Rethinking bioequivalence and equivalence requirements of orally inhaled drug products

Al-Numani, Dina; Colucci, Philippe; Ducharme, Murray P.

doi:10.1016/j.ajps.2015.08.006

Cited by 13 publications

(9 citation statements)

References 37 publications

(45 reference statements)

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“… 46 An important problem with COPD medication costs is the lack of availability of cheap generics; in part because regulatory agencies, such as the US Food and Drug Administration, have higher expectations for inhaled generic equivalents than for oral generics. 119 …”

Section: Health Care Accessmentioning

confidence: 99%

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Defining and targeting health disparities in chronic obstructive pulmonary disease

Pleasants

Riley

Mannino

2016

COPD

138

136

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The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and etiologies, it is also associated with worsened COPD health outcomes. Effective interventions in these people are needed to decrease these disparities. Efforts that may help lessen these health inequities in low SES include 1) better surveillance targeting diagnosed and undiagnosed COPD in disadvantaged people, 2) educating the public and those involved in health care provision about the disease, 3) improving access to cost-effective and affordable health care, and 4) markedly increasing the efforts to prevent disease through smoking cessation, minimizing use and exposure to BF, and decreasing occupational exposures. COPD is considered to be one the most preventable major causes of death from a chronic disease in the world; therefore, effective interventions could have a major impact on reducing the global burden of the disease, especially in socioeconomically disadvantaged populations.

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Section: Health Care Accessmentioning

confidence: 99%

“…This has been the major impediment toward declaring a “global worldwide reference product” that generic pharmaceutical companies could use in their development. 119 …”

Section: Strategies To Aid the Diagnosis And Management Of Copd Patiementioning

confidence: 99%

Defining and targeting health disparities in chronic obstructive pulmonary disease

Pleasants

Riley

Mannino

2016

COPD

138

136

View full text Add to dashboard Cite

show abstract

“…The FDA uses an approach of an aggregate weight of the evidence, which means their request results in the three categories mentioned previously. On the other hand, the EMA uses a stepwise approach based only in in vitro studies if the proposal meets all the requirements for approval; otherwise, the other categories are required [ 57 ]. This section, along with Figure 3 , briefly describes the requirements needed by two of the major agencies for the approval of bioequivalent inhaled drugs.…”

Section: Current Regulation and Official Methodologies For Inhaled Bioequivalencementioning

confidence: 99%

“…While PK studies are often used as evidence of bioequivalence for other routes of administration, these have been particularly challenging for OIDPs. It can be difficult to evaluate plasma concentrations with many OIDPs because most of these therapies are intended to act locally [ 57 ]. Additionally, a measurement of their systemic exposure may not reflect the local PK of the drug after administration, which may be key to its efficacy and duration of action.…”

Section: Current Regulation and Official Methodologies For Inhaled Bioequivalencementioning

confidence: 99%

Innovating on Inhaled Bioequivalence: A Critical Analysis of the Current Limitations, Potential Solutions and Stakeholders of the Process

Gallegos-Catalán

Warnken²,

Bahamondez-Canas

et al. 2021

Pharmaceutics

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Orally inhaled drug products (OIDPs) are an important group of medicines traditionally used to treat pulmonary diseases. Over the past decade, this trend has broadened, increasing their use in other conditions such as diabetes, expanding the interest in this administration route. Thus, the bioequivalence of OIDPs is more important than ever, aiming to increase access to affordable, safe and effective medicines, which translates into better public health policies. However, regulatory agencies leading the bioequivalence process are still deciding the best approach for ensuring a proposed inhalable product is bioequivalent. This lack of agreement translates into less cost-effective strategies to determine bioequivalence, discouraging innovation in this field. The Next-Generation Impactor (NGI) is an example of the slow pace at which the inhalation field evolves. The NGI was officially implemented in 2003, being the last equipment innovation for OIDP characterization. Even though it was a breakthrough in the field, it did not solve other deficiencies of the BE process such as dissolution rate analysis on physiologically relevant conditions, being the last attempt of transferring technology into the field. This review aims to reveal the steps required for innovation in the regulations defining the bioequivalence of OIDPs, elucidating the pitfalls of implementing new technologies in the current standards. To do so, we collected the opinion of experts from the literature to explain these trends, showing, for the first time, the stakeholders of the OIDP market. This review analyzes the stakeholders involved in the development, improvement and implementation of methodologies that can help assess bioequivalence between OIDPs. Additionally, it presents a list of methods potentially useful to overcome some of the current limitations of the bioequivalence standard methodologies. Finally, we review one of the most revolutionary approaches, the inhaled Biopharmaceutical Classification System (IBCs), which can help establish priorities and order in both the innovation process and in regulations for OIDPs.

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“…A vital element of a therapeutic equivalence study using a clinical endpoint is demonstration of dose-response relationship, in order to confirm that a lack of difference in the clinical endpoint is truly because test and reference formulations generate a similar level of effect, and not because the study lacks sensitivity in detecting differences [13]. For salmeterol, the dose-response relationship is flat when assessment is done using either bronchodilation or bronchospasm models [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Pharmacokinetic and Pharmacodynamic Effects of Two Hydrofluoroalkane Formulations of Salmeterol

Morde¹,

Rebello²,

Brashier³

et al. 2017

J Bioequiv Availab

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Rethinking bioequivalence and equivalence requirements of orally inhaled drug products

Cited by 13 publications

References 37 publications

Defining and targeting health disparities in chronic obstructive pulmonary disease

Defining and targeting health disparities in chronic obstructive pulmonary disease

Innovating on Inhaled Bioequivalence: A Critical Analysis of the Current Limitations, Potential Solutions and Stakeholders of the Process

Comparison of Pharmacokinetic and Pharmacodynamic Effects of Two Hydrofluoroalkane Formulations of Salmeterol

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