Pharmaceutical Technology Editors

Sander Van Gessel, MEng, Business Unit Director, DFE Pharma, discusses the recent findings of nitrosamine impurities in human drugs as a part of his session, "Reducing Nitrosamines Without the Use of Scavengers: The Critical Role of Excipients - An Excipient Manufacturer's View."

 So, since 18, there's been a lot of investigation into nitrosamines as a potential carcinogenic, yeah can impact drug safety. So naturally across the supply chain of drug manufacturer, the partners within the industry have all been looking at it, including players like DFE pharma, supplying decisions to the industry. And we're continuously investigating and, you know, one of the challenges that we as an industry have also needed to overcome is, you know, also looking at the analytical techniques that are necessary to not only detect the nitrosamines in the end product, but also the potential root causes of those nitrosamine formations in the entire supply chain.

 There are a lot of potential root causes of nitrosamine impurities. And we've been studying this since 2018. A lot of the suppliers of raw materials, such as excipients, have been looking at nitrosamine levels with in their products that can lead to those nitrosamine impurities in in drug, end product drugs. I think you know, for most reliable reputable suppliers, this is now pretty much under control. To take the pharma as an example, we've studied the nitrosamine levels in our excipients, and they're all below two ppb parts per billion. To put parts per billion into perspective to control a football field... It's like controlling a football field to 10 particles of sand to get to that two ppb level. However, the industry has moved on a little bit from nitrosamines to actually looking at what are potential causes of nitrosamines being created in the end product itself. And over here, the research is into the pathways leading to nitrosamine creation in the end product after it's been manufactured. If we look at what what's happening there we have, for example, nitride impurities, which are within different raw materials that can react with a means in certain API's to create nitrosamines over time and product.

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The Recent Discoveries of Nitrosamine Impurities (PDA/FDA Joint Regulatory Conference 2023)

Humberto Vega, PhD, Executive Director, Bristol Myers Squibb, discusses the requirements needed to be successful in global cell therapy as a part of his session, "Successfully Navigating Global Cell Therapy Requirements."

 Well, that is an interesting question. As I mentioned before, in terms of the challenges from the regulatory space, each country have its specific requirements. Some of them are common across the different countries. However, some are very specific to the country. For example, in China, there are multiple offices that manage requests around cell therapies in the US or fewer offices within FDA; in Europe, same thing. So each group each particular sub office, in a regulatory body, we have different roles and having or presenting a product to different countries will have a requirement to want to extend their specific country requirements to ensure you satisfy them. And you answer their questions and expectations in a satisfactory manner to avoid going back and forth or delays in the approval of your problem. 

 There's so much... internal landscape in the regulatory space. Each company as each product is now being launched into different countries, it is critical to understand the expectation for that country, critical to understand what others have done, that helped shape the expectation from the regulatory point of view. If that exercise is not properly conducted, the chances for failure will increase because it's not an issue of building or creating your own elements, it's making sure as an industry everyone target the same requirements and help shape the regulations around the world and avoid different directions across countries.

Global Cell Therapy Requirements Need Thorough Understanding

Humberto Vega, PhD, Executive Director, Bristol Myers Squibb, discusses the journey from clinical to commercial cell therapies as a part of his session, "Successfully Navigating Global Cell Therapy Requirements."

 The case of cell therapies is one word data is now being generated. And the different companies are learning about processes and products, as they are in development. It is not a new journey, it began back in the 70s and even earlier, but the learning about sales and the immune system really grew during the last 20 years with the advantage of technologies and that is one challenge that is being overcome. Now, the regulatory space and the compliance space is something that is now being developed, is growing, and each country has various specific requirements, looking not only on having a product that is safe, but also protecting the patient from the use of the cells and how those products are now develop use, and in the future, they will become the mainstream. So, the challenge is making sure that all the regulatory aspects are properly addressed during clinical stage and development all the way into the routine commercial promotion.


 One key element is understanding what is expected from the regulatory space, having a close communication with the agency, having clear, a change of information with those regulatory bodies to ensure their expectations, their regulatory space, is very clear to the company and the group developing and transitioning into a commercial space in particular products. So, there are no surprises at the time, the product is fine, and all the information required by the regulatory group is provided and explain and justify, and then once approved, how to maintain the quality and the regulatory posture as a production is now in a commercial stage.

The Challenges of the Journey from Clinical to Commercial Cell Therapies

Bassem Gayed, PhD, Senior Technical Director of CAR-T Process Engineering, Manufacturing Science & Technology at Bristol Myers Squibb, discusses the importance of CAR-T as a modality and other highlights from his part of the session, "Process Validation for CAR-T Products: A Continuous Journey."

 Sure, I'd like to just echo the CAR-T is a very important new modality that's able to use the patient's own cells, patient own immune system to be able to treat disease, mostly cancer today. But it's a very, very important element for the industry that we have been learning a lot about in the last few years. And I think it will be a lot of interest in coming years. We talked about the continuous journey for validation and add into that our ability to communicate and share the learnings among each other, not just within the same company or across the industry. That's, I think it's a very unique time for this modality and being in a setting like the FDA/PDA conference, we need to be able to share the knowledge, communicate, and hope to fast forward these learnings across.


 I think it's, it's very important to think about the time we enter this modality and how young it is and draw parallel to maybe biologics and 30 years ago or so, and see how fast we can make an improvement and more advancement in technology today, than 30 years ago. I think we can really really make an impact much faster and we can really take this modality and the benefit that it will bring for treatments or really serious disease for patients in need.

Bassem Gayed, PhD, Senior Technical Director of CAR-T Process Engineering, Manufacturing Science & Technology at Bristol Myers Squibb, discusses the importance of CAR-T as a modality.

Highlighting CAR-T as an Important Modality (PDA/FDA Joint Regulatory Conference 2023)

In part of the session "Process Validation for CAR-T Products: A Continuous Journey" at the PDA/FDA Joint Regulatory Conference, Bassem Gayed, PhD, Senior Technical Director of CAR-T Process Engineering, Manufacturing Science & Technology at Bristol Myers Squibb, discusses the connection of process validation and CAR-T processes.

Process validation is providing the assurance through collective scientific evidence that the manufacturing process or process in general that is consistently able to deliver a quality product. And for CAR-T, it's unique due to the nature of the individualized treatment for our software.

 So it's, it's all about the knowledge that we accumulate, these products are relatively new, it's a new modality, so the more knowledge that starts all the way from development, starts from process characterization, and continues through all the process knowledge we learn from the process of validation and continuous rock process validation. So to continue, it said, it's a body of knowledge that we continuously need to keep building to be able to learn more about these products and be able to continuously monitor them and continuously improve our manufacturing processes control strategy. So I would like to see and think of validation is not one time and it's a continuous journey. So the learning is continuous and it's a feedback that will go back and adjust the process controls and process control strategy that we have set up based on modern and additional information.

Bassem Gayed, PhD, Senior Technical Director of CAR-T Process Engineering, Manufacturing Science & Technology at Bristol Myers Squibb, discusses the connection of process validation and CAR-T processes.

CAR-T and Process Validation (PDA/FDA Joint Regulatory Conference 2023)

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The ROSS line of Dual Shaft Mixers are robust, versatile systems with enough power to batch dispersions, suspensions, and emulsions with viscosities up to several hundred thousand centipoise.