ElevateBio

Powering the creation of cell & gene therapies at a speed the world deserves.

Regulatory & CMC Strategy

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Throughout my career in cell and gene therapy, I’ve witnessed our industry evolve from scientific possibility to clinical reality. Yet as we scale these transformative therapies, I’m consistently reminded that success hinges not just on the elegance of the science, but on the pragmatic realities of manufacturing.

Choosing a cell therapy contract development and manufacturing organization (CDMO) isn’t a one-time vendor decision. It’s a strategic partnership that will determine whether your therapy reaches patients or joins the sobering percentage of programs that encounter preventable manufacturing setbacks.

Having led process development, manufacturing and global technology transfers early in my career at Bluebird bio, and now serving as Chief Technology Officer at ElevateBio, where I oversee programs across the industry, I’ve identified critical considerations that separate successful partnerships from costly misalignments. The following is a 10-question framework to help inform your decision when choosing a cell therapy CDMO, born from both industry best practices and hard-learned lessons. They’re designed to reveal not what CDMOs promise, but what they can prove and what will determine your program’s success.

1

What are your cell therapy manufacturing success rates?

In my experience, the most revealing metric isn’t what a CDMO highlights in presentations, but their comprehensive performance data. Request their first-time-right manufacturing success rate across all programs. While industry standards hover around 85-90%, exceptional organizations consistently exceed 95%. At ElevateBio BaseCamp, we’ve achieved 98%, though the number itself matters less than the transparency to share it.

Beyond headline metrics, examine deviation rates, failed batches, and out-of-specification results. These indicators reveal the operational consistency that ultimately defines your program. Remember, your batch performance becomes the FDA’s lens into your process control. Inconsistencies documented during early development often resurface as critical observations during BLA review.

2

What experience does your cell therapy manufacturing team have?

Leadership vision matters, but I’ve learned that program success depends on the expertise of those who actually handle your product. In our industry, average GMP manufacturing operator tenure runs one to two years – sufficient for basic proficiency but rarely enough to develop the expertise that distinguishes good from great.

At leading CDMOs, including ElevateBio BaseCamp, you’ll find operators with four to five years or more of specialized experience. Request to meet the manufacturing science, quality, and process development teams who will steward your program daily. Their backgrounds and tenure often predict your program’s trajectory more accurately than executive credentials.

3

Do you offer person-in-plant access during GMP manufacturing?

The question of access reveals much about a CDMO’s operational philosophy. What’s their formal position on person-in-plant presence? Can your team participate in training or observe clean room operations during GMP manufacturing? Is there a limit on the frequency of site visits or are there extensive pre-approvals to do so?

Some organizations restrict access, citing quality or confidentiality concerns. However, I’ve found that transparency typically indicates confidence in both systems and capabilities. At ElevateBio BaseCamp, we actively encourage client collaboration – whether working alongside our technicians during a technology transfer, observing through our in-suite, high-definition cameras, or participating in real-time problem-solving.

4

Can you optimize my cell therapy process or just execute manufacturing?

Nearly half of the programs we’ve worked with at ElevateBio BaseCamp have benefited from process optimization. This isn’t a reflection on our clients’ capabilities, but rather a recognition that cell therapy remains an evolving science where each program presents unique challenges.

Evaluate whether your potential partner maintains dedicated manufacturing science and technology teams that bridge development and production. Request examples of process improvements they’ve implemented. The distinction between a CDMO that merely executes protocols versus one that can scientifically troubleshoot and enhance and industrialize your process often determines whether you’ll navigate challenges successfully or encounter recurring obstacles.

5

Have you passed pre-approval inspection for cell therapy products?

Regulatory readiness extends beyond maintaining compliant systems. It requires demonstrating those systems under the scrutiny of commercial standards. If a CDMO hasn’t yet navigated a pre-approval inspection, investigate what commercial readiness validations they’ve pursued. Third-party certification, like the Initiative for Certification of Manufacturing Capabilities (ICMC™), provide independent verification of quality system maturity.

This consideration carries particular weight given the fact that a significant portion of FDA Complete Response Letters issued between 2020 and 2024 cite manufacturing or quality problems.1 The partnership decisions we make during early development often establish patterns that persist through regulatory review. It’s far more efficient to build commercial-ready rigor from the outset than to retrofit quality systems under regulatory pressure.

6

What’s your standard technology transfer timeline for cell therapy programs?

Technology transfer represents one of the most underestimated risks in our industry. I’ve seen programs lose momentum – and sometimes commercial competitiveness – due to protracted or failed transfers. Ask potential partners about their recent track record: How many transfers have you completed successfully over the past three years? What percentage met original timelines versus requiring extensions?

The financial and reputational costs of a failed CDMO relationship extend well beyond direct expenses. Programs can lose years and deplete resources that can’t be recovered, leaving teams to navigate compressed timelines with diminished funding. Historical performance, particularly with programs similar to yours, offers the clearest indicator of future success.

7

Can you scale cell therapy manufacturing from Phase 1 to commercial?

Success in cell therapy can paradoxically create its own challenges if your manufacturing partner lacks scaling capability. I’ve observed promising programs stall not from clinical failures but from inability to demonstrate manufacturing consistency at increased scale, a regulatory requirement that catches many teams unprepared.

Request concrete evidence of scaling experience: documented capacity expansion plans, not aspirations. Understand whether capacity is reserved for existing partners or subject to competitive allocation when demand peaks. Most importantly, verify they’ve successfully transitioned programs from clinical-scale production to commercial volumes while maintaining the consistency regulators require. Your manufacturing partner’s growth trajectory must align with your program’s ambitions.

8

What regulatory expertise and infrastructure do you provide for BLA submissions?

The FDA doesn’t just review your final product – they review your entire journey and product lifecycle. Can your CDMO demonstrate successful navigation of FDA feedback? How many INDs and BLAs have they actually supported? Do they have former FDA staff who understand how reviews really work, not just theoretical knowledge?

Equally critical is the digital infrastructure supporting your regulatory submissions. What systems ensure the data integrity FDA demands? Electronic batch records, integrated quality management systems, and comprehensive audit trails are regulatory requirements. Review the systems your CDMO has in place and ask for specific examples of how they’ve managed inspection observations to turn potential issues into approvals. The difference between a CDMO that reactively responds to regulatory requirements and one that proactively anticipates and addresses them often determines whether your program proceeds smoothly or encounters unexpected delays.

9

Was your facility purpose-built for cell therapy, and how does your team integrate new technologies?

There’s a fundamental difference between facilities designed for cell therapy and those retrofitted from other modalities. ElevateBio BaseCamp was built with FDA input specifically for multimodal, multiproduct production of cell, gene and mRNA therapies, with infrastructure optimized from material flow to contamination control and environmental monitoring. In contrast, so-called “flexible” facilities originally designed for stable molecules or well-characterized biologics are often compromised across these requirements.

Equally important is how that infrastructure evolves. The cell and gene therapy field evolves rapidly, yet many CDMOs hesitate to integrate innovations that could benefit their clients’ programs. Ask for specific examples of recently implemented technologies. How do they evaluate new automation or analytical methods? Do they have a technology development lab where innovations can be tested without risking GMP production? At ElevateBio BaseCamp, we’ve implemented more than ten new technologies in the past year alone, from automated processing platforms to advanced analytical methods. The willingness and capability to evolve with the science often distinguishes partners who will advance your program from those who might constrain it.

10

What are your sustainability commitments and environmental certifications?

Many biopharmaceutical companies look for environmental commitments from their suppliers, becoming just as important as quality systems in vendor selections. Ask how your CDMO considers environment and occupational health certifications. At ElevateBio BaseCamp, we pursued International Organization for Standardization (ISO) 45001 and 14001 certifications early, recognizing that our commercial partners would eventually require this level of rigor from their supply chain.

As we scale cell therapies toward broader patient populations, demonstrating sustainable manufacturing practices becomes part of our collective responsibility to deliver these treatments responsibly.

These questions are designed to reveal which partners truly understand the complexity of cell therapy manufacturing. The right CDMO won’t hesitate to share specific metrics, provide references, or open their doors for inspection. They’ll welcome these questions because they’ve already built their operations around answering them.

At ElevateBio BaseCamp, we built our operations specifically to address these challenges. From our purpose-built facilities to our experienced team and commercial scale, we welcome these tough questions.

Learn more about ElevateBio BaseCamp’s approach

References: 

  1. Slabodkin, Greg. “FDA’s CRLs Reveal 74% of Applications Rejected for Quality, Manufacturing Issues.” Pharma Manufacturing, 14 July 2025, www.pharmamanufacturing.com/all-articles/article/55302937/fdas-crls-reveal-74-of-applications-rejected-for-quality-manufacturing-issues.

Mike Paglia, Chief Technology Officer

Michael Paglia is the Chief Technology Officer at ElevateBio, a technology-driven company commercializing its enabling technologies, manufacturing capabilities, and industry-leading expertise to accelerate the development of genetic medicines to treat human diseases. He has more than two decades of experience in facility design, start up, and operations ensuring the highest standards of quality, safety, and regulatory compliance. 

At ElevateBio, Michael led the design, construction and operations of the BaseCamp manufacturing facility that was recognized as the Facility of the Year, Operational Excellence by International Society for Pharmaceutical Engineering (ISPE) in 2021.  Michael established the process development and manufacturing capability and leads manufacturing operations, CMC regulatory, process/analytical development, and the advancement of innovative process technologies. 

Prior to ElevateBio, Michael was the Vice President of CMC Operations at Oncorus responsible for the development and manufacturing of novel genetically modified oncolytic herpes virus for the treatment of cancer and prior to that, Head of Technical Operations, Cellular Process Development and Manufacturing Operations at bluebird bio where he led the early process development, manufacturing, and global technology transfer of four approved genetically modified autologous cell therapies.  Early in his career at Tolerx, Michal lead process development, and late-stage manufacturing of novel therapeutic antibody products designed to treat patients by reprogramming the immune system.

Michael received his undergraduate degree from Providence College and a Master’s of Science in Biochemistry and Cellular Biology from the University of New Hampshire where he was honored with the Distinguished Alumni Award from the College of Life Science and Agriculture (COLSA) in 2023 for his career guidance and ongoing initiatives in COLSA to enhance STEM workforce development initiatives.

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In the race to bring transformative cell and gene therapies to patients, speed often dominates early decision-making but industry data reveals a significant trend: between 2020 and 2024 a significant portion of FDA Complete Response Letters (CRLs) issued by the U.S. Food and Drug Administration involve manufacturing and quality issues.1 This industry trend is also reflected specifically in cell and gene therapy, where complex processes and novel modalities amplify the risk. These setbacks are rarely caused by last-minute missteps. More often, they trace back to decisions made years earlier during preclinical and Phase 1 testing when programs are under pressure to move fast and reduce costs.

A Predictable Pattern of Late-Stage Setbacks

Across the industry, the same challenges continue to emerge late in development. These findings don’t arise overnight – they expose gaps that were embedded in development programs years earlier.

The consequences surface at the worst possible moment: when a company is advancing toward approval, investor expectations are highest, and five or more years of development – and significant capital – have already been invested. The results are major approval delays, immense unplanned costs, and challenges that can fundamentally alter a company’s trajectory.

Cell Therapy Intensifies the Challenge

While these statistics highlight industry-wide trends, cell therapy adds unique challenges that magnify these risks. In this space, early decisions carry disproportionate weight: deficiencies in process design or scale-up can ripple through development and delay approval, even years later.

These risks tend to play out in consistent ways across programs, pointing to key areas that must be managed carefully to ensure successful development.

Critical issues to avoid:

Unresolved CMC and facility readiness issues, with critical details missing from Chemistry, Manufacturing, and Controls (CMC) packages, and manufacturing sites not fully prepared for FDA inspection

Assays not built for late-stage demand, often revealing limitations because they were designed for early research rather than commercial scale, robustness, and regulatory expectations

Product quality and manufacturing success-rate challenges, where teams struggle to consistently produce product that meets specifications, particularly around viability, stability, and other critical quality attributes

Difficulty scaling manufacturing, where processes that work at early stage can fail under commercial demand, making it hard to demonstrate comparability, reproducibility, or consistent performance

Building Success from the Start: ElevateBio Addresses the Root Causes

At ElevateBio, we’re focused on advancing the field of cell and gene therapy by combining genetic medicine technologies with manufacturing scale and expertise. So, we understand that manufacturing cell therapy is inherently complex, requiring robust processes, careful planning, and rigorous quality systems from the very start. This requires the right processes, the right people, and a quality-first mindset embedded from day one, so we can help our partners avoid the costly mistakes that set their programs back.

ElevateBio BaseCamp® is dedicated to the development and manufacturing of genetic medicines to address these challenges. Designed to be an integrated part of our partners’ development and approval journey, BaseCamp provides the foundation needed to withstand late-stage scrutiny and accelerate time to patients.

What sets ElevateBio BaseCamp apart:

  • A world-class team with proven experience manufacturing and releasing complex cell and gene therapy products
  • Expanding commercial manufacturing infrastructure engineered for reliability, scale, and regulatory readiness
  • Deep product understanding, supported by regulatory expertise and advanced analytical capabilities
  • A culture of quality and collaboration that prioritizes speed with accuracy, transparency, and true partnership

This combination matters because ElevateBio has already solved the problems others are discovering too late. Our partners benefit from established systems, extensive experience, and an operational model designed to anticipate regulatory and manufacturing challenges.

Manufacturing Setbacks are Not Inevitable

Many issues stem from rushing early development, choosing the wrong partners, or re-learning lessons the industry already knows.

The promise of genetic medicines is real. These therapies are transforming care for diseases once considered untreatable. But realizing that promise requires treating manufacturing as a strategic driver, not a downstream function. In cell and gene therapy, regulatory success is shaped years before submission and depends on partners with the right processes and quality systems in place from the start. That is what ElevateBio provides: the experience, infrastructure, and commitment to quality needed to turn scientific breakthroughs into approved therapies – and ultimately deliver them to patients who are waiting.

Learn more about ElevateBio BaseCamp’s approach

References: 

  1. Slabodkin, Greg. “FDA’s CRLs Reveal 74% of Applications Rejected for Quality, Manufacturing Issues.” Pharma Manufacturing, 14 July 2025, www.pharmamanufacturing.com/all-articles/article/55302937/fdas-crls-reveal-74-of-applications-rejected-for-quality-manufacturing-issues.

Cindy Riggins, Ph.D., Vice President, CMC Regulatory Affairs

Cindy Riggins, Ph.D. is Vice President, CMC Regulatory Affairs at ElevateBio. Cindy started her career in cell and gene therapies in 2001 at FDA/CBER as a post-doctoral fellow studying xenotransplantation and later transitioning to product reviewer for various cell therapy products. After leaving FDA in 2008, she has been involved in development of monoclonal, cell, and gene therapies through CMC Regulatory Affairs roles at AstraZeneca, Novartis, Autolus and ElevateBio. She was part of the regulatory team at Novartis responsible for submission and approval of Kymriah®, the first gene therapy product approved in the USA.

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The development of cell and gene therapies (CGTs) is highly complex and challenging. While incredible strides have been made in the field, this area of the biotech industry is still maturing, especially when it comes to manufacturing. Because we’re just starting to see the first wave of cell and gene therapies reach commercialization, managing the entire life cycle of CGT product development is still a very specialized skill.

Along with specific technical challenges of CGT process development and manufacturing, CGT life cycle management involves complex supply chains, traceability systems and analytics to guarantee safety and navigating the CGT regulatory environment. The cost of failure is also quite high in terms of additional expenditures, lost time, and patients’ lives that may hang in the balance.

All of these factors underscore the importance of correctly managing the life cycle of a CGT product the first time around, by knowing upfront what’s needed for regulatory approval and then developing the product to meet those needs from the start. But the challenges of “getting it right, right from the start” are more than just technological. Success depends on having both the right processes across the life cycle and the right people to develop and execute those processes. Having one but not the other is a recipe for failure.

Process in the CGT product life cycle

The life cycle of a CGT product starts with procurement of materials, including reagents and cells from donors or patients for autologous products, and extends through dose administration for clinical use. All along that complex supply chain, many different controls must be in place to define, characterize, test and validate the materials. A key element in the supply chain is traceability, which is the process of keeping cellular materials segregated, safe, and well identified from their sourcing through manufacturing and into the patient, and it requires very specific systems and analytics.

Traceability is especially critical for autologous cell therapies. When a patient’s blood sample comes to the manufacturing facility and the starting cells are isolated from that sample, it is necessary to ensure the right patient’s cells are modified in the right way – to generate the needed CGT – and then sent back and administered to that same patient. Lack of certainty anywhere along that chain of custody creates a major safety concern: administration of the CGT product to the wrong patient will induce an immune response (rejection) that could severely sicken the patient.

Securing the CGT chain of custody is highly important, but so are the analytics needed to identify and validate the cells along that chain. For example, in-house release testing methods for an autologous therapy must be able to correctly identify the original patient’s cells, even after they have been genetically modified. The chain of custody also includes logistical components, such as training hospital staff to receive and administer the cells.

All of these factors come into play when navigating the complex regulatory environment, which is the primary hurdle that CGT companies face, especially on the manufacturing side. A CGT company must be in constant communication with the U.S. Food and Drug Administration (FDA) to get the Agency’s input and feedback. When a company does submit an IND for an autologous CGT product, the FDA’s top questions are always, “What is your traceability matrix?” and “What is your control around the traceability for the product?”

Materials used for CGT manufacture are defined, tested and regulated very differently than materials for other drug products. Regulations for each CGT material differ among regulatory agencies around the world.

Therefore, knowing the domestic and global regulatory environment, especially from a CMC perspective, is critical to success. If the CGT team hasn’t lived this life cycle approach to CGTs and their regulation, it has to start from scratch; and without someone who has that hands-on experience, the learning curve is very steep.

The importance of getting it right the first time

In addition to managing the life cycle components described above, it’s also necessary to understand how each of those components ties into manufacturing, and how to make critical development decisions around them, early on the development of a product. Whether the issue is raw materials, developing a process or gaining regulatory approval, waiting to think about these things until the product is approaching the clinic – or even after it has completed clinical testing – makes it harder to introduce the necessary changes later.

The main regulatory hurdle for CGTs is not getting FDA to accept an IND; the agency does accept INDs based on how products have been characterized for Phase 1 testing. The real hurdle comes later, when a company has to conduct process performance qualification (PPQ), which is the characterization and validation required to produce commercial batches of CGT product.

If the PPQ hasn’t been worked out before submitting the IND and entering the clinic, then later clinical development and commercialization will be an uphill battle. The company will have to demonstrate comparability between the previous (IND-related) and newer (approval-related) processes; otherwise it will not be able to use the data generated throughout clinical development to seek regulatory approval. If comparability cannot be shown, the company may have to repeat clinical trials using the new PPQs.

In fact, one of the main reasons the FDA puts products on clinical hold relates to CMC activities or deficiencies, such as lack of comparability. Therefore, a CGT company must anticipate where its product will need to be at the commercial end of the life cycle and develop the product with those needs in mind from the outset. Doing this may involve more work on the front end of the cycle, but it ultimately results in lower costs and development burdens downstream – both of which accelerate the commercialization of the CGT product.

Building the right team

People are just as critical to successful CGT product development as the processes. If a CGT company has one but not the other, the potential for failure is high, because developing and implementing processes correctly requires a team with experience and know-how across the entire life cycle. Putting together the right team comes down to recruiting, hiring and, above all, retaining the right people.

Given that the CGT sector is still in the early stage of growth, the talent pool is quite limited, and it’s practically impossible to staff an entire company only with people who have CGT expertise. But finding the right people is achievable by viewing people’s backgrounds and experiences through the appropriate lenses rather than strictly seeking CGT experience.

To be sure, at any CGT company there are some roles where it is essential to have people with prior CGT experience in order to accelerate development. These include such roles as managing technical operations across the entire life cycle and developing the specialized electronic systems for traceability. However, there are other roles that can be filled by people who don’t have any CGT experience but do have transferable skills. The key is educating and training those people to redeploy their extensive expertise for CGT applications.

This redeployment approach can work well for many, but not all, potential CGT employees. For example, it’s hard to teach someone who has “lived” small molecules throughout their entire career how to reapply that knowledge to CGTs; whereas for people who have worked with proteins, enzymes, and antibodies, the transition to CGT comes more naturally.

In the end, the real challenge in assembling the right CGT team isn’t hiring people; it’s retaining them, because the still-limited pool of CGT is highly sought-after and competitive as the field continues to grow. Therefore, the key to keeping an experienced team on board is offering them a variety of products, projects, roles and opportunities, so that they remain happy, excited and fulfilled.

How the ElevateBio model gets it right

At ElevateBio, we have everything it takes to get CGT development and manufacturing right the first time: an infrastructure for the entire product life cycle; a world-class team of drug developers and operators who can get the job done successfully; and a diverse and growing portfolio of innovative CGT products. Having all three – infrastructure, people and product diversity – in one place benefits us in several ways.

First, because we don’t have to line up CDMOs, we can control our own timelines which saves us time and money.

Second, we have a great deal of talent under one roof; this promotes rapid knowledge transfer among team members and gives us the flexibility to assign our people to multiple products, platforms and technical areas.

Third, we anticipate our employee retention will be higher than conventional CGT companies precisely because we can offer people a wide variety of opportunities within one organization, and we believe this variety will continue to draw additional talent to us.

Together, these benefits translate into an ability to accelerate the development of affordable CGTs and deliver them to as many patients as possible.

The CGT sector continues to grow at a rapid pace. There are now many sophisticated CGT companies and a host of exciting new technologies, from electronic traceability systems to robotics, that are advancing how CGT products are developed and manufactured. However, all of the technology and automation in the world will not guarantee success without having the right processes and the right people in place across the whole life cycle of a CGT product.

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