Below is the list of possible topics for your Capstone paper. For some topics, you may find it easier to write from the view of a specific company and product. This can be your current or previous company or a fictional company. These topics are a starting point and will need to be refined to fit the Capstone paper requirements for this class. There is a limit to the number of students who can write about each topic so you will need to submit your proposal and receive approval before beginning to write.

COVID-19/Pandemic-Related Topics

1. Assessment of the Emergency Use Authorization (EUA) program and how it was applied to the COVID-19 pandemic.
   • Evaluate one EUA approved product from the EUA list of products and provide your regulatory assessment of whether you feel the data submitted adequately represented a safe and effective product. If not, what data do you consider is inadequate or missing?

OR

• Explore how the EUA approval process could be used for approvals of life-threatening diseases post-pandemic and what changes may or should occur based on the EUA approvals during the pandemic. Use specific examples of products that were approved during the pandemic and potential products or class of products that could be approved post-pandemic to support your findings.

OR

• Choose one of these topics and identify the parallels in Europe: https://ec.europa.eu/commission/presscorner/detail/en/qanda_20_2390

2. Conducting clinical studies during a pandemic. Discuss the impact of the “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic” (most recent version (as of writing) 27 January 2021) that was quickly issued in response to COVID-19. As the regulatory person, what will your advice to the clinical team be in one of the following scenarios? Support your recommendations with information from the Guidance and specific examples.
   • Assume you have a phase 3 double-blind placebo-controlled trial underway with a planned enrollment of 1,500 subjects. Planned treatment duration is 48 weeks with a 4-week follow-up. You are also planning to have an open-label extension trial available for subjects who complete the 12-month treatment period. At present, approximately 650 subjects have enrolled. There is a planned interim analysis when 750 subjects have been treated for 3 months or longer.

Based on the FDA Guidance, what do you do now to protect the integrity of the trial? You were already doing risk-based monitoring. Do you keep it going? Do you stop? Does it matter whether the product is a new chemical entity or a biologic? Does it matter what the indication is? Does it matter whether US only or multinational?

OR

• Assume you just about to launch a phase 3 double-blind placebo-controlled trial with a planned enrollment of 1,500 subjects. You have already had an End-of-Phase 2 meeting and have agreed primary and secondary endpoints. Assessments include, among others, standard safety lab studies, MRIs (0, 6, 12 months), ECGs (0, 12 months), and a quality-of-life assessment administered by site personnel.

Planned treatment duration is 48 weeks with a 4-week follow-up. You are also planning to have an open-label extension trial available for subjects who complete the 12-month treatment period. At present, approximately 25 centers have been qualified; 20 are set to screen/enroll. There is a planned interim analysis when 750 subjects have been treated for 3 months or longer.

Based on the FDA Guidance, what do you do now? Do you re-design? Do you start as is? Do you discuss with FDA? Do you stop? The clinical operations plan includes risk-based monitoring; if you are continuing the study, how do you modify to protect the integrity of the trial and perform adequate monitoring? Does it matter whether the product is a new chemical entity or a biologic? Does it matter what the indication is? Does it matter whether US only or multinational?

OR

• What changes and adjustments to clinical studies during the pandemic will remain, and what will revert back to pre-pandemic practices? For this topic you must provide specific examples and analysis of what would change and why. You will need to choose a specific company and clinical trial program to discuss what would or would not change after the pandemic.

3. The ethics of medical research in emergency (including epidemic and pandemic) situations
   • Ebola and Covid-19 presented very different kinds of stresses. What constitutes an emergency for purposes of relaxing guidelines? When, if ever, is it appropriate to blur the distinction between research and treatment? Is moving forward after animal studies, but without complete human studies, ever justified? Support your findings with specific examples and case studies.
4. Strategies in Dose Finding for a Vaccine
   • Possible case study: You work for an US-based multinational manufacturing vaccine for seasonal flu. The vaccine is a synthetic peptide. How will you conduct the preclinical study and map out a way to find the right starting dose in humans? Will you use the NOAEL or MABEL path? Please justify your stand when requesting a pre-IND meeting on this topic with the FDA. Ref: https://www.ema.europa.eu/en/documents/presentation/calculation-minimum-anticipated-biological-effect-level-mabel-1st-dose-human-jennifer-sims_en.pdf).
5. Human challenge trials during a pandemic
   • The need to respond quickly in circumstances of a pandemic is a reason to pursue human challenge trials as the recent Covid-19 experience shows. But in the case of the Zika virus, unlike Covid-19, human challenge trials were rejected as unethical. What are the ethical concerns regarding human challenge trials? Under what kind of conditions might they be justified? Support your findings with specific examples and case studies.

Regulatory Affairs: Pre-Market

1. HCT/P regulations and how effectively they are implemented from a manufacturer and FDA perspective; this would be a case study applied to a specific company/product.
2. Create a regulatory strategy for an example product; this would be a case study of a specific company/product.
3. Accelerated pathways to market – Do they help reduce the timeline for an approval/clearance (e.g., Breakthrough, STEP, etc.) not just in theory but in actual practice? Do they help ensure a safe and effective product? Support your findings with specific statistics, examples, and case studies.

Regulatory Operations: Pre-Market

1. The Premarket Approval Process and the Product’s Safety and Effectiveness; this would be a case study of a specific company/product.
2. Analysis and Data Integrity Remediation; this would be a case study of a specific company/product.

Regulatory Intelligence/Strategy: Pre-Market

1. Examining the Rarity of Rare Disease Development; this should be applied to a specific product. Regulatory Intelligence/Strategy: Post-Market
2. The Importance of Business Continuity and Disaster Recovery Strategy in the Pharmaceutical, medical device, biologic, food, or dietary supplement Industry; this would be a specific case study for one of the product types.

Regulatory Intelligence/Strategy: International

1. Global Product Development Strategy: Pick a product category (e.g., drug, device, biologic, in vitro diagnostic, dietary supplement, etc.) and specific product (may be fictional or one currently under development) then provide a product development strategy for that product. Select a focus area of ONE of the following: 1) pre-clinical IND/CTA enabling strategy, 2) pre-market development or 3) post-marketing / life-cycle management. Consider regulations in both the US and EU. Be sure to consider the following areas in your plan:
   • Regulatory Strategy/Evolving regulatory landscape
   • Clinical
   • Non-Clinical
2. Brexit, Turkxit, and Swixit – Regulatory strategy implications for small, medium, and large medical product companies. Support your findings with specific examples or case studies.

Quality/GXP: Each of these topics needs to be applied to a specific company

1. How to ensure supply chain integrity. Identifying weak links and mitigating risks.
2. An analysis of the importance of Quality Systems for Pharmaceuticals, Devices, Biologics, Combination Products, or Dietary Supplements.
3. Patient Safety: Quality is More Important than Quantity; this could be an assessment of the Case for Quality (Devices) or Quality by Design (Drugs)
4. Draft a full Quality Management Plan for a phase 1 drug clinical trial for a one product start-up located in a university campus. This entails quality policy, identification and drafting of key SOPs, inspection readiness, etc.

Clinical Trials

1. Business and clinical trial strategy implications for complying with ISO 14155:2020 or ISO 20916:2019. Support your findings with specific examples or case studies.