16.08.2025

Beyond Generic AI: How Domain Expertise Creates Breakthrough Tools for Pharmaceutical Operations

By Josh Magnus
Cleanroom and aseptic expert CEO Magnus Solutions

From Environmental Monitoring to Documentation Intelligence

A biologics manufacturer was preparing for a critical FDA pre-approval inspection. Their regulatory team faced months of manual document review to identify potential compliance gaps across thousands of SOPs, validation reports, and quality records. Instead, they deployed an SME-guided AI system that analyzed their entire quality management system in just two days, identifying 23 potential gaps with surgical precision. But the AI didn’t stop there—it suggested specific corrections for each gap, automatically rewrote non-compliant sections of documents, and analyzed recent FDA warning letters and 483 observations to help the compliance team prepare for likely inspection focus areas. This comprehensive regulatory intelligence, combining human expertise with AI capabilities, transformed months of manual work into days of strategic preparation.

The SME-AI Partnership: Beyond What Either Could Achieve Alone

In pharmaceutical manufacturing, the transformational opportunity lies in subject matter experts (SMEs) working with AI to create specialized tools that leverage both human expertise and machine capabilities. While generic AI tools offer broad functionality, they lack the nuanced understanding of pharmaceutical operations needed to distinguish meaningful patterns from statistical noise.

The breakthrough comes when pharmaceutical SMEs harness AI’s computational power to amplify their domain knowledge. Human experts understand what correlations matter pharmaceutically and why, while AI provides the analytical capability to process massive datasets and identify patterns that would require immense human time and effort to detect manually.

The Environmental Monitoring Revolution: Real-World SME-AI Collaboration

Environmental monitoring in pharmaceutical facilities generates enormous data volumes—thousands of daily measurements across temperature, humidity, pressure, particle counts, and microbial parameters. While SMEs understand these parameters’ pharmaceutical significance, manually analyzing vast datasets for complex correlations would be practically impossible.

Consider our environmental monitoring data analysis software, developed through SME-AI collaboration. Environmental monitoring experts intimately understand the pain points of their field—the countless hours spent manually entering EM data into spreadsheets, the weeks required to analyze trends across multiple parameters, and the tedious process of writing comprehensive reports that often delay critical decision-making. This firsthand knowledge of time-intensive, repetitive tasks became the driving force to create a tool that goes beyond traditional analysis.

The SME-designed system doesn’t just analyze large amounts of data and find correlations—it’s specifically engineered to eliminate the inefficiencies that SMEs know consume enormous time and resources. Environmental monitoring experts provide the pharmaceutical framework, understanding that contamination events result from complex interactions between multiple parameters, personnel activities, and equipment operations. They know which parameter combinations indicate real contamination risks and what thresholds require immediate investigation. But equally important, they understand which routine tasks can be automated to save time and money while improving accuracy.

AI amplifies this expertise by continuously analyzing datasets across multiple facilities, processing in minutes what would take human experts weeks to analyze comprehensively. The system simultaneously tracks hundreds of parameter relationships, identifying correlations that SMEs know are pharmaceutically significant but would require enormous manual effort to detect.

For instance, the system detected a subtle correlation between specific humidity fluctuations and increased particle counts in a filling suite. The SMEs provided the crucial pharmaceutical context—understanding that elevated humidity creates favorable conditions for microorganisms such as mold and fungi to thrive, leading to increased microbial contamination risks that threaten product sterility. AI provided the computational power to identify this specific correlation among thousands of potential relationships across months of historical data.

This represents true operational intelligence: human experts provide pharmaceutical understanding of why patterns matter, while AI provides the computational capability to find these patterns in complex, multi-dimensional datasets that would overwhelm human analytical capacity.

Transforming Operations Across Multiple Domains

Regulatory Compliance: SME-guided AI systems can process thousands of regulatory documents in days versus months of manual review. The biologics manufacturer mentioned earlier implemented such a system where regulatory experts defined the analytical framework while AI provided the processing power, achieving higher accuracy than traditional consultant engagements.

SOP Development: Quality SMEs provide pharmaceutical frameworks while AI rapidly generates comprehensive procedure drafts with consistent terminology and regulatory references. A contract manufacturing organization reduced SOP development time by 70% while improving quality through this approach.

Documentation Intelligence: Pharmaceutical facilities generate enormous documentation volumes that would take months to analyze manually. SME-guided AI systems can identify patterns across massive document repositories. One facility’s system recognized that seemingly unrelated deviations in different departments were actually symptomatic of a training gap, leading to targeted interventions that reduced similar deviations by 60%.

The Competitive Advantage

Generic AI offers limited pharmaceutical value because it lacks the domain context that distinguishes meaningful patterns from statistical artifacts. Pure human analysis, while pharmaceutically meaningful, cannot scale to handle the massive datasets and complex correlations that modern pharmaceutical operations generate.

The organizations investing in SME-AI collaborative systems—where environmental monitoring specialists partner with AI for comprehensive data analysis, regulatory professionals collaborate with AI for document intelligence, and quality experts work with AI for systematic trend analysis—will have significant competitive advantages in operational efficiency, regulatory compliance, and product quality.

The Strategic Imperative

For pharmaceutical facility managers and bio-startup founders, the choice isn’t whether to implement AI—it’s whether to pursue SME-AI collaboration or settle for generic automation that lacks pharmaceutical intelligence.

As regulatory expectations increase and operational complexity grows, the facilities that combine irreplaceable human pharmaceutical expertise with AI’s computational capabilities will lead the industry’s transformation. This partnership creates specialized solutions that turn data into insights and insights into operational excellence.

The transformation is already beginning. The question isn’t whether SME-AI collaboration will reshape pharmaceutical operations—it’s whether your facility will lead or follow this fundamental shift toward pharmaceutical intelligence that amplifies human expertise through artificial capabilities.

At Magnus Solutions, we don’t just build tools. We build capability—so pharmaceutical facilities can stop reacting to problems and start anticipating them.

About the author

Josh Magnus

Cleanroom and aseptic expert CEO Magnus Solutions

Magnus Solutions is a consulting and training firm specializing in cleanroom operations, contamination control, and AI-powered tools for pharmaceutical and medical device companies. We combine deep industry expertise with tailored technology to help clients improve compliance, reduce deviations, and streamline critical processes. By blending subject matter expertise with smart automation, Magnus Solutions helps facilities move from manual work to strategic insight – without compromising on quality or compliance.

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15.08.2025

AI in Clinical Trials: From Promise to Practice

By Hadas Nachmanson
Director, Clinical Operations & Trial Management | Consultant | Founder of Myrtle Clinical – Independent Clinical Trial Solutions | Expert in Regulatory Submissions, Site Management, CRA Leadership & Vendor Oversight

The clinical trial landscape is undergoing a profound transformation, with artificial intelligence (AI) at its core. No longer a futuristic concept, AI has become a practical and applied force, reshaping every phase of clinical research. This article explores a selection of AI-driven technologies already in active use and how they are redefining drug and device development.

One of the most prominent commercial tools is the platform developed by Israeli HealthTech company QuantHealth , which helps design precise, data-driven clinical protocols. Their system simulates trial outcomes, predicts primary endpoint results, and flags risks of poor design or under-recruitment – all based on a vast dataset of real patient information. According to the company, their model achieves approximately 85% accuracy and has reduced planning time by up to six months. Biotech firms and investors have already adopted the platform.

Patient recruitment a known bottleneck in clinical trials, has also benefited from operational AI tools. U.S. based companies such as Deep 6 AI , Leal Health , and Antidote deploy advanced algorithms to mine electronic health records, identifying eligible participants with impressive speed and accuracy. For example, Deep 6 AI reports that in an oncology trial, its system identified 36 suitable patients within 45 minutes – compared to only 30 patients found manually after screening over 5,000 records across two months.

In another groundbreaking application, Unlearn.AI is redefining control groups using “digital twins” – computational models that simulate how a patient’s disease would progress without treatment. These twins evolve in parallel with real participants, allowing partial or full virtual control arms that reduce double recruitment and enhance patient experience. According to the company, this approach can reduce control group size by ~33% and shave off four months of recruitment in Phase 3 trials, without compromising statistical power.

One more transformative shift in clinical research today is the rise of Decentralized Clinical Trials (DCTs), where data is collected outside traditional sites – often directly from patients’ homes, using wearable devices and AI-powered platforms.

A standout example is the solution developed by Biofourmis, powered by its proprietary Biovitals™ Analytics Engine. In combination with wearable sensors provided by Ametris, the system continuously analyzes vital signs using AI trained on real-world data from thousands of patients. This approach represents more than a technical upgrade – it marks a shift from reactive care to predictive, proactive patient safety. According to Biofourmis, implementation of its platform has led to a 70% reduction in 30-day hospital readmissions, clinical deterioration detected 21 hours earlier, and up to a 38% reduction in cost of care.

Looking ahead, several partially implemented technologies are poised to become standard. For instance, anomaly detection systems powered by AI, which alert study teams to data deviations in real time, are already being piloted with pharma partners. Similarly, AI integration within EDC and CTMS platforms is entering commercialization. Medidata and Veeva have begun offering predictive tools and smart operational assistance, with significant expansion expected in the next two years.

On the regulatory front, the FDA is actively promoting the integration of AI within digital health products and is regularly updating its guidance for AI-driven medical devices. Requirements include transparency, documentation, and traceability of decision-making processes. Even AI solutions operating behind the scenes such as patient-matching engines, risk prediction, and trial success modeling must meet high standards of data quality (GxP), privacy, and cybersecurity, even if they don’t require formal approval. In conclusion, AI in clinical research is no longer theoretical. It is an expanding set of real-world tools that deliver measurable value. A full index of current AI technologies in clinical trials is available upon request.

About the author

Hadas Nachmanson

Director, Clinical Operations & Trial Management | Consultant | Founder of Myrtle Clinical – Independent Clinical Trial Solutions | Expert in Regulatory Submissions, Site Management, CRA Leadership & Vendor Oversight

Supporting biotech and medtech companies with end-to-end clinical trial planning, oversight, and execution across the US, Europe, and Asia, with a focus on quality, compliance, and practical solutions.

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15.08.2025

Clear, Clinically Validated Communication: Transforming Patient Care

By Karin Hason-Novoselsky
Co-Founder & CTO, Patiently

The First 60 Minutes after Diagnosis Often Dictate the Next Six Months of a Patient’s Care.

Maya felt the room tilt when the rheumatologist finally named it, systemic lupus erythematosus. Stunned, she kept nodding, promising she got it, even as the explanations dissolved into static. She clutched the bulky discharge packet, telling herself that at home, away from the rising panic, she’d re-read every word and the whole conversation would click. Yet on the bus ride back, terms such as anti-dsDNA titers, steroid-sparing immunosuppressants, and complement C3/C4 levels stared back like a foreign language. The very document meant to guide her next steps now magnified her confusion, setting the stage for missed doses, needless flare-ups, and preventable ER visits. Without clear, accessible communication, many patients like Maya struggle to follow their treatment plans, leading to avoidable hospital visits, complications, and poorer health outcomes. This affects anyone, from those managing diabetes or heart disease to patients facing acute conditions or preventive screenings.

The Persistent Challenge of Health Literacy

Despite advances in medical science and digital health technologies, nearly 90% of U.S. adults struggle to comprehend the information their healthcare providers share. Digital portals have multiplied, and Telehealth is now mainstream, yet comprehension has not improved. Most systems still hand patients the same dense PDF summary and hope they decode it at home. Worldwide, this problem spans age groups and socioeconomic backgrounds, but is most pronounced among chronic illness patients, seniors, and non‑native speakers. Misinterpreted instructions can cause medication errors, reduced adherence to treatment, increased hospital visits, and higher care costs.

Technology Is Not the Whole Prescription

Digital health is advancing rapidly. By 2025, 80% of U.S. physicians will rely on Telehealth, and hospitals are heavily investing in connected platforms. These tools accelerate information sharing and broaden access, but they address only part of patient care. Comprehensive care includes medications, follow-up appointments, medical devices, treatment protocols, and direct interactions with clinicians. Unless patients understand why each medication is prescribed, how to operate a device, and what their next steps are, even the most sophisticated technologies cannot deliver full benefit. Unlocking the promise of modern healthcare requires clear, personalized explanations in plain language at every touchpoint, from the clinic to the patient’s home.

Establishing a New Standard Beyond AI: Clinically Validated Communication

At Patiently, we recognize that effective patient communication is foundational to positive health outcomes. Our approach is rooted in the principle that every piece of health information delivered to patients should be clinically validated and presented with clarity. Leveraging advanced natural language processing and a rigorously maintained medical knowledge base, we translate complex clinical language into explanations that are both precise and understandable. Unlike solutions that rely on black box algorithms or probabilistic text generation, each Patiently explanation is fully traceable to peer-reviewed research and aligned with current medical guidelines. This evidence-based approach deepens patient understanding and builds confidence among clinicians, payers, and health systems.

Driving Patient Engagement and Healthcare Efficiency

Having set a new benchmark for communication, Patiently next demonstrates a measurable impact on engagement and efficiency. Clear, trustworthy explanations increase patients’ confidence and encourage them to take an active role in their care. Studies show that improving health literacy reduces readmission rates by up to 20% and increases medication adherence by 15%. By making complex information accessible, Patiently delivers better clinical metrics, lowers costs, and streamlines workflows for providers.

Looking Ahead: A Future of Truly Patient-Centered Care

As healthcare evolves, demand for personalized, clinically sound communication will intensify. Patiently is committed to leading this transformation, ensuring every individual has access to the clear information they need to make informed decisions. Patiently is expanding multilingual support, integrating seamlessly with electronic health records, and scaling our clinical processes. Together with our partners, we envision a future where no patient ever feels lost in translation. But we do more than clarify information. We foster earlier engagement with patients, improve screening processes and communication from the very first interaction with the healthcare system, and support more efficient and optimized workflows for healthcare providers.

About the author

Karin Hason-Novoselsky

Co-Founder & CTO, Patiently

A medical engineer who grew to learn more about how Patiently can empower your patients and clinical teams, visit patiently-app.com. Join us in setting a new benchmark for health communication and patient engagement.

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15.08.2025

Nature’s Blueprint: How 3D Protein Modeling is Powering the Next Wave of Human‑like Nutraceuticals

By Yuval Appelbaum
Chief Technology Officer at Maolac

Finding Human Proteins in Nature

The next generation of nutraceuticals is built on a simple but profound insight: nature already holds the key to bifunctionality, with naturally occurring proteins with the potential to affect real change in the human body. The challenge is to find them. At Maolac, our proprietary AI platform combines massive data mining with deep 3D structural modeling to do exactly that.

Beyond Sequence: The 3D Advantage

Sequence similarity is not enough. Proteins with similar amino acid strings can fold into very different shapes. What really defines functionality is the 3D structure. Using state-of-the-art tools such as AlphaFold 3, our platform predicts protein structures with near-laboratory accuracy, then aligns them to human proteins. We use RMSD and domain-level comparisons to ensure structural congruence – often reaching 95% structural biosimilarity. This level of matching is what allows proteins sourced from natural sources to behave as if they were made by the human body.

Human Milk as Nature’s Gold Standard

Human breast milk is the blueprint for our search. It has been shaped over millions of years to provide optimal support for immunity, gut integrity, and healthy growth. Our AI scouts for proteins in natural sources – colostrum, plants, other biological structures – that have a high 3D and functional similarity to human milk proteins. This bio-inspired approach allows us to transfer the gold standard of early-life nutrition to adult health.

From Structure to Function: Indication-Specific Protein Selection

Once structurally similar proteins are identified, we filter them by function: gut barrier repair, anti-inflammatory activity, immune modulation, or muscle recovery. AlphaFold 3’s ability to model multi-molecule complexes helps us predict not only structure but interactions – how these proteins will bind, trigger, or regulate biological pathways.

This precision has already led to three commercial formulations: – Super Colostrum™ – for vitality and immune resilience – MaolactinGI™ – supports gut health and barrier function – MaolactinFMR™ – accelerates muscle recovery and reduces inflammation.

Clinical Proof and Market Validation

Science doesn’t stop at prediction. Our AI-designed ingredients undergo rigorous testing, including randomized clinical trials. Results show measurable benefits in gut health, muscle recovery, and immune resilience. These proven results have driven successful partnerships in the U.S., where our ingredients are already integrated into consumer brands.

Why It Matters

This combination of natural sourcing, 3D biosimilarity, and clinical validation is redefining what nutraceuticals can be. Instead of synthetic guesswork, we now have: – Proteins with 95%+ similarity to human proteins – Lower dosages and higher efficacy – Products that have been clinically tested and are already in market

For the future of functional health products, structure truly matters.

About the author

Yuval Appelbaum

Chief Technology Officer at Maolac

Yuval Appelbaum is the CTO of MAOLAC, with a B.Sc. in Biotechnology Engineering from Ben-Gurion University of the Negev. She is a co-inventor on several patents and was central to developing and scaling up the company's colostrum and plant-based products. Her expertise includes protein extraction technologies, managing the company's analytical lab, and ensuring compliance with quality standards like ISO and GMP.

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21.04.2025

MIRROR BIOLOGICS CREATING A NEW CLASS OF IMMUNOTHERAPY

By Michael Har-Noy
Chief Medical Officer of Mirror Biologics.

Mirror Biologics, Inc. (“Mirror”) was born in Jerusalem and currently operates as a Delaware corporation headquartered in Tampa, Florida with a wholly-owned GMP aseptic manufacturing subsidiary in Jerusalem. Mirror is pioneering novel immunotherapy approaches for treating metastatic cancer and reversing the decline in cellular immune function that occurs as we age. These novel approaches are protected by over 200 issued patents worldwide.

Mirror’s immunotherapy is unique in that it is not a pill or a protein, but instead is a living immune cell made into a drug called AlloStim^®. AlloStim^® is derived from the blood of healthy donors. Mirror has pioneered the methods for blood collection, blood cell component isolation, expansion and differentiation protocols and the harvesting, packaging, vialing, freezing, shipping and distribution of the living cell drug product. The Jerusalem manufacturing facility is capable to scale-up to commercial quantities of this living immune cell drug and methods for distribution are established currently in USA and SE Asia.

AlloStim^® is a novel living cell drug which has a novel mechanism of action. Interestingly, AlloStim^® is designed to be rejected by the host immune system and does not directly engage to eliminate tumors or viral infected cells. Rather, AlloStim^® immune rejection acts in a manner that serves to re-program, rather than boost, the immune system. Since AlloStim^® is quickly rejected by the host immune system, it does not persist long enough to cause any significant side-effects. The rejection of AlloStim^® releases ‘danger signals’ which serve as an adjuvant to reverse immune suppression and results in immunity to AlloStim^® which serves to modulate the host immune system to an enhanced state of cellular immune function.

The immune system is capable of immune surveillance, constantly hunting down and then eliminating nascent tumor cells and viral infected cells before the aberrant cells form tumors or viruses spread to become disease. Mirror believes cancer and viral disease to be a failure of this immune system surveillance function, which is mostly mediated by the innate and adaptive cellular immune system. Mirror’s unique approach targets re-programming of both the innate and adaptive immune cell components of a patient’s immune system in order to modulate a failed immune response into an effective response.

Many current immunotherapy approaches under development for cancer work to boost the resident failed immune response that originally allowed the disease to occur. The idea to boost the immune system of cancer patients assumes cancer is a disease of a weakened immune system. However, these immune boosting approaches often fail and sometimes make the disease worse. Mirror believes that cancer is a disease of a wrong immune response rather than a weak response. Boosting a failed immune system only provides a stronger failed immune response. Mirror’s approach is different, rather than boost a failed immune response, Mirror first modulates the immune system to change the immune response from a failed response to an effective response. Once the immune system has been properly modulated to respond correctly to a tumor or virus, this new immune response can then be boosted.

Metastatic cancer is a significant therapeutic challenge. Tumors can be shrunk and life can be extended with chemotherapy and radiation, but metastatic disease generally can not be cured. Harnessing the power of the immune system to cure cancer has long been sought out as a treatment strategy that could replace mainstay chemo-radiation therapy. While chemotherapy and radiation can extend life, these treatments are very harsh and some patients refuse or cut short these treatments as they feel it is not worth living longer without quality of life.

For decades, the attempts to harness the immune system to control cancer have had disappointing results in the clinic, leading most oncologists at the time to believe that immunotherapy could never be more powerful than chemotherapy. However, the recent clinical success of checkpoint inhibition drugs has created more widespread awareness and acceptance of immunotherapy as a viable cancer treatment modality. These drugs have produced clinical responses and durable remissions in patients with a variety of cancers, including some with chemotherapy-refractory metastatic disease.

These unprecedented results led Science magazine to select cancer immunotherapy as the 2013 “Breakthrough of the Year”. The American Society of Clinical Oncology (ASCO) named Immunotherapy as the “Advance of the Year” in 2017 due to the continued success of the checkpoint inhibition drugs and the emerging potential of CAR-T adoptive immunotherapy approaches.

In 2017, the FDA approved the first CAR-T drugs, opening a new category of immunotherapy using autologous living, genetically-engineered, cytolytic T-lymphocyte (CTL) “killer” T-cells as a drug. Killer T-cells recognize tumors through interaction with a molecule called MHC I on the surface of cells. However, tumors generally do not express MHC I, making them invisible to killer T cells.

Tumor surface antigens are recognizable by antibodies. However, antibodies are ineffective at killing tumor cells. To harness the killing power of killer T-cells and overcome the lack of MHC I expression on tumors, a strategy was developed to genetically modify killer T-cells so that they can recognize surface antigens like an antibody through a chimeric antigen receptor (CAR). In this manner, a CAR-T is an engineered killer cell that can potentially recognize a tumor like an antibody, but kill like a killer T-cell.

The genetic manipulation, expansion and adoptive transfer of autologous CAR-T is logistically complex and extremely expensive to translate to clinical use. Genetic manipulation of the cells has resulted in some treated patients developing secondary tumors, causing US FDA to place a warning label on these products. Furthermore, this technology is only useful for directing an immune response against cell surface molecules. However, solid tumors do not express surface molecules that are unique to the cancer. For this reason, current CAR-T immunotherapy products are limited to blood cancer indications which can target a tissue type, like all B-cells.

Mirror’s AlloStim^® immunotherapy has many advantages over CAR-T cells. While both are living immune cell therapies, AlloStim^® is not genetically-manipulated and is an allogeneic “off-the-shelf” product. As an “off-the-shelf” product, one blood donor can produce sufficient product for hundreds of patients, providing a significant economy of scale to lower cost. CAR-T cells are manufactured for each individual patient. The lack of economy of scale makes CAR-T cells extremely expensive (~$500,000 per treatment). In addition, CAR-T are highly toxic, requiring administration in a hospital in-patient setting, further increasing the cost. AlloStim has a very benign safety profile and is administered in an out-patient setting.

While AlloStim^® has significant advantages over checkpoint inhibitor and CAR-T immunotherapies, Mirror has a bigger vision than just to compete with these existing immunotherapies. Mirror is seeking a future potential cure. Checkpoint inhibitor and CAR-T immunotherapies generally are not cures for cancer. To cure cancer, a treatment must eliminate every last microscopic cancer cell in the body and then provide continuous protection against disease recurrence. Only by creating a cancer vaccine will there be potential for a cure. However, therapeutic cancer vaccines have historically been the least effective immunotherapies under development. Mirror intends to reverse this trend and create the first universally effect therapeutic cancer vaccine immunotherapy. A therapeutic vaccine treats existing disease, as opposed to standard vaccines designed to prevent disease.

The main cancer treatment modalities, including chemotherapy, radiation, surgery, and various new targeted therapies cannot completely eliminate tumors on a microscopic level, nor do they provide continuous protection from disease recurrence. Only an immunotherapy that acts like a vaccine has the technological capability of producing a “cure”, as the vaccinated immune system can be trained to elicit both a “sterilizing” anti-tumor immune response followed by a “memory” response for long-term disease suppression. Harnessing the curative potential of the human immune system through vaccination continues to be a major focus of cancer research efforts worldwide and is being pioneered by Mirror.

Previous and current therapeutic cancer vaccine protocols have had difficulty in eliciting tumor-specific memory responses. A major obstacle faced in developing therapeutic cancer vaccines is the ability of tumors to evade and adapt to an effective anti-tumor immune response. Tumors that evade immune destruction after therapeutic vaccination may have a selective advantage and become resistant to the elicited anti-tumor immune response through a mechanism known as tumor “immunoediting”. Immunoediting occurs when tumors escape initial immune elimination and accumulate further DNA mutations or changes in gene expression. These mutations exert selective pressure on the immune system, causing elimination of the more susceptible tumor clones and survival of the most resistant ones. Thus, incomplete immune elimination of tumors after vaccination often results in the development of new disease that is highly resistant to immune control

The host immune system’s ability to protect against tumor growth and metastasis is known to be hindered by several factors, including: (1) tumor immunoavoidance through tumor-induced impairment of antigen presentation, downregulation of MHC molecules, defective co-stimulation, and tumor production of immunosuppressive cytokines (such as IL-10 and TGF-β); (2) poor tumor antigen immunogenicity due to “self” nature; (3) heterogeneous expression of tumor antigens within tumors and in distant tumors; (4) tumor-influenced activation of tolerance-inducing immunosuppressive circuits, including induction of suppressor regulatory T cells (Treg), suppressive natural killer T cells (NKT2), myeloid-derived suppressor cells (MDSC), and immunosuppressive subsets of mature dendritic cells (DC2); (5) loss of cellular immunity due to immunosenescence as we age and/or tumor-induced cellular immune suppression; and (6) immunosuppression due to heavy medical pretreatment and the presence of large tumor burdens.

Cancer vaccine development continues to struggle with these obstacles while attempting to produce effective clinical responses. Mirror believes that anti-tumor mechanism that needs to be elicited by an effective therapeutic cancer vaccine must have both a spatial and a temporal component. This is because immune deviation from permissive or suppressive anti-tumor responses can occur in different locations (lymph node, peripheral tissues, tumor stroma) and at different times.

Multiple administrations of tumor antigens can result in high titers of circulating memory killer T-cells. Standard vaccination practice, where tumor antigens are injected together with adjuvant, does not address the timing of the multiple decision points that occur during anti-tumor immune cascade development. Also, standard vaccination protocols do not interfere with the bidirectional cross talk occurring between the existing tumor lesions and their surroundings, and consequently cannot stop the immunosuppression and avoidance mechanisms which facilitate tumor progression.

The Mirror therapeutic vaccine protocols are the first to incorporate spatial and temporal components. The Mirror therapeutic vaccine protocols feature weekly AlloStim^® injections over 3-4 months which alternate from intradermal (ID) to intravenous (IV).

The clinical benefit of past therapeutic cancer vaccines has been almost negligible despite the use of a variety of highly novel and innovative technologies, antigens, adjuvants and administration schedules. The obstacles impeding successful therapeutic cancer vaccine development are numerous and are extremely difficult to overcome. The overwhelming complexity of these problems have caused many researchers to conclude that the development of an effective therapeutic cancer vaccine is not possible.

Mirror, however, has been at the cutting edge of solving the problems of translating an effective therapeutic cancer vaccine to the clinic. Mirror believes that the past failures of past and current extremely innovative therapeutic vaccine designs and new adjuvant technologies, it may be that these innovations represent solutions for the wrong problem. Accordingly, a completely new approach was thought to be needed in order to design a clinically useful therapeutic cancer vaccine. Such a new approach must introduce a mechanism that is different from that has previously failed, as well as provide an explanation as to how the new approach would succeed in light of the numerous previously failed approaches.

Rather than attempt to improve vaccine platforms that had previously failed, Mirror aimed to develop a next generation therapeutic immunotherapy vaccine platform patterned after an anti-tumor immune cascade that is already known to overcome tumor immune suppression and avoidance and to mediate tumor killing. The most powerful and only immune cascade known that is capable of eliminating chemotherapy-refractory metastatic disease is the graft vs. tumor (GVT) effect that occurs after allogeneic, non-myeloablative, stem cell transplant (ASCT) procedures. Mirror has mapped this mechanism and reversed engineered the GVT effect into a host vs tumor (HVT) effect, which is the ‘mirror’ of the GVT effect.

The powerful GVT immune effect is proven capable of killing chemotherapy-resistant metastatic tumor lesions, but is intimately linked to a toxic side-effect known as graft vs. host disease (GVHD). The high morbidity and mortality of GVHD severely limits the use of ASCT procedures. The intimate and proportional relationship between the beneficial GVT effect and detrimental GVHD effect have made these effects difficult to separate. The clinical application of the ASCT procedures is further complicated by the requirements for matched tissue donors, toxic chemotherapy conditioning and need to establish a stable chimeric immune system in order to observe GVT/GVHD effects.

Mirror developed the “Mirror Effect” hypothesis to address the difficulties of harnessing the power of the GVT effect without GVHD toxicity. The Mirror Effect hypothesis proposed to maintain the intimate relationship of the GVT/GVHD cascades, but reverse the direction of the immunological flow. In the reverse flow ‘Mirror Effect’ model, the effector cells are from the host, rather than from the graft, whereby there is a non-toxic host vs. graft (HVG) rejection, the ‘mirror’ of GVHD, as an adjuvant supporting a host vs. tumor (HVT) effect, the ‘mirror’ of GVT.

To elicit the Mirror Effect mechanism in immunocompetent patients without requirement for first creating a chimeric immune system, Mirror designed AlloStim^®, to provide the same immune signaling as is provided by chemotherapy conditioning used prior to chimera formation and the same danger signals released by GVHD in ASCT procedures upon rejection by the host immune system. AllloStim^® is the first cell therapy designed to be rejected, rather than perform an effector function.

The alloantigens on the mismatched AlloStim^® cells serve as a potent immune stimulus. The immune mechanisms that influence responsiveness to the triggering allo-antigens hold the key to the ability to manipulate the immune system for therapeutic purposes. The type of immune response that occurs after encounter with alloantigen depends upon the place the antigen recognition occurs and the inflammatory status of the microenvironment.

Under non-inflammatory conditions, injections of alloantigens can cause the development of a tolerant response to the alloantigens. For this reason, the AlloStim^® cells must be administered with ant-CD3/anti-CD28-coated microbeads to assure they are activated and producing type 1 cytokines at the time of administration and rejection. This assures rejection results in enhanced cellular immunity to the alloantigens. When administered intradermally, the alloantigens from rejected AlloStim^® are processed by Langerhans cells (LCs), which are abundant in the skin, which then orchestrate the polarization of immune responses towards Th1 cellular immunity.

The AlloStim^® protocols re-engineer the tumor microenvironment to create inflammation. In the context of this inflammation, which can be thought of as a vaccine adjuvant, the killing of tumor cells by activated NK cells recruited to the tumor releases tumor neoantigens. The release of neoantigens and the adjuvant effect of the inflammation creates a personalized ‘in-situ’ vaccine. This in-situ vaccine mechanism has the unique result of an off-the-shelf immunotherapy resulting in a patient-specific immune response customized to each patient’s own tumor.

Mirror is currently in late clinical development with novel immunotherapy, having completed accrual in the StimVax clinical trial in metastatic colorectal cancer patients refractory to chemotherapy and immunotherapy. The protocol uses 3 cycles of a combination of weekly intradermal AlloStim^® priming doses, which serves to increase the Th1/Th2 balance by increasing titers of allo-specific Th1/CTL and then at the end of each cycle an intravenous infusion which causes the extravasation of activated NK and memory T-cells to tumor lesions.

In previous Phase IIA and Phase IIB studies in third-line microsatellite stable (MSS) metastatic colorectal cancer (known as ‘cold’ tumors unresponsive to immunotherapy), the subjects’ clinical presentation remained stable and median overall survival was approximately double the survival reported in historical controlled studies in this population. Plans are now being made to advance AlloStim® to a registration trial in metastatic colorectal cancer.

Immune checkpoint blockade (ICB) immunotherapy has shown great potential and power in cancer treatment. However, these drugs only work in approximately 20% of human tumors that are characterized as highly inflamed ‘hot’ tumors. The AlloStim® mechanism converts ‘cold’ tumors to ‘hot’ tumors, potentially broadening the market potential for ICB immunotherapy and providing potential for collaborations with the big pharma companies which dominate the ICB market.

Recently, Mirror Biologics announced clearance from US FDA and a collaboration with Merck, Darmstadt Germany for a new Phase II study of AlloStim in combination with Avelumab (Bavencio) in fourth-line metastatic colorectal cancer patients refractory to both chemotherapy and immunotherapy.

In another application of AlloStim®, Mirror Biologics has designed a vaccination method that modulates the immune system of elderly patients in a manner that converts the immune system from being senescent to one that works like a young healthy person. This conversion can provide universal viral protection against both known and unknown viruses and their variants without the need to have prior knowledge of the antigenic and genetic phenotype of the viruses. In addition, this novel mechanism features a self-amplification mechanism which eliminates the need for annual booster injections. Mirror has completed a Phase I/II clinical trial in 40 healthy adults over 65yo with final results expected to be released early in 2025.

Mirror is thinking outside the box and is pioneering new ideas in immunotherapy of cancer and infectious disease. Mirror is on track to bring this new technology to the market and potentially benefit patients and society for the evils of cancer and the adverse effects of aging.

About the author

Michael Har-Noy

Chief Medical Officer of Mirror Biologics.

Michael has over 30 years experience in immunotherapy of cancer and infectious diseases and over 200 issued patents. He attended a MD-PhD program at Rush Medical School in Chicago and did his post-doctoral training at the University of Minnesota and fellowship at Harvard Medical School. He most recently was employed at Hadassah-Hebrew University Medical School in the Department of Bone Marrow Transplantation and Immunotherapy.

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06.02.2025

Understanding U.S. Market Access: A Foundation for Patient-Centric Success

By Darron Segall
Co-Founder & Managing Partner at Dream Big Health

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:

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.

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.

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.

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.

About the author

Darron Segall

Co-Founder & Managing Partner at Dream Big Health

The author is a visionary market access leader with extensive experience in health technology reimbursement, value creation, and payer access.

Darron, who recently emigrated to Israel, is co-founder and managing partner of Dream Big Health.

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06.02.2025

USA Issue Crossword

«Crossword Theme»

Across:

U.S. law that mandates privacy compliance for healthcare entities

U.S. agency responsible for regulating medical devices and drugs

Technology rapidly developing in healthcare, requiring risk management plans

In vitro diagnostic products designed, manufactured, and used within a single laboratory

U.S. insurance coverage affecting pricing and sales potential

Compliance required for handling medical data, especially under HIPAA

U.S. President whose policies could impact the biotech market

U.S. research institution that may see varying funding levels under different administrations

U.S. federal health insurance program for people aged 65 and older

Adherence to regulatory requirements in healthcare and biotech industries

Industry that could benefit from deregulation and domestic incentives

Considerations in the development of digital health technologies

Access pathway ensuring healthcare solutions reach patients

Essential for demonstrating the value of medical innovations

Critical aspect of business strategy in digital health

Coverage that affects market entry and sales potential in the U.S.

Type of trials and data required for market access and reimbursement

Medical products that may require FDA approval or clearance

Type of company that needs a strong marketing and communications infrastructure

A concern in clinical decisionmaking tools that hospitals must mitigate

Medical Device Reporting requirements for adverse events

Reporting requirements for corrective actions taken to address health risks

System complaint files required by the FDA for LDTs

Central focus of U.S. market access strategies

Centers for Medicare amp; Medicaid Services, involved in reimbursement decisions

European data protection regulation relevant to clinical trials

Contract Research Organization, often used for clinical trials

A startup’s first crucial sales goal in a new market

Down:

Score: 0

00 : 00

Completed: 0 / 0

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06.02.2025

INTERACT vs. Pre-IND Meetings: Navigating Early FDA Pathways for Biopharma Startups

By Rivka Zaibel
President and Founder @ ADRES International Biotech Consultation and Execution

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.

About the author

Rivka Zaibel

President and Founder @ ADRES International Biotech Consultation and Execution

With over 35 years in biopharmaceutics and biotechnology, Ms. Zaibel has led an impressive number of multidisciplinary projects, supports startups globally, and has secured FDA and EMA approvals for recombinant proteins, vaccines, and medical devices. In 2019-2020, Ms. Zaibel joined the Weizmann Institute of Science SPARK project as a mentor and also became a member of the advisory board and lecturer for a new Master's degree in Regulatory and Drug Development at TAU. In 2022, the ADRES team led by Ms. Zaibel joined the BIODESIGN ISRAEL Rambam healthcare campus program as mentors. In 2023, Rivka was accepted as a mentor by EIT Health.

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06.02.2025

Navigating U.S. State Privacy Laws in Clinical Research: Exemptions and Applicability

By Diana Andrade
Founder & Managing Director

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:

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

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.

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.

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.

About the author

Diana Andrade

Founder & Managing Director

Diana Andrade, Founder and Managing Director of RD Privacy, is an EU-qualified attorney and DPO. With over 12 years of experience, she specializes in strategic privacy guidance for global pharmaceutical and life sciences companies, focusing on small biopharma firms and clinical research. dianaandrade@rdprivacy.com

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06.02.2025

Regulatory and Other Considerations in the Development of Digital Therapeutics

By Thomas Seoh
CEO of Kinexum

By Kelliann Payne
Partner in the Global Regulatory practice of Hogan Lovells

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.

Navigating Regulatory Pathways for Digital Therapeutics

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

Comprehensive Overview: FDA’s DTx Approvals in 2023

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

About the authors

Thomas Seoh

CEO of Kinexum

Thomas Seoh is CEO of Kinexum, a regulatory, clinical, product and corporate development advisory firm, representing clients before FDA, MHRA and EMA, performing sell- and buy-side due diligence for banks, funds and companies, and advising emerging companies on development strategy and planning, and EVP of the not-for-profit Kitalys Institute, promoting the preemption of chronic diseases and extension of healthy longevity.  He previously held senior management and board roles in emerging biotech, pharmaceutical and medtech companies and startups, after practicing corporate law in New York City and London.

Kelliann Payne

Partner in the Global Regulatory practice of Hogan Lovells

Kelliann Payne is a Partner in the Global Regulatory practice of Hogan Lovells, specializing in medical devices, including digital health and diagnostic products and machine learning-based clinical decision support software.  She has extensive experience with premarket submissions and medical device regulatory development strategy, as well as advertising and litigation.  Previously, she was Assistant General Counsel at QVC, Inc., counseling on FDA and FTC regulation on health, wellness, beauty and cosmetic products.

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