Abstract:
:Since the early 1960s, there has been a continuous evolution in scientific understanding regarding bioequivalence (BE) of oral dosage forms, intermittently punctuated by some breakthrough research findings and conceptual advances. The accumulated knowledge from this body of research has been translated into a sophisticated risk management framework of regulations and guidelines supported by an extensive set of tools and decision rules. This has permitted us to arrive at a state that now allows, in the majority of cases, not only the unrestricted substitution of a generic product for the innovator version, but also unquestioned substitution between different generic manufacturers. This framework has been successfully extended or adapted to go beyond oral dosage forms to include, for example, topical semisolid applications and nasal sprays. In the case of orally inhaled locally acting drug products (OIP), a similar level of success has yet to be realized. For OIP's, the risk management toolbox is incompletely outfitted due to missing science, knowledge, and experience in some key areas. This article presents a gap analysis of the situation highlighting unresolved residual risks. Assessment of the residual risks by US and EU medicines authorities has interestingly led to different regulatory positions with respect to BE for this class of drug products in these two regions. A parallel comparison with the history for BE of oral dosage forms shows that resolution for inhaled products will come eventually with the final outcome and timeframe, depending as much on science as it does on economics and the degree to which legislators intervene.
journal_name
J Aerosol Med Pulm Drug Delivjournal_title
Journal of aerosol medicine and pulmonary drug deliveryauthors
Horhota STdoi
10.1089/jamp.2014.1144subject
Has Abstractpub_date
2014-12-01 00:00:00pages
408-13issue
6eissn
1941-2711issn
1941-2703journal_volume
27pub_type
杂志文章,评审abstract:BACKGROUND:Programmed cell death 4 (PDCD4), a protein that binds to eukaryotic initiation factor 4A (eIF4A), inhibits the initiation of translation. Although a number of tumor suppressors target transcription, Pdcd4 is the first suppressor targeting protein translation, and has also been suggested to function as a tumo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2009.0778
更新日期:2010-10-01 00:00:00
abstract:PURPOSE:The objective of this study was to determine optimal aerosol delivery conditions for a full-term (3.6 kg) infant receiving invasive mechanical ventilation by evaluating the effects of aerosol particle size, a new wye connector, and timing of aerosol delivery. METHODS:In vitro experiments used a vibrating mesh ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2013.1077
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Predicting local lung tissue pharmacodynamic (PD) responses of inhaled drugs is a longstanding challenge related to the lack of experimental techniques to determine local free drug concentrations. This has prompted the use of physiologically based pharmacokinetic (PBPK) modeling to potentially predict local ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1436
更新日期:2019-02-01 00:00:00
abstract::The available toxicity data of benzalkonium chloride (BKC) clearly shows that it is toxic; however, the weight of evidence favors the view that at doses encountered in nasally and orally inhaled pharmaceutical preparations it is well tolerated. The adverse toxicological data predominantly come from in vitro and animal...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2017.1390
更新日期:2018-02-01 00:00:00
abstract::The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the am...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.29029.cd
更新日期:2020-08-01 00:00:00
abstract::Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled in...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0876
更新日期:2011-10-01 00:00:00
abstract::The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were rec...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2008.0690
更新日期:2008-09-01 00:00:00
abstract::Flexhaler is a multiple-dose, inspiratory flow-driven dry powder inhaler that is a newer version of Turbuhaler, and is identical to the Symbicort Turbuhaler. Sustained performance is of the utmost importance to ensure consistent drug delivery throughout the lifespan of the inhaler. We report functionality testing resu...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0700
更新日期:2008-12-01 00:00:00
abstract:: Background: Many substances used in inhalation research are water soluble and can be administered as nebulized solutions. Typical examples are therapeutic, small-molecular agents, or macromolecules. Another category is a number of water-soluble agents used for airway diagn...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2019.1554
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. METHODS:An abbreviated impactor base...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2011.0925
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Researchers, using checklists, have identified that 30%-90% of patients make errors in inhaler use. It is not certain whether these errors affect the delivery of medication. We have developed an electronic monitor (INCA™) that records audio each time an inhaler is used, providing objective information on inh...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2016.1334
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Very little is known about the role of nasal morphology due to ethnic variation on particle deposition pattern in the sinonasal cavity. This preliminary study utilizes computational fluid dynamics (CFD) modeling to investigate sinonasal airway morphology and deposition patterns of intranasal sprayed particle...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1205
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Particle size and velocity are two of the most significant factors that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in the mouth cavity. pMDIs are prominently used around the world in the treatment of patients suffering from a variety of lung diseases such as asthma and chronic ob...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1264
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Use of a valved holding chamber (VHC) in conjunction with a pressurized metered dose inhaler (pMDI) can reduce issues relating to poor actuation-inhalation coordination and potentially improve the lung deposition of aerosol, compared with use of a pMDI alone. However, the performance of a VHC is influenced b...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2013.1067
更新日期:2014-08-01 00:00:00
abstract::Antibiotic-resistant bacterial infections have renewed interest in finding substitute methods of treatment. The purpose of the present in vitro study was to investigate the possibility of respiratory delivery of a Burkholderia cepacia complex (BCC) bacteriophage by nebulized aerosol administration. Bacteriophages in i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0701
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Inhaled alpha1-antitrypsin (AAT) is being developed for treatment of cystic fibrosis to protect the lungs from excessive free elastase. High drug costs mandate a very efficient aerosol system to deliver a high payload to the airways. The I-neb Adaptive Aerosol Delivery (AAD) System is a portable, electronic,...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2009.0793
更新日期:2010-04-01 00:00:00
abstract::Upper respiratory tract infections (URTIs), primarily acute rhinopharyngitis, tonsillitis, adenoiditis, and rhinosinusitis (RS), are major causes of morbidity in both children and adults of any age. In addition to the frequent occurrence of related medical problems and the associated socioeconomic costs, URTIs have a ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2016.1300
更新日期:2017-02-01 00:00:00
abstract::This article provides a concise review of the use of magnetic resonance imaging (MRI) for measurement of regional aerosol deposition in the lungs. Basic aspects of MRI and its use in lung imaging and measurement of regional ventilation are introduced. Imaging of hydrogen protons (water) and inhaled hyperpolarized gase...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0897
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine deliv...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2011.0948
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Preclinical evaluation of new chemical entities (NCEs) designed to be administered by inhalation route requires lung administration to rodents, especially in the discovery phase. Different administration methods have been used until now, but more efforts are required to obtain controlled and reproducible lun...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1369
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:Secondary lung infections are the primary cause of morbidity associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation is potentially advantageous but has limited effectiveness due to altered airway aerodynamics and deposition patterns that limit drug access to infected regions. One pot...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1412
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:The effectiveness of metered-dose inhalers (MDIs) in delivering medication to the lungs highly depends on its correct usage technique. Current guidelines state optimal technique for high lung deposition should include a slow inhalation (>5 seconds) at an inspiratory flow rate of 30 L/min and inhaler actuatio...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1278
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Understanding the regional partition of deposition of inhaled particles within the lung is important for improving targeted delivery of inhaled aerosolized drugs. One factor affecting regional deposition is gravity. As the lung deforms under its own weight, changes in lung volume, in airway geometries, and i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1189
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and T...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1216
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol in...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2016.1320
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an oppo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1191
更新日期:2015-12-01 00:00:00
abstract:: Background: Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a c...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1376
更新日期:2018-12-01 00:00:00
abstract:: Background: Many countries have introduced a compulsory use of community masks for certain public areas during the SARS-CoV-2 pandemic. Different manufacturers offer reusable community masks in large quantities. The efficacy of these masks, however, is unknown. ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.1635
更新日期:2020-09-23 00:00:00
abstract:BACKGROUND:High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1219
更新日期:2016-04-01 00:00:00
abstract:: Background: The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalat...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.1610
更新日期:2020-11-04 00:00:00