Nicholas Saraceno

Generally speaking, patient support services encompass a plethora of offerings, such as manufacturer-sponsored patient outreach, patient assistance and specialty pharma services, to name a few. Impacting these areas are continuously evolving legal developments in the biopharma and healthcare spaces, which uncover new trends and contribute to new approaches in compliance and transactional matters.

This past December, for example, the US Supreme Court issued its ruling in 

Rutledge v. Pharmaceutical Care Management Association (PCMA)

, deciding in favor of the interests of community pharmacies, unanimously (8-0). These pharmacies had been fighting for several years to regulate pharmacy benefit managers (PBMs)—the middlemen that handle the prescription drug benefits for health insurers, large employers and Medicare Part D drug plans, among others. 

, the High Court investigated the degree to which the federal Employee Retirement Income Security Act of 1974 (ERISA), which standardizes private employee benefit plans, prevents states from regulating the amount that PBMs pay pharmacies to distribute prescription drugs that are covered by an employer-sponsored health plan.

Simone Colgan Dunlap, a partner at Quarles & Brady LLP’s Phoenix branch, points out that the PBM lobby has been successful in using ERISA to strike down unfavorable state laws, and this recent ruling could push pharma lobbyists to test the limits of the decision.

“ERISA preemption has historically been an effective tool for striking down state laws that regulate PBM activity,” says Dunlap. “I predict that the 

 decision will encourage states and pharmacy lobbyists to try to enact laws similar to Arkansas’ Act 900 (the law at issue in Rutledge), and to pursue more expansive laws that push the boundaries of Rutledge. The ruling enhances a state’s ability to enact and enforce laws governing PBM activity.”

Further management of PBM authority will also allow community pharmacies to have more control of PBMs’ maximum allowable cost (MAC) lists—the maximum allowable price that a plan will pay for generic drugs, along with brand drugs that have generic alternatives.

“Additional regulation of PBMs will generally be positive for community pharmacies that stand to benefit from laws that require PBMs to do things like update MAC lists and allow pharmacies to rebill claims when the pharmacy cannot obtain a drug at a cost that is lower than or at least equal to the MAC price,” adds Dunlap.

Later in December, the Centers for Medicare & Medicaid Services (CMS) made changes to Medicaid prescription drug pricing, an announcement that would also impact the day-to-day of PBMs. CMS issued a final rule related to cost-sharing assistance, including co-payment assistance cards.

“The new rules make clear that if the discounts are not benefiting the patient and instead lower the costs for health insurance companies and theirs [PBMs], they must be counted in drug manufacturers’ reporting to CMS for Medicaid rebate purposes, as required by law,” says Maria Kirsch, SVP and head of patient services operations at Eversana, a life sciences commercial services company. “CMS is delaying the effective date of this policy until Jan. 1, 2023, to give manufacturers and payers time to make any necessary changes to their patient assistance programs and reporting mechanisms.”

In response to this ruling, Kirsch says that Eversana is currently forming solutions aimed toward direct-to-patient (DTP) mechanisms to guarantee compliance, including a smart enrollment tool that assesses product affordability based on detection of formulary design, such as redirection to a cash program and using alternative reimbursement methods.

Community pharmacies are integral patient-support providers, but sometimes, experts observe, these pharmacists can find themselves getting caught up in the details surrounding rules and regulations. A recent 

American Association of Colleges of Pharmacy article

 describes just that, even with, as authors Athena Ponushis and Nidhi Gandhi, PharmD, note, community pharmacists anticipating their focus increasingly shifting from dispensing to offering convenient clinical care.

In the article, Jennifer Adams, PharmD, EdD, associate dean for academic affairs, director of interprofessional education, and clinical associate professor at Idaho State University College of Pharmacy, is quoted: “What our board of pharmacy learned from our healthcare colleagues was, pardon the pun, but pharmacists tend to be really prescriptive in their regulations. We write out the exact details of how hot the water in the pharmacy needs to be, the amount of counter space that needs to be provided; we get way into the weeds, rather than saying the facility needs to be appropriate so that the practitioners in the facility can provide the appropriate standard of care.”

The ongoing pandemic has caused healthcare providers (HCPs) to shift and adapt to a new future—one in which telehealth is a go-to option. For this to be possible, however, it has required a collaborative effort on behalf of multiple tiers of government, involving revisions to their modes of compliance. “States and federal government—along with regulatory bodies—really took notice of the challenges and began rethinking some of the more restrictive guidelines that were preventing people from having access to much needed care during these times,” says Steve Gransden, SVP of strategy and commercial planning for KnippeRx Inc., an independent specialty pharmacy. “One of the prominent areas of realignment has been taking place within telehealth—some reevaluating of the guidelines has made healthcare far more accessible to those people who are highly restricted.”

Dunlap notes that early legal-support efforts were prioritized toward helping clients digest and react to new guidance and regulations in the form of waivers, state of emergency declarations, emergency board guidance and instituting measures to ensure continuity of patient care and protection of pharmacy staff.

“After that, there was a return to focus on more ‘normal’ topics like [usual and customary] pricing reporting, licensing, compliantly engaging with pharmaceutical manufacturers and shared services arrangements,” she says.

Articles

More leverage for community-based pharmacies and rules changes for drug-pricing reporting

The legal landscape for patient support services

With a passion for furthering the advancement of cell therapy manufacturing, Fabian Gerlinghaus co-founded and helped launch Cellares, a startup focused on ways to make cell therapy more widely available and affordable.

Pointing to the field’s still-new presence on the commercial stage, which began with the approval of the first two CAR-T drugs in 2017, Gerlinghaus says there is a need to address the "elephant in the room"—large-scale production constraints. By 2030, he notes, the cell therapy manufacturing market is expected to grow to $11.6 billion, but only 5-10% of the required manufacturing capacity currently exists. This only scratches the surface regarding the various "bottlenecks" that the sector is combatting, he believes.

 chatted with Gerlinghaus to uncover his company's role in this therapeutic market and what he expects from the field down the road.

Could you discuss Cellares’ story as a startup, and how it came to fruition?

I co-founded Cellares along with Omar Kurdi, our president, and Alex Pesch, our chief technology officer, in 2019 to solve the problems that currently plague the field of cell therapy manufacturing. What we’re bringing to the table as a founding team is a unique track record of successfully inventing, developing and commercializing complex bioprocessing technologies from scratch.

Prior to starting Cellares, I was the chief innovation officer at Synthego, a leading CRISPR (clustered regularly interspaced short palindromic repeats)-based genome engineering company, where I had the pleasure of working with Omar and Alex. Within two years, we took Synthego’s proprietary RNA synthesis technology from a paper napkin sketch to commercial readiness. This enabled Synthego to be first to market with its CRISPR-based genome engineering portfolio in 2016 and flourish into a thriving business. During my tenure, we grew the company from five to more than 240 employees.

Omar, Alex and I started Cellares because we care deeply about making a meaningful technology-enabled contribution to society. As we started to look into the challenges associated with manufacturing cell therapies, we realized that the opportunity was even bigger than we had imagined.

Our team recognized the need for innovation to unlock the full potential of cell therapy, so we set out to accelerate access to these revolutionary medicines by developing a solution that enables industrial scale cell therapy manufacturing in a way that is cost-effective and reliable. To that end, we raised $18 million in Series A funding, largely based on our track records, revolutionary intellectual property and a focused plan to capture this tremendous business opportunity. The round was led by Eclipse Ventures with participation from 8VC and EcoR1 Capital.

How would you assess the current state of the cell therapy market? What are companies doing operationally to navigate this market?

Cell therapies are revolutionizing modern medicine, but there is one major hurdle in the way of this bright future—the cell therapy manufacturing bottleneck. Today, the addressable patient population for current generation CAR-T cell therapies is about 450,000 patients—a figure projected to exceed 2,000,000 in five to 10 years. Yet right now, even the most pioneering companies in the cell therapy field struggle to treat a few thousand patients per year, due to the lack of scalable manufacturing technologies.

This problem will get significantly worse as more cell therapies move from the clinical to the commercial stage, with patient demand often exceeding tens of thousands of doses per year. The number of newly registered cell therapy trials has grown by an order of magnitude over the last decade. As of 2019, more than 600 cell therapy trials were underway, and the FDA predicts 10 to 20 new cell and gene therapy approvals per year by 2025. This is why the cell therapy manufacturing market is expected to grow to $11.6 billion by 2030.

Only 5-10% of the required manufacturing capacity exists today. In the absence of automated manufacturing technologies, cell therapy companies are brute forcing their way to scale with manual methods. This involves building GMP facilities the size of football fields, which are extremely expensive and require thousands of employees to operate—a problem that is further exacerbated by the current shortage of cell therapy talent.

The technology we are developing at Cellares has enormous potential to address this opportunity by reducing the amount of cleanroom space that’s required on a per-patient basis by about 80% and reducing required human labor by up to 75%. This yields a reduction in the overall manufacturing cost of most cell therapy products by up to 70%.

You’ve referenced manufacturing bottlenecks as being responsible for limiting patients’ access to treatments. How are you working to remove those?

Most cell therapies today are produced for a single patient at a time, using that patient’s cells as the starting material. This one-dose-at-a-time approach is very labor-intensive, failure prone and extremely difficult to scale with manual methods.

Cellares is working to remove these bottlenecks by revolutionizing the way that cell therapies are manufactured at scale. Our solution, the Cell Shuttle, is a factory-in-a-box which offers true walk-away end-to-end automation—from loading a patient’s cells to unloading a cell therapy dose ready for infusion. Cell Shuttle is the first platform designed for industrial scale manufacturing. Importantly, it has the ability to produce 10 unique patient products simultaneously.

Describe some of the challenges and complexities, along with the process, that come with manufacturing cell therapies? Do these hold true for the gene side as well?

In order to produce a single autologous dose today, a team of highly trained professionals are spending up to two weeks in expensive cleanrooms, executing on the order of 50 manual processing steps while clocking about 80 hours of touch time. The logistical complexity of scaling this to tens of thousands of patients per year per drug is tremendous. It’s very difficult to hire and train enough people, let alone ensure that no one ever makes a mistake.

I spoke to the CSO of a cell therapy company who told me employees quit because they couldn’t handle the pressure of potentially making mistakes that would lead to process failures and the potential loss of patient lives. Through automating and closing the manufacturing process, we are eliminating opportunities for operator error and contamination, leading to a three-fold reduction in the overall risk of process failure.

Additionally, manufacturers today are manually generating about 500 pages of documentation for every individual patient dose. While the Cell Shuttle fully automates the manufacturing process and generates significant amounts of in-process QC data, our software solution can auto-generate electronic batch records.

cell therapies, which is what we’re focused on at Cellares. Pure gene therapies have their own challenges, but also share some of the cell therapy obstacles. For example, the shortage of viral vectors negatively impacts the supply chain of both genetically modified cell therapies as well as gene therapies.

What are some promising disease-specific approaches with cell therapy?

Most cell therapies today are based on T cells and focused on cancers. Additionally, there are several very exciting cell therapy approaches based on hematopoietic stem cells (HSCs), which target congenital diseases of the blood such as alpha thalassemia, beta thalassemia or sickle cell disease. As an example, HSCs of patients with sickle cell anemia have a genetic defect that prevents the production of healthy blood cells. The basic principle behind cell therapies for congenital diseases is to insert the correct copy of the broken gene by means of an 

 process, and then to re-engraft these cells back into the bone marrow of the patient where they start producing healthy blood cells.

Cellares technology supports most cell therapy modalities including CAR-T, HSC, TCR, NK, TIL, Treg and γδ T cells, collectively making up about 80% of the market today. While most 

 cell therapies have many processing steps in common, they vary in the details. Hence, the importance of building a manufacturing solution that is flexible enough to support a wide variety of different workflows in an automated fashion. At Cellares, we’re achieving this by building a modular and customizable hardware solution in combination with a powerful process design software that allows our customers to design and execute precisely the processes that produce their cell therapy products.

Cellares recently welcomed the Fred Hutchinson Cancer Research Center as the first organization to join its Early Access Partnership Program (EAPP). Could you dive into the specifics of the EAPP and what this partnership means for the future of cell therapy?

To ensure that our manufacturing platform meets the needs of the industry, we are fostering partnerships with leading researchers, academic centers and commercial organizations to ensure the Cell Shuttle’s broad applicability, and to deliver it to the market at scale. Fred Hutch is a pioneer in the research and development of cell therapies for the treatment of cancer and other life-threatening diseases, and is an ideal strategic partner to help validate the Cell Shuttle and ensure it overcomes the challenges associated with both current and forward-looking cell therapy manufacturing processes.

Fred Hutch will provide Cellares with valuable insights into key manufacturing workflows for CAR-T cell therapies, natural killer cell therapies and other cell therapy modalities. The center will also participate in user studies, inform system specifications and provide feedback on the Cell Shuttle to help ensure product-market fit.

In addition to the EAPP, we have assembled a world-class advisory board, comprising leading experts in the field of cell therapy, including Dr. Carl June, director of the Center for Cellular Immunotherapies at the Perelman School of Medicine at the University of Pennsylvania. Our board's insights are invaluable in guiding the further development of the Cell Shuttle.

A one-on-one with Fabian Gerlinghaus, co-founder and CEO of Cellares, who discusses the quest to overcome bottlenecks in industrial scale cell therapy manufacturing