Practical Pointers for Drug Development and Medical Affairs

Authors: 

  • MedSurgPI: Gerald L. Klein, MD; Roger E. Morgan, MD; Freddy Byrth; Marion Stamp-Cole, Stephen Haworth, MD

  • SMART BioWorks: Eric Hacherl, PhD

  • Exquisite Biomedical Consulting: Shabnam Vaezzadeh, MD

  • Global Life Sciences Alliance: Denise McNerney

  • Independent DSMB Coordinator: Jamie Lazar

  • LBF BioPharma Consulting: Larry Florin

  • The Brown Group: Gail Brown, MD

Drug Development

New Guidelines from ICH E6(R3)

The International Council for Harmonisation (ICH) Guideline E6(R3), Good Clinical Practice revision represents a pivotal step toward modernizing clinical trial conduct and oversight. This update redefines how sponsors, investigators, and Medical Affairs teams manage quality and risk, emphasizing participant protection, data integrity, and responsible use of digital technologies.

1. Dynamic Risk Assessments (DRA): From Static to Adaptive Oversight

ICH E6(R3) suggests that sponsors develop a risk-based approach to clinical trial/development oversight, with the intensity and focus of activities such as monitoring, data review, and auditing adjusted based on the clinical trial’s complexity and potential impact on the study participants. Importantly, R3 builds upon prior versions of ICH E6 that emphasized Quality by Design (QbD), reinforcing that proactive, design-level quality principles should guide how risks are identified, prioritized, and managed throughout the study lifecycle.

Continuous evolution: These risk assessments should be periodically reviewed and, if needed, updated/changed based on the availability of new/additional data, changes in sites (number, geographic location, operational instructions, etc.), or technology (systems, site-facing interfaces, etc.) that may introduce new risks.

Adaptive monitoring: Replace standardized monitoring plans with real-time, adaptive strategies triggered by defined indicators:

  • Protocol deviations

  • Missing or inconsistent data

  • Emerging safety trends or unexpected adverse events

Independent oversight: Medical monitors and Data Safety Monitoring Boards (DSMBs) play a greater role in interpreting risk signals and ensuring participant safety, extending beyond passive review to include adaptive, data-informed interventions.

This shift aligns with regulatory trends emphasizing quality by design (QbD), risk-based monitoring (RBM), and fit-for-purpose quality systems—concepts central to ICH E8(R1) and E6(R3) alignment. At the heart of this evolution is a focus on “Critical-to-Quality” (CtQ) factors, as oversight activities should concentrate on the processes and data that are essential to assuring participant safety and the accumulation of reliable, interpretable patient data. A key crux of E6(R3) is the shift away from traditional, exhaustive source data verification (SDV) toward data-driven, centralized (statistical) monitoring strategies with a keen focus on critical data.

 2. Reaffirming Participant Safety, Rights, and Well-Being

ICH E6(R3) reaffirms its ethical foundation: participant protection is paramount. Beyond compliance, sponsors must ensure participants are fully informed, empowered, and respected throughout the trial.

Transparency and accessibility: Investigators must have real-time access to new safety data, protocol amendments, and risk communications to ensure timely action at the site level.

Participant communication: Sponsors and Clinical Research Organizations (CROs) must provide safety information that is clear, understandable, and culturally appropriate, supporting autonomy and continued informed consent.

Ethical obligation: Sponsors are responsible not only for data collection but for safeguarding trust which is crucial for sustaining public confidence in research.

 3. Digital Tools: From Operational Efficiency to Ethical Rigor

The guideline acknowledges the growing role of digital and decentralized technologies but reframes their purpose beyond efficiency and cost containment to ensure scientific validity and ethical implementation.

Fit-for-purpose validation: All digital tools (ePRO, wearables, AI analytics) must undergo formal validation to confirm they accurately capture, store, and transmit data as intended.

Ethical use and governance: Establish clear frameworks for data privacy, participant consent, and system reliability, particularly when technology intermediates participant interaction.

Integration with quality management: Digital systems should integrate seamlessly into the trial's risk-based quality framework to reinforce, not replace, scientific and ethical rigor.

Medical Affairs

Upholding Oversight and Quality

 

1.      Medical Affairs (MA) teams serve as the interface between science, ethics, and communication, ensuring post-marketing and real-world activities align with ICH E6(R3) expectations. As AI becomes embedded in literature surveillance, scientific communication, medical review, and real-world data workflows, MA teams must ensure these tools are used responsibly, transparently, and in alignment with ICH E6(R3)’s quality and data-integrity principles.

 2.      System validation and data integrity: All computerized systems under MA control must be fully validated with robust audit trails, user-access controls, and metadata capture (author, reviewer, approver, time/date stamps). This applies to:

  • Key Opinion Leader (KOL) and stakeholder tracking (Customer Relationship Management) platforms

  • Publication planning and review systems

  • Real-world evidence and registry databases

  • AI-assisted content generation, literature monitoring, and medical insight analytics tools

 3.      Vendor oversight and accountability: Contracts with scientific vendors, communications agencies, and publication partners should clearly define:

  • Scope of work and deliverables

  • Delegated responsibilities and accountability

  • Oversight structure (Medical Affairs vs. vendor roles)

  • Performance metrics: timeliness, data accuracy, conflict-of-interest management, GxP compliance

  • Vendor training requirements: GCP, data privacy, and quality expectations

  • Clearly define Intellectual Property (IP) and practices to maintain IP protections

 4.      Documentation and training: Maintain oversight logs documenting all delegated activities and ensure team members receive training in essential areas, including, but not limited to:

  • Vendor selection and qualification criteria

  • Delegation and accountability management

  • Vendor audits and quality oversight procedures ensuring that participant care and safety decisions are made by competent professionals

  • Scope of work, deliverables, and agreed Key Performance Indicators (KPI)s

These practices demonstrate due diligence and establish clear traceability—key principles reinforced in ICH E6(R3).

Key Takeaway

ICH E6(R3) is not merely a compliance exercise; it's a call to rethink trial oversight as a living system. The guideline promotes balance between flexibility and accountability, urging organizations to align quality, ethics, and innovation at every stage of the trial lifecycle. For sponsors, CROs, and Medical Affairs teams, success depends on transparency, adaptability, and a proactive approach to risk management—hallmarks of modern, patient-centered research.

Practical Pointers for Medical Affairs / June 2025

Authors:  Gerald L. Klein, MD; Roger E. Morgan, MD; Johannes Wolff, MD; Freddy Byrth; Marion Stamp-Cole; Melissa Palmer, MD

bridging innovation and practical application

As treatment regimens for both surgical and medical interventions grow increasingly complex, there is heightened need for focused medical affairs efforts to deliver thorough training and guidance to healthcare providers. Innovations in therapy often come with intricate dosing algorithms, novel mechanisms of action, and sophisticated delivery systems, all of which require clear, accessible, and evidence-based communication from medical teams. Practical aspects such as patient selection, dosage, safety, and tolerability should be clearly and concisely defined. Most devices require a human factors validation study, particularly those intended for patient self-use or in high-stakes clinical environments.

RWE Growth and Alignment

There has been a significant increase in the number of real-world evidence-based studies and their significance in both medical affairs and in product development. For example, PubMedindexed real-world evidence (RWE) publications nearly tripled between 2016 - 2018, rising from 326 to over 930 studies.[1] To foster better communication around this evolving body of work, the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have developed a standardized glossary of terms specific to real-world data (RWD) and RWE.[2] Adoption of these terms helps ensure consistent interpretation, improves stakeholder communication, and supports regulatory alignment when using RWE in product development and labeling strategies.

Post-Launch Insights that matter

Launching a new product is a tremendous undertaking and also presents a valuable opportunity to gather timely, real-world insights through what we refer to as post-launch data capture. There is generally increased interest and excitement about a new product and early adapters are keen to try this, so it is an ideal time to capture important medical affairs information.

  • This is the time to query patients, healthcare providers (HCPs) and pharmacists on the following:

    • How well is the product understood: This gauges the depth of knowledge and clarity around the product’s mechanism of action, indication, administration route and monitoring requirements. Misunderstandings may lead to suboptimal use or hesitancy in adoption and the feedback helps inform targeted educational intervention.

    • Is it appropriately prescribed and dosed: This evaluates whether prescribers are using the product in accordance with the approved label, real-world best practices, and any clinical guidelines. Dosing errors or off-label trends may indicate gaps in education or highlight the need for label refinement or further clinical clarification.

    • Product effectiveness: This assesses whether the clinical benefits observed in  trials are being replicated in routine clinical practice. Factors such as adherence, comorbidities, and healthcare access may influence this and require RWE follow-up.

    • Perceived product value: Assess the economic and therapeutic value as perceived by both patients and HCPs.  Are the benefits seen as commensurate with the cost, burden of use, or any associated monitoring requirements?  This is critical for market access, payer discussions, and retention. ▪ Willingness for HCPs to prescribe the product:  Investigating barriers that may hinder prescribing behavior (clinical, logistical, financial or psychological). Even highly efficacious products may struggle if providers lack confidence or clarity in how or when to use them.

    • Willingness for patients to use the product: Examining patient acceptance, particularly around tolerability, ease of use, and alignment with lifestyle may lead to the understanding of cultural, social, or health literacy factors that shape decision-making.

    • Additional side effects: Examining emerging safety signals or tolerability concerns that may not have been apparent in the controlled environment of clinical trials which may include mild but impactful events that affect adherence and satisfaction.

    • Additional benefits: Possibly identifying positive secondary outcomes or “halo” effects that weren’t the primary focus of trials but are meaningful to patients or providers. These may include improvements in energy, mood, or comorbidity control and can become valuable talking points in peer-to-peer education and lifecycle management.

References

  1. Makady A, de Boer A, Hillege H, Klungel O, Goettsch W. What is real‑world data? A review of definitions based on literature and stakeholder interviews. Value Health. 2017;20(7):858‑865. doi:10.1016/j.jval.2017.03.008.

  2. Rivera DR, Cutler TL, McShane L, et al. Modernizing Research and Evidence Consensus Definitions: A Food and Drug Administration–National Institutes of Health Collaboration. JAMA Netw Open. 2025;8(6):e2516674. doi:10.1001/jamanetworkopen.2025.16674.

Practical Pointers for Product Development / June 2025

Authors:  Gerald L. Klein, MD; Roger E. Morgan, MD; Johannes Wolff, MD; Freddy Byrth; Marion Stamp-Cole; Melissa Palmer, MD

Developing Drugs for Obesity and Weight loss

  • The general recommendation for a sample size to assess the safety of a weight-reduction drug is 3,000 subjects randomized to the investigational drug within the to-be-recommended dosage range and no fewer than 1,500 subjects randomized to placebo for at least one year of treatment at the maintenance dosage. Sponsors developing multiple dosing regimens should consider a randomization scheme that assigns more subjects to higher doses and are encouraged to discuss the overall size of the safety database with the Agency at or before the end of Phase 2.[1] In addition to these safety considerations, sponsors should align with FDA guidance recommending at least one unsuccessful attempt at lifestyle modification (e.g., diet and exercise) prior to enrollment and should consider removing the ≥5% long-term weight loss requirement as a singular efficacy benchmark. Inclusion of electronic Clinical Outcome Assessments (eCOA) and validated Quality of life (QOL) measures as secondary endpoints is also advised to support potential labeling claims. Furthermore, sponsors are encouraged to propose a pediatric sub-study to address the pressing issue of childhood obesity and explore opportunities for pediatric exclusivity through regulatory pathways that may support patent extension.[2]

  • The recommended sample size will provide 80% power to detect, with 95% confidence, an approximately 50% increase in the incidence of an adverse event that occurs at a rate of 3% in the placebo group (i.e. 4.5% vs. 3%).

  • This sample size would also allow for efficacy and safety analyses to be conducted within important subgroups such as age, sex, race, ethnicity, and baseline BMI, provided that a sufficient number are enrolled in each of these groups.

For all products

  • We recommend strategic refinement to the traditional FDA requirement of two well-controlled Phase 3 clinical trials. Specifically, we propose a hybrid development and approval model designed to maintain scientific rigor while enhancing speed to market and real-world relevance demonstrating robust and statistically significant results. Notably, the FDA has previously granted approval based on a single pivotal study in certain high-need indications, such as Elzonris, approved for blastic plasmacytoid dendritic cell neoplasm (BPDCN) based on a single Phase 2 trial of 94 patients, and Lumoxiti, approved for relapsed/refractory hairy cell leukemia based on a single-arm, open label Phase 3 trial of 80 patients.[3] These examples demonstrate that regulatory flexibility exists when the benefit-risk profile is compelling. We suggest the following approach:

    • Primary Pivotal Trial: Conduct one well-controlled Phase 3 trial demonstrating statistically robust efficacy, safety and tolerability under traditional randomized, controlled conditions. This trial would serve as the primary basis for conditional approval.

    • Conditional Approval Linked to real-World Validation: Upon successful completion of the pivotal trial, conditional approval would be granted with a clear commitment to complete a second Phase 3 trial within a defined timeframe. This second trial would be designed to:

      • Incorporate real-world evidence (RWE) methodologies (e.g., pragmatic design, broader inclusion criteria, decentralized elements).

      • Provide confirmatory data on effectiveness, safety, and tolerability in routine clinical practice.

      • Serve as a tool for refining labeling, guiding post-marketing surveillance, and supporting payer decisions.

This two-step model offers several advantages:

  • Accelerates access to promising therapies for patients in need.

  • Incentivizes real-world accountability through mandatory confirmatory RWE trials.

  • Mitigates risk by anchoring initial approval to high-quality evidence while ensuring continued scrutiny.

  • Aligns with FDAs evolving openness to RWE and flexible development frameworks (e.g., as reflected in 21st Century Cures Act and FDAs guidance). This approach has the potential to accelerate approvals, prevent the approval of ineffectual medications and provide greater safety and tolerability of actual real-world events.[4]

planned protocol deviations

Planned protocol deviations should be avoided in clinical trials to maintain scientific integrity and regulatory compliance. However, in certain complex settings, such as oncology or cell and gene therapy trials, predefined deviations may be necessary due to the individualized nature of treatment or logistical constraints. In such cases, advanced Institutional Review Board (IRB) approval must be obtained, and the rational clearly documented on the protocol or amendment to ensure ethical oversight and participant safety.[5]

References:

  1. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs

  2. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pediatric-drug-development-regulatoryconsiderations-complying-pediatric-research-equity-act-and?utm

  3. U.S. Food and Drug Administration. Drug Trial Snapshot: ELZONRIS. FDA website. Published December 21, 2018. Accessed July 2, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-elzonris

  4. Burns L, Roux NL, Kalesnik-Orszulak R, Christian J, Hukkelhoven M, Rockhold F, Khozin S, O’Donnell J. Real-world evidence for regulatory decision-making guidance from around the world. Clinical Therapeutics. 2022;44(3):420-437. doi:10.1016/j.clinthera.2021.12.013.

  5. U.S. Food and Drug Administration. Protocol Deviations – A Regulatory Perspective: Draft Guidance for Industry. Silver Spring, MD: FDA; April 2024. Available at: https://www.fda.gov/media/184745/download.

Practical Pointers for Product Development and Medical Affairs / May 2023

Written by: Gerald L. Klein, MD; Roger E. Morgan, MD; Shabnam Vaezzadeh, MD; Burak Pakkal, MD and Michael Fath, PhD

Product Development

  • Academic Innovation Centers can serve as pivotal hubs in the context of product development. These hubs can be a focal point in the development of entrepreneurial centers. The ideal center combines diverse university schools of science, nursing, engineering, dental, pharmacology, and dentistry medicine along with a business school. If they can break down the myriad of academic political walls and combine forces with regional governments, state governments, and industry, they can develop a scientific and economic powerhouse. Tremendous centers of innovation and entrepreneurship have been established in the Boston, San Francisco, San Diego, NJ/NY Corridor, and in Research Triangle Park, North Carolina. Academic leadership should proactively enhance the effectiveness of their innovation centers in order to be more effective.

  • Efficient clinical trial enrollment is a critical factor in successful product development. Poor patient enrollment into clinical trials is one of the main reasons for study failure. This is an expensive, time-consuming process. One way that may aid this process is to use Artificial Intelligence (AI) to help with enrollment. There are many AI systems available to achieve this critical goal. Some examples include:

    • IBM Watson Health: Uses machine learning and Natural Language Processing (NLP) to analyze medical records and identify eligible patients for clinical trials. Provides predictive analytics for patient recruitment and engagement.

    • Deep 6 AI: Leverages AI to match patients to clinical trials by analyzing structured and unstructured data from electronic health records. Focuses on speed and accuracy in patient identification.

    • TriNetX: A global health research network that uses real-time access to HER data to identify eligible patients for clinical trials. Offers analytics and patient recruitment solutions.

    • Antidote: Utilizes AI to connect patients with relevant clinical trials. Uses advanced search algorithms to match patient profiles with trial eligibility criteria.

    • CureMetrix: Employs AI to enhance patient identification and engagement through medical imaging analysis and predictive analytics. Helps improve the accuracy of patient matching and recruitment.

    • Clinical AI: Uses AI to streamline the clinical trial process, from patient recruitment to data analysis. Focuses on automating trial management and enhancing patient engagement through AI-driven insights.

  • Include clinical research training for students in health care related programs. Providing proper training for students in medical, nursing, PA, PharmD, and other health care related programs can contribute significantly to product development. We believe that it is important to teach the basic elements of clinical research to all health care students in order to instill the following virtues:

    • Increase their scientific curiosity

    • Enhance their ability to understand the scientific literature

      • Increase their capability to analyze pharmaceutical product effectiveness and adverse effects.

    • Improve their interpretation of clinical trials

    • Be able to apply scientific literature to clinical pracctice

    • Increase the likelihood that students will engage in conducting clinical research and publication

Medical Affairs

  • Webinars serve as a powerful way to get your message out. In order for this to be successful, the target audience must be persuaded to watch this event in either real time or at a later date. This can be enhanced by the following:

    • Selecting appropriate speakers

    • Timing of the event

    • Cutting edge or important subject matter

    • Promotional campaign to attract an audience

  • Strategy: One key strategy in product promotion is to identify a medical need. This could be:

    • Specific populations: consider unique patient groups (e.g., pediatric, geriatric or rare diseases) that require tailored solutions.

    • Intolerant patients: highlight cases where patients cannot tolerate existing therapies. Position your product as an alternative.

    • Niche Situations: Explore scenarios where your product fills a gap. Initiate communication with key opinion leaders (KOLs) and other healthcare providers.

  • Cost-effective data generation using surveys and small studies: The use of surveys and small studies are a cost-effective way to produce data for poster sessions at scientific conferences. This data can be published in a brief publication, and then followed up with subsequent studies and publications. It may be a way to initiate a marketing campaign when you are faced with a low budget.

Practical Pointers

Practical Pointers: Product Development and Medical Affairs

Written by: Gerald L. Klein, MD; Burak Pakkal, MD, Roger E. Morgan, MD; Renu Jain, PhD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Larry Florin, MBA; Victoria Manax, MD

Product Development

  1. Data Monitoring Committees in Clinical Trials: The new FDA Guidance on “Use of Data Monitoring Committees in Clinical Trials” (DMC) just came out in February 2024. [1] The FDA strongly recommends using a DMC if there is a risk of a serious mortality or morbidity due to the participant’s medical condition or if the investigation may cause serious unexpected adverse events during the trial. The agency further states that the use of such a committee is practical.

    MedSurgPI suggests that when the study is short in duration, a Safety Review Committee, (SRC) may be a more practical approach to further ensure safety of the clinical trial. This consists of a medical monitor, the principal investigator, and another medical safety expert.

  2. Overview of Device Regulation: The FDA has just issued the “Quality Management System Regulation (QMSR) Final Rule”, which amends the good manufacturing practices requirements of the Quality System Regulation (21 CFR Part 820).[2]

    Medical device manufacturers of US medical devices must adhere to the following:

    US FDA Registration Guidance | US Medical Device Registration

    Device Registration and Listing

    Premarket Notification 510(k) unless exempt, or Premarket Approval (PMA)

    Investigational Device Exemption (IDE) for clinical studies

    Quality System (QS) regulation

    Labeling Requirements

    Medical Device Reporting (MDR)

  3. Still a Need to Improve More Diverse Populations in Clinical Trials: Clinical Trials need to involve more diverse populations such as racial and ethnic minorities, the elderly, rural populations, women, etc.[3] The FDA has published a new guidance document that explains how this data is to be collected during a clinical trial: “Collection of Race and Ethnicity Data in Clinical Trials, and Clinical Studies for FDA-Regulated Medical Products: Draft Guidance for Industry.”[4] One resource, with tools and other information to help improve this situation, may be found at the National Institute of Minority Health and Health Disparities website.

Medical Affairs

  1. Keeping Current: Presenting yourself as an expert goes beyond just understanding your product; it’s crucial to be deeply knowledgeable about the conditions it treats. This requires a commitment to continuously monitoring and analyzing relevant medical literature, including newsletters, attending conferences, and reviewing clinical trial data. Keeping abreast of advancements in the field ensures that you remain a comprehensive resource for both your product and its application. This ensures that your team can provide accurate and up-to-date information, establishing yourself as a reliable source.

  2. AI Chatbots for Medical Education: Some medical information tasks can be automated by the use of AI chatbots for providing such information to health professionals and patients about medication and device indications, adverse effects, dosages, and drug interactions.

  3. Medical Affairs Microgrants: Our experience suggests that a ‘microgrant’ program can be a useful tool in obtaining greater healthcare professional (HCP) engagement. This entails establishing a very modest grant program that allows HCPs who do not conduct formal clinical trials to defray the cost of such activities as creating an article (case history), small study (observational, history, etc.) of interest to your company.

[1] https://www.fda.gov/media/176107/download.

[2] https:www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/overview-device-regulation#reg.

[3] Kim J and McDaniel D.  From Words to Action: Advancing Efforts to Reduce the Racial Gap in Clinical Research. Applied Clinical Trials. Feb 7, 2024.

[4] https://www.fda.gov/regulatory-information/search-fda-guidance-documents/collection-race-and-ethnicity-data-clinical-trials-and-clinical-studies-fda-regulated-medical.

Practical Pointers Special Edition - Investment Essentials

Written by: Gerald L. Klein, MD; Roger E. Morgan, MD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Burak Pakkal, MD; Michael Fath, PhD; Renu Jain, PhD; Larry Florin, MBA; Victoria Manax, MD

In light of the recent conclusion of the JP Morgan Healthcare Conference in San Francisco, a pivotal event for global investment, there’s a noticeable shift in focus among companies and investment groups. As they reassess strategies for raising capital and evaluating a wide spectrum of sectors - including biotech, tech, digital, device, pharmaceuticals, and diagnostic technologies - we find it timely and pertinent to dedicate this month’s Practical Pointers to these emerging trends, which are currently at the forefront of investor and founder discussions.

Fundamental Topics Related to the Technology and Pathway

  1. What is the medical or technological need?

  2. What is the background science?

  3. Is there rational data proving the hypothesis?

  4. What is the patent portfolio?

  5. What is the regulatory pathway?

  6. What is the clinical trial strategy/pathway?

  7. What is the expected clinical benefit?

  8. What is the reimbursement strategy?

  9. Is there an experienced product development team running the organization?

  10. What are the competitive products?

  11. What is the exit strategy?

  12. What is the market size?

  13. What are the risks of the project?

What is the Medical Need? This is one of the most quintessential questions that helps determine the value of a scientific product. The more significant the medical need the more it may lead to quicker funding, quicker regulatory review, and more investigator engagement. For example, there is a huge need for better oncology treatments, so these products are highly valued, and a tremendous amount of venture capital is being poured into many of these companies. Meanwhile, cancer prevention is what has led to a recent reduction in cancer mortality in the U.S. Another example of a critical area is the need for vast improvement in cardiovascular disease.

What is the Science? Is the technology based on plausible and good scientific work? Can the results be replicated? What is the level of expertise of the scientists who have conducted the experiments? Is the scientific hypothesis convincing?

Is there Rational Data Proving the Hypothesis? Does the data support the hypothesis? Are there other plausible explanations for the observed effect? Does this stand up to critical scientific review?

What is the Patent Portfolio? What is the status of patent filings? Have provisional patents been filed? Are patents pending? Which countries are covered? How much longer do the patents last? Are the patents adequate to provide protection vis-a-vis current and future competition? Who owns the patents? If it is a university, what are the licensing terms? It is essential to answer the following questions: Are the patents on the composition of matter; formulation/process; methods of use; and is there confirmation of freedom to operate?

What is the Regulatory Strategy? Is the technology going to be regulated by the FDA? Will it require filing an Investigational New Drug (IND) application or an Investigational Device Exemption (IDE)? What regulatory division of FDA/EMA will review this? Is there potential for special designation; orphan drug, expedited review, breakthrough? Have you had preliminary discussions with FDA/EMA regarding regulatory and clinical pathways? Will Phase I be in a healthy normal population? At what stage will you attempt to obtain proof of concept?

What is the Clinical Strategy/Pathway? What kind of clinical data will be required? Do you have information from the FDA/EMA as to their requirements? How are you planning to generate the clinical data? Are there competitive products on the market or in development that will affect your development plan?

Will you utilize a contract research organization (CRO), fractional service providers, or your own team? Do you have the medical, clinical, and scientific expertise to create a clinical strategy to plan clinical development in the most direct, economic, and efficient manner? Will you work with academic institutions, a site management organization, and/or independent investigators? What will be the duration and expense of each clinical phase? What will be the geographic scope of the clinical program?

What is the Expected Clinical Benefit? Will this product significantly modify a disease, prolong life, improve quality of life, or have fewer side effects than current therapy? Will it improve disease diagnosis? In addition, are there pharmacoeconomic benefits of the product?

What is Your Reimbursement Strategy? Is the technology a novel product or a “me too” (one that closely imitates an existing product)? Will it treat a rare disease? If there are competing products on the market, does it have significant medical or economic benefits? Will it extend life or improve quality of life? Are there reimbursement codes or do you need to lobby for them? Are you planning to generate data for Medicare reimbursement if applicable? Who will provide reimbursement pathway advice to your team?

Do You Have an Experienced Product Development Team? How many people are on your team? Do you have full-time dedicated staff? Has your team developed similar products before? Have they attained a New Drug Application (NDA), Biologics License Application (BLA), or clearance? Does your group work in other countries besides the U.S.? What types of companies and roles has your senior leadership team been involved with in terms of their experience?

What are the Competitive Products? What are the competitive products already on the market or in development? What is your competitive advantage over them? How will they affect your clinical development, commercialization, and market potential? What other products are in development and how might they affect your development and/or commercialization strategy?

What is Your Exit Strategy? Are you planning to sell the product (or company) when you have demonstrated proof of concept? Will you try and obtain product approval before an exit? Do you intend to manufacture, and commercialize the technology yourself, seek partnership, hand off, or some combination in different geographies?

What is the Market Size? Have you identified your Total Addressable Market (TAM)? What is the overall market size, and which is your addressable market? Which geographies and populations will you target? What is your order of entry strategy? Would there be opportunities for expanding the market?

What are the Risks of the Project? Have you characterized the project risks across the full range of functional areas? Have these been quantified in a risk register? Do you have mitigations for the relevant risks?

Practical Pointers for Drug Development and Medical Affairs

Written by: Gerald L. Klein, MD: Burak Pakkal, MD; Roger E. Morgan, MD; Renu Jain, PhD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Larry Florin, MBA; Victoria Manax, MD

Drug Development

In 2023, the U.S. Food and Drug Administration (FDA) published numerous significant guidance documents. Below is a selection of these key publications.

  1. Numerous types of real-world data can be analyzed in non-clinical trials such as registries, electronic health records, medical claims, and data on products used in clinical practice as part of a package for FDA regulatory product approval.[1]

    • The FDA suggests the following:

      • Early engagement will allow for timely identification of challenges in the design and planning of a non-interventional study and for discussion of how such challenges might be addressed.

      • When submitting a meeting request, sponsors should include adequate information - as outlined in FDA guidance for formal meetings - for FDA to both assess the potential utility of a meeting and to identify relevant FDA subject matter experts who should address the proposed agenda items.

  2. Optimizing the dosage for oncology products now requires a strong rationale for choice of dosage which should be provided before initiating registration trial(s):

    • To support a subsequent indication and usage:

      • Especially for oncologic diseases not adequately represented in completed dose-finding trials or for new combination regimens.

      • If sufficient rationale for choice of dosage cannot be provided, additional dose-finding should be conducted.[2]

    • The FDA further states that different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology patient population, treatment setting, and concurrent therapies (for combination regimens), among other factors.

      • Applicable nonclinical and clinical data should be considered to support the proposed.

    • Different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology, patient population, treatment settings, and concurrent therapies (for combination regimens), among other factors.

      • Applicable nonclinical and clinical data should be considered to support the proposed.

    • For additional information, please see FDA’s Project Optimus:

  3. When developing drugs for rare indications, the FDA frequently allows the use of innovative trial designs. These should be discussed with the appropriate division very early on. This may include Bayesian methods, n-of-1 clinical studies, randomized delayed-start designs, crossover designs, and master protocol.[3] These studies require a detailed statistical analysis plan including key features of the clinical investigation design and preplanned analysis discussed with the review team before the study initiatives.

    Canadian Regulatory Pointers

    On December 4, 2023, Health Canada’s Regulatory Operations and Enforcement Branch revised the medical device establishment licence (MDEL) application form. The form is used to:

    • Apply for an MDEL

    • Apply for an MDEL after a cancellation

    • Submit changes to your existing MDEL

    • Cancel your MDEL

    • Apply for a reinstatement of your MDEL after a suspension

      For specific details, visit the following website: https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/establishment-licences/medical-devices-compliance-bulletin/updates-frm0292-instructions.html

      Medical Affairs

      Direct-to-Consumer Prescription Drug Advertisements in television and radio in new guidance document:[4]

    • First Standard: The major statement is presented in consumer-friendly language and terminology is readily understandable.

    • Second Standard: The major statement’s audio information, in terms of the volume, articulation, and pacing used, is at least as understandable as the audio information presented in the rest of the advertisement.

    • Third Standard: In advertisements in television format, the major statement is presented concurrently using both audio and text.

    • Fourth Standard: In advertisements in television format, for the text portion of the major statement, the size and style of font, the contrast with the background, and the placement on the screen allow the information to be read easily.

    • Fifth Standard: During the presentation of the major statement, the advertisement does not include audio or visual elements, alone or in combination, which are likely to interfere with comprehension of the major statement.


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    2. Optimizing the dosage of human prescription drugs and biological products for the treatment of oncologic diseases. Guidance for Industry January 2023.

    3. Rare Diseases: Considerations for the development of drugs and biological products. Guidance for industry. December 2023.

    4. Direct-to-consumer prescription drug advertisements: presentation of the major statement in a clear, conspicuous, and neutral manner in advertisements in television and radio format final rule Q&A. Guidance for Industry December 2023.