Stem Cell Clinic

Cell Therapy CMC and Analytics – The Bioprocessing Summit

Cambridge Healthtech Institute s 3rd Annual August 13-14, 2018

To ensure the quality, safety and rapid production of cell therapies, companies must keep on top of their CMC and analytical strateigies. However, cell-based therapies are extremely complex to analysis with high variability.

Cambridge Healthtech Institutes Cell Therapy CMC and Analytics meeting focuses on the technical and regulatory requirements needed to advance the analysis, quality and development of cell therapies with in-depth case studies and regulatory feedback on CMC development, product release, assay development and validation, flow cytometry, target product profiles, critical quality attributes, critical process parameters, and product release.

Final Agenda

Day 1 | Day 2 | Speaker Biographies

Monday, August 13

8:00 am Short Course Registration Open (Grand Ballroom Foyer) and Morning Coffee (Break Foyer)

11:30 Main Conference Registration Open (Grand Ballroom Foyer)

1:00 pm Chairpersons Opening Remarks

Fouad Atouf, PhD, Vice President, Global Biologics, USP

1:10 Cell Therapy Product Manufacturing Considerations

Bernadette Keane, PhD, Principal, Keane Consultancy

Cell therapies are substantially more complex than small molecule or biological approaches to medicine. This complexity poses challenges for both academic groups and companies developing cell therapies, as well as for regulators seeking to oversee this growing area of medicine. In this interactive session, we will discuss some of the common challenges and lessons learned along the way and explore how collaborations between industry and the regulators can help lead to successful translation and commercialization of cell therapies.

1:45 Regulatory Aspects of Manufacturing and Control of Genetically Modified Cells

Matthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

In respect to manufacturing and quality control, genetically modified cells are considered to be most complex medicinal products. Regulatory aspects considering the fundamental steps in manufacturing and control of these medicinal products will be presented, and the regulatory framework for these products which are classified in the EU as advanced therapy medicinal products and are regulated centrally by the European Commission and the European Medicines Agency will be given.

2:15 Standards and Best Practices Applicable for Advanced Therapies

Fouad Atouf, PhD, Vice President, Global Biologics, USP

Qualification of raw materials used in the manufacturing of cellular therapies, requires the use of risk assessment strategies to categorize the critical components of a manufacturing process. In addition to cell culture supplements, excipients and other formulations components must meet the required quality to ensure consistency in manufacturing and subsequently the quality and safety of finished cell therapy products. This presentation will discuss the critical strategies facing the development of cell therapies as per USP recommendations.

2:45 Refreshment Break (Foyer)

3:15 FDAs CMC Review of a Cell Therapeutics

William Lee, PhD, Vice President, Regulatory Affairs, Cato Research

This talk will focus on two case studies. The first case study will discuss FDAs CMC issues with a stem cell therapy that were raised at a pre-IND meeting. The second case study will discuss FDAs CMC questions for an investigational cell therapy during the pre-IND meeting and then subsequently during the IND 30-day review after initial IND submission.

3:45 PANEL DISCUSSION: Regulatory and CMC Strategies for Cell Therapies

Moderator:

Fouad Atouf, PhD, Vice President, Global Biologics, USP

Panelists:

Bernadette Keane, PhD, Principal, Keane Consultancy

Matthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

4:30 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Accelerating Cell Therapy Development

Moderator: Fouad Atouf, PhD, Vice President, Global Biologics, USP

Matthias Renner, PhD, Scientist, Federal Institute for Vaccines and Biomedicines, Paul Ehrlich Institute

Bernadette Keane, PhD, Principal, Keane Consultancy

Commercial Manufacturing of Gene-Modified Cell Therapies: The Challenges Ahead

Moderator: Michael D. Jacobson, PhD., Managing Partner, Cambridge Biostrategy Associates

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Grand Ballroom)

7:00 End of Day

Day 1 | Day 2 | Speaker Biographies

Tuesday, August 14

7:30 am Registration Open and Morning Coffee (Grand Ballroom Foyer)

7:55 Chairpersons Remarks

Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

8:00 Tools and Strategies to Improve Confidence in Cell Counting Measurements

Laura Pierce, PhD, Biomedical Engineer, Biosystems and Biomaterials Division, Biomaterials Group, NIST

Cell count, a routinely performed fundamental measurement in the biosciences, underpins key decisions in the manufacturing, commercialization, and release of cell-based therapies. The industry seeks tools to gain greater confidence in cell counting measurements. NIST, in collaboration with industry and other government agencies, is developing strategies to provide fit-for-purpose measurement assurance for cell counting, in the forms of written standards, experimental designs, and control materials.

8:30 Towards Rigor and Reproducibility in Single Cell Analytics for Therapeutic Cell Products

Ruud Hulspas, PhD, Independent Consultant, Cellular Technologies Bioconsulting, LLC

Cell characterization occurs at multiple checkpoints of the manufacturing process and is particularly important at product release. In contrast to bulk analysis, single cell analysis offers detailed information about the composition of therapeutic cell products. Flow cytometry provides rapid analysis of millions of cells for up to 30 cellular parameters, simultaneously measured on individual cells, but it can also be difficult, unreliable and expensive. Existing expertise and new developments are applied for successful integration in cell therapy.

9:00 Assays in Purification of Targeted Cell Populations

Patricia Rogers, Manager, Cell Sorting Capability, Broad Institute of MIT and Harvard

Cell purification of targeted populations is necessary when specific populations are needed for downstream applications. Instrumentation needed in order to purify cell populations is often complicated and hard to standardize. Also, there is biological variation between samples that needs to be accounted for. This presentation will focus on understanding the key areas for variation and developing tools to standardize each part of the assay in order to provide reproducible results.

9:30 Advancing Rapid Microbial Testing Methods for Cell-Based Therapies

Jacqueline Wolfrum, PhD, Associate Director, Biomanufacturing Program (BioMAN), Center for Biomedical Innovation, Massachusetts Institute of Technology

Cell therapy manufacturers need rapid microbial testing methods (RMTM) to provide evidence of process and product safety in timeframes relevant to the manufacturing process, product shelf life, and patient treatment protocol. The Standards Coordinating Body is driving a collaborative effort to meet this shared need for RMTM by identifying, developing, and validating needed standards and methods. Interested stakeholders are encouraged to participate in this project.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:30 Potency Assay Development and Qualification for B-Thalassemia and Sickle Cell Disease Autologous Gene Therapy Drug Products

Ilya Shestopalov, PhD, Senior Scientist, Cellular Process Characterization and Analytics, bluebird bio

Quantitative potency assays were developed to demonstrate correction of b-thalassemia and sickle cell disease properties in an in vitro cell culture system. Potency was found to be specific to the beta-globin lentiviral vector and dependent on transduction efficiency of the autologous gene therapy drug product, demonstrating ability to reject sub-functional drug products. Considerations for assay development, qualification results, and redundancy to transduction efficiency methods will be discussed.

11:00 Product Release towards Rapid Quality Control

Junxia Wang, PhD., Director, Analytical Development, Mustang Bio, Inc.

As living drugs, cell therapies pose unique analytical characterization challenges; these challenges extend from the research bench to the cGMP manufacturing setting. This talk will review common analytical methods for cell therapies, specifically CAR T- and TCR-based therapies, with a specific emphasis on the limitations of current methods and the move towards automated analytical methods.

11:30 PANEL DISCUSSION: Automation in Analytics and Manufacturing

Moderator:

Rodney Rietz, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis

Panelists:

Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

Junxia Wang, PhD., Director, Analytical Development, Mustang Bio, Inc..

Jacqueline Wolfrum, PhD, Associate Director, Biomanufacturing Program (BioMAN), Center for Biomedical Innovation, Massachusetts Institute of Technology

12:00 pm Single Cell Proteomics for Evaluating Function & Clinical Utility in Cell Therapy

Sean Mackay, CEO, IsoPlexis

By capturing 40+ secreted proteins per single cell, thousands of cells at at time, researchers can determine the functional activity and strength of immune cells and cellular products. Using the IsoCode technology to define T-cell functional strength, Kite Pharma has used their pre-infusion product to predict objective response to CAR-T therapy. Isocode technology has also provided biomarker correlates to objective response in checkpoint inhibitor therapy - both from TILs and PBMC.

12:30Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

1:55 Chairpersons Remarks

Scott R. Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC

2:00 Assessment of Comparability of a Gene Therapy Drug Product after Manufacturing Site and Process Changes

Stephen J. Duguay, PhD, Director, Cellular Process Characterization and Analytics, bluebird bio

Manufacturing site changes and process improvements were implemented during clinical evaluation of an autologous cell-based gene therapy. A risk based approach was used to rank the potential impact of the changes to product quality, safety and efficacy. Statistical evaluation of study results included equivalence testing, quality ranges and qualitative comparisons. The study design, results and conclusions will be discussed.

2:30 In vitro Product Characterization and Stability Studies of CAR T Cell Therapies

Carlotta Peticone, PhD, Senior Scientist I, Process Development, Autolus

3:00 How Much Information Do I Need to Present for the Vector of My Genetically Modified Cell Product?

Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.

How do regulatory agencies view the vector of a genetically modified cell? Does the vector need to be GMP; from what point in manufacture would this apply? Can I use a drug masterfile? How much information, including data, should I provide in the dossier for clinical trials; will this be different for approval?

3:30 Refreshment Break in the Exhibit Hall with 1st Session Poster Winner Announced (Grand Ballroom)

4:15 Designing Strategies for Data-Driven Product Characterization

Marc-Olivier Baradez, PhD, Lead Analytical Development Scientist, Cell and Gene Therapy Catapult

In the development of cell therapy products, the ability to characterize the product during its manufacture is becoming as valuable as the ability to control and optimize the process itself. This presentation will explain the current limitations and opportunities associated with such dual product/process characterization, and it will cover the principles behind a suitable data-driven strategy for efficient product/process development in the context of industrialization.

4:45 Big Data Strategies for Cell Therapy Manufacturing

Scott R. Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC

The quest to retrieve, analyze, and leverage that data has become the new gold rush in life sciences. This presentation will discuss the role of big data in cell therapy process development, real time analytics and commercial scale manufacturing.

5:15 End of Conference

6:00 - 8:30 Recommended Dinner Short Course*

Day 1 | Day 2 | Speaker Biographies

See original here:
Cell Therapy CMC and Analytics - The Bioprocessing Summit

Stem Cell PhD Program | Institute for Stem Cell Biology …

In 2011, the Stanford University Interdisciplinary PhD Program in Stem Cell Biology and Regenerative Medicine was the first new School of Medicine doctoral program to be approved by the Faculty Senate in more than 20 years. When chartered, the SCBRM Program also became the first graduate program in the world to offer specialized training at the intersection of basic and clinical science with specific emphasis on Stem Cell Biology and Regenerative Medicine. Typically, this intersection is referred to as pre-clinical or translational science and this unique discipline has become an area of intense interest at medical schools and universities in the US and abroad.

The initial program concept grew out of an increasing recognition that academic and industry positions for scientists, as advertised in the major scientific journals seek to recruit translational scientists with broad cross-disciplinary training. Such openings increasingly target those with demonstrated training and experience in human stem cell biology, regenerative medicine, and translation. Traditionally, doctoral programs in biomedical sciences across the US, including Stanford, have focused on the basic sciences with little interaction with translation and clinical application. The Stem Cell and Regenerative Medicine Program at Stanford became the first graduate program at Stanford to bridge this gap with specific intent to provide young scientists with expertise in both basic discovery and in the application of discoveries to improve human health and wellbeing.

What's different about the Stanford Stem Cell PhD program?

Our program offers advanced training at the intersection of basic science and clinical application with a specific emphasis on Stem Cell Biology and Regenerative Medicine. This program is one of the first in the nation and abroad to specifically offer doctoral degrees in the translational sciences.

Traditionally, doctoral programs in biomedical sciences have focused on the basic sciences with emphasis on model systems such as bacteria, yeast, flies, worms, frogs and mice. This educational formula is based on the concept that clinically-relevant discoveries will naturally emerge from the basic sciences, that the human organism is of such complexity that model systems are preferable, and that there will be a growing need for scientists with narrow expertise in the basic sciences. Little emphasis has been placed on clinical translation of the basic science discoveries. However with the introduction of new tools and technologies of the last decade, it is clear that human biology is amenable to rigorous inquiry and that we can expand career opportunities for our graduates by providing them with the skills and knowledge to encompass the continuum of basic, translational and clinical sciences.Human stem cells enable these new lines of enquiry and translation. Tissue-derived and pluripotent stem cells allow investigators to create authentic human biological systems in vitro and in animals. Emerging tools in genetic engineering and in single cell biology allow us to begin targeting disease at the source and to create interventions that are precisely tailored to the mechanisms underlying disease.

Our doctoral program provides exceptional didactic education and research experience in the basic sciences underlying stem cell biology. In addition, program participants will receive specialized training in the development and clinical application of discoveries in the basic sciences to achieve regenerative therapies. Thus, our graduates will be uniquely positioned to develop successful translational careers in Stem Cell Biology and Regenerative Medicine, and will emerge prepared to deliver on their passion to improve the human condition.

The Center for Definitive and Curative Medicine

The Institute for Stem Cell Biology and Regenerative Medicine is home to theCenter for Definitive and Curative Medicine. The effort is led by the Institutes Co-Director, Dr. Maria-Grazia Roncorolo. Clinician investigators and researchers at Stanford have created one of the first dedicated translational medicine centers located on an academic campus. The Center and the Stem Cell PhD program strongly encourage graduate students to consider a research path and dissertation that engages the resources of The Center. The explicit intent of The Center is to enable discoveries to transition to the clinic within a well-integrated and fully self-contained pipeline that spans from the research bench to the first application of cell and gene therapy in humans. Many of the Stem Cell PhD Program faculty participate in clinically-targeted research projects and students in the Stem Cell Program have an unprecedented opportunity to gain experience in the unique science and regulatory environment of first-in-human clinical trials.

Extraordinary Freedom to Design your own Doctoral Research Program and Dissertation.Our commitment is to fully fund any student admitted to the Stem Cell PhD Program for the first 4 years of graduate school. A student no longer needs to ask a prospective faculty member Do you have funding to support a graduate student? The faculty members of the Institute for Regenerative Medicine represent the cutting edge of Stem Cell Biology and Regenerative Medicine and we encourage students to take full advantage of program faculty. However, we also recognize that there are many faculty members on the larger Stanford campus whose groundbreaking advances provide the biological breakthroughs, technologies, and tools for the next generation of treatments and cures. Many Stem Cell PhD students design dissertations that are immersed in the disciplines of physics, photonics, chemistry, materials sciences and engineering, bioengineering, and computational biology. Students in the Stem Cell PhD Program can rotate with any faculty member at Stanford University and, if the faculty member agrees, the student can select a dissertation co-mentor or primary advisor from any department or graduate program.

More:
Stem Cell PhD Program | Institute for Stem Cell Biology ...

Using Cells as Medicine | Harvard Medical School

Growing replacement organs? Reengineering a patients own cells to erase disease? Guiding stem cells to replenish injured or aging tissues?

Once a far-off dream, regenerative medicine is rapidly becoming a reality.

Get more HMS news here

On May 31, Harvard Medical School and Harvard School of Dental Medicine alumni gathered in the Joseph B. Martin Conference Center to celebrate the communitys latest achievements along the path toward using stem cells to repair tissues and treat disease.

The scientific symposium Discovery at HMS: Regenerative Biology, featuring four keynote speakers, took place duringReunion 2018, a three-day program for visiting HMS/HSDM alumni. A.W. Karchmer, MD 64, chair of Alumni Relations at HMS, moderated the event.

Theres no better time than now to pursue regenerative medicine research; no better city than Boston; and no better dean for HMS than George Q. Daley, said Douglas Melton, the Xander University Professor at Harvard University.

You are at the worlds epicenter of thinking about whether and how to use the power of cells to treat disease, Melton said.

Blood from a petri dish

Daley, MD 91, described the odyssey he and other scientists have undertaken over the past 20 years to engineer human blood stem cells that share all the properties of natural blood stem cells.

Im dean, but Im still masquerading as a scientist, said Daley, also the Caroline Shields Walker Professor of Medicine at HMS.

One of the hardest decisions I had to make in taking on the role was to back away from a decades-long career in science and a decades-long struggle to get to where I will describe today, a place where were tantalizingly close to realizing how to transform the future of bone marrow transplantation, he said.

Daley said he was initially motivated by seeing patients with chronic myeloid leukemia who werent eligible for bone marrow transplantation or did not have matching donors.

I set out with the goal of using stem cell biology to create a universal donor stem cell that would not trigger immune system attacks in patients, he said. The real goal was to make stem cells from every individual who might need it, so we all might become our own donors.

Daley and others in the field have since expanded their efforts into engineering platelets, red and white blood cells, and T and B cells.

The results could help researchers to better model human diseases and could also lead to new treatments for primary immune deficiency, bone marrow failure, hemoglobin disorders such as sickle cell disease, cancer and more, Daley said.

Already, Daley and his collaborators haveused stem cells derived from patients with Diamond-Blackfan anemiato discover potential new drugs for the disease.

We hope that is the first of many successes, Daley said.

As scientists make strides in coaxing induced pluripotent stem (iPS) cells to differentiate into specialized blood cell types, attention has been turning to lowering costs and scaling up.

Cancer immunotherapies such as CAR-T cell therapies, for example, have been startlingly successful for certain pediatric and adult cancers, but they come with staggering price tags, said Daley. If we could make T cells from stem cells, we could skip the patient-specific approach and drive the price down considerably.

We can harness iPS cells, Daley continued. This is coming down the pike and will revolutionize and ultimately democratize CAR-T cell therapy.

No more injections: Transforming diabetes treatment with cellular therapy

Melton described his laboratorys efforts to turn human stem cells into functional, insulin-producing pancreatic beta cells that could one day be used to treat diabetes.

Such an achievement would provide patients with better blood-sugar control than current glucose monitoring and insulin injection techniques for patients who dont have enough beta cells, such as those with type 1 diabetes or who have had their pancreas removed, Melton said.

Melton described how his group has learned to produce functional beta cells in the lab. He showed video footage of a tray of flasks, each of which brews enough beta cells to treat a person, he said.

The team is now fiddling with the protocol to see if they can better control the cell types they grow and their efficiency. Even at this point, however, Meltons group is confident enough in their findings to move into clinical trials to test whether the cells will function as expected and are not harmful.

Melton said that the lab-grown beta cells promise to solve two challenges posed by islet cell transplantation, an experimental treatment for type 1 diabetes in which patients receive insulin-producing cells from the pancreas of a deceased donor.

First, Melton said, his labs technique should be able to produce enough beta cells to alleviate the global donor shortage. Second, he said, while current islet cell transplants require lifelong immune suppression, a company he founded is working to wrap the lab-grown cells in a permeable material that would let critical hormones such as insulin pass through while shielding the cells from immune detection.

Nothing tells me it wont be possible to conquer the problem of making an unlimited supply of functional human islets, Melton said. Its possible to change the course of diabetes by using cells rather than insulin.

Moving towards the regeneration of joints

April Craft, assistant professor of orthopedic surgery at HMS and Boston Childrens Hospital, described her labs and others efforts to engineer stem cells that repair damaged and degenerating cartilage.

Current treatments for cartilage problems often have shortcomings, Craft said, such as reducing pain but not improving function, a lack of certain biochemical and biomechanical properties of normal cartilage, or being able to heal only small injuries. She said she believes stem cell therapies could overcome these constraints.

The journey, however, has not been easy. Craft said some stem cells have made cartilage well in lab dishes, only to turn into bone when tested in mice. Successful stem cell engineering not only must produce the right types of cartilage cells but also needs to integrate well with the existing cartilage in a patients joint, look and function like normal cartilage, avoid immune attack, come from a robust and renewable source and more, she said.

So far researchers, including Craft, have been able to direct stem cells to grow articular cartilage, which makes joints glide smoothly, and growth-plate cartilage, which allows bones to grow longer, in animal models. They are moving into preclinical studies to see whether human clinical trials are feasible.

We know what cartilage cells we have to make, and we know where the stem cells are, so [its a question of] how do we get there, said Craft. For that, we can use developmental biology as a guide.

As they advance regenerative medicine for cartilage, Craft said she hopes that learning more about stem cell differentiation and normal developmental biology will also help the field make strides in generating meniscus, ligament and tendon tissues.

Growing organs on demand

Harald Ott, associate professor of surgery at HMS and a thoracic surgeon at Massachusetts General Hospital, reviewed his labs progress in regenerating whole organs for transplantation.

Organ failure is a global problem that will affect many of us, he said. Living tissue and organ grafts provide a sustainable solution, and adult-derived stem cells provide an unlimited supply of personalized building blocks for these tissues.

Medicine has evolved to the point where millions of people each year survive heart attacks, strokes and other acute health crises and chronic conditions but now face organ failure and a shortage of donor organs, Ott said.

He and others are tackling the problem by looking at human organs as biologic devices that can be replicated through a combination of regenerative biology, engineering and surgery.

Replacement organs dont even need to be perfect at this stage, Ott said, so long as they perform their basic functions and improve patients quality of life.

Ott described his groups core strategy: build or obtain a scaffold for the organ, seed it with living cells, coax it through a tissue-assembly process to form a 3D structure and transplant it into an organism.

One way to build a scaffold is to use a technique Ott developed called perfusion decellularization, in which an organ from a cadaver or other organism is washed clean of cells and other materials, leaving only the semi-transparent extracellular matrix behind.

Ott also walked the audience through the process needed to direct stem cells to become the appropriate kinds of cells to populate those organ scaffolds.

He then outlined a method called directed morphogenesis, which hastens the generation of the 3D organ structures. The hope, he said, is that it wouldnt take months to grow an organ for a patient whose health is rapidly failing.

In closing, Ott shared recent successes in biofabricating lungs, and parts of lungs, that can perform gas exchange. Tests in animal models have been promising, he said.

Looking to the future, Ott said he envisions even better-performing replacement organs that can grow with young patients and survive challenges such as infection with the flu.

Whereas the first generation of such organs are made of tissue grafts built on natural platforms, the second generation might be more advanced fabrication inspired by nature, he said.

A packed Reunion program

The scientific symposium was held alongside the Class of 1993 25th Reunion Symposium, Medicine 2.0: The Fourth Aim, Finding Joy. That program featured four panels focusing on joy in discovery, teaching and mentorship, healing and caring, and beyond medicine.

Formal Reunion programming continued on June 1 with the Harvard Medical Alumni Association Annual Business Meeting; the HMS Alumni Day Symposium Advances in Medicine: It Takes a Biomedical Village; the HSDM Alumni Day Symposium Oral Health on a Global Scale; and the HMS and HSDM State of the School addresses.

Original post:
Using Cells as Medicine | Harvard Medical School