed to an immediate approach. Some factors to consider when implementing an Electronic Resource Planning package include project planning, “feature creep,” business process mapping, customization, training, time, and rapid implementation packages.Electronic Resource Planning buyers can help to ensure that they are obtaining the optimal solution for their companies by arming themselves with adequate information. A properly chosen and implemented Electronic Resource Planning solution will likely improve business processes, increase efficiency, and accurately measure results.

Since the Internet of Things (IoT) will be entwined with everything we use in our daily life, the consequence of security flaws escalates. Smart objects will govern most of the home appliances and car engines yielding potential disaster scenarios. In this context, successful attacks could lead to chaos and scary scenarios (www.darkreading.com). Unprotected personal information may expose sensitive and embarrassing data to the public and attacks may threaten not only our computers and smart devices, but our intimacy and perhaps our lives too. Because persons and objects will be bonded with each other, user consent becomes critical. Therefore, thing, object, and user Identity will be the focus of future IoT security solutions, yielding a Trust, Security, and Privacy (TSP) paradigm, which may constitute the Achilles' heel of IoT. While security issues are quite straightforward, mainly from background knowledge, privacy issues are far more complex. Privacy constitutes a rather challenging task, even for the m...

Clinical Prioritization of Antispike Monoclonal Antibody Treatment of Mild to Moderate COVID-19

*These authors contributed to the devlopment and review of this manuscript but are unable to endorse the request for NIH funding. On Sept. 20, 2011, the American Association for Cancer Research (AACR) released its inaugural AACR Cancer Progress Report to commemorate the

Effective immunization programs have markedly diminished the incidence of vaccine-preventable diseases. As a result, there now exists in society a lower awareness of the actual risks associated with the diseases themselves and a greater prominence of the potential risks of adverse effects associated with vaccines.Concern regarding public reactions to new vaccine safety issues may place pressure on policymakers and/or health care providers to act quickly in response to new information. However, this concern must be tempered by the necessary caution required to assess the intended and unintended risks and benefits of any action undertaken. The interplay of these potentially competing demands is well illustrated by the recent safety concern involving the use of thimerosal in vaccines.Thimerosal is a mercury-containing compound that has been widely used as an antimicrobial agent in vaccines for over 60 years. Human exposure to mercury may have potentially significant health consequences. By mid-1999, the Food and Drug Administration (FDA) had discovered that children could be exposed to an amount of mercury from vaccines that exceeded 1 of 3 existing federal safety thresholds. After this realization, the organized medical and public health communities in the United States became involved in a series of urgent and intense discussions to determine an appropriate response to the issue. This manuscript describes and analyzes the process that led to the July 7, 1999, joint American Academy of Pediatrics (AAP)/US Public Health Service (PHS) statement on thimerosal,1 with the goal of suggesting improvements for managing similar vaccine safety concerns in the future.We conducted structured interviews with over 15 individuals involved in the discussions and negotiations leading to the joint AAP/PHS statement on thimerosal. The individuals represented both the governmental agencies and nongovernmental organizations involved, including the FDA, the Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention (CDC), the National Vaccine Program Office (NVPO), the AAP, and the American Academy of Family Physicians (AAFP). Interviews were conducted through face-to-face meetings or by telephone between January and April 2001. Table 1 lists the individuals interviewed who allowed their identities to be published.The development and implementation of immunization policy in the United States is a cooperative effort among many entities in the public and private sectors (Table 2).The concern over thimerosal in vaccines originated from a confluence of independent events, 1 informal and 1 formal, within the FDA. In the spring of 1998, some individuals within the FDA's Center for Biologics Evaluation and Research (CBER) began to informally consider the increased number of recommended vaccines and the amount of substances, such as mercury, contained in them to which vaccine recipients were exposed. Available literature to help quantify their concern was limited.The formal identification of thimerosal as a concern arose through the FDA's efforts to comply with the Food and Drug Administration 2Modernization Act.2 As mandated by Congress, Section 413(a) of the Act required the FDA to compile a list of drugs and foods that contain "intentionally introduced" mercury compounds and to provide a quantitative and qualitative analysis of these compounds within 2 years of the Act's enactment.The FDA's previous formal review of thimerosal in biological products had occurred in 1976. The convergence of concerns over mercury in vaccines that occurred within the CBER beginning in April 1998 prompted the agency to reassess the risks of thimerosal.3One of the steps of this risk assessment was to investigate the potential exposure of humans to thimerosal in vaccines. Based on the information submitted by industry and FDA internal data, the CBER determined that thimerosal was present in over 30 licensed vaccines in the United States.4,5 The amount of mercury by weight present in each of these vaccines was calculated. The CBER then referred to the recommended childhood immunization schedule to determine the amount of mercury to which young children may be exposed. Of the vaccines that a child could receive in the first 2 years of life, those that contained thimerosal were the 2 available formulations of the hepatitis B vaccine and some formulations of the diphtheria-tetanus-acellular pertussis and Haemophilus influenzae type b vaccines. Looking at cumulative exposure over the first 6 months of life, an infant 6 months old who received all recommended vaccine doses on schedule could be exposed to up to 187.5 μg of mercury.Another step in the risk assessment process was to determine whether thimerosal actually constituted a true health risk; that is, whether there were data demonstrating that this amount of mercury could be potentially harmful to children. To identify whether there were any known health risks from exposure to thimerosal, the CBER conducted a literature review and queried the Vaccine Adverse Event Reporting System, a national surveillance system for voluntarily reported adverse events associated with vaccines. The CBER found that at low doses, thimerosal has been associated with rare hypersensitivity reactions, such as persistent skin sensitization at the site of vaccination. At very high doses (ie, 1000 times higher than levels found in vaccines), thimerosal has been reported to cause neurologic and renal toxicity.An early assessment of the health risks of all forms of mercury by the World Health Organization (WHO) found that insufficient information was available to perform risk calculations for human exposure to ethyl mercury compounds, the type of mercury contained in thimerosal.6 However, the WHO did note that the limited data available suggested that ethyl mercury was probably less hazardous than methyl mercury, because it is metabolized faster in the body.The WHO and 3 US governmental agencies—the FDA, the EPA, and the Agency for Toxic Substances and Disease Registry (ATSDR)—had developed independent guidelines for safe exposure to methyl mercury (Table 3).7–10 Because no guidelines exist for ethyl mercury exposure, the FDA used the guidelines for safe exposure to methyl mercury as a guide for determining whether the mercury (ethyl) dose from thimerosal in vaccines approached a level of concern or health risk.The existence of 3 differing US federal guidelines for methyl mercury was a source of confusion and contention in determining the appropriate response to concern regarding thimerosal in vaccines. Each agency developed their guidelines for different purposes. The most conservative of these guidelines was the level established by the EPA to serve as a warning of mercury in the environment to trigger additional investigation. The ATSDR guideline is set below levels that might cause an adverse health impact in those most sensitive to a particular substance. The FDA guidelines were developed as safe limits for long-term consumption of food contaminated with mercury, particularly fish, which is the main exposure route of humans to methyl mercury. No guidelines were available to assess the risk of exposure in bolus doses by intramuscular injection.Nevertheless, the existing methyl mercury guidelines were the best information available at the time for assessing risk from ethyl mercury exposure. The CBER calculated exposure limits for each of these guidelines based on the average weight at various percentiles in female infants between birth and 26 weeks of age (Table 4). Based on these calculations, the CBER determined that potential exposure to mercury from the recommended childhood vaccines in the first 6 months of life could exceed the EPA methyl mercury guideline, but not the ATSDR, FDA, or WHO guidelines. However, the CBER was unable to determine with certainty whether exposure to thimerosal in vaccines was harmful.In April 1999, results from the preliminary risk assessment were discussed at an internal FDA meeting, and participants realized that there was a clear need for additional data. The CBER began to consult with toxicologists both within the FDA and at the National Center for Environmental Health, and several vaccine researchers, including Neal Halsey, MD, Director of the Institute for Vaccine Safety at Johns Hopkins University. The FDA also initiated discussions with vaccine manufacturers regarding the need to develop thimerosal-free vaccines.3Dr Halsey was invited by the FDA to an internal meeting in mid-June 1999 where he was asked to provide feedback on the results of their preliminary risk assessment regarding thimerosal. On learning of the FDA data, and personally verifying the calculations of the levels of mercury to which children could be exposed, he believed that the issue warranted serious concern and urgent action. At the time, Dr Halsey was soon to complete his term as Chair of the AAP Committee on Infectious Diseases (COID). Dr Halsey previously worked within the CDC's immunization program and had been a member of the Advisory Committee on Immunization Practices (ACIP). As such, he had extensive experience and professional relationships within the US immunization policymaking arena. Beginning around June 24, 1999, Dr Halsey informed many of these contacts of his concern regarding the potential health effects of thimerosal and the results of the FDA's preliminary risk assessment. After notifying the Director of the CDC's National Immunization Program, Dr Halsey met with CDC personnel at the National Immunization Conference on June 25. He also informed several other individuals, including the incoming Chair of the COID, the Chair of the ACIP, and a member of the AAP Board of Directors. In addition to his concern regarding the potential health effects of mercury exposure in infants, Dr Halsey expressed the need for urgent action on the issue because the FDA was planning to send a letter to vaccine manufacturers in the beginning of July 1999 regarding the need to remove thimerosal from vaccines, at which point the information about thimerosal would become public. He believed that publicity surrounding this issue, without action on the part of the PHS and/or the AAP, could result in long-term damage to public confidence in the national immunization system.After Dr Halsey informed these initial contacts of his concerns regarding thimerosal, conversations began to occur among the parties. The Interagency Vaccine Group (IAG) held a conference call on June 28 and reviewed the information from the FDA's preliminary risk assessment. After this call, the IAG formed a special workgroup to address the thimerosal issue. CDC immunization officials also conferred with the AAP, vaccine companies, and internal CDC toxicologists.Significant differences of opinion surfaced regarding the accuracy of the exposure and risk-assessment information concerning thimerosal, its importance, and the need for any immediate discussion or action.To quickly bring representatives of several organizations involved in immunization policymaking together to discuss the issue, a meeting was organized by Dr Halsey and Dr Cooper for June 30, 1999, at the AAP offices in Washington, DC. The selection of the venue for this meeting was deliberate. The initial course of action for the government normally would have been for the ACIP and the National Vaccine Advisory Committee (NVAC) to meet to discuss the issue. However, governmental advisory boards are required by the Federal Advisory Committee Act to provide adequate public notice of meetings and publish meeting agendas in the Federal Register. Given how quickly some individuals believed a meeting should occur, it was not possible to officially convene these advisory bodies in such a short time frame. By having an informal meeting at the offices of the AAP, a frank discussion of the scientific and biological veracity of all available information could take place without delay. As a result, however, this meeting precluded the formal involvement of the ACIP and the NVAC.Drs Cooper and Halsey developed a list of invitees, which included representatives of the CDC, FDA, EPA, AAP, vaccine manufacturers, and toxicologic consultants. An initial goal of the meeting was to achieve consensus on a course of action, as many believed that public presentation of differing views would likely confuse practitioners and parents, and potentially undermine confidence in the national immunization system.At the meeting, FDA representatives shared the results of their preliminary risk assessment, outlining what was known and unknown about the issue and describing the difficulties in determining whether the level of mercury in vaccines should be of concern. Because of the complexities in interpreting the data regarding the potential risk of harm from thimerosal, there was disagreement among the parties present as to its significance. Disagreements existed between organizations, within organizations, and among the toxicologists present at the meeting. Some participants believed strongly that the potential threat to health from thimerosal was significant; others believed that there was no clear evidence that thimerosal was harmful, particularly when compared with the clear health risks of delaying childhood vaccines. The 2 AAP committees represented at the meeting, the COID and the Committee on Environmental Health, were in sharp disagreement on this point. There was also a varied sense of exigency, with some participants believing that urgent action was required, whereas others thought the process should slow down to include other parties in the discussion and address perceived significant gaps in the scientific data. Actions proposed by participants at the meeting ranged from immediately stopping administration of all vaccines containing thimerosal to children under 6 months of age to encouraging vaccine manufacturers to expedite the elimination of thimerosal from vaccines.An overriding concern expressed by all parties at the meeting was the need to maintain the public's trust in the US immunization system by striking the appropriate balance between acknowledgment of the potential risk of harm from thimerosal and the actual risk of harm from not immunizing against vaccine-preventable diseases.It became clear during the June 30, 1999 meeting that no consensus would be reached that day regarding an appropriate course of action. Sharp disagreements regarding the clinical significance of thimerosal exposure were not resolved. Specific individuals who felt most strongly regarding the potential health risk of thimerosal exposure stated that they would independently make public statements if their respective organizations did not support their contentions. The meeting concluded with all participants agreeing that no statement would be released by any individual or organization until after the July 4th weekend, and that discussions between the PHS and the AAP would continue in an attempt to achieve a unified public statement. Leadership in both the AAP and the PHS believed that releasing a joint public statement was crucial for preserving the public's trust in the immunization system.PHS officials in the CDC and elsewhere believed that vaccine manufacturers should be encouraged to expedite the elimination of thimerosal from vaccines, but did not want to make any changes to the childhood immunization schedule. However, CDC officials also felt strongly that it would be in the best interests of the national immunization system and the public's trust for a statement to be developed jointly with the AAP. This prompted David Satcher, MD, PhD, the US Surgeon General and Assistant Secretary for Health, to be involved in the negotiations.After the June 30 meeting, there was significant debate within the AAP as to the appropriate course of action to be taken. Over the next several days, there was constant reconsideration and revision of positions taken among both individuals and committees.On review of available information and opinions, the AAP Board of Directors decided to put forth the position in their negotiations with the PHS that the birth dose of the hepatitis B vaccine be temporarily delayed. They considered the risk of disease to be low except for infants of HBsAg-positive mothers. The Board of Directors believed that hospitals should already have procedures in place to determine the hepatitis B status of mothers and treat the infants of HBsAg-positive status mothers appropriately.Other parties were informally involved in the discussions leading to the joint statement. The AAFP did not think the issue warranted such urgency and believed that the health effects data for methyl mercury on which the EPA guidelines were based were questionable.Many conference calls, meetings, and sharing of draft statements occurred within and between the AAP and the PHS over the course of the July 4, 1999 holiday weekend. The Surgeon General held several discussions with the AAP president to negotiate a compromise position. Although they were extremely concerned about both the short- and long-term consequences of delaying administration of the hepatitis B vaccine, PHS officials agreed to the recommendation to present a unified position to the public.The joint statement was officially released in the late afternoon of July 7, 1999,11 and was published in the MMWR Morbidity and Mortality Weekly Report on July 9, 1999.1First and foremost, it is clear that all parties involved in this process acted in the manner they believed was in the best interest of children in the United States. Even parties that differed most strongly never doubted the intent or purpose of those with whom they disagreed.Only 2 weeks transpired between the time that leaders of the major national organizations involved in US immunization policy learned about the issue of thimerosal in vaccines and the release of the joint AAP/PHS statement. During that time, these individuals and their organizations worked diligently to develop a response that they believed balanced the potential risk from exposure to thimerosal with the actual risk of vaccine-preventable disease and would ensure continued public confidence in the nations' immunization system. Considering the complexity of the information available and the gaps in information relevant to specific concerns, it is not surprising there was significant disagreement regarding the potential risk associated with thimerosal. To some, the process could be considered a success, in that compromise was reached and the "crisis" was addressed. However, others have publicly the that the recommendation to the birth dose of hepatitis B vaccine practitioners and put infants at risk for hepatitis B vaccine as to that the process was a of how not to public health of the IAG would have first learned of the thimerosal issue from FDA who would have informed the of its review of the thimerosal in vaccines. In this however, an individual of the government was the first to many of these soon the FDA should have is a of as is how information should have been other parties. The FDA was to an issue with the IAG when there were many surrounding the potential health risks In the FDA must be sensitive to issues to any under its IAG is to among federal agencies with vaccine issues through meetings and other To the IAG must achieve a balance between that are informed of and agencies to data to other parties the information is released to the public. such to be there must be confidence among the parties that their all from and shared efforts with each the must be as independent and to its of this issue is to ensure that the and of the are not under the or perceived or of any the through the that serious be by the Office of the Secretary for Health and Human to the of the of the including the of and the of meeting that occurred at the AAP offices in Washington, on June 30, 1999, was a in the discussions leading to the joint statement. the of this type of meeting and the in which it was organized was for the AAP, the of action was of the of the Board of are as to the of who or was concern expressed from many was the of vaccine industry representatives at the meeting. The meeting occurred the time of the vaccine safety in Congress, and in a environment in which of between industry and immunization policymakers had been Some participants at the meeting believed that having industry representatives at a meeting could have this may also have the of some meeting the of the vaccine industry to a immunization system be Vaccine manufacturers a of vaccine development and and their in different of immunization policy is concern is that some parties did not in this meeting such as the AAFP or representatives of hospitals that would be by the in the hepatitis B the of the 2 federal immunization advisory the ACIP and the did not in the initial thimerosal because of the perceived of the Federal Advisory Committee Act on meetings on very short The CDC and the have reviewed the and have found that exist for meetings on an to the birth dose of hepatitis B vaccine was not taken by any to the the risk of thimerosal exposure with the known risk of of hepatitis B disease was for However, in some leading to the joint AAP/PHS of the potential impact of delaying the birth dose of the hepatitis B vaccine did not receive some in of stopping the birth dose of hepatitis B vaccine, there was acknowledgment of the potentially significant of the of hospitals the the for this policy to these or the of procedures for determining the hepatitis B status of mothers. There to be effort to the existing literature on the impact of changes in immunization and the times for the of there was an confidence by some in the of hospitals to all mothers for hepatitis B status previous had of such of the impact of the joint statement on infant hepatitis B are now beginning to be have that some hospitals all with hepatitis B vaccine, including those to HBsAg-positive possible is the of information or of the recommendation by hospitals and Because of the of appropriate for and the hepatitis B status of this in policy has led to the of at 1 infant from hepatitis have also that many hospitals have not to doses of the hepatitis B vaccine the of thimerosal-free The of the first dose of hepatitis B vaccine at birth is illustrated by a recent that that children who received the first dose at birth were likely to complete the hepatitis B times of regarding immunization that all parties involved to the short- and long-term intended and unintended consequences of their proposed This type of analysis could take the of the and structured risk assessment process used by other government such as the of the major issues concern and urgency among all parties was the manner in which the would the issue. over the accuracy of in and for vaccine issues in is well However, an overriding issue is the of how should concern over the time of for public or individual health with policymaking must balance concern over the risk of public regarding safety issues with concern over the to ensure that information be to the public.The FDA the safety and of products they are for use and the process of a constant of products available to However, the of thimerosal an to FDA In the when thimerosal was for use in this there were limited available to assess for the of there is no for the FDA to vaccine with is in to some other federal such as the In was that be by the EPA years. Because no such process has been for the FDA, thimerosal not In for a containing mercury, the of most concern is on system At this time, the FDA has no for of the products it the FDA not have a to identify the cumulative amount of thimerosal, which children would receive over the course of the recommended immunization schedule. Each vaccine was for use as an independent agent and the amount of thimerosal contained in each individual vaccine no concern. was when the cumulative amount from all the vaccines contained in the recommended immunization schedule was calculated that concern that should consider to the FDA the to perform of vaccine In that the FDA its and the FDA develop a for of the cumulative amount of to which individuals may be exposed as a result of specific federal of the issues to all parties involved was the existence of differing federal for exposure to mercury from the EPA, the FDA, and the Although each agency had a different purpose in a specific safety the that there was no clear federal consensus on this issue was This allowed different parties to the discussion to over to support their federal agencies that have differing safety for exposure to specific to develop a federal consensus on safe exposure levels determine under which the different guidelines are to be than 1 federal is each agency should be with the for determining a different safety AAP is an organization for its to the of the health and of children. the internal debate that place within the AAP on this issue involved disagreement on the course of action that would be of to the children of the United AAP Board of Directors to its committees for and information regarding specific issues on which it must set However, the exists that the course of within the was in some than the Board of Directors on this issue from specific individuals were to the they may have represented the of the AAP is very that all be to maintain use of this in times of This help ensure that the consensus of than specific individuals, are to help guide the AAP Board of Directors regarding policy have on a of immunization The of these has been and At point efforts have been to information of those involved in immunization policy and in the or review of from the Institute of are now to in such committees for of and having their publicly and public if have the potential to cause significant and professional involvement of leading in the on childhood vaccines were to soon after the June 30, 1999, meeting at the AAP As such, concern over the manner in which any action or might be perceived in this type of environment a of concern and over many this was perceived as a course of action under by a process not in the best interests of the immunization system or children. This also to the development of a and the to act in interviewed but not of the parties involved in this As such, have an and assessment of the events that place in late June and early July However, there exists the that some information may not have been In these interviews were conducted 2 years after this process there may be some of the information process that in the in immunization as a result of concern to thimerosal was and Although there are significant differences of opinion regarding the of the the immunization system in the United States and was by the Program for and Health,

The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy.

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Putting pharmacogenomics into practice

High Prescription Drug Prices and the Influence of the Food and Drug Administration

The Filovirus Animal Non-Clinical Group (FANG) is a US interdepartmental and interagency group established to support and facilitate the advanced development of filovirus Medical Countermeasures (MCM), both vaccines and therapeutics. It is co-led by one representative from the Department of Defense (DoD), the first author, and one from the Department of Health and Human Services (HHS), the second author. The FANG membership includes operational level program staff and Subject Matter Experts (SME) from performing organizations as well as scientific staff and program managers from DoD and HHS funding and regulatory agencies. Focus areas include animal models, assays, reagents, product manufacture and characterization, and other interagency product development issues that will support Food and Drug Administration (FDA) licensure of safe and effective filovirus MCMs. The FANG continues to develop strategies to address broadly applicable and interagency product development challenges relevant to filovirus MCM development. This paper summarizes FANG structure and accomplishments and is meant to heighten community awareness of this government-led collaborative effort.

The Covid-19 pandemic accelerated digital transformation and usage of the fourth industrial revolution tools in most developing countries where teaching and learning most occurred through face-to-face interaction. To reap successes in the digitally transforming teaching and learning in universities, it is crucial to reconcile the key essential (factors) that need consideration for digital transformation and the challenges hindering the phenomenon. This study explored the fundamental factors for harnessing technologies for teaching and learning in State universities in Zimbabwe. The study employed a desk research approach. The study revealed that tertiary institutions were struggling to effectively implement online learning due to factors such as lack of strategy and vision on the implementation process, lack of financial resources, poor technological infrastructure, poor digital competences among lecturers and students as well as lack of adequate technical support. Instructors in these institutions mostly resorted to asynchronous online learning approaches because they lacked up to date gadgets for synchronous teaching and learning. Similarly, students preferred asynchronous learning due to data challenges as it offered self-pacing and flexibility. In limited cases lecturers make use of WhatsApp, Google Classroom, Google Meet and Zoom. The findings were that in order to institutionalise online learning as key component of digital transformation in state universities the fundamentals to be addressed include of procurement current and compatible IT infrastructure, comprehensive training and education to improve digital competences, incorporate digital transformation and the fourth industrial revolution into university curriculum to equip students, provision of internet data and improved internet connectivity.