U.S. Market Access is the pathway by which innovative healthcare solutions reach patients, ensuring they receive and benefit from these interventions while navigating health insurance (payer) systems, regulatory requirements, and economic considerations. Market access involves a comprehensive approach to address reimbursement, evidence generation, stakeholder engagement, and payer strategies, all aimed at delivering equitable and affordable access to medical innovations. 

Breaking Down U.S. Market Access 

For those new to the concept, U.S. market access can be understood through four key components: 

1. Reimbursement – Reimbursement covers payer medical policy coverage decisions, appropriate coding, and ensuring fair payment rates. It also encompasses billing processes and programs that support patient access to care. 

2. Clinical/Health Economics/Patient & Provider Impact – Demonstrating the value of a medical innovation requires robust data, including clinical effectiveness, cost-efficiency, and its potential impact on patient and provider experience. 

3. Stakeholder-Specific Value – Different stakeholders, including payers, providers, patients, and policymakers have unique priorities. A successful strategy addresses these specific needs to support adoption and use. 

4. Managed Care Payer Strategies – Medicare, Medicaid, Commercial Insurance, companies as well as self-insured employers and health systems play a central role in patient access. Establishing a cohesive payer access plan is critical to success.  

Together, these components emphasize the need for a coordinated and evidence-based approach to navigate complex healthcare payers like Medicare, Medicaid, and private insurance. 

An Example of Market Access in Action: Prostate Cancer Diagnostic Test 

A recent example of effective market access involved a prostate cancer AI molecular diagnostic test facing challenges with proposed Medicare reimbursement. The Centers for Medicare & Medicaid Services (CMS) initially proposed a reimbursement rate of $760 per test, which did not align with the test’s complexity, resource utilization and costs. 

Dream Big Health market access consulting played a key role in supporting the test’s pricing strategy. Despite an initial rejection of our crosswalk pricing recommendation, we worked closely with the client to develop a structured approach to rebut Medicare’s proposed pricing.  

• Drafting and submitting a letter to CMS detailing critical technological, process and resource requirement differences versus our recommendation and that of CMS.  

• Engaging directly with CMS through formal review and public comment reconsideration processes. 

As a result, CMS reversed its decision, approving a reimbursement rate of $3,800 per test—a fivefold increase. This case study illustrates the need for proactive planning and specialized market access expertise. 

In the United States, the Food and Drug Administration (FDA) offers two pivotal early-stage meetings for biopharmaceutical companies: the Initial Targeted Engagement for Regulatory Advice on CBER/CDER Products (INTERACT) meeting and the Pre-Investigational New Drug (Pre-IND) meeting. Each serves distinct purposes within the drug development process, and understanding their differences is crucial for startups aiming to navigate the regulatory landscape effectively. 

INTERACT Meetings 

The INTERACT meeting is designed for novel products that present unique challenges due to unknown safety profiles, complex manufacturing technologies, or innovative devices. It provides an opportunity for sponsors to obtain initial, non-binding advice from the FDA regarding chemistry, manufacturing, and controls (CMC), pharmacology/toxicology, and early clinical aspects of the development program. This meeting is particularly beneficial when a sponsor has identified the investigational product to be evaluated in a clinical study and conducted some preliminary preclinical proof-of-concept studies but has not yet designed and conducted definitive toxicology studies. 
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-interact-meetings 

Pre-IND Meetings 

The Pre-IND meeting serves as a platform for sponsors to discuss their development programs and seek regulatory guidance before submitting an IND application. It allows for the review and feedback on the design of preclinical studies, the initial IND study, and product manufacturing and quality controls needed to initiate human studies. This meeting is appropriate when the sponsor has defined the manufacturing process to be used for the clinical studies, developed assays and preliminary lot release criteria, and completed proof-of-concept and possibly some preliminary preclinical GLP safety/toxicology studies. 
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otp-pre-ind-meetings 

Key Differences 

• Timing in Development: INTERACT meetings are intended for earlier stages of development, prior to definitive toxicology studies, while Pre-IND meetings are suitable when the development program is more advanced, with defined manufacturing processes and completed proof-of-concept studies. 

• Purpose and Focus: INTERACT meetings focus on obtaining initial advice on early product characterization and preclinical proof-of-concept studies, whereas Pre-IND meetings provide detailed feedback on IND-enabling studies, including CMC, pharmacology/toxicology, and clinical trial design. 

Strategic Considerations for Startups 

Choosing the appropriate meeting type is critical for startups to align their development programs with FDA expectations, optimize resources, and mitigate risks. Engaging in an INTERACT meeting can be advantageous for addressing novel challenges early, while a Pre-IND meeting is beneficial for refining plans as the program progresses toward clinical trials. 

Worth mentioning that FDA may decide, after getting an INTERACT briefing package to advice the company that it is too early for such interaction, meaning that the level and amount of data is not mature enough for such an interaction. While in other cases the FDA will change the format of the meeting to a Pre-IND or a Type C meeting if the sponsor focus is the clinical development of the product.  

Recent FDA Trends 

The FDA has been enhancing its engagement with sponsors through initiatives like the introduction of Type D meetings, which provide a mechanism for addressing narrow questions that can be resolved in a shorter timeframe. Additionally, the formalization of INTERACT meetings reflects the FDA’s commitment to facilitating early communication, especially for innovative products that may present unique challenges. 
 

Conclusion 

For biopharma startups, understanding the distinctions between INTERACT and Pre-IND meetings is essential for effective regulatory strategy. By selecting the appropriate meeting type and engaging with the FDA at optimal stages, companies can enhance their development programs, ensure compliance, and expedite the path to market. 

The landscape of data privacy is shifting rapidly in the United States, with numerous states enacting comprehensive privacy laws aimed at protecting consumer data. These laws, such as the California Consumer Privacy Act (CCPA) and Virginia Consumer Data Protection Act (VCDPA), are reshaping how organizations process personal data. However, for the pharmaceutical and clinical research sectors, the intersection of these laws with the strict regulatory frameworks already governing clinical trials presents a nuanced challenge. 

Applicability of U.S. State Privacy Laws to Pharmaceuticals 

U.S. state privacy laws often impose thresholds that many pharmaceutical companies, particularly smaller ones, do not meet. For example, under the CCPA, a business is only subject to the law if it satisfies one of the following conditions: 

• Has annual gross revenues exceeding $25 million. 

• Buys, receives, or sells the personal information of 100,000 or more California residents, households, or devices. 

• Derives 50% or more of its annual revenue from selling personal information. 

Similar thresholds exist in other state privacy laws, including the VCDPA and Colorado Privacy Act (CPA). Smaller pharmaceutical companies, especially those in early stages of development or focused on business-to-business (B2B) operations rather than direct consumer interaction, often do not meet these thresholds. As a result, they are frequently outside the scope of such laws. 

This reality provides a level of relief for many biopharmaceutical firms, enabling them to prioritize compliance with specialized regulations that govern their operations, such as those issued by the U.S. Food and Drug Administration (FDA) and international frameworks like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice (ICH-GCP) guidelines. 

Exemptions for Clinical Trial Data 

A key factor distinguishing clinical research from other sectors is the comprehensive regulatory oversight that governs the processing of personal data in clinical trials. Most U.S. state privacy laws recognize these existing frameworks and exempt data processed for research purposes under certain conditions. 

For instance: 

• CCPA/CPRA: Excludes personal data used exclusively for scientific, historical, or statistical research in the public interest, provided the research adheres to applicable ethics and privacy laws, such as the Common Rule (45 C.F.R. Part 46), and is overseen by an Institutional Review Board (IRB) or similar entity. 

• VCDPA and CPA: Offer similar exemptions for personal data processed for research purposes that are conducted in compliance with recognized ethical and legal standards. 

• Texas Data Privacy and Security Act (TDPSA): Explicitly exempts identifiable private information collected as part of human subjects research under FDA regulations, ICH-GCP, or the Common Rule. 

These exemptions ensure that data used in clinical trials is governed by a regulatory regime tailored to the unique requirements of clinical research, prioritizing participant safety, data accuracy, and ethical standards. 

A Nuanced Approach to Investigators’ Data 

While data collected about investigators and medical staff is crucial for clinical trial operations, its treatment under privacy laws depends on the context. If this data is processed strictly within the scope of the trial, in compliance with FDA regulations and ICH-GCP, it is typically exempt from U.S. state privacy laws. However, if the same data is used for purposes outside the trial—such as employment-related activities or marketing—and the threshold for application is met, it may fall under the purview of applicable privacy laws. 

Sponsors should exercise caution and limit the processing of investigators’ personal data to the purposes necessary for the trial. Misusing such data outside its intended scope could trigger compliance obligations under U.S. state privacy laws or other applicable regulations. 

Practical Recommendations for Compliance 

Pharmaceutical companies and clinical trial sponsors should take the following steps to ensure compliance: 

1. Assess Applicability: Determine whether state privacy laws apply based on thresholds, business operations, and data processing activities. 

2. Document Exemptions: Clearly document that data used in clinical trials complies with FDA regulations, ICH-GCP guidelines, and ethical standards, demonstrating its exemption from state privacy laws. 

3. Limit Data Use: Restrict the use of investigators’ and staff data to the purposes necessary for trial conduct, avoiding processing for unrelated purposes that could trigger privacy law obligations. 

4. Prepare for GDPR Compliance: For companies running trials in the EU, ensure full alignment with GDPR requirements, including appointing an EU data protection representative, is mandatory. 

Conclusion 

While the growing web of U.S. state privacy laws presents new compliance challenges for businesses, the pharmaceutical and clinical research sectors benefit from tailored exemptions recognizing the rigorous regulatory frameworks already in place. By ensuring that clinical trial data complies with FDA regulations, ICH-GCP, and other applicable laws, sponsors can maintain focus on advancing medical research while respecting data protection requirements, nonetheless, U.S. companies must be vigilant and if conducting trials in the EU, GDPR compliance must be ensured.  

In this evolving landscape, a proactive approach to compliance—rooted in understanding the scope and exemptions of privacy laws—can help pharmaceutical companies navigate complexities and continue driving innovation in clinical research. 

You are an innovator who sees a healthcare problem that can be addressed, in whole or part, by digital technology (a software-enabled device delivering feedback and improvement in user feel, function, or other metrics).   

One of the earliest determinations you need to make is whether your product will be a consumer-facing or a regulated product, with implications for pathway to market, commercial value, funding, your team, and other strategic matters. 

An illustrative example is a consumer-facing wearable device focused on general wellness that reports on e.g. heartrate or the number of hours you’ve slept in a non-medical setting, that the FDA does not regulate,FN1 in contrast to Continuous Glucose Monitors, or CGMs (even those cleared this year by the FDA for Over-the-Counter, i.e., non-prescription, use), which require at least FDA 510(k) clearance.FN2 

If the intended use and claim for your device is to diagnose or cure, mitigate, treat or prevent a disease, it will be subject to FDA regulation.  While development of an FDA-regulated medical device will require more time, money and clinical data, such a product will typically command a (much) higher price and commercial value. 

Digital therapeutics (or DTx), a category of medical devices that has exploded over the past decade, are software-based medical devices, the use of which are supported by randomized, controlled clinical data to diagnose or cure, mitigate, treat or prevent a disease or condition in a particular patient population.FN3   

Over three dozen DTx products have been approved or cleared by the FDA, for indications in mental health (such as depression, anxiety, schizophrenia, ADHD and insomnia), cardiometabolic diseases (such as diabetes monitoring and treatment), and treatment, prevention of chronic conditions (such as pain), among others.FN4   

FDA’s Center for Devices and Radiological Health (CDRH) regulates DTx as medical devices, technically, as a type of Software-as-a-Medical Device.FN5  Thus, general regulatory considerations, standards and requirements for e.g. Class II 510(k) clearance or Class III De Novo determination, as the case may be, apply.  However, FDA has recognized that software, particularly when combined with Machine Learning/AI that iteratively improves with incremental use via mechanisms such as predetermined change control plans (PCCPs), is different from a pharmacological product, where practically every variation constitutes a new product, necessitating a new safety and efficacy assessment.FN6  The FDA has a Digital Health Center of Excellence that spearheads thinking and policy about digital technologies, including DTx.FN7 Informal inquiries regarding the potential regulatory status of such software products are typically submitted to the Digital Health Center of Excellence’s general mailbox at ﷟HYPERLINK “mailto:DigitalHealth@fda.hhs.gov” for initial agency feedback. 

Regulatory issues are not the only challenges for DTx.  Early leaders stumbled on what observers have characterized as reimbursement and business model issues.  However, the potential of DTx appears undeniable, with next generation approaches that are tackling the challenges,FN8 and Medicare proposing to reimburse for mental health DTx.FN9 Despite these current challenges and in light of the proposed next generation approaches, manufacturers continue to seek clearance for digital therapeutics, especially in the mental health space, where there is a significant need for more at home technologies.  For example, the following additional software devices intended to address mental health conditions have recently been cleared in 2024: 

• MamaLift Plus  – a prescription device intended to treat mild to moderate postpartum depression by improving a patient’s symptoms of depression.FN10 

• Sleepio – a prescription device intended to treat chronic insomnia as an adjunct to usual care.FN11 

• Daylight  – a prescription digital therapeutic intended to treat generalized anxiety disorder by improving a patient’s GAD symptoms as an adjunct to usual care.FN12 

It is important to note that the recent clearances cited above were all supported by robust clinical trials that included a control arm. 

Additional uncertainties have arisen with the returning administration of US President-elect Donald Trump, and his nominees such as Robert F. Kennedy, Jr. to head the Department of Health and Human Services (with oversight over the FDA, the National Institutes of Health, the Centers for Disease Control and the Centers for Medicare and Medicaid Services) and Marty Makary to head FDA, and the recent appointment of Michelle Tarvin as the new CDRH director, after Jeff Shuren’s 15-year tenure.  Crosscurrents such as deregulation and reduction of the administrative state, on the one hand, and greater transparency and safety of regulated products, on the other, portend a period of heightened risks and opportunities for developers of DTx and other rapidly innovating life science products. 

____________  

FN1  See, e.g.:  chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.fda.gov/media/90652/download  

FN2  See, e.g.:  https://www.youtube.com/watch?v=IAJQqQ3oVpE&t=157s) 

FN3 See, e.g.:   https://htdhealth.com/insights/digital-therapeutics-explained/#:~:text=What%20is%20unique%20about%20digital,remove%20the%20health%20provider%20entirely.  

FN4  https://www.nature.com/articles/s41746-023-00777-z#Tab3 

FN5  https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd 

FN6  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial.   

FN7  https://www.fda.gov/medical-devices/digital-health-center-excellence/guidances-digital-health-content 

FN8  See e.g.:  https://pharmaphorum.com/digital/fall-and-rise-digital-therapeutics 

FN9  https://www.statnews.com/2024/07/25/health-tech-news-medicare-dtx-codes-hhs-revamp-fda/  

FN10 K223515.pdf 

FN11 K233577.pdf 

FN12 K233872.pdf 

Considering legal and regulatory aspects early in product development is crucial for streamlining time-to-market and enhancing business strategy. Legal issues can become obstacles during due diligence or serve as valuable assets for investors. Proper planning avoids delays, facilitates a robust business model, and aligns with long-term goals. 

Why Regulation is Critical for Business Strategy: In digital health, the line between regulated medical devices (e.g., “software as medical device”) and non-regulated software can be thin. Regulatory status influences the business model, time-to-market, and sales strategies. Adhering to regulatory requirements during development prevents costly last-minute changes and accelerates market readiness. 

When to Consider Regulatory Requirements: Regulatory assessments should begin during the initial stages of product planning and development. A detailed understanding of your product’s features, intended use, and indications ensures the viability of the business model and mitigates future hurdles. 

Highly Regulated Environment: The U.S. healthcare sector is extensively regulated, with federal and state laws governing healthcare provision, institutions, professions, and medical data. Tailored regulatory evaluations are essential for compliance and should account for product-specific requirements. 

What to Check 

• Privacy Protection: Privacy compliance is mandatory, especially in healthcare. In the U.S., HIPAA compliance is essential for products involving “covered entities” (e.g., hospital, physicians, clinics) or “business associates” (e.g., a supplier to a covered entity). For business-to-client models, and when HIPAA does not apply, federal and state privacy laws can be relevant. This legislation varies by state, necessitating a thorough review. DNA & biometric data may trigger  specific legislation as they usually attract regulatory attention.  

• Regulatory Authorization: Determining whether your product qualifies as a medical device can impact timelines and costs. Regulatory frameworks for “software as medical device” are evolving, with significant FDA guidance on mobile medical apps, clinical decision-support tools, and AI-enabled devices. Regulatory compliance spans the product’s lifecycle, covering quality control, design, risk management, and labeling. 

• Artificial Intelligence: AI regulation is rapidly developing. While no federal AI law exists in the U.S., hospitals (and other medical institutions) are required by federal law to implement measures aimed at mitigating bias in clinical decision-making tools, and the FDA has issued draft guidance on AI in medical devices and clinical trials. In addition, several states have enacted AI specific state laws that might be relevant. In this period of regulatory uncertainty, adopting AI risk management plans is strongly encouraged to align with emerging standards and best practices, mitigate exposure, meet the expectations of major companies, and attract investor interest. 

• Apps, Websites, and Patient Interfaces: Legal aspects such as terms of use, privacy policies, and informed consent must comply with privacy laws, consumer protection laws, advertising regulations, and disability legislation. Special care is needed for claims about medical benefits and products targeting healthcare professionals. 

• Reimbursement/Insurance: U.S. insurance coverage, known as reimbursement, affects pricing, sales potential, and clinical data requirements. Regulatory approval alone does not guarantee reimbursement, making reimbursement/Insurance expert consultation vital for market entry. 

Additional Considerations: Regulatory choices influence tax planning and Intellectual Property (IP) strategies. For instance, claiming regulatory similarity to existing devices for approval may expose your product to IP challenges. Strategic alignment with regulatory requirements can assist with smoother market integration and long-term success. 

This newsletter is provided for educational purposes only and does not constitute legal advice or legal opinion. Do not act on the information presented without appropriate professional advice after a comprehensive and thorough examination of the specific situation. 

An “orphan designation” is granted by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for a drug/biologic to create financial incentives for developing therapies for rare diseases.  

This article focuses on the FDA orphan designation program in respect to the incentives offered, the prevalence that defines an orphan disease, as well as the procedural process of obtaining the designation. 

Keywords 

ODD, OMPD, orphan, prevalence, rare  

Introduction 

A rare disease is, as implied, a disease that affects a relatively low number of patients in the population. Many (over 6,000) rare diseases have been identified to date, and it is estimated that 3.5% – 5.9% of the worldwide population is affected by these diseases. 72% of rare diseases are genetic, while others result from infections, allergies, and environmental causes. Due to the low prevalence of each disease, medical expertise is rare, and knowledge and effective care are extensively lacking. In the past, drug manufacturers would not invest in therapies for rare diseases as they could not cover the vast costs of drug development and profit from marketing drugs to such small groups of patients. Despite the urgent need for rare disease¹ medicines, they came to be known as orphans of health systems, as companies would not develop these medicines, and the patient was often denied proper diagnosis and treatment² of therapies for orphan diseases.   

In order to encourage the development, the US Food and Drug Administration (FDA)  launched programs to create financial incentives for developing these therapies. An “orphan designation” is granted for a drug/biologic developed to treat an orphan disease.  

Since their inception, orphan designation programs have successfully created incentives for developing orphan drugs. For example, in 1983, the US Congress passed the Orphan Drug Act (ODA) laid down in 21 Code of Federal Regulations (CFR) §316³ to create financial incentives for orphan drug developers. Since 1983, the Act has resulted in the development of more than 250 orphan drugs, which are available to treat a potential patient population of more than 13 million Americans². 

Orphan Drug Designation in the US 

To be eligible for Orphan Drug Designation (ODD) granted by the FDA, a drug or biologic product should be intended for the safe and effective treatment, diagnosis, or prevention of rare diseases/disorders. To be defined as a rare disease in the US, the disease should affect fewer than 200,000 people in the US (prevalence is <200,000 persons) or affect more than 200,000 persons but not expected to recover the costs of developing and marketing a treatment drug (drugs that will not be profitable within 7 years following approval by the FDA).  

How to Submit a Request for ODD Designation  

An application⁴ of ~30 pages is submitted to the Office of Orphan Products Development (OOPD) by a US representative⁵.  

The basic elements in US FDA orphan designation⁴ application  

• Administrative information 

• Information on the disease or condition: Pathophysiology, etiology, treatment options and prognosis 

• Scientific rationale that demonstrates the drug’s “promise” to treat, diagnose or prevent the disease/condition, e.g., drug description and mode of action relevant to disease/condition; proof of concept studies, in vitro and in vivo data, clinical studies relevant to drug and disease/condition (if available) 

• Regulatory status 

• Determining the population estimate to support that the disease is rare: calculate the number of patients in the US based on established literature references and current US population estimates to show prevalence is < 200,000  

The evaluation process takes a maximum of 90 days from application submission. The application can be submitted on any date.   

The benefits of a US FDA orphan designation  

• Potential 7-year marketing exclusivity after approval 

• Exemption from user fees (waiver of NDA/BLA user fees) 

• Tax credits for qualified clinical testing  

Annual report  

An annual summary of information on the status of orphan drug development should be submitted. These are short documents (~10 pages) submitted between 12 and 14 months from the date of initial designation acceptance annually. The summaries include a review of preclinical and clinical studies performed and planned, a short description of the investigation plan for the coming year, and any anticipated or current problems/difficulties in testing/potential changes that may impact orphan designation.  

Acronyms and abbreviations 

BLA, Biologics License Application; CARs, Cumulative Abnormal Returns; CFR, Code of Federal Regulations; FDA, [US] Food and Drug Administration; NDA, New Drug Application; ODA, Orphan Drug Act; ODD, Orphan Drug Designation; OMPD, Orphan Medicinal Product Designation; OOPD, Office of Orphan Products Development;  

References 

(1) EURORDIS Rare Diseases Europe. What is a rare disease? www.eurordis.org/information-support/what-is-a-rare-disease/ (accessed). 

 
(2) US FDA. Orphan Products: Hope for People With Rare Diseases. 2018. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/orphan-products-hope-people-rare-diseases (accessed). 

(3) US FDA. 21 CFR §316. 2023. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=316 (accessed. 

4) US FDA. Recommended Tips for Creating an Orphan Drug Designation Application. 2018. https://www.fda.gov/media/111762/download (accessed. 

(5) ADRES Ltd. Guiding you through regulatory processes. https://adres.co.il/regulatory-affairs/ (accessed). 

About the authors 

Liron Gibbs-Bar, PhD, is an associate senior regulatory and scientific consultant at ADRES and ADRES EU. She has more than eight years of experience in regulatory affairs, including regulatory strategy, briefing packages, and clinical trial applications writing, as well as interactions with regulatory authorities.  
Dr. Gibbs-Bar has a PhD in developmental biology from the Weizmann Institute of Science. She can be reached at liron@adres.bio 

In May 2024, the FDA finalized a rule that will bring significant changes to the regulation of Laboratory Developed Tests (LDTs)*, marking an end to decades of enforcement discretion. Under this new framework, laboratories that manufacture nonexempt LDTs will be required to comply with medical device regulations, phased in gradually over the next four years. Stage One of compliance is fast approaching, with key deadlines and requirements set for May 6, 2025. 

*LDTs are in vitro diagnostic products (IVDs) that are intended for clinical use and are designed, manufactured, and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and meets the regulatory requirements under CLIA to perform high complexity testing. 

Here’s what laboratories need to know and do to stay compliant with Stage One: 

🔹 Medical Device Reporting (MDR) Requirements: 
By May 6, 2025, laboratories must comply with MDR regulations, which require reporting to the FDA any adverse events where an LDT may have caused or contributed to a death or serious injury, or if an LDT malfunctions in a way that could lead to harm. Even potential issues (e.g., design flaws or user errors) must be reported. Once a laboratory becomes aware of such an event, a report must be submitted within 30 days (or 5 days for urgent public health risks). Make sure your team establishes robust processes to identify, document, and report these events on time via the FDA’s Electronic Submissions Gateway. 

🔹 Correction and Removal Reporting Requirements: 
Labs will also need to comply with the FDA’s correction and removal requirements. Any corrective actions (such as repairs, modifications, or removals) taken to address health risks or unlawful activities related to an LDT must be reported to the FDA within 10 working days. Even if no report is necessary, detailed records must still be kept of all corrections and removals for FDA inspection. Now is the time to set up your system for tracking, documenting, and reporting these activities. 

🔹 Quality System Complaint Files: 
The FDA also requires that laboratories maintain formal Quality System complaint files. This means you must have a designated unit to manage and review complaints about your LDTs, ensuring that all complaints—both oral and written—are properly documented and evaluated. If a complaint relates to a potential adverse event, it may trigger additional MDR reporting. Make sure your complaint-handling procedures are solid, with thorough documentation and trend analysis capabilities to ensure compliance during FDA inspections. 

Who Needs to Comply? 

The FDA’s rule applies to most laboratories offering nonexempt LDTs. Some exceptions exist, such as: 

1. LDTs similar to those used in 1976, performed manually in a single CLIA-certified laboratory. 

2. LDTs used for human leukocyte antigen (HLA) testing in transplant activities. 

3. Forensic tests for law enforcement purposes. 

4. LDTs manufactured and used within the Department of Defense or Veterans Health Administration. 

However, if your laboratory offers any LDTs outside of these categories, it’s time to ensure compliance with the FDA’s Stage One requirements. 

Why Prepare Now? 

While there are ongoing legal challenges to the FDA’s authority over LDTs, including lawsuits from the American Clinical Laboratory Association (ACLA) and other groups, labs should not wait for these cases to be resolved before acting. It is unclear if the courts will rule before the May 2025 deadline, and waiting could lead to last-minute infrastructure investments and rushed compliance efforts. 

Setting up the necessary infrastructure for adverse event reporting, correction and removal systems, and complaint handling processes will take time. Start assessing your laboratory’s current capabilities now and develop an action plan to ensure you’re ready to meet these new regulatory obligations. 

Next Steps: 

1. Assess compliance needs: Evaluate whether your LDTs are exempt or subject to Stage One requirements. 

2. Implement reporting systems: Set up the processes and technology needed to meet MDR, correction, and removal obligations. 

3. Establish complaint procedures: Designate and train a formal complaint unit, and develop comprehensive documentation practices. 

4. Stay informed: Keep an eye on the evolving legal landscape and any updates from the FDA or courts that could impact your compliance timeline. 

The FDA’s rule represents a major shift for the industry, and the deadlines are approaching fast. Now is the time to get ahead of the curve and ensure your laboratory is fully compliant by May 6, 2025.  

The ADRES team is here to support you in ensuring your laboratory achieves full compliance with the latest FDA regulations.

While watching this movie might not be very helpful to a medical device company that wants to launch its product in the US, it will make you laugh. However, there are some truths in the movie that are worth noting. Coming to America with little preparation and knowledge can wind up in some precarious situations. The culture is different, and many of the rules, processes, and things that make the transition easier may not come naturally. 

For a medical device company contemplating launching in the US there are some things that are obvious. Regulatory compliance with the FDA is essential to sell any medical device in the US and this includes having an appropriate QMS (Quality Management System). There are numerous resources on this topic, and this of course is one area that we focus on. 

Many companies look at this hurdle as the first one to overcome in preparing to launch in the US. While it is necessary, it’s rarely the first step. 

Let us consider what the end goal is. In 100% of all our clients, the primary goal is to sell their product in the US. Gaining regulatory approval does not mean success in the market. So, what are the questions that need to be answered and how should we consider accomplishing that? 

First question: Is there a market? 

Just because the device might have been successful in other markets, or even because the device has a benefit to the patient, does not necessarily mean it will be purchased in the US market. There are multiple aspects to consider. It’s not as simple as “the surgeon will want this.” That could be true, and it’s important to have a champion that wants the product. This is usually a physician, nurse, or, in some cases, administration that makes their life easier. But it’s unlikely the champion is paying for the device. So, one has to always look at the economics of a purchasing decision. What value does it bring to the purchaser? Is it replacing something else?  

Customer discovery should always be at the forefront of the process. We generally put together a group of all stakeholders and determine who wants the product, who doesn’t want the product, and possibly most importantly, what are the healthcare economics around the utilization of the product.  

Second question: How big is the market? 

There’s also the question of how big the market is. Is it an existing market or an emerging market? Emerging markets take much longer to penetrate usually, but it also means the market hasn’t been penetrated. In existing markets, one has always to consider the possibility that while there might be a big market, it’s already saturated, and the available market is only a replacement market. This can happen when there’s good reimbursement and replacing a device that may only be a few years old offers no return on investment to the hospital. This goes back to understanding the economics of the purchase. 

Always evaluate the market thoroughly before going through the expense of getting cleared by the FDA. If there is no market or the market opportunity is very limited, it may not be wise to pursue it. 

Third question: Is there reimbursement? 

This is usually key to being able to scale sales in the US. There are often early adopters without reimbursement, but this usually doesn’t amount enough to establish stability in the market. Reimbursement is paramount, and if reimbursement does not exist, it’s likely that it will need to be pursued. There’s an article on the Reimbursement Strategies here (https://www.rivesconsult.com/post/reimbursement-strategies-for-early-stage-medical-devices) 

Reimbursement often has some very specific language on what qualifies for reimbursement, and this can be important for any regulatory filings. The regulatory claims need to be aligned with any reimbursement that will be pursued.  

We had one client come to us with claims of “prevention.” Prevention is not reimbursable, but early detection is. For this reason, we recommended changing their marketing stance to “early detection.” No changes were necessary for the device, only how it was positioned in the marketplace and the language that would be used for filing with the FDA. 

Fourth question: Who are the leaders in the field? 

Particularly for early-stage innovative devices, we always recommend working with leaders (KOLs) in the field. These leaders can often help with everything from reimbursement to clinical trials, but they can also be part of a medical advisory board. This is a good article on the importance of a medical advisory board. (https://tincture.io/how-to-build-an-effective-medical-advisory-board-in-seven-steps-59eb92e794ce) 

We always recommend embracing these leaders. They’ve spent their career in the area where your device is relevant, and they can be of tremendous value in not only helping you launch your product but also in advising on the ongoing development of the product. They can also help point out pitfalls and obstacles you may have in successfully gaining market share. 

Fifth question: What are the indications for use and intended use? 

This will be a primary part of an FDA application. If there is reimbursement, this must be aligned with how likely it is to get reimbursed. We always stress the importance of considering this very carefully, including the possibility of limiting the indications for use and intended use beyond what one may consider the broadest market. Let’s say, for example, the device tends to have a bigger effect on more older adults, perhaps 65 and older, but there is also some evidence that it can have a good effect on anyone over the age of 40. A study to include the whole potential patient population may be significantly larger and more expensive and must be weighed against the market sizes. In some cases, it makes sense to enter the market with narrower indications for use and intended use and then add additional studies and do a subsequent filing with the FDA to expand these later.  

When working with the FDA, it is important to have someone with experience and a good relationship with the FDA. Many people see the FDA as a barrier to entry, and while to some degree that’s true, the FDA is not trying to keep companies and devices from entering the market. They are only ensuring that they are safe and effective, with an emphasis on safety. If a device has an additional risk to patients, those risks will need to be outweighed by the potential benefits to the patient. In our experience, the FDA has been very open and easy to work with, particularly with early-stage innovative companies.  

Another aspect of working with the FDA is understanding some of the subtleties in the language used. Two phrases may appear to have the same meaning, such as being cleared or approved by the FDA. However, being cleared and approved are two different things to the FDA. A 510(k) application is cleared to market, and a PMA application is approved by the FDA. Another often misunderstood word is labeling. Many think this is the label that goes on the device, but to the FDA, labeling is everything about the device, including instructions for use, the operator’s manual, safety requirements, storage requirements, training materials, etc. Subtle wording in indications for use and intended use can make significant differences not only in reimbursement but also how one can market the product.  

Sixth question: Do you need a clinical trial or usability study? 

Oftentimes, one of these is necessary for FDA clearance. Usually, the KOLs can assist with this, or in some cases, if there is the need for a large clinical study, such as a PMA application, employing a CRO can help. One thing to note, though, with CROs is they are not working to build a relationship with KOLs. Their job is to get a clinical study accomplished. So, it’s important to understand this and manage expectations. Another very important aspect of working with a CRO is being sure you have the right CRO and staying on top of monitoring or overseeing their process. A CRO that’s too big for a company or set up for therapeutic trials is probably not the right fit for an early-stage innovative medical device company. We recommend interviewing and getting quotes from multiple CROs and interviewing them before making a decision on who to work with. Our company decided to hire an expert who had run a CRO previously to do this for our clients. 

Seventh question: How are you going to get your first five sales? 

You will never scale a business if you can’t get the first five sales. So, what does it take to get those sales? Who is your champion? Who or what are the obstacles to getting the sale? Selling into hospitals is complex, and the bigger the hospital system, the more complex it tends to be. On top of that, you’re a new vendor, and purchasing is not thrilled about qualifying and adding vendors. Are you connected to the hospital network? Is patient information part of the data connected to the network? Another hurdle with IT in the hospital to address.  

One of the biggest challenges for new innovative device companies can be a change in workflow. If the device is truly unique and is not replacing another device, there is almost definitely a change in workflow. This can be a barrier to entry and has to be handled appropriately. We often use the analogy of changing workflow in a healthcare setting, which is a little like steering an iceberg. It can be done, but it isn’t easy, and it takes time. Change in workflow almost always comes with some resistance, and one must understand what that is and how to overcome it.  

We generally recommend getting these first sales directly. You need firsthand knowledge from some different institutions about what it’s going to take to achieve sales. Channel distribution can be effective down the road once you have the formula for a successful sales transaction. 

Eighth question: What are the resources necessary to launch? 

What kind of personnel will you need in the US initially to sell, train, and support the product? Most clients from Europe that have been successfully selling in the EU have a pretty good handle on this. But if one has not been selling or is selling very early in selling in another location, then it can be more difficult. The sales side is fairly simple, particularly if a soft launch is the plan. The service side can sometimes be more daunting as it often needs the expertise of engineers within the company. How will service calls be handled initially and ultimately resolved? How much additional staff is needed to accomplish this?  

What are the hours of needing to have customer service support? In use, we generally recommend from 8 am Eastern time to 5 pm Pacific time Monday through Friday for devices that are not used in emergency situations. For devices used in emergency situations, support may need to be available 24/7.  

Once these questions can be answered at least to a reasonable level of certainty, a financial proforma can be refined for resource planning. 

Ninth question: What did I not think about? 

This is one of the most important questions. The first eight questions will probably seem somewhat obvious and necessary to launch a medical device in the US, but what are the things needed to execute it that have been overlooked? These are often the details that can be critical if not addressed. Many of the details have to do with some basic aspects of selling medical devices in the US. First, there is the issue of having an Initial Importer by the FDA. This is similar to the function of a EU representative in the European Union. One solution is to set up a subsidiary for the parent company, but there are other solutions involving outsourcing this to companies based in the US. What is optimal in terms of manufacturing? Importing in the US can be expensive and needs to be considered.  

Also, there are HR (human resource) requirements and compliance for HR. These can include certain legal requirements, such as having appropriate workers comp insurance to paying and withholding required taxes. 

Some other items that must be considered are liability insurance, which protects the company should anything go wrong. Hospitals are also generally required to purchase the product. They want to be sure they are protected should anything malfunction. Logistics and planning on how to ship, receive, and install the technology, as well as have timely training. Other taxes and registrations are required for both sales tax, medical device tax, and possibly import taxes and duties. 

Summary: 

I’d love to say this is a full, comprehensive list of everything that needs to be considered when planning to launch a medical device in the US, but it’s not even close. It is a good high-level overview of the main areas that need to be considered and hopefully is helpful to anyone on the journey of Coming to America!