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Testing Strategies and Custom Assay Development for Cell and Cell-based Therapies

Written Jan. 6, 2021 by Michael Adeniya, Event Director, Phacilitate

An Interview with Ward Carter, Chief Operating Officer, QualTex Laboratories

As the cell therapy industry grows and matures, demand for testing has soared. Is testing a bottleneck in getting therapies to market?

It can be, for several reasons. The number of cell therapy development programs has increased dramatically in recent years, and as they progress toward commercialization, demand for testing has grown exponentially. At the same time, only a few laboratories provide testing services for these types of therapeutics.
 
Increasing capacity and obtaining the required global accreditations takes time and considerable effort, which many organizations are not willing to do, or it doesn’t fit with their growth plans.
 
Just to give you an example, the Alliance for Regenerative Medicine reported that between 2015 and 2020, the number of regenerative medicine companies grew from 672 to 1,001, and the number of clinical trials went from 631 to 1,078. All this growth means there is a critical need for more testing to ensure safety and performance of these potential new therapies.

Fully automated testing laboratory

How does testing fit in the overall development and commercialization of cell therapies?

Every therapeutic development process begins with qualification of donor material. Depending on the nature of the product, whether it’s a 1:1 product (autologous or allogeneic) or 1:many (allogeneic), the number and complexity of needed tests changes. It’s important to understand that range up front.
 
Recent feedback from the FDA has highlighted the impact of Critical Quality Attributes (CQAs). Therapeutic developers need to understand their target indication and identify or develop a clear set of potency assays or functional assays early on to support their regulatory approval. The FDA’s recent position regarding a therapy showing clinical benefit, but with insufficient CQAs, makes it clear that moving forward without this understanding is risky.
 
Researchers also need to make sure a testing laboratory has a process for tech transfer of assays if required, at the pre-clinical, clinical and commercial phases.
 
In the case of autologous therapies, turnaround times are tight, so there isn’t much available for backup samples. And while tests tend to focus more on whether the cell manipulation worked, the key is making sure the sample passes more standard donor safety requirements. This is especially true in the case of infectious diseases.
 
And how does testing fit in the overall supply chain?
 
Testing is an integral part of every step of therapeutic development, and it takes a full-service laboratory with a robust infrastructure to handle receiving and tracking a wide range of sample types. That laboratory also needs to be able to develop custom assays.
 
In addition, reporting requirements for cell therapies can vary, and the timing of those reports can affect production. It’s critical to the process that testing providers and therapeutic developers stay in regular communications about needs and results.
 
Given the complexity of the supply chain and the number of stakeholders, it is really important for therapeutic developers to be working with their testing laboratory in tandem with all other partners to establish their testing program, including custom assays.
 
At what point should biotech organizations be looking at custom assay development?
 
If they want to be successful, they need to focus on custom assays early in the process. There are Critical Quality Attributes that are essential for approvals throughout the development process, and standard characterization assays often are not going to be sufficient. Critical 
 
Because there are no established standards for potency, it’s essential that researchers define their own standards that may require multiple assays using different platforms. There also are going to be different assays for different time points through the development process. They could start with functional assays – characterization and possibly potency – in animal models, and then look at other assays at different times, for safety, potency and/or characterization.
 
There are safety assays that will be required before a clinical trial can get underway. Others will need to be converted from in-vivo models into those that can be used in clinical phases of trials.
 
As a testing partner, we offer both research grade and GxP assays. Biotech companies will need both options, based on where they are in the process of developing and commercializing their product – from qualification to quality control and release testing.

QualTex and BioBridge Global headquarters in San Antonio, Texas

Can you tell us more about BioBridge Global’s journey into cell therapy testing?
 
BioBridge Global began as a community blood bank in 1974, and in the last 45-plus years, the number and complexity of tests required by the FDA has grown dramatically. We have been performing those tests in-house for many years. Gradually we expanded into testing donations from other blood centers, and then to other types of donor screening, including plasma and human tissue, as well as custom assay development. Our footprint has become global, with accreditations in the United States, Canada, the European Union, Asia and Australia.
 
In 2016, BioBridge Global was awarded an MTEC contract to develop manufacturing capabilities for cellular products, as well as stand-up capabilities for cell therapy testing. At that time, we decided to invest in a biomanufacturing facility and in the testing required for it. We’re continuing to build a portfolio of cellular therapy assays to support therapeutic developers in their clinical and commercial efforts.

QualTex Laboratories adds Ortho Diagnostics VITROS® Anti-SARS-CoV-2 IgG assay

Test detects antibodies developed during a COVID-19 infection 

QualTex Laboratories, a subsidiary of San Antonio-based nonprofit BioBridge Global, has begun offering the Ortho Diagnostics VITROS® Anti-SARS-CoV-2 IgG assay for use in detecting COVID-19 antibodies. 

The assay helps health care professionals determine if a person’s immune system has developed antibodies to the virus that causes COVID-19. It was approved for Emergency Use Authorization for qualifying COVID convalescent plasma (CCP) by the Food and Drug Administration on Aug. 23. 

Given the recent increase in COVID-19 cases and hospitalizations, the addition of the assay is a timely addition in the battle against the pandemic. 

The FDA has issued an EUA for COVID convalescent plasma, which is donated by those who have recovered from COVID-19, for use in patients with active COVID-19 infections. 

The Ortho IgG test has demonstrated 100% specificity and is currently the only assay approved by the FDA for COVID convalescent plasma qualification. The test runs on Ortho’s high-throughput, fully automated analyzers, and it measures IgG antibodies to the SARS-CoV-2 virus. 

COVID Convalescent plasma is currently being used to save the lives of those most severely affected by COVID-19. This assay provides a powerful tool to identify those blood donors with the highest antibody concentrations to aid in COVID-19 treatment.

QualTex Launches Cellular Therapy Testing Services

Lab to support researchers developing new treatments for global healthcare market

QualTex Laboratories, a subsidiary of San Antonio-based nonprofit BioBridge Global, has expanded its offerings to include cellular therapy testing services in support of advanced therapeutics clinical developers.

The new service provides a full range of research use only (RUO), current good manufacturing practices (cGMP), and good laboratory practices (GLP) qualified assays to support a variety of cellular therapy industry testing needs.

The cellular therapy testing service will allow QualTex to collaborate with clients to get their products to market, while at the same time adhering to the strictest quality standards. Through these collaborations, QualTex will work to develop new assays for the next generation of lifesaving treatments. 

“Every client and every project is unique. Our team’s goals are simple – be nimble enough to meet the needs of clients and at the same time follow the quality practices that are at the core of our organization,” said Ward Carter, Chief Operating Officer of QualTex Laboratories.

The laboratory can expand cell samples and either perform testing in-house or work with partner laboratories to provide a certificate of analysis, as well as individual test reports. 

This new QualTex service offering includes: 

  • Analytical assay development
  • Cell line characterization
  • Expandability and potency testing 
  • Lot and final release assays 
  • Stability testing 

“We have quality processes in place allowing us to provide phase-appropriate and risk-based testing solutions assuring the safety, purity, and potency of cell-based products,” Carter said.

Martin Landon, Chief Executive Officer of BioBridge Global, added “The launch of our cellular testing services provides another expansion to our end-to-end capabilities supporting regenerative and personalized medicine here in San Antonio and across the globe.”

GenCure joins with Sentien Biotechnologies, Rooster Bio on $2.4 million contract

Partners will develop potency assay for mesenchymal stromal cells

The federal Medical Technology Enterprise Consortium (MTEC) has identified the need for potency testing as critical to new cellular therapies.

Sentien Biotechnologies, Inc., a clinical-stage biotechnology company developing novel approaches to cell therapy, has been awarded a $2.4 million contract from MTEC.

GenCure and RoosterBio, which is a developer of MSCs and bioprocess media, are partners with Sentien Biotechnologies in the contract.

Together, this team will develop a potency assay framework using MSCs, spanning large-scale biomanufacturing, in vitro assay development and in vivo biomarker analytics. 

The award was granted by the U.S. Army Medical Research & Development Command (USAMRDC) in collaboration with the Medical Technology Enterprise Consortium (MTEC), a 501(c)(3) biomedical technology consortium working in partnership with the Department of Defense (DoD). 

The Defense Health Agency has identified a need for quality management in the biomanufacturing of regenerative medicine-based products. For cell therapy products, the potency assay is the most robust quality metric, representing the biological ability of a product to effect a clinical outcome. Developing a potency assay is a complex challenge, requiring significant characterization of process parameters and quality attributes throughout the preclinical and clinical development stages. 

This work will take an integrated, cross-functional approach to potency assay development. First, biomanufacturing process parameters and quality attributes will be evaluated during the expansion of MSCs derived from different tissue sources. Second, the resulting cell banks 

will be analyzed using Sentien’s ex-vivo bioreactor platform to assess the immunomodulatory effects of the MSCs and generate putative potency markers. Finally, the putative potency markers will be matched against clinical trial samples from subjects with systemic inflammatory conditions who have been treated with SBI-101, Sentien’s lead product. 

SBI-101 is a combination biologic product, in which MSCs reside on the exterior of hollow fibers, while blood flows through the interior. The unique design of SBI-101 enables real-time sampling of both MSC-secreted factors (pharmacokinetics) and their effect on patient blood (pharmacodynamics), which will provide particular value for this project. The ultimate goal of the project is to develop a broadly applicable potency assay framework that members of the regenerative medicine community can leverage for their particular biomanufacturing process, product and indication of interest. 

“Sentien is grateful to MTEC and the DoD for recognizing the potential impact of our proposal and awarding the funds to undertake this work. We have an opportunity to add real value to the regenerative medicine community by developing this potency assay framework which spans R&D, biomanufacturing and clinical translation,” said Chris Gemmiti, Senior Vice President of Operations at Sentien. “This award demonstrates external recognition of how our proprietary microreactor platform can offer unique insights into MSC biology. This is very timely as the interest in MSCs has been increasingly heightened in the context of COVID-19 trials,” said Rita Bárcia, Vice President of R&D at Sentien. “We are very excited to be partnering with RoosterBio and GenCure on this project,” added Sentien CEO, Brian Miller. “We believe this team of collaborators, with complementary technologies and skills, will together produce a valuable, widely applicable deliverable.” 

“We are very much looking forward to this collaboration to provide our platform solutions and expertise in MSC manufacturing in support of this project,” said RoosterBio CEO, Margot Connor. “The development of a MSC potency assay framework is really the cornerstone of a successful regenerative medicine product thus we are grateful for the opportunity to contribute to this team effort.” 

Becky Cap, Chief Operating Officer for GenCure, a subsidiary of BioBridge Global, commented, “GenCure values creative approaches to solving difficult problems, and the Sentien team has developed some highly innovative approaches to treatment with SBI-101. With this project, they are finding ways to leverage that innovation to address more fundamental questions about potency and the impact of tissue source on both potency and therapeutic benefit. We are honored to be part of this project.”