PROCESS VALIDATION AND REGULATORY REQUIREMENTS OF METERED-DOSE INHALERS: AN OVERVIEW

The goal of the validation is to assure that quality is built into the system at every step, and not just tested for at the end. The validation activities will commonly include training on production material and operating procedures, training of people involved, and monitoring of the system while in production. Each and every doses form needs to be validated to reduce the chances of batch failures and market recalls. In case of metered-dose inhalers (MDIs) also it becomes mandatory. US Food and Drug Administration defines process validation as “establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.” MDIs are known as device that is made to deliver a specific amount of aerosolized medication in the form of short burst directly to the lungs when inhaled by the patient. Furthermore, the inhalational drug delivery causes less pain and is convenient for administration. The patients of asthma, emphysema, and chronic obstructive pulmonary disease are prescribed for quicker relief. The present paper is a summary of process involved in the manufacturing of MDIs and focuses on the regulatory requirements along with their process validation.

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Pressurised metered-dose inhalers versus all other hand-held inhalers devices to deliver bronchodilators for chronic obstructive pulmonary disease

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd002170 ◽

2002 ◽

Cited By ~ 2

Author(s):

Felix SF Ram ◽

David DM Brocklebank ◽

Martin Muers ◽

John J Wright ◽

Paul Jones

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Metered Dose Inhalers ◽

Obstructive Pulmonary Disease ◽

Other Hand ◽

Metered Dose ◽

Pressurised Metered Dose Inhalers

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Medication Administration With Inhalers or Nebulizers

Canadian Journal of Health Technologies ◽

10.51731/cjht.2021.192 ◽

2021 ◽

Vol 1 (11) ◽

Author(s):

Khai Than ◽

Aleksandra Grobelna

Keyword(s):

Clinical Effectiveness ◽

Medication Administration ◽

Chronic Obstructive ◽

Dry Powder Inhalers ◽

Metered Dose Inhalers ◽

Dry Powder ◽

Obstructive Pulmonary Disease ◽

Metered Dose ◽

The Cost ◽

Evidence Based Guidelines

Delivery of medication via metered-dose inhalers to children or adults with asthma, or adults with chronic obstructive pulmonary disease at emergency departments or intensive care units, may be as effective as nebulizers in terms of clinical parameters and health care resource use. Limited data on adverse events showed no significant differences between metered-dose inhalers and nebulizers. No evidence was found on the clinical effectiveness of dry powder inhalers in comparison with nebulizers or metered-dose inhalers. No evidence was found on the cost-effectiveness of medication administration via metered-dose inhalers, nebulizers, or dry powder inhalers in comparison with each other. No evidence-based guidelines with recommendations regarding the comparative use of metered-dose inhalers, dry powder inhalers, or nebulizers for administration of medication were identified.

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Design of a Metered-Dose Inhaler Actuated by Shape Memory Alloy

Journal of Engineering and Science in Medical Diagnostics and Therapy ◽

10.1115/1.4043403 ◽

2019 ◽

Vol 2 (3) ◽

Author(s):

Brent Utter

Keyword(s):

Shape Memory Alloy ◽

Shape Memory ◽

Dose Inhaler ◽

Chronic Obstructive ◽

Metered Dose Inhalers ◽

Obstructive Pulmonary Disease ◽

Metered Dose ◽

Sma Actuator ◽

Differential Pressure Sensor ◽

Inhaled Medication

The global prevalence of asthma and chronic obstructive pulmonary disease (COPD) is on the order of hundreds of millions of individuals. The most common treatment approach is to take a self-administered inhaled medication. This study focuses on pressurized metered-dose inhalers (MDIs) where, unfortunately, rates of mishandling and misuse are extremely high and lead to improper treatment. One significant challenge results from the timing miscoordination of the medicine dispersion and inhalation breath. To address this, this study demonstrates the feasibility of automating the timing of the medicine dispersion by integrating a shape memory alloy (SMA) actuator and a differential pressure sensor into the casing of a traditional MDI. The approach is to measure the vacuum pressure created by an inspiratory breath, evaluate criteria indicating an acceptable breath, and if those criteria are met, heat the SMA actuator to depress the cartridge and disperse medicine. To meet actuation requirements and reliably depress the inhaler cartridge, two concepts for configuring an SMA wire were designed and compared with respect to complexity, actuation timing, and energy consumption. The proposed concept was able to disperse medicine in 263 ms, averaged over 100 actuations on a single battery charge, facilitating the early dispersion of medicine during an inhalation breath. By describing the design process of an SMA-actuated MDI that does not result in a significant increase of its weight or size, this study provides a practical technological approach for reducing the improper treatment of asthma and COPD due to timing miscoordination.

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Pharmacotherapy of Chronic Obstructive Pulmonary Disease: Focus on Arformoterol Tartrate

Clinical Medicine Therapeutics ◽

10.4137/cmt.s2584 ◽

2009 ◽

Vol 1 ◽

pp. CMT.S2584

Author(s):

Paul T King

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Dose Inhaler ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Metered Dose ◽

Low Incidence ◽

Long Acting ◽

High Degree

Arformoterol tartrate is a newly developed long-acting ssβ2-agonist with both acute and prolonged bronchodilator effects. It is formed of 2 isomers (R,R/R,R) which distinguishes it from the more commonly used racemic formoterol (R,R/S,S). The active isomer is the (R,R) and in vitro arformoterol may have more potent anti-inflammatory effects than formoterol. It can only be given by a nebulizer. There have been 5 randomized, blinded trials which have assessed the use of arformoterol in chronic obstructive pulmonary disease (COPD). Arformoterol has been demonstrated to improve lung function and symptoms but the subjects tested did have a high degree of airway reactivity. The medication was well tolerated with a low incidence of side effects but the trials may not have been of sufficient duration to assess this adequately. Arformoterol should be used with caution in subjects with underlying cardiac disease. The current main use of arformoterol is in those subjects with COPD who require a long acting β2-agonist but who cannot use a dry powder or metered dose inhaler preparation. Arformoterol may only need to be given once a day and can be combined with other inhaled medication particularly tiotropium for additional benefit. It potentially has a role in the management of acute exacerbations.

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Original Article. Improving the Inhalation Technique in Patients with Obstructive Pulmonary Diseases

Journal of Biomedical and Clinical Research ◽

10.1515/jbcr-2016-0015 ◽

2016 ◽

Vol 9 (2) ◽

pp. 107-113 ◽

Cited By ~ 2

Author(s):

Zlatina I. Ivanova ◽

Nikolay H. Kyuchukov ◽

Iliya I. Krachunov ◽

Nikolay A. Yanev ◽

Pavlina Ts. Glogovska ◽

...

Keyword(s):

Pulmonary Disease ◽

Short Duration ◽

Pulmonary Diseases ◽

Inhalation Technique ◽

Chronic Obstructive ◽

Objective Method ◽

Metered Dose Inhalers ◽

Obstructive Pulmonary Disease ◽

Metered Dose ◽

Poor Inhalation Technique

Summary The study aimed to assess the inhalation technique of patients with bronchial asthma/chronic obstructive pulmonary disease (COPD) via an objective method and to evaluate the effect of training in patients with incorrect technique. Тhe inhalation technique of 120 patients with obstructive pulmonary disease was tested. The patients were divided into two groups: using metered dose inhalers (MDI) - 34 patients (28%) and dry powered inhalers (DPI) - 86 patients (72%). The most frequent mistakes in the MDIgroup were short duration of the inhalation (55.88%) and bad synchronization between activating the canister and the inhalation (29.41%). For the DPIgroup, the inhalation was not forceful enough (48.84%) and the short duration of the inhalation (12.79%). Patients claiming to have good inhalation technique accounted for 97%of those in the MDIgroup, and 96.5%of those in the DPIgroup. There were two patients (5.88%) with correct inhalation technique in the MDIgroup at their first attempt, and 31 patients (36.05%) in the DPIgroup. We found that in the MDIgroup there wasasignificant reduction in the number of mistakes (p<0.001). In the DPIgroup, such correlation was not found but during visit 2 there were no patients with more than 1 mistake. Correcting poor inhalation technique led to reduction of the number of mistakes during inhalation.

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Effectiveness of the BreatheSuite MDI in assessing the technique of Metered Dose Inhalers: an observational study (Preprint)

10.2196/preprints.26556 ◽

2020 ◽

Author(s):

Meshari F. Alwashmi ◽

Gerald Mugford ◽

Brett Vokey ◽

Waseem Abu-Ashour ◽

John Hawboldt

Keyword(s):

Observational Study ◽

Newfoundland And Labrador ◽

Prospective Observational Study ◽

Digital Health ◽

Chronic Obstructive ◽

Metered Dose Inhalers ◽

Obstructive Pulmonary Disease ◽

Chronic Lung Diseases ◽

Metered Dose ◽

Health Applications

BACKGROUND The majority of medications used in the treatment of asthma and chronic obstructive pulmonary disease (COPD) are taken by metered-dose inhalers (MDIs) Studies have reported that most patients demonstrate poor inhaler technique which resulted in poor disease control. Digital Health applications have the potential to improve the technique and adherence to inhaled medicications. OBJECTIVE The purpose of the prospective observational study is to validate the effectiveness of the BreatheSuite MDI device in assessing the technique of taking a dose via an MDI. METHODS The study was a prospective observational study. Thirty participants who self-reported a diagnosis of asthma or COPD were recruited from community pharmacies in Newfoundland and Labrador, Canada. Participants used a BreatheSuite MDI device attached to a placebo MDI and resembled taking three doses. Pharmacists used a scoring sheet to evaluate the technique of using the MDI. An independent researcher compared the results of the pharmacist’s scoring sheet with the BreatheSuite device results. RESULTS This study found that the BreatheSuite MDI can objectively detect several MDI technique errors. The data recorded by the BreatheSuite MDI device showed that all participants performed at least one error in using the MDI. The BreatheSuite device captured approximately 40% more errors compared to observation alone. The distribution of participants performing errors in MDI steps as recorded by BreathSuite compared to errors reported by observation alone were as follows: shaking before actuation 33.3% vs. 25.5%; upright orientation of inhaler during actuation 66.7% vs 18.87%; coordination (actuating after the start of inhalation) 75.6% vs 35.5%; duration of inspiration 96.7% vs. 34.4%. CONCLUSIONS The BreatheSuite MDI can objectively detect several MDI technique errors that were missed by observation alone. It has the potential to enhance treatment outcomes among patients with chronic lung diseases.

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Inhaler usability of a pressurized metered dose inhaler and a soft mist inhaler in patients with COPD: A simulated-use study

Chronic Respiratory Disease ◽

10.1177/1479972318787914 ◽

2018 ◽

Vol 16 ◽

pp. 147997231878791 ◽

Cited By ~ 7

Author(s):

Bo Ding ◽

Shahid Siddiqui ◽

Michael DePietro ◽

Gunilla Petersson ◽

Ubaldo J Martin

Keyword(s):

Dose Inhaler ◽

Chronic Obstructive ◽

Metered Dose Inhaler ◽

Metered Dose Inhalers ◽

Patient Centered ◽

Obstructive Pulmonary Disease ◽

Routine Patient Care ◽

Metered Dose ◽

Key Aspects ◽

Delivered Dose

The objective of this study was to evaluate task performance and handling errors with soft mist inhalers (SMIs) or pressurized metered-dose inhalers (pMDIs) among patients with chronic obstructive pulmonary disease (COPD) experienced with, but not recently trained in, using these devices. This exploratory, noninterventional, simulated-use study (D5970R00004) assessed handling/usability of SMIs and pMDIs in inhaler-experienced patients with COPD (40–78 years; diagnosis ≥6 months). Patients received a device and instruction-for-use leaflet but no training and were recorded while performing tasks required for checking the device, priming, and dosing. Errors that could substantially affect the lung-delivered dose were considered critical. Sixteen of 61 patients (52% male) had used SMIs and 55 had used pMDIs. Thirty-one patients received an SMI and 30 a pMDI. Overall, 79% made ≥5 performance errors (SMI 94%; pMDI 63%) and 49% made ≥5 critical errors (SMI 68%; pMDI 30%). All patients made ≥1 error; three (all pMDI) made no critical errors. Regardless of the device used and previous inhaler experience, patient-centered training, education, and continuous retraining on correct inhaler use should be key aspects of routine patient care in COPD.

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