Abstract:
BACKGROUND:Biosimilars are defined as biologic products that are highly similar to reference products, notwithstanding minor differences in clinically inactive components, with no clinically meaningful differences between the biologic product and the reference product in terms of safety profile, purity, and potency. Due to the high cost of innovator biologics, as well as an increase in the number of these products reaching patent expiry, the development of a process for approving biosimilar products has become a crucial regulatory issue in the United States. OBJECTIVE:This commentary explores the relationship between structural/biophysical variation and the risk/benefit profile of biosimilars and reference biologics that have undergone process changes in the context of the most recent biophysical, nonclinical, and clinical data available. METHODS:The search strategy used PubMed, EMBASE, and MEDLINE for the retrieval of documents pertaining to biologic manufacturing, comparative analysis of biosimilars and originator biologics, and relevant review articles on biosimilars. For regulatory documents pertaining to the processes of the approval of biosimilars, biologics, and generics, a search for legislative decisions, briefing summaries, concept papers, guidance, and evaluations of approved and rejected applications for biosimilars published by the World Health Organization, US Food and Drug Administration, European Medicines Agency (EMA), and other national regulatory authorities was conducted. Selected articles from key opinion leaders and manufacturers were also reviewed. These searches were conducted to provide a review of historical and contemporary issues in the consideration of the current status of worldwide biosimilar use and regulation. RESULTS:A total of 18 marketing applications covering 9 development programs were surveyed. Of these, 14 applications were approved and 4 were rejected by the EMA. None of the biosimilars were reported to have evidence of significant clinical variation relative to reference compounds in the absence of corresponding differences in biophysical properties. A single biosimilar (Omnitrope(®) [somatropin]) was reported to have evidence of significant variation in both biophysical and clinical parameters in premarketing studies. Biophysical variation in the absence of relevant differences in the efficacy and safety profiles compared with the reference brands was noted for 2 biosimilar epoetin products. CONCLUSIONS:This commentary provides evidence that current EU guidelines have resulted in the approval of biosimilar therapeutics with comparable efficacy and safety profiles for the recommended indications of their respective reference originator biologics. It is anticipated that these precedents will serve as a starting point in the development of a process for approving biosimilars in the United States and worldwide to provide efficacious and tolerable biotherapeutics with a significant cost advantage for national health care programs and consumers.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Ahmed I,Kaspar B,Sharma Udoi
10.1016/j.clinthera.2011.12.005subject
Has Abstractpub_date
2012-02-01 00:00:00pages
400-19issue
2eissn
0149-2918issn
1879-114Xpii
S0149-2918(11)00840-Xjournal_volume
34pub_type
杂志文章,评审abstract::Steady-state bioavailability of a sustained-release quinidine gluconate formulation was compared with that of a sustained-release quinidine sulfate preparation in a crossover study. Sixteen healthy men were given multiple doses (two tablets every 12 hours) of the two drugs in randomized sequence. Blood samples were ob...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1983-01-01 00:00:00
abstract::Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::Forty patients with symptoms of rheumatoid arthritis were treated with daily injections of 100 micrograms of human leukocyte interferon or saline placebo. Twenty patients received the interferon for nine weeks and were then switched to placebo for nine weeks, and 20 patients were started on placebo and were then switc...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::An open clinical trial with prifinium bromide, an anticholinergic agent, was carried out in 21 patients with irritable bowel syndrome showing clear psychosomatic characteristics. The clinical efficacy was evaluated by comparing the symptomatic severity before, during, and after treatment with prifinium bromide, 90 mg/...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Optimal treatment regimens for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are not well-defined. OBJECTIVES:This study describes the treatment and outcomes in patients with urinary tract infection (UTI) caused by KPC-producing Enterobacteriaceae. METHODS:This...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.05.002
更新日期:2012-06-01 00:00:00
abstract::Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. It has been the subject of more than 8,000 published papers, which include clinical reports of its usefulness in approximately 100 diseases and symptoms. In the United States the only indications for use in the official labelin...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::The efficacy and safety of transferring 76 patients with poorly controlled type II diabetes mellitus from various self-mixed human insulin regimens to a premixed insulin regimen (Novolin 70/30, 70% NPH and 30% Regular insulin, semisynthetic) were evaluated in a 24-week, multicenter, open-label study. During the initia...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1994-01-01 00:00:00
abstract::Twenty-six women (aged 26 to 60) with stress incontinence underwent urodynamic investigation before and after oral administration of 5 mg of midodrine, a new adrenergic agent with alpha-stimulant activity. A significant increase in maximum urethral closing pressure combined with a nonsignificant increase in flow time ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::A total of 128 corticosteroid-independent adults with chronic allergic asthma were treated for six weeks with 400 micrograms/day of beclomethasone dipropionate aerosol. Most patients (114 or 89%) had a good to excellent response, characterized by a marked improvement in the signs and symptoms of asthma. Substantial im...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::The purpose of this study was to estimate the impact of the introduction of propentofylline, a glial-cell modulator with neuroprotective properties, on the costs of dementia care in Sweden. To estimate the clinical effects of propentofylline treatment on dementia, we conducted a meta-analysis of four double-masked, pl...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/s0149-2918(98)80065-9
更新日期:1998-05-01 00:00:00
abstract::To determine the cost relative to efficacy and tolerability of two antimicrobial regimens, a prospective, multicenter study compared imipenem-cilastatin (I-C) monotherapy with clindamycin+aminoglycoside (C+A) in the treatment of serious lower respiratory, intra-abdominal, gynecologic, and urinary tract infections. The...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Patients with mild intermittent or mild persistent asthma represent 70% of asthma sufferers. Inhaled corticosteroids (ICSs) are the mainstay of treatment for persistent asthma, although many of the early clinical studies of these drugs included only patients with moderate to severe asthma. OBJECTIVE:This ar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80017-0
更新日期:2002-07-01 00:00:00
abstract:PURPOSE:Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. METHODS:Pati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.10.013
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:This was a prospective observational cohort study that aimed to determine whether fetal sex influences the maternal and fetal outcomes of gestational diabetes mellitus (GDM). METHODS:In this study, 327 European primiparous women were consecutively recruited after diagnosis of GDM. AUC on the oral glucose toler...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.02.015
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:The median time to approval of new drugs in Canada decreased considerably in the mid-1990s, although it continued to be longer than in such countries as Australia, Sweden, the United Kingdom, and the United States. Ongoing concern about approval times pointed to a need for a further international comparison....
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(03)80080-2
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:The worldwide prevalence of asthma is increasing by approximately 50% per decade. Budesonide is one of several inhaled corticosteroids available for the treatment of asthma and has been extensively evaluated in clinical trials. OBJECTIVE:This article reviews the published literature on the efficacy of budes...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80005-4
更新日期:2002-06-01 00:00:00
abstract:PURPOSE:The Enhancing Quality of Prescribing Practices for Older Veterans Discharged From the Emergency Department (EQUIPPED) program is a quality improvement initiative that combines education, clinical decision support (ie, geriatric pharmacy order sets), and in-person academic detailing coupled with audit and feedba...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.02.013
更新日期:2020-04-01 00:00:00
abstract::This commentary reviews the difficulties in formulating oral products for children. The significance of the fragmentation of the pediatric population in terms of development and ability to ingest different dosage formulations is examined. It is postulated that a flexible formulation, acceptable by all patient groups, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.01.010
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for t...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(02)80027-3
更新日期:2002-07-01 00:00:00
abstract::Hemodynamic and electrophysiologic effects of procainamide, the pharmacokinetic properties of conventional and sustained-release forms of the drug, guidelines for its administration and dosage, and contraindications for and adverse effects of its use are outlined. A review of clinical studies of procainamide therapy c...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers. M...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.09.022
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with th...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(03)80171-6
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2018.01.014
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Combined therapy with cilostazol, an antiplatelet agent, and probucol, an antihyperlipidemic agent, has been reported to prevent restenosis after percutaneous transluminal coronary angioplasty. However, the potential for pharmacokinetic drug interactions between the 2 agents has not been evaluated. OBJECTIV...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.10.005
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administrati...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(03)90096-8
更新日期:2003-12-01 00:00:00
abstract::A 28-day, double-blind study involving 56 outpatients ws initiated to compare the anxiolytic efficacy and safety of ketazolam once a day at bedtime (HS) with diazepam given three times a day (TID) and placebo HS or TID. Ketazolam HS was at least equivalent, and in some respects superior, to diazepam TID with fewer, le...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract:PURPOSE:Although the efficacy of canagliflozin has been well established in clinical trials, research regarding its use and impact on outcomes in clinical practice has been limited by the availability of data on observations up to and beyond 6 months after the initial use of canagliflozin. The purpose of this study was...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.07.009
更新日期:2016-09-01 00:00:00
abstract:PURPOSE:The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertens...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.05.015
更新日期:2020-07-01 00:00:00
abstract::Idiopathic chronic hiccup (ICH) is defined as recurring hiccup attacks that last for longer than an arbitrary time limit (eg, 1 month) and for which no organic cause can be found. In patients with ICH, therapy is largely empiric. For practical purposes, idiopathic hiccup can be assumed to have its origin either in the...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(97)80055-0
更新日期:1997-09-01 00:00:00
abstract::A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens includ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(96)80212-8
更新日期:1996-07-01 00:00:00