How Digital Orchestration Is Redefining Regulatory Infrastructure for Cell and Gene Therapy

The rapid growth of cell and gene therapies is exposing structural limitations in how traditional biopharmaceutical systems were designed. Unlike batch-based manufacturing models, these therapies are patient-specific, requiring tightly coordinated execution across clinical, manufacturing, and quality domains.

In this environment, maintaining chain-of-identity and chain-of-custody is not simply a regulatory requirement, but a foundational design constraint. As programs move from early clinical development into global commercialization, gaps in system-level orchestration can translate directly into compliance and operational risk.

These pressures are driving renewed attention toward how digital infrastructure is architected in regulated life sciences, particularly around validation, traceability, and cross-system integration.

Monika Birdi, global product strategy leader for SAP’s Cell and Gene Therapy Orchestration (CGTO) platform, has spent more than two decades working on regulated enterprise systems across industries, with a recent focus on advanced therapy manufacturing and supply chains. In this interview with GEN, Birdi discusses SAP CGTO’s architecture, regulatory design in SAP Batch Release Hub (BRH) and Intelligent Clinical Supply Management (ICSM), and digital frameworks for inspection readiness, jurisdictional control, and chain-of-identity enforcement. She also shares insights on balancing innovation with GxP validation and building digital infrastructure for global commercialization of patient-specific therapies.

GEN: What foundational lessons about compliance architecture, data integrity, and large-scale system design most influenced your transition into life sciences and cell and gene therapy?

MB: The biggest shift I experienced after moving to life sciences was in perspective and significance. During the many years I worked building large-scale regulated systems in diverse industries, a failure of data integrity meant financial loss or reputational damage. However, when I moved into the pharma and biotech life science sectors, I realized that in this domain, there was zero margin for error. If the chain-identity breaks anywhere in that journey, there is no fallback.

Monika Birdi
Monika Birdi

This reality puts compliance at the heart of architecture. Controls need to be built from the start and cannot be retrofitted later. We must stop treating compliance and scalability as competing priorities, because when you architect them together, one enables the other.

 

 

GEN: When you began working in advanced therapies, what operational or digital fragilities did you observe in early-stage programs that signaled a structural gap in how regulated supply chains were being architected?

MB: The first thing we need to understand is that advanced therapies are completely different from traditional small molecule manufacturing. Hence, for organizations that have been in the pharma business, shifting to manufacture advanced therapies is different from both scientific and architectural perspectives. The same tools that worked for small molecules will not serve the end-to-end business for advanced therapies.

The common structural gaps I observed were around chain of identity and chain of custody tracking. Since these are typically not part of the native system design, every single process runs via piles of papers that are difficult to organize and trace. In these cases, there was no orchestration layer and all the systems—such as clinical, manufacturing, quality—were running in silos.

GEN: You have led the design and commercialization of SAP CGTO. What operational failures or regulatory risks did you observe in early-stage CGT programs that convinced you digital orchestration had to be architected differently from traditional pharma systems?

MB: Traditional pharma systems are built around batch manufacturing, where thousands of units are manufactured in one batch. Even if one batch fails the compliance, the next batch can be used by discarding the non-compliant batch. Chain-of-identity is being maintained through a combination of spreadsheets. This is what convinced me to rethink orchestration. You can’t take a traditional batch management system and configure your way into CGT compliance.

The right therapy needs to reach the right patient. So, with CGTO, the design question was never “how do we adapt existing functionality” to make a compliant solution. Our approach was to ask, “if we are building this from scratch for one patient and one batch, what should the process actually look like?”

GEN: Autologous cell and gene therapy manufacturing is patient-specific and tightly synchronized. How did you architect SAP CGTO to enforce chain-of-identity and chain-of-custody controls at every transition point rather than relying on retrospective reconciliation?

MB: Personalized advanced therapies operate under a unique manufacturing cycle, which makes conventional post-production reconciliation processes ineffective. We needed an architecture that shifts the control point from “detect and correct” to “prevent and confirm” for every transaction.

With SAP CGTO, every transition point, from receipt at the plant, disposition, manufacturing start, and allocation to final shipment, is within an order and includes validations to make sure the right patient gets the right therapy. The system won’t let you proceed with a mismatched identity. These validations ensure that the process is stopped immediately, instead of alerting the user at a later point in time.

GEN: In your work on SAP BRH, you focused on jurisdiction control and regulatory components. How do digital release architectures need to evolve to support multi-country regulatory environments while preserving data integrity and inspection readiness?

MB: Most organizations use local Standard Operating Procedures (SOPs) and spreadsheets, utilized by people who have been around long enough to manage the regulatory requirements. This system will likely fail if a critical employee leaves, or if you are entering a new market under pressure, or when an inspector asks you to reconstruct a release decision from two years ago.

Jurisdictional controls should be part of the solution. Once validations are embedded directly into workflows, compliance becomes part of the business process. The audit trails are thus automatically created as a natural result of doing the job.

GEN: You believe designing infrastructure before scale exposes operational gaps. What are the most common digital fragilities you see when sponsors defer enterprise architecture decisions until Phase III or Phase IV?

MB: In cell and gene therapy, many sponsors treat digital infrastructure like office furniture: something to worry about later. The largest problems tend to be in two areas: traceability and coordination.

gene therapy
Credit: Metamorworks/Getty Images

In terms of traceability, it’s common for programs to track materials in whatever way is convenient at that time, such as spreadsheets, half-set-up software, or systems that don’t talk to one another. But for a hundred patients across many sites, it becomes nearly impossible to track it all correctly, especially when the FDA starts asking questions.

But as trials get bigger, it becomes difficult to manage all of it through those means—and in fact, it can become dangerous. Then, as the trial advances, scale your investment in alignment with emerging trial results.

GEN: Across CGTO, BRH, and ICSM, you have helped define regulatory-ready digital architectures for emerging therapy models. What measurable operational or compliance outcomes have resulted from these implementations, and how do they demonstrate advancement in the field’s digital maturity?

MB: The actual benefit of digitalization in advanced therapies shows up in audits and inspections. By ensuring that digital systems are properly implemented from the beginning and integrated with quality and batch record systems, decisions regarding the release of batches are much faster and more accurate.

In the area of clinical trials, integrated systems enable teams to predict and prevent problems rather than simply reacting to them. This results in fewer delays, and the benefits are easy to demonstrate and prove to the authorities.

GEN:  What principles guide your approach to building compliant cloud-native platforms that remain modular, secure, and extensible?

MB: I believe modularity itself is a compliance strategy. Highly integrated platforms introduce hidden risk, because every regulatory change or market requirement can trigger system‑wide retesting.

I design security and extensibility together, with clear separation between what is validated, configurable, and subject to formal change control. That clarity allows teams to move faster without compromising compliance.

Commercialization teaches you that adoption depends on validation of reality. A platform can be technically strong, but if it is difficult to validate and operate in a regulated environment, it will not be scaled. The most successful products do not transfer the customer’s validation burden.

GEN: As advanced therapy pipelines expand and manufacturing networks become more geographically distributed, which architectural capabilities will determine whether organizations can sustain compliant commercialization without repeated remediation cycles?

MB: We need to start building compliance as the core of architecture instead of treating it as per each unique market need. Once the foundation has been set, market regulations can be adjusted accordingly. A few capabilities in which I would invest early include real-time chain-of-identity enforcement, jurisdictional logic embedded in workflows rather than documented beside them, and audit structures that generate inspection-ready data as a natural output, as opposed to a reconstruction exercise. What really matters most is the flexibility of architecture. Regulations evolve, new markets pop up, and manufacturing networks constantly adapt and relocate. This requires organizations to build adaptable and modular architecture that can evolve with growth.

 

The post How Digital Orchestration Is Redefining Regulatory Infrastructure for Cell and Gene Therapy appeared first on GEN – Genetic Engineering and Biotechnology News.

What Is Traumatic Separation?

You may have a memory of being separated from a parent when you were a child, even just for a few minutes. Maybe you lost them in a crowd or wandered a little too far at the store and felt panicked and afraid.

A moment like this might be among your earliest memories because the feeling was so intense, says Caitlyn Downie, LCSW, the Director of Trauma and Resilience at the Child Mind Institute. That offers some insight into the fear of a child of any age who is separated from a parent or caregiver in a more serious way. The effects of this stress are so powerful they can actually change the way a child develops.

A toddler whose mother goes to prison. A kindergartener whose father is detained and deported. A teen who is placed in foster care. These are a few examples of what experts call traumatic separation, a clinical concept based on the importance of the parent-child bond and the profound effects that can result from breaking it.

What is traumatic separation?

Traumatic separation isn’t a clinical diagnosis, but research shows that it can be profoundly harmful to kids. What makes it traumatic (as opposed to routine partings, like when an adult regularly leaves their child to go to work) is the character of the separation: ones that are sudden, unexpected, or confusing, or those that come about through larger distressing events, like a natural disaster or war. It’s not defined by the time spent apart — both short and long-term separations can be harmful.

Some common examples of separation that can become traumatic include:

  • Parental deportation
  • Immigration (e.g., forced separation at the border)
  • Parental military deployment
  • Parental incarceration
  • Termination of parental rights

Separating from a parent or primary caregiver can be distressing to a child even when it’s deemed necessary for their safety, as in cases where the parent they have been separated from has abused them, says Kimberly Alexander, PsyD, a psychologist at the Child Mind Institute. “There’s still a natural attachment that occurs. And the separation disrupts that relationship, even if it’s for the support and care of the child.”

Why is traumatic separation harmful?

More than eight decades of research has shown the profound developmental importance of the parent-child bond. This is the guiding principle of attachment theory, which was pioneered by a British psychologist who studied children who were evacuated during the Blitz, the aerial bombardment of London in World War II.

Here’s what the research tells us about the harms of traumatic separation:

It can disrupt secure attachment

Think of secure attachment as a “fundamental sense of security and safety” that a child feels with a parent or caregiver, says Dylan Gee, PhD, a psychologist at Yale University who studies how early-life stress affects children’s development.

“Attachment is the lens through which children come to know what they can expect from the world around them,” she explains. “Is this going to be a safe place or a dangerous place? This is foundational to a child’s sense of their ability to navigate the world. Traumatic separation can shatter that sense of safety.”

It can affect neurobiological development

Children’s brains are especially plastic, says Dr. Gee, constantly learning to understand their environment and how to deal with stress. “Trauma that occurs in childhood can be even more consequential than trauma that occurs later in life,” she says, and experiencing these disruptions in childhood can affect the way your brain and body are primed to react to stress later on.

But heightened plasticity is a paradox, she adds. “It confers more vulnerability, but it also confers more potential for resilience — children have heightened potential for supportive intervention and for healing and recovery.”

What do the effects of traumatic separation look like?

There are acute and short-term effects that are common across kids of all ages:

Sleep problems: “It’s often one of the first things that we see: nightmares, trouble falling asleep, or a lot of crying as kids are trying to fall asleep,” Dr. Gee says.

Separation anxiety: This might look like distraction, withdrawal, or clinginess because of fear of being separated from their new caregivers, Dr. Alexander says.

But signs may take weeks or months to show up. Dr. Alexander advises caregivers to consider the child’s baseline — their typical patterns of eating, sleeping, or engaging with others. “If they’re having more trouble with sleep, they’re eating more, eating less, they’re withdrawing or expressing a lot of worried thoughts three or four months later — that’s something worth getting looked at by a clinician,” she says.

Signs of traumatic separation at different ages

“Sometimes people ask, ‘Well, when is separation the most harmful?’ It can be extremely harmful at any age,” Dr. Gee emphasizes. But there are specific signs at different developmental stages:

Infants

Babies may not be as consciously aware of being separated from a parent as older children, “but they’re fundamentally aware that their primary source of regulation and safety is missing,” Dr. Gee says. Because infants are so reliant on caregivers for nurturing and sustenance, the separation “can be experienced as a threat to their survival.” That might look like “crying a lot or becoming withdrawn,” she says. “And at any age we can see intense fear.”

Toddlers and young children (3–6)

Toddlers and young children might become extra clingy with new caregivers or show regressive behaviors like bedwetting or baby talk. Regressive behaviors happen when kids are overwhelmed by stress and can’t express themselves another way, Downie says. “It’s like your nervous system goes kind of haywire,” she explains, “so it uses the body to signal that something is wrong.”

Similarly, kids at this age might act out more, throwing more tantrums, or withdraw. They might develop selective mutism, a condition where kids are too anxious or distressed to speak, even when they want to, in certain situations or with certain people.

School-age children

School-age children might act out or experience separation anxiety. They may also struggle to understand the meaning of the separation, why it happened, or who is at fault for it. Thus, kids at this age are more prone to magical or distorted thinking and feelings of guilt, thinking or saying things like, “I’m the one that caused this” or “This is my fault.”

The weight of these distorted thoughts or other worries, Dr. Alexander says, might make it appear as though a child is struggling to concentrate or that they’re disengaged or distracted. They might withdraw in a group or be averse to stepping outside of their comfort zone.

Children who are school age or older can also experience emotional desensitization — a kind of emptiness of feeling — Downie says, which can look like spikes in irritability, a lack of empathy, not smiling or expressing positive emotions, or an inability to relate to others.

Preteens and teenagers

“I’ve seen teenagers have a lot of mistrust with systems and be very oppositional,” says Downie. “Like, ‘I don’t trust you. I don’t trust my teacher. I don’t trust this child services worker.’” It might make sense that, say, a teen in foster care would be wary of the foster care system. But Downie says it’s often a larger instinct for anger and mistrust, one that extends beyond any specific entity or person.

The teenage years are also when kids are forming their identity, and traumatic separation can fundamentally alter that process. For example, a teen with younger siblings may step into a parent role, taking on new worries and responsibilities. Conversely, teens may become more reckless in a caregiver’s absence, putting them at risk for substance abuse or incarceration.

How to help kids separated from a parent

Adults caring for a child who has been separated from a parent — family members, foster parents, teachers — “can play a profound role in supporting their mental health and resilience,” says Dr. Gee.

Validate feelings

One of the most important things caregivers can do is be present as a child reacts to their experiences, especially if and when scary feelings come up. But be careful not to lead kids or assume they feel a certain way. “You don’t want to make something more distressing to a child if it’s not presenting itself,” says Downie.

If a child expresses guilt, or says something like, “This is my fault,” there are still ways to validate the feeling without endorsing the statement, says Dr. Alexander. You might say something like: “I can understand why that thought comes to mind and how difficult it is to feel that way. When you’re ready, let’s think about other possibilities to this situation.”

Create consistency and stability

One of the hardest things about traumatic separation is the uncertainty — Where did they go? When will they come back? What is happening? Giving kids some sense of consistency and stability can help them feel safe despite the unknowns. So as much as possible, help them stick to any routines: going to school, seeing friends, doing activities they enjoy.

Dr. Alexander advises focusing on things you can control — for example, shielding kids from potentially worrying discussions in a family where a parent has been deported.

“There would likely be a lot of conversations in the home about the situation, maybe a lot of watching the news, maybe making a lot of phone calls to attorneys,” she explains. “So where are you having those conversations, and can you have them in an area or at a time of day where your kid isn’t overhearing the discussions out of context?”

For young kids, it might be as simple as asking them to play in their room. For teens, it might be better to have certain conversations when they are out of the house and invite them to participate directly in others.

Be honest but reassuring

Caregivers might not have all the answers — like knowing when a child’s parent is coming back — but they can create a sense of consistency and stability in how they respond to kids’ questions, too.

Avoid undue reassurance (“Everything is going to be fine”) or over-promising (“They’ll be back in two weeks”) by focusing on what kids can expect, says Dr. Gee. For example: “What I can tell you is that I’m here for you, and I’m going to be with you until he’s back,” or “You’re safe with me, and I’m going to stay with you through this really hard time.”

Model handling stress

Children are sensitive to tone, Dr. Alexander says. “So, if you’re having really big emotions that are out of context for a child, the child is looking at these emotions and trying to understand what’s happening. ‘Am I in danger in this specific moment?’”

She says it helps to have conversations about these moments, especially with younger kids. “Like, ‘I know you noticed mommy crying. We’re feeling really big feelings, and this is how we’re going to deal with those big feelings. I’m going to take a break. I’m going to get a sip of water. Whenever you’re having big feelings, I want you to let me know so that I can help you try doing the same things,’” Dr. Alexander says, explaining the importance of naming the emotion and then teaching kids that there are ways of dealing with it.

Long-term risks of traumatic separation

The effects of traumatic separation can persist even after a child and their caregiver are reunited. Traumatic separation, like other adverse childhood experiences, puts kids at risk for a host of long-term medical and mental health conditions, including depression, anxiety, attention issues, and post-traumatic stress disorder (PTSD).

But Downie notes that not everyone who experiences traumatic separation develops PTSD. “Just because someone’s experiencing trauma now doesn’t mean that it’s going to become a PTSD diagnosis,” she says. “A lot of the behaviors that we’re talking about are normal and expected. There’s an adjustment period when a separation happens.” But if symptoms persist or escalate over several months, a child may need more serious support.

Treatment for a trauma diagnosis

While not every child who experiences a separation may receive a trauma diagnosis or require treatment, cognitive behavioral therapy (CBT) — and the more specific trauma-focused cognitive behavioral therapy (TF-CBT) — is the “gold standard,” says Downie. TF-CBT is specifically for children experiencing trauma-related symptoms. An important component of TF-CBT is creating a trauma narrative, where kids create a story about what happened to help them process it. “But if you have a child who is not ready to process and integrate that trauma, you can’t force the pacing of the treatment,” she says.

In short, a good clinician will follow a child’s lead — even if that means just sitting in the same room with them to build trust. “People really need to feel like they’re being heard and that they can trust someone,” Downie says. Which is why a supportive caregiver or trusted adult can make a big difference.

“If people can take anything away from this, it’s that you want to make kids understand that that they’re not responsible for what’s happened and that people do care about them,” Downie says. “Kids are really resilient, and they can adapt in a good-enough environment. They don’t have to have everything to be successful.”

The post What Is Traumatic Separation? appeared first on Child Mind Institute.

Spain readies for evacuations as a hantavirus-hit cruise ship heads for the Canary Islands

MADRID — Spanish authorities on Friday were preparing to receive more than 140 passengers and crew members on board a hantavirus-stricken cruise ship headed for the Canary Islands, where health officials have said they will perform careful evacuations.

The vessel is expected to arrive Sunday at the Spanish island of Tenerife, off the coast of West Africa, and passengers will be taken to a “completely isolated, cordoned-off area,” said the head of Spain’s emergency services, Virginia Barcones.

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STAT+: Roche to buy PathAI for $750 million

Roche has signed a deal to pay $750 million upfront for Boston-based PathAI, an acquisition by the Swiss pharmaceutical giant to speed up its use of artificial intelligence to help pathologists diagnose disease.

The agreement, which is expected to close in the second half of the year, could generate an additional $300 million for PathAI if it leads to the achievement of certain milestones.

“Joining forces with Roche marks a new era for PathAI, enabling us to realize our mission of improving patient outcomes through AI-powered pathology at unprecedented scale and speed,” said Andy Beck, chief executive and cofounder of PathAI, in a statement. “Roche’s global infrastructure and expertise will bring our digital diagnostics technology to patients worldwide.”

Continue to STAT+ to read the full story…

Medical Marijuana Initiation and Simulated Driving Performance Among Mid-to-Late-Life Adults With Chronic Pain: Prospective Observational Feasibility Cohort Study With Matched Controls

Background: Marijuana initiation among adults aged 50 years and older has increased substantially. Although acute tetrahydrocannabinol exposure can impair psychomotor function, less is known about how real-world medical marijuana initiation relates to functional tasks such as driving in mid-to-late life. Objective: The objective of our study was to evaluate the feasibility of recruiting and retaining adults aged 50 years and older, who are newly registered for medical marijuana, and matched non–marijuana-using controls, into a longitudinal high-fidelity driving simulator protocol, and to explore preliminary associations between medical marijuana initiation and simulated driving performance. Methods: This prospective, nonrandomized feasibility cohort study enrolled adults aged 50 years and older who are newly registered in the Florida Medical Marijuana Use Registry, along with age-, race-, and sex-matched controls. Assessments occurred at baseline (T1; preinitiation) and at 1 month (T2). Primary feasibility outcomes included recruitment, retention, simulator completion and tolerance, and exposure verification. Exploratory outcomes included reaction time and divided attention (DA) performance, which are measured using an immersive, high-fidelity driving simulator. Results: Recruitment and exposure verification procedures were feasible, but simulator sickness contributed to substantial missing data. Exploratory analyses suggested group differences in select DA outcomes at T2. At T2, reaction time to DA situation 3 (DA3) was significantly shorter in the medical marijuana group (n=14, mean 2.57, SD 1.63) than in the control group (n=7, mean 5.79, SD 4.32; =−2.50, =.02, =−1.11, 95% CI −2.04 to −0.16). These findings should be interpreted cautiously, given the small sample size, missing data, and multiple comparisons. Conclusions: A prospective protocol examining medical marijuana initiation and simulated driving among mid-to-late-life adults is feasible, but future studies should incorporate design and analytic refinements to address simulator sickness and missing data and to better characterize exposure timing and patterns. Trial Registration: ClinicalTrials.gov NCT04629716; https://clinicaltrials.gov/study/NCT04629716
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Communication-Based Teaching on Childhood Obesity and the Planetary Health Diet in Medical Education: Proof-of-Concept Study Comparing 4 Information Sources

Background: Childhood obesity constitutes a complex medical and psychosocial challenge that requires both nutritional knowledge and sensitive, relationship-oriented doctor-patient communication. The Planetary Health Diet links individual health promotion with environmental sustainability and represents a relevant framework for contemporary medical education. Objective: This proof-of-concept study investigated how different information sources influence medical students’ acquisition, structuring, and application of knowledge on childhood obesity and the Planetary Health Diet within a communication-based teaching setting, including the exploratory use of artificial intelligence–based tools. Methods: A total of 359 second-year medical students participated in a mandatory communication seminar during the 2023‐2024 academic year. Following a precourse knowledge assessment and a brief theoretical introduction, students worked on a standardized counseling scenario addressing childhood obesity. In small groups, students used only 1 assigned information source (ChatGPT, Google Search, scientific papers, or instructional videos) to prepare a counseling approach. Group outcomes were assessed using a predefined scoring system based on a sample solution, complemented by thematic content analysis. Results: All information sources enabled students to acquire relevant knowledge on childhood obesity and the Planetary Health Diet. However, groups differed with regard to the depth, differentiation, and structuring of their responses. The ChatGPT group achieved the highest conformity scores with the sample solution and provided the most additional information, followed by the Google and video groups, while the paper group achieved the lowest scores. Prior to the course, students reported limited knowledge of the Planetary Health Diet and little practical experience in counseling children with obesity and their families. Conclusions: Communication-based teaching formats provide an effective framework for introducing medical students to complex topics such as childhood obesity and sustainability-related nutrition early in their training. Easily accessible digital tools, including artificial intelligence–based systems, may facilitate knowledge acquisition and elaboration; however, their use requires explicit didactic framing, critical source evaluation, and reflection on the complexity of chronic conditions to support responsible and realistic learning outcomes in future physicians.
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