Platform Tech For Cell & Gene Therapy Processing Scale-Up

It is well to be noted that since as early as the 1970s, gene therapy has gone on to promise treatments for numerous diseases ranging from cancer as well as HIV to cystic fibrosis and also spinal muscular atrophy. With the first patient happen to be receiving gene therapy in 1990, the overall impact of this therapeutic class is just beginning to get realized. The fact is that cell therapy has been around for even longer; however, as the biopharmaceutical sector progresses, so will the understanding of such kinds of medicines, as well as their demand when it comes to treating even more patients.

However, there are challenges that do remain in the production of cells as well as gene therapies- CGTs, specifically when it comes to the transition from lab manufacture to commercialization, with intricate processing requirements along with high costs restricting patient accessibility. As medicines grow from the corridor of research and development, towards clinical trials, and right on to the market, production must scale in order to meet this rising demand. A combination of planning as well as technology can enable to overcome these issues, and as approvals within this field continue to gain momentum, an official from the FDA has gone on to predict that 2024 is going to be the breakout year when it comes to addressing major challenges pertaining to cell and gene therapies.

Apparently, fill/finish may as well seem like a straight-forward stage in the manufacturing process, and as it happens to be one of the final actions, and can be overlooked until later. But it is indeed vital to take it into account early on. So how can platform technologies help in the desired scale up of fill/finish operations in cell and gene therapy processing.

CGT Complexities

It is well to be noted that the biological nature of CGTs needs a precise control of processing conditions as well as extremely gentle handling so as to maintain product integrity. As the traditional sterilization approaches could go on to damage structure as well as function, maintaining sterility by way of the manufacturing process is key. Batch sizes are most likely to remain small; hence, the bench top production methods that are used for research and development may as well satisfy the volumes required, however, they will not meet the regulatory requirements needed when it comes to commercialization and efficiency. There is a crystal-clear requirement for customized technologies that have been designed especially for these treatments and overcome the issues in a reliable and efficient way.

Contamination Prevention

It is well worth noting that the risk of contamination goes on to develop significant challenges in cell and gene therapy production. CGTs happen to be often delivered intravenously straight into vulnerable patients, and even trace contamination levels can prove fatal. The biological nature of such therapies happens to prevent any final product sterilization, and therefore an absolute contamination control strategy is indeed vital. This is not only key to safeguarding the patient but, at the same time, avoiding product loss along with the associated costs as well as time delays. Operator protection is yet another important consideration since these therapies often make use of bio-hazardous materials like genetically modified viral vectors during the course of production.

Notably, the containment requirements vary dependent on a product’s makeup as well as application, and hence a best fit solution is required, specifically for those organizations that produce numerous therapies. These systems will need to meet the scale up timescale as well as a cost plan, while still controlling viable as well as non-viable contamination along with the associated bioburden. This can very well be achieved by way of apt barrier technologies or the incorporation in terms of pre-sterilised single-use components.

Human intervention happens to be yet another potential source of contamination, however, automation can and should be used so as to manage this. Sterility can get more enhanced by way of using barrier technologies that are powered by automation. Although the possibility of complete automation might be very appealing, it is indeed imperative to incorporate accessibility into the process and equipment design. Controlled accessibility enables interventions to be made in order to resolve issues when they go on to occur sans compromising the aseptic, Grade A environment or even ruining batches. Automation brings the added advantage of increased process control as well as monitoring, along with improved efficiency.

The recent revisions to Good Manufacturing Practices- GMP Annex 1 require manufacturers to elevate contamination control measures, such as barrier technology as well as automation, in order to reduce risk to patients as well as operators. A comprehensive strategy should make use of a focused, risk-based approach in order to protect critical areas. It is therefore indeed vital that developers select the exact technology and equipment partners so as to support the requirements and delivery of GMP.

Modular, flexible solutions

As a varied class of therapeutics, CGTs happen to be having different manufacturing needs. Processing platforms, therefore, need to be flexible, thereby incorporating standardized components so as to ensure regulatory compliance. Platforms also require accommodating varied batch sizes, ranging from container sizes as well as fill volumes, as required for numerous therapies.

One way so as to achieve flexibility is by way of making use of pre-validated, enclosed, as well as automated modular systems that can be fully configurable as well as arranged to process a range of varied products, which may be with or without containment, thereby helping to address many issues that float around regulatory compliance, safety, waste reduction, as well as changeover between the products.

Exact Product Selection

While considering overarching traits pertaining to a platform, exact components must also meet the intricate requirements pertaining to cell and gene therapies. The need for gentle processes happens to make the pump selection a major concern. Efficient production goes on to rely on high-performing pumps, but such scenarios can go on to cause large pressure fluctuations that can also lead to damage to cells as well as biologic therapies. Low-shear pumps that are specifically designed so as to minimize this very potential damage, are a key component when it comes to any fill or finish line. So as to be commercially viable, they also need to meet the desired delivery speeds and offer precise volume control. Peristaltic pumps are a popular choice in terms of cell and gene therapies as they look to have inherently low shear and as the fluid is completely contained within a tube, and that too is usually single-use; it never gets into contact with the pump itself, thereby providing improved sterility.

Interestingly, single-use technology happens to be yet another clear choice for CGT processing as it goes on to offer the opportunity to replace the overall fluid pathway with a new pre-validated system across each batch. This eradicates the need for clean-in-place- CIP or sterilize-in-place- SIP systems and can hence guarantee sterility in a way that goes on to meet the needs of small-batch as well as bespoke manufacturing. Single-use pathways happen to very likely come pre-validated in terms of regulatory compliance, and it is also true of specifically automated, modular equipment. Pre-validated systems require industry standards to bypass the bespoke validation and design processes needed, offering a key part of a robust Contamination Control Strategy- CCS and thereby leading to rapid regulatory approval.

Skilled Workforce

There are many industries that are facing a skills shortage, and the biopharma industry is no different, specifically within manufacturing and GMP expertise. There happen to be promising signs that this is indeed changing, with employees joining cell therapy, gene therapy, as well as multifunctional facilities across the UK growing by 23% in 2022, but this progress goes on to bring an increased training demand. Designing processes that happen to be easy to use as well as maintain will hence go on to benefit all organizations, with automation in a process decreasing the burden on staffing levels and at the same time delivering GMP best practice.

Partnering for Success

Significantly, often therapies that happen to look promising in early-stage development ultimately go on to fail to deliver in clinical trials, in certain cases due to the fact that the processes could not be successfully scaled up. In the early stages of research and development, manufacturing can as well be seen as a distant concern, but by way of considering processing requirements as early as possible, organizations can go ahead and avoid later hold-ups.

The usage pertaining to benchtop fillers that apply similar technology across the scale-up in dispense as well as single-use fluid path technologies can go ahead and limit the time and cost of validation while at the same time ensuring consistent output. Selecting a supplier that can scale by way of therapy using common technologies goes on to give producers peace of mind that they can scale safely after having tried, tested, as well as supported and validated solutions.

As one sees the development of novel treatments speed up, manufacturing solutions are required to match this innovation so as to ensure this does not become a bottleneck in terms of the delivery of effective medicines. By way of understanding current as well as future processing needs early, partners would be better able to deliver value as well as the expertise that’s required. Current as well as future challenges will be on to get navigated by working collaboratively with manufacturing partners who comprehend the distinct demands of this promising sector.