Regulatory Agency (regulatory + agency)

Distribution by Scientific Domains

Selected Abstracts

Early communication of drug safety concerns: a feasibility study on enhancing interaction between the pharmaceutical industry and regulators

Elizabeth Swain BPharm, MRPharmS
Abstract Purpose The responsibility for monitoring the safety of marketed medicines is shared between regulatory authorities and the pharmaceutical industry and is underpinned by legal obligations on both sides. Both marketing authorisation holders (MAHs) and regulators initially evaluate and investigate potential safety concerns, and then work together on further review as appropriate. We wanted to test the feasibility of enhanced interaction between MAH and regulator via a regular monthly, two-way communication of potential safety concerns between the MAHs and the Medicines and Healthcare Products Regulatory Agency (MHRA). It was envisaged that such a process would aid prioritisation and planning by both parties, avoid duplication of effort and support a collaborative approach for decision making. Methods Four MAHs took part in the pilot, which was conducted between July 2007 and June 2008. Potential safety concerns were exchanged on a monthly basis. The MAH/MHRA proposed a timeline for evaluation of each potential safety concern. The pilot did not include serious public health issues which are immediately reported to regulatory authorities. Results During the pilot, 136 potential safety concerns were exchanged. Thirteen per cent of these resulted in a change to product information for health professionals and patients. There was concurrence between the MAHs and MHRA on timelines proposed for evaluation. Conclusions The pilot proved feasible for the companies involved and indicated potential benefits of a system for avoiding duplication of effort and supporting a collaborative approach to planning and prioritisation of investigation of potential safety concerns between pharmaceutical industry and regulatory authorities. Copyright 2009 John Wiley & Sons, Ltd. This article was published online on December 27, 2009. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected (08/01/10). [source]

Latest news and product developments

PRESCRIBER, Issue 22 2007
Article first published online: 28 DEC 200
Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre ( show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost 83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients 39.50, and GPs will be entitled to charge patients 10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is 9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs 3777 for a loading dose, then 7553-8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were 30 200 for adalimumab, 24 600 for etanercept and 39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source]

Latest news and product developments

PRESCRIBER, Issue 8 2007
Article first published online: 23 JUL 200
Lamotrigine for partial, valproate for generalised A large UK trial has shown that lamotrigine is the most effective choice in the treatment of partial epilepsy (Lancet 2007;369: 1000-15). The SANAD trial, commissioned by the National Institute for Health Research's Health Technology Assessment programme, randomised 1721 patients (for whom carbamazepine monotherapy would have been the treatment of choice) to treatment with carbamazepine, gabapentin, lamotrigine, oxcarbazepine (Trileptal) or topiramate (Topamax). Lamotrigine was associated with a longer time to treatment failure, though time to 12-month remission favoured carbamazepine. Over four years' follow-up, lamotrigine was numerically but not significantly superior. The authors concluded lamotrigine is clinically superior to carbamazepine for partial epilepsy A second arm of the trial, yet to be published, evaluated the treatment of generalised epilepsy and found valproate to be clinically most effective, though topiramate was cost effective for some patients. Chronic pain common in nursing homes Most residents in nursing homes say they have long- term pain but only one in seven say a health professional has ever discussed its treatment with them, according to a report by the Patients' Association ( Pain in Older People ,A Hidden Problem was a qualitative study of 77 older residents in care homes in England. Most were frail and suffered long-term illness. The study found that 85 per cent of residents said they were often troubled by aches or pains and these lasted over a year in 74 per cent. Most described their pain as moderate (33 per cent) or severe (38 per cent) but 8 per cent said it was excruciating. Many reported limitations on mobility and social activities despite a high level of stoicism. All but one were taking medication to relive pain; one-third experienced adverse effects but 78 per cent believed drugs offered the most effective treatment. One-quarter said a doctor or nurse had discussed how to stop their pain worsening, and 15 per cent said they had discussed how to treat their pain. Visits from GPs appeared to be uncommon. Atherothrombotic events despite treatment Between one in five and one in seven of high-risk patients experience atherothrombotic events despite evidence-based treatment, the REACH study has shown (J Am Med Assoc 2007;297:1197-1206). REACH (REduction of Atherothrombosis for Continued Health) is an international observational study involving 68 236 patients with atherothrombotic disease or at least three risk factors. Most were taking conventional evidence-based medication. After one year, the incidence of the combined endpoint of cardiovascular death, myocardial infarction, stroke or hospitalisation for atherothrombotic events was approximately 15 per cent for patients with coronary artery disease or cardiovascular disease, and 21 per cent in patients with peripheral artery disease and established coronary disease. Event rates increased with the number of vascular beds affected, rising to 26 per cent in patients with three symptomatic arterial disease locations. Extended CD prescribing by nurses and pharmacists The Medicines and Healthcare products Regulatory Agency (MHRA) is consulting on expanding the prescribing of controlled drugs (CDs) by nonmedical prescribers. Currently, nurse independent prescribers can prescribe 12 CDs, including diamorphine and morphine, but pharmacist independent prescribers may not prescribe any CDs. The proposal is to allow both professions to prescribe any CDs within their competence, with the exception of cocaine, diamorphine or dipipanone for the management of addiction. The closing date for consultation is 15 June. Consultation is also underway on expanding the range of CDs nurses and pharmacists can prescribe under a patient group direction (PGD), and their use for pain relief. The closing date for consultation is 20 April. Intrinsa: transdermal testosterone for women A transdermal formulation of testosterone has been introduced for the treatment of low sexual desire associated with distress in women who have experienced an early menopause following hysterectomy involving a bilateral oophorectomy and are receiving concomitant oestrogen therapy. Manufacturer Procter & Gamble says that Intrinsa, a twice-weekly patch, delivers testosterone 300g every 24 hours, achieving premenopausal serum testosterone levels. Clinical trials showed that Intrinsa reduced distress in 65-68 per cent and increased satisfying sexual activity in 51-74 per cent of women. A month's treatment (eight patches) costs 28.00. Fish oil for secondary ,not primary ,prevention of CHD Supplementing statin therapy with eicosapentaenoic acid (EPA) reduces the risk of major coronary events in patients with coronary heart disease (CHD) ,but not in patients with no history of CHD Lancet 2007;369:1090-8). The five-year study in 18 645 patients with total cholesterol levels of 6.5mmol per litre or greater found that the incidence of sudden cardiac death, fatal and nonfatal myocardial infarction in CHD patients treated with EPA plus a statin was 8.7 per cent compared with 10.7 per cent with a statin alone (relative risk reduction 19 per cent). A similar relative risk reduction in patients with no CHD was not statistically significant. There was no difference in mortality between the groups but EPA did reduce unstable angina and nonfatal coronary events. Department pilots information prescriptions The Department of Health has announced 20 sites to pilot information prescriptions prior to a nationwide roll-out in 2008. The prescriptions will guide people with long-term conditions such as diabetes and cancer to sources of support and information about their condition. The Department hopes the project will increase patients' understanding of their discussions with health professionals, empower them to locate the information they need, and provide long-term support. NPSA guidelines for safer prescribing The National Patient Safety Agency ( has published five guidelines to improve medication safety in the NHS. Targeting ,high-risk issues', the guidance covers anticoagulant prescribing, liquid medicines for oral or enteral administration, injectable medicines, epidural injections and infusions, and paediatric intravenous infusions. The implementation of each guide is supported by additional tools and resources. Better adherence not matched to outcomes A systematic review has found that interventions can increase adherence to prescribed medication but there is no evidence that clinical outcomes also improve (Arch Intern Med 2007;167:540-9). The review of 37 trials identified 20 reporting increased adherence. The most effective interventions were behavioural changes to reduce dose demands and those involving monitoring and feedback. Improvements in clinical outcomes were variable and did not correspond to changes in adherence. Antidepressant plus mood stabiliser no better US investigators have found that combining a mood stabiliser with an antidepressant is no more effective than a mood stabiliser alone in preventing mood changes (N Engl J Med 2007; published online 28 March, doi.10.1056/NEJMoa064135). The study found durable recovery occurred in 23.5 per cent of patients treated with a mood stabiliser and adjunctive antidepressant therapy for six months compared with 27.3 per cent of those taking a mood stabiliser plus placebo. [source]

Trends and opportunities in the metabolic syndrome

John H. "Wick" JohnsonArticle first published online: 16 NOV 200
Abstract Metabolic Syndrome consists of a multifactoral set of indications and, unfortunately, definitions. There is, at present, no consensus definition for Metabolic Syndrome and physicians who recognize the syndrome use different definitions. Some of the major stakeholder associations do not believe that Metabolic Syndrome is an approvable indication and no regulatory agency has weighed in on the matter. This has been the cause of confusion among many physicians resulting in different emphasis on intervention. However, there is close agreement between physicians surveyed in major markets as to the top three indications. The largest unmet medical need among these indications is obesity and obesity represents the largest opportunity. However, any single NCE or combination of existing drugs that can treat 3 indications will be a major advance. Any therapy will be an intervention and will have to have a very clean safety profile. Morbidity and mortality studies with existing therapies and combinations will be needed to establish outcomes. Drug Dev. Res. 67:539,544, 2006. 2006 Wiley-Liss, Inc. [source]

,Mad Cows' and Eurocrats,Community Responses to the BSE Crisis

Keith Vincent
Responding to criticisms and recommendations made in the aftermath of the initial crisis, particularly by the European Parliament, the EU has embarked on a process of reforming the administrative landscape in this area. This has included the setting-up of a new regulatory agency, the European Food Safety Agency, and a commitment to the more effective use of scientific information. It is submitted that this could lead to the development of new information-based scientific networks that inform and direct EU governance, networks which should contain the European Food Safety Agency at their centre. [source]

Regulation of Injected Ground Water Tracers

GROUND WATER, Issue 4 2000
Skelly A. Holmbeck-Pelham
Ground water tracer tests are routinely performed to estimate aquifer flow and transport properties, including the determination of well capture zones, hydrogeologic parameters, and contaminant travel times. Investigators may be unaware of tracer test reporting requirements and may fail to notify their regulatory agency prior to conducting tracer tests. The injection of tracers falls under the jurisdiction of the federal Underground Injection Control (UIC) program, which regulates the introduction of substances into underground sources of drinking water as part of the Safe Drinking Water Act. The UIC program is administered by the U.S. Environmental Protection Agency (EPA) and by states with EPA-approved programs. The federal UIC program requires that tracer tests must not endanger underground sources of drinking water, and all tracer tests must be reported prior to injection. We contacted the UIC program administrator for every state in early 1997. Some states report having more stringent requirements, while some states do not meet minimum federal requirements. Although the primary responsibility for ground water tracer selection and use rests on the investigator, national guidance is required to assure compliance with the UIC program. To assist investigators, we present acceptable tracers that have been identified by two states, Nevada and South Carolina, that require no further regulatory review. [source]

Evaluation of natural attenuation at a 1,4-dioxane-contaminated site

REMEDIATION, Issue 1 2008
Dora Sheau-Yun Chiang
1,4-Dioxane entered the environment as a result of historic leaks and spills in the production area at an industrial facility in the southeastern coastal plain. The areal extent of the 1,4-dioxane plume is several hundred acres and is largely contained on the site. Land use adjacent to the plant property is primarily undeveloped (wetlands or woods) or industrial, with a small area of mixed land use (commercial/residential) to the southwest and north. The surficial aquifer is a relatively simple hydrogeologic system with well-defined boundaries and is comprised of a 50- to 70-foot-thick deposit of alluvial/fluvial sand and gravel that overlies an aquitard in excess of 100 feet thick. A groundwater flow model, developed and calibrated using field-measured data, was used for the fate-and-transport modeling of 1,4-dioxane. The flow-and-transport model, combined with the evaluation of other site geochemical data, was used to support the selection of monitored natural attenuation (MNA) as the proposed groundwater remedy for the site. Since the active sources of contamination have been removed and the modeling/field data demonstrated that the plume was stable and not expanding, the proposed MNA approach was accepted and approved by the regulatory agency for implementation in 2004. Subsequent accumulated data confirm that concentrations in the 1,4-dioxane plume are declining as predicted by the fate-and-transport modeling. 2008 Wiley Periodicals, Inc. [source]

Perimeter air monitoring for soil remediation

REMEDIATION, Issue 4 2007
Guy J. Graening
Most environmental project managers are well versed in characterizing and remediating contaminants in soil and water media. When soil remediation activities are conducted at an environmental site, however, some project managers are faced with monitoring contaminants in the air medium for the first time. Remediation activities can disturb contaminants that are normally immobile in soil and transfer them to air. The resulting increase in airborne concentrations of contaminants, even if temporary, may be a health concern for individuals in neighboring residences or businesses. Perimeter air monitoring may be required by a regulatory agency to determine if unhealthy conditions are created and if work practices should be limited or modified. This article serves as a resource for project managers involved in perimeter air monitoring for soil remediation and provides a general summary of candidate sites, remediation activities that release contaminants, regulatory requirements, equipment and target contaminants, monitoring locations and schedule, analytical methods, and data interpretation. 2007 Wiley Periodicals, Inc. [source]