July 24, 2023
July 24, 2023
Patients typically go through the same thought process when they have been diagnosed. After the relief of knowing that their ailment was correctly diagnosed, most patients want to know the path back to good health. Patients have the best outcomes when the treatment is safe, effective and provided at the right time. Decentralizing cell & gene therapy generation enables treating physicians to drive the treatment and make informed decisions about options, thus putting the patient first and creating the best possible outcome.
Cell and gene therapies have been around for decades, but recently achieved zeitgeist status when news of people being cured of death sentence illnesses reached the public. The last 5 years have created a series of high-profile cures as well as a technology boom in the cell and gene therapy space allowing treatment options, raw materials, and process equipment to become standardized, automated and efficient. Both cell and gene therapies are developed utilizing human starting materials to create a treatment.
The challenges created by the current centralized approach for cell and gene therapies include logistics, costing, cost, timeliness, and patient access. Each of these challenges is outlined below.
Autologous treatments typically represent the best option for patients as the genetic material is easily assimilated by patients and concerns about cross matching are eliminated. Allogenic treatments have greater flexibility but face significant challenges for patients. Autologous treatments require patient blood collection, cryofreezing, shipment, thawing, treatment administration, release, cryofreezing, transport, thawing, release and then administration. The cryofreezing aspects as well as transport and handling steps reduce treatment quality, increase timelines, and add steps where errors can affect the patient.
Cost and time constraints are major factors that the physician needs to address when determining the best treatment path. A cost benefit ratio is required for prior approval authorization. Prior approval requires personnel to extrapolate the estimated value of treatment options and resulting in difficult decisions and challenging discussions. The additional time requirements outlined above are also factored into treatment decisions.
Access to cell and gene therapies for patients is currently limited by production capacity. Treatments take significant resource time, equipment utilization and raw materials to complete a single treatment resulting in significant delays and tough decision making.
Physicians with access to a local cell and gene therapy laboratory can work with the local staff to create prior approval, schedule collection, create treatment, release treatment and administer the treatment in the fastest way possible.
Rate limiting factors are reduced since the patient material is available locally to the decentralized treatment center. The decentralized treatments still have logistical challenges, but those are limited to raw materials. Years ago, this would have been considered a rate limiting factor, but there are currently multiple firms that specialize in raw materials for individualized treatments, thus reducing the likelihood that raw material availability will cause a delay.
Everyone is different, that is why most cell and gene therapy treatments are considered individualized. During the screening process, several factors are important to understand including the patient history. A patient's physician will have the best understanding of patient profiles allowing a specific treatment to be tailored to the patient.
The approach to decentralized manufacturing seems challenging until it is divided into the following components. First is the establishment of local cell and gene therapy centers, followed by creation of on demand manufacturing capabilities and finally ensuring point of care administration.
Building and staffing a compliant cell and gene therapy laboratory is a significant investment and takes 12 months to achieve Foundation for the Accreditation of Cellular Therapy (FACT) accreditation. The steps to complete the build, staffing, qualification, and accreditation are well established but require a degree of customization based upon the respective patient population, geography and subject matter expert availability. FACT accreditation requires partnerships and planning.
The ability to create on demand treatments requires significant analytics, process knowledge and quality systems to ensure safe and effective treatments. Recent advancements in technology combined with a global network of researchers and healthcare professionals allows treatments which were once confined to one lab to now be implemented globally, bringing the treatment to the patient.
Patient support networks including friends, family as well as trusted physicians and advocates often aid in creating positive outcomes. Establishing point of care administration of individualized treatments synergizes treatment and administration for the best outcomes while reducing the overall patient and healthcare provider costs.
The COVID pandemic established a new normal for remote patient monitoring and data collection. Platforms were established to monitor, inform, and report on the effects on billions of vaccine recipients and patients. Centralized platforms allow for a single patient located anywhere in the world to receive standard of care while providing valuable data to create a holistic treatment view.
Decentralized treatments need to follow an approved platform for safe and effective identification, collection, testing, treatment creation, release, and administration. Many of these platforms already exist and can be extrapolated to reach a wider audience through approved sound scientific methodology. The virtual trial platform utilizes effective risk identification, reduction, and controls to ensure safe and effective treatment options.
The establishment of a collective network of researchers, physicians, clinicians, regulators, and industry created a forum to allow effective treatments to move from benchtop to bedside in record time. The vast array of networks can be difficult to navigate resulting in analysis paralysis. There are several leaders in establishing networks and partnerships including FACT.
The benefits and potential impacts of decentralization cannot be underestimated. The first is the enhanced patient outcome and satisfaction. Second is streamlining the regulatory process to bring cures to patients who need them. Third is enabling accelerated innovation and commercialization of treatments. Fourth is the reduction in overall healthcare costs and finally the ethical consideration of patient empowerment.
As stated previously, streamlined patient treatments combined with the physician/patient connection typically create the best outcomes. The ability to create fresh, individualized treatments administered at the time that works best for the patient's health changes and the established paradigm.
Compassionate use, Physician initiated Investigational New Drug (IND) and Investigational IND are the typical regulatory approvals needed to obtain release to treat patients. The regulatory methodology is streamlined once the decentralization platform has been developed and sponsors have been identified. Regulatory agencies have established and accepted content requirements that enable decentralized teams to treat patients quickly and safely with compliant solutions.
Following a standardized platform with clearly defined steps allows the decentralized platform to adapt technological innovations by identifying the improvements, demonstrating the value, and minimizing the risks to patients and staff. Safe, effective, compliant treatments come after the science is understood. Innovation occurs after a connection is established between current dogma and future needs. Commercialization of that innovation is based upon the perceived value.
Treatment costs are driven by several factors including raw materials, equipment/facility time, logistics, and human resources. Decentralization reduces the overall costs by reducing the amount of labor for preparation, removes some of the logistics and spreads the costs over a larger population allowing economies of scale to drive down the costs. Cost reductions will not be dramatic at first but will be driven down as treatments become standardized and technology reduces the overall human requirements.
Providing effective treatments sooner, with direct input from managing physicians at reduced costs is an ethical responsibility for healthcare. Establishing the most effective treatments as a standard is what drives many healthcare professionals. Enabling patients to achieve wellness sooner empowers them to take control of their lives and improve their outcomes.
There are several challenges and considerations that need to be addressed for decentralization of cell and gene therapies to be effective and standardized including regulatory/quality control challenges, standardization and harmonization of processes, training, and education of clinicians, and finally adoption and integration within existing healthcare systems.
As mentioned before, the regulatory challenges for decentralized cell and gene therapies are achievable once centers understand the regulatory requirements and establish systems to ensure patient treatments are compliant. Implementing well-defined regulatory strategies requires oversight from the medical affairs staff as well as a thorough understanding of cell and gene therapy science. A quality management plan needs to be put in place after the regulatory strategy has been defined and agreed with the respective regulatory agencies. The quality management plan defines the systems, as well as roles and responsibilities to ensure patient safety is maintained and regulatory adherence is met. The quality team needs to ensure that policies and procedures are written and followed to ensure requirements are met. Specifically, that a system of prevention is built requiring all suppliers to be audited, their materials tested for compliance and released prior to use, all treatments meet the release criteria and all deviations from approved procedures are thoroughly investigated with effective corrective action.
Multiple agencies, working groups, companies and societies provide different formats and methods to standardize treatments for decentralized providers. Working groups and the National Institutes of Health (NIH) are great sources for draft protocols. Development of standard platforms utilizing updated technologies enable clinicians and physicians to develop quick, effective, and compliant solutions. Individualized changes can be adapted to patient needs with minimal risk.
Applicable training and education of clinicians is one of the biggest hurdles facing decentralization. Companies manufacturing cell and gene therapies have had similar challenges. The typical solution has been to hire a physician with manufacturing science and technology leader with extensive experience in both cell and gene therapies to lead the unit. The leader builds a team who develops protocols based on accepted science and proven methods. The team expands its capabilities through an accreditation process which ensures each treatment is manufactured according to specific requirements.
The three mechanisms for treatment development and delivery were discussed earlier but have not been widely utilized for decentralized cell and gene therapies. Adoption of decentralized cell and gene therapies will occur as additional decentralized centers are established. Decentralized models allow better patient outcomes. Better patient outcomes are what patients are searching for when they are diagnosed with a treatable condition resulting in more patients supporting the center.
Most of the greatest accomplishments in medicine occurred at a decentralized location. The first successful cell and gene treatments occurred at research centers. These accomplishments occurred because the right physician was at the facility where the patient was located. The physician was supported by a network of scientists, nurses, and support personnel who made the treatments possible.
Several lessons have been learned after working with multiple sites who decentralized cell and gene treatments. The first is to plan for the future. Cell and Gene treatment options continue to expand exponentially resulting in a backlog of individualized patient treatment availability. Hospitals and clinics who offer these treatments quickly find that they need to grow. Ideally all of the decentralized cell and gene services for an institution will be placed in a central location which can rapidly expand 4x the initial size to accommodate new patients. Additionally internal treatment capabilities allow faster patient turnover which allows more efficient resource allocation.
The second lesson is to connect with other practitioners both locally and globally. We have seen the value in being able to synergize treatments with teams who are working with similar malignancies. Changes in raw materials, patients and technologies are often shared experiences which can allow a mistake to be made once rather than repeated.
The third lesson is to understand at a molecular level what is occurring and translate that to the gene and cellular level. Going back to the science pays huge dividends when sampling and identifying why cell growth or other factors are not proceeding to plan. This knowledge allows effective corrective action as well a writing the justification for why a treatment is safe after modifications were made.
Best practices for cell and gene therapies include ensuring that you have effectively identified your patient population and isolated exactly which patient population the treatment will be effective for. This includes the long-term outlook. Remember that regulatory requirements require following up with patients for up to 19 years. Every adverse event that a patient has will be evaluated against the treatment that was provided resulting in a lifetime of second guessing.
Healthcare has been headed towards the decentralization of cell and gene therapies for the last 20 years with firms creating better automation and emerging technologies, and changes in policies and regulations are also opening the doors for decentralization.
Artificial intelligence and technology lead the emerging trends. Algorithms now identify potential treatment pathways and utilize patient data to generate the best outcomes for patients. At ProPharma, we are currently working on a fully automated isolation solution which can be placed in a Grade D space and has a rapid transfer port to load daily coded kits containing all components required to create treatments. The systems are equipped with the relevant laboratory instruments to perform in line testing and Artificial Intelligence (AI) systems provide the physician recipes for corrective actions when the treatment isn't following the anticipated pattern. Batch records allow parametric release enabling the patients to receive their treatment as quickly as possible and avoiding freezing / thawing.
Logistics companies are building supply chains to provide exact treatment components just in time to ensure "fresh" components created specifically for the patient based upon intended growth and viability patterns. They can also store cryogenically frozen materials in case the patient has a relapse or a familial member experiences a similar illness.
Technology companies continue to refine biomarkers and sequencing equipment allows earlier diagnosis, develop more effective treatments, and create more effective follow up. These technologies are all interconnected to provide a digital roadmap of each person and treatment.
Regulatory agencies are working quickly (in regulatory terms) to ensure the safety and efficacy of cell and gene treatments by building the frameworks, extending patient options and opening doors for more treatments. The challenge is that technology is advancing so quickly and outpacing the regulatory frameworks which are needed to ensure patient safety. Clinicians typically start working on developing first in human materials technology which will be obsolete by the time treatments are ready for approval requiring a technology transfer and comparability study. Therefore, opening up the treatment options to a decentralized approach will allow the technology and the treatment to advance simultaneously.
Charles Dickens once wrote "It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity,…" Every generation reads these words and believes Charles is speaking about today. Decentralization of Cell and Gene Therapies provides the power to change healthcare in incredibly positive ways by allowing those closest to the patient to utilize the greatest scientific and technological advancements to create the best possible outcomes.
By exploring the concept of decentralization in cell and gene therapy, this blog aims to shed light on the potential benefits, challenges, and future perspectives of adopting a decentralized approach in the field. Through case studies, examples, and patient testimonials, readers will gain insights into how decentralization can improve patient access, enhance treatment outcomes, and pave the way for innovation in this rapidly advancing field.
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