Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions.

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency (∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Effect of the Similarity of Formulations and Excipients of Approved Generic Drug Products on In Vivo Bioequivalence for Putative Biopharmaceutics Classification System Class III Drugs.

One of the potential essential factors that restricts generic industry from applying the Biopharmaceutics Classification System (BCS) Class III biowaiver is adherence to the stringent formulation criteria for formulation qualitative (Q1) sameness and quantitative (Q2) similarity. The present study has investigated formulations and excipients from 16 putative BCS Class III drug substances in a total of 19 drug products via 133 approved abbreviated new drug applications (ANDAs) containing in vivo bioequivalence (BE) studies in human subjects during the time period from 2006 to 2022. We included the BCS Class III drugs in this study by referring to published literature, the World Health Organization (WHO) BCS Class I-IV list, FDA internal assessments, and physicochemical properties (high solubility and low permeability) of specific drug substances. Based upon all 133 approved generic formulations in this study, the highest amount of each different compendial excipient with a total of 40 is defined as its corresponding typical amount that has not shown any potential impact on in vivo drug absorption. In the present study, although only 30.08% of the investigated generic formulations met Q1 the same/Q2 similar formulation criteria for the BCS Class III biowaiver, and while approximately 69.92% failed to meet those criteria with non-Q1/Q2 similar formulations, all test/reference ratios (T/R) and 90% confidence intervals for all instrumental PK parameters (AUC0-t, AUC0-inf, and Cmax) met the bioequivalence (BE) criteria (80-125%). The results of formulation assessment suggest that the commonly used excipients without atypical amounts did not impact absorption of 16 putative BCS Class III drug substances. The rate and extent of absorption of drugs appears to be more dependent upon the biopharmaceutic and physiochemical properties of BCS Class III drug substance and less, or not dependent upon their formulations, excipients, and the excipients class. Our findings may lead to a more flexible formulation design space regarding the stringent BCS Class III formulation criteria.

Particle size affects pharmacokinetics of milled oxycodone hydrochloride tablet products following nasal insufflation in nondependent, recreational opioid users.

This study assessed the impact of product particle sizes (fine: 106-500 µm; coarse: 500-1000 µm) on oxycodone pharmacokinetics (PK) following nasal insufflation of milled oxycodone extended-release (ER) abuse-deterrent (AD) tablets using immediate-release (IR) non-AD product as reference. Additionally, this study assessed the effects of different excipient to drug ratio (EDR) by comparing two products with fine particle size but different EDRs, again using IR non-AD as the control. Thirty milligrams of oxycodone were administered in each treatment. Coarsely milled 30 mg ER tablets demonstrated significantly lower maximum plasma concentration (Cmax ) and partial areas under the concentration-time curve (AUCs) than those of the finely milled IR tablets. Finely milled ER tablets demonstrated similar Cmax and partial AUCs but higher total systemic exposures than those of finely milled IR tablets. Finely milled 80 mg ER tablets were bioequivalent to IR tablet on all parameters. The finely milled 30 mg ER tablet was not bioequivalent to the coarsely milled 30 mg ER tablet and had higher values for all parameters. The finely milled 30 mg ER tablets (EDR 6.9) showed no PK differences with finely milled 80 mg ER tablets (EDR 4.9). No serious adverse events were reported. The study demonstrated a significant effect of particle sizes (106-1000 µm) on PK of milled and insufflated oxycodone ER AD tablets. EDR difference did not have any significant effects on the PK of finely milled oxycodone ER AD tablets. Particle size distribution should be considered when nasal AD properties of opioid drug products are investigated during drug development.

Patient and caregiver opinions about an FDA-developed generic drug educational handout: A pilot cross-sectional survey.

OBJECTIVE: To examine patient and caregiver opinions and "receptivity" regarding generic drug educational material in terms of content, format and design, delivery channel, and level of satisfaction. METHODS: Interviewer-administered surveys were conducted with patients and caregivers who were clients of a regional medication management program or pharmacy services clinic to gather perceptions about generic drugs and input on a generic drug educational handout developed by the U.S. Food and Drug Administration (FDA). Survey questions were developed by the investigators and pretested before use. Data were analyzed using descriptive statistics, and responses to open-ended questions were assessed using qualitative content analysis. Survey psychometrics were examined using exploratory factor analysis (EFA). RESULTS: Of the 100 survey participants, most (93%) had positive perceptions about generic drug safety and effectiveness after reading the handout. Most participants were satisfied or very satisfied with the handout's content (87%) as well as format and design (92%). However, more than 20% of participants were still unsure about the benefits and risks of generic drugs compared with those of brand drugs, and more than 15% were still unsure about which benefits and risks mattered most to them. The participants' preferred source for the handout was a pharmacy (49%) or doctor's office (27%). In an EFA of the survey instrument, 2 factors emerged related to the educational handout's content: (1) generic drug information, a 7-item factor (Cronbach alpha = 0.882); and (2) personal relevance, a 3-item factor (Cronbach alpha = 0.692). CONCLUSION: The findings indicate an overall positive "receptiveness" toward generic drug informational materials from patients and caregivers, which highlights the feasibility and importance of educational outreach programs about generic drugs targeted toward this population. Future studies may focus on more diverse populations and tailor materials to the needs of specific patient and caregiver subgroups and health literacy levels.

Healthcare provider opinions about a generic drug educational newsletter.

BACKGROUND: Increasing the prescribing and dispensing of generic drugs, compared to branded drugs, may increase patient access to affordable drug treatments. Healthcare providers have information needs regarding generic drugs, but available, tailored education materials designed for provider use are lacking. OBJECTIVES: To examine healthcare provider opinions and receptivity regarding generic drug educational materials in content, format and design, delivery channel, and level of satisfaction. METHODS: A national online survey was conducted in summer 2018 to gather practicing healthcare prescribers' (i.e., physicians, nurse practitioners, physician assistants) and pharmacists' opinions on an educational newsletter developed through a collaboration between the investigators and the U.S. Food and Drug Administration (FDA). Survey data were analyzed using descriptive statistics. Quantitative analyses were performed using SPSS version 24 (IBM, Armonk, NY), while responses to open-ended questions were assessed using qualitative content analysis in Excel. RESULTS: A total of 208 surveys were completed. Overall, participants expressed positive opinions about the newsletter's content and format/design. About 69% of prescribers and 60% of pharmacists stated the newsletter gave information that will help them better serve patients. While 15% of surveyed pharmacists stated that they did not have resources to help them get information on generic drug availability and cost, more prescribers (37%) responded similarly. Both prescribers and pharmacists preferred to receive this newsletter via email from the FDA or a professional association. CONCLUSIONS: Findings indicate the feasibility of educational outreach programs about generic drugs targeted towards healthcare providers. There is room for improvement in making prescribers and pharmacists aware of resources for learning about generic drug availability and cost. Future studies may test alternate versions of the newsletter that have been tailored to the needs of specific provider specialties or provider practices serving specific patient sub-groups, as well as preferred dissemination frequency.

Development and testing of a web module to IMPROVE generic prescribing of oral contraceptives among primary care physicians.

WHAT IS KNOWN AND OBJECTIVE: The use of generic oral contraceptives (OCPs) can improve adherence and reduce healthcare costs, yet scepticism of generic drugs remains a barrier to generic OCP discussion and prescription. An educational web module was developed to reduce generic scepticism related to OCPs, improve knowledge of generic drugs and increase physician willingness to discuss and prescribe generic OCPs. METHODS: A needs assessment was completed using in-person focus groups at American College of Physicians (ACP) Annual Meeting and a survey targeting baseline generic scepticism. Insights gained were used to build an educational web module detailing barriers and benefits of generic OCP prescription. The module was disseminated via email to an ACP research panel who completed our baseline survey. Post-module evaluation measured learner reaction, knowledge and intention to change behaviour along with generic scepticism. RESULTS AND DISCUSSION: The module had a response rate of 56% (n = 208/369). Individuals defined as generic sceptics at baseline were significantly less likely to complete our module compared to non-sceptics (responders 9.6% vs non-responders 16.8%, P = 0.04). The majority (85%, n = 17/20) of baseline sceptics were converted to non-sceptics (P < 0.01) following completion of the module. Compared to non-sceptics, post-module generic sceptics reported less willingness to discuss (sceptic 33.3% vs non-sceptic 71.5%, P < 0.01), but not less willingness to prescribe generic OCPs (sceptic 53.3% vs non-sceptic 67.9%, P = 0.25). Non-white physicians and international medical graduates (IMG) were more likely to be generic sceptics at baseline (non-white 86.9% vs white 69.9%, P = 0.01, IMG 13.0% vs USMG 5.0% vs unknown 18.2%, P = 0.03) but were also more likely to report intention to prescribe generic OCPs as a result of the module (non-white 78.7% vs white 57.3%, P < 0.01, IMG 76.1% vs USMG 50.3% vs unknown 77.3%, P = 0.03). WHAT IS NEW AND CONCLUSION: A brief educational web module can be used to promote prescribing of generic OCPs and reduce generic scepticism.

Communicating benefits and risks of generic drugs to consumers: Patient and caregiver opinions of two FDA-developed educational materials.

BACKGROUND: Increasing prescribing and dispensing of generic drugs, compared to brand drugs, may increase patient access to affordable medications. However, little is known about patients' and caregivers' needs and receptiveness regarding the design of educational materials about generic drugs. METHODS: The research used focus groups of patients and caregivers who were students or employees of one university in the Southeastern U.S. to gather input on the optimal content, format and design, delivery channel, and level of satisfaction for two existing, FDA-developed educational materials about generic drugs (infographic and brochure). RESULTS: Participants stated a need for the materials to modernize their graphics, emphasize generic drug cost-savings for consumers, reduce scare tactics when discussing adverse events, and be disseminated directly from physician's offices and pharmacies. Despite an overall positive impression of the materials, participants wanted more consumer-oriented materials that were tailored to fit the needs of different types of patients/caregivers, including older adults. CONCLUSIONS: This paper discusses how these findings relate to theories of multimedia learning and guidelines for designing health educational materials, as well as implications for the development of tailored generic drug educational materials for use in public health campaigns to improve access to medication therapy.