During the past decade, oncology drug production has experienced several significant advancements that, collectively, have resulted in much-improved cancer treatments.
Breakthroughs in genetic and molecular profiling have enabled the development of therapies that specifically target cancer cells, for example, thereby minimising harm to healthy tissues.
A key example here is the rise of antibody-drug conjugates (ADCs) that combine monoclonal antibodies with cytotoxic drugs to deliver treatment(s) directly to cancer cells.
Likewise, immuno-oncology has transformed cancer treatment by harnessing the immune system to combat tumours. Chimeric Antigen Receptor T-cell (CAR-T) therapies, which involve modifying a patient’s T-cells, have shown remarkable success, particularly in haematologic cancers.
In the same vein, the approval of tissue-agnostic drugs, which treat cancers based on specific genetic mutations rather than tumour location, marks a paradigm shift in oncology.
On a more pragmatic level, nanotechnology is now being used to improve drug delivery systems in oncology.
And, of course, AI has become an integral part of accelerating drug discovery and development processes. In addition, regulatory bodies such as the US Food and Drug Administration (FDA) have introduced initiatives such as Project Optimus to enhance the safety of oncology drugs.
This programme encourages revisiting dosing strategies in clinical trials to balance efficacy and safety, moving away from traditional high-dose approaches that often lead to severe side-effects.
From a manufacturing perspective, one of the most critical aspects of producing highly potent actives is containment.
Here, as well, significant progress has been made to ensure the safety of workers, patients, and the environment. Many pharmaceutical companies have built dedicated containment facilities for the high-potency active pharmaceutical ingredients (HPAPIs) used in cancer treatments.
Often using specialised isolators and restricted access barrier systems (RABS), these systems minimise human exposure to highly potent oncology drugs and reduce contamination risks.
There has also been a marked rise in the application of single-use technologies (SUTs) in this field. Disposable bioreactors, bags, and filters reduce the risk of cross-contamination between batches, and SUTs facilitate rapid production changes, making it easier to manufacture personalised oncology drugs.
At an infrastructure level, high-efficiency particulate air (HEPA) filtration and closed-system handling help to prevent airborne exposure, and the industry has firmly embraced cutting-edge automation and robotics in drug manufacturing.
For example, automated drug formulation and filling systems reduce human interaction with toxic compounds, and robotics improve precision when handling small-molecule oncology drugs and CAR-T cell therapies.
Processing potent products
With an increasing emphasis on both operator safety and product protection, manufacturing oncology drugs, hormonal products and/or other highly potent compounds has been put under the pharmaceutical spotlight in recent years.
Historically, the only option was to use cumbersome air suits to prevent the operators from being exposed to the drug being processed and to avoid cross-contamination with other products manufactured in the same facility.
GEA Pharma & Healthcare specialises in contained materials handling solutions for pharmaceutical and healthcare companies and believes that personal protection equipment (PPE)-free drug production is a near-future possibility.
It’s more than that, says Phil Gabb, Strategic Business Director, Pharma Solid Dosage: It’s a real possibility, right now, because that’s what we’ve achieved with several of our existing customers.
We’re already using a combination of in-house containment technologies, he explained, and not just for the main processing operations but also for the transfer steps between the unit operations — for cleaning-in-place or for contained offline cleaning and for sampling and in-process control.
Irrespective of whether you’re running a batch or continuous manufacturing line, he added, there’s no longer a need for any drug production system to have personal protective equipment (PPE).
A key requirement to operate such a process train is a higher standard of operator training and a better maintenance regime.
You’re using engineering solutions and equipment design solutions to achieve operator protection, as opposed to wearing PPE, which is a relatively easy thing for companies to train their staff to use. This is a higher technical requirement, so whereas some customers and some markets take to that very easily, others find it something of a challenge.
Drivers and benefits
There are several drivers behind this switch to PPE-free manufacturing: first is the ongoing and increasing focus on operator safety; European and American customers have had this in place for many years.
Yet, some people miss the fact that every country in the world — including those that are sometimes considered to be less well developed — is under increasing pressure from governments and from their national health and safety executives to improve the working conditions of their personnel.
This applies both in general and in the pharmaceutical industry, in particular, with regards to operators being exposed to what are increasingly potent drugs, Phil points out.
From a regulatory perspective, there is an ongoing push for more stringent guidance with geographically diverse timescales: Europe and North America implemented legislation several years ago, for example, and in China, under the aegis of a so-called “increased GMP standard,” there is a massive drive for improved operator safety.
There are financial implications as well. There are cost penalties to implementing a containment solution, but there are also financial benefits, says Phil.
If you keep the problem inside the system, you don’t contaminate the exterior of the equipment, and you don’t contaminate the room. And when you come to clean the line, for product changeover for example, or to start a new batch, the amount of downtime or labour required to clean the room and/or the outside of the equipment is dramatically reduced.
You get a higher level of more cost-effective operability.
Simply better containment solutions
GEA has a long history of expertise and an unparalleled depth of experience in the field of containment. The company not only offers a comprehensive range of robust and compliant products but also boasts unrivalled experience when it comes to identifying the most appropriate solution and a thorough understanding of containment risk analysis.
And, although there’s a vast array of available equipment and machinery from many suppliers, one of the key benefits of working with GEA is that we can supply an entire, completely integrated containment system, from raw materials handling right the way through to tableting, notes Phil. One of the big challenges with any containment system is the integration of all the different pieces of process equipment.
To cite an example, GEA has introduced a new way to protect the health and safety of system operators.
Based on the traditional concept of a live coal mine canary, this 21st-century equivalent is a continuous real-time monitoring system that’s been designed to detect breaches from contained pharmaceutical production lines and eliminate the need for routine occupational health monitoring.
The patented GEA BUCK® Digital Canary comprises an aerosol spectrometer-based sensor that provides a constant reading (compared with a baseline) of any product exposure at the sampling point.
Programmed to accommodate a specific particle size distribution if required, the information is relayed to a control system that initiates an alarm and corrective action if out-of-specification data is received.
Modern pharmaceutical equipment is designed to operate in a completely dust-tight manner, but it’s critical to be fully prepared for worst-case scenarios, such as an unexpected containment breach.
As the level of potentially dangerous airborne particles is often far below what can be seen with the naked eye, the Digital Canary is designed to be a fully integrated and reassuring part of your production line.
Conclusion
It’s not just about having split valves and the right sensors, says Phil; it’s about making sure that the materials-handling system integrates with the granulation equipment and with the tablet press.
GEA offers a portfolio of technical solutions that can be implemented into complete lines. This is becoming increasingly important with the growth in oncology and hormonal products, especially in direct compression systems.
Looking further ahead, if PPE-free working environments are already with us, what does the future hold for containment? Just a few years ago, says Phil, the trend was to develop equipment that was as contained as possible.
What we’ve now put more of an emphasis on is applying some science to evaluating operator risk and establishing how much containment is needed for a particular process or application.
It’s very easy to over-specify the containment requirement for a product. And if you do that, you end up with equipment that’s not only more expensive to buy, but it’s also more difficult to operate, maintain and clean. And that doesn’t benefit anybody.
Product loss and downtime can be costly. More seriously, exposing personnel to toxic or highly potent dust could be catastrophic.
GEA can assist and advise you to determine what level of containment is required where and when, optimising the manufacturing process and making it efficient, safe and cost-effective. We provide tailor-made containment for the pharmaceutical industry — for now and for the future.
