Susan Haigney

INTERPHEX 2025: Advancing Treatments for Ultra-Rare Diseases

According to Joe Katakowski, director of Research at the RTW Foundation, parents of children with rare diseases are the driving force behind the development of treatments for ultra-rare diseases. “[RTW Foundation has] funded a lot of academic research grants, but the missing component was the embedment of these parents and patients in those efforts. So, we've restructured our granting approach now to make the rare disease parents and foundations, the owners, and the accountable party to the academic researchers,” Katakowski explains. “And we think this model is going to be far more successful than just funding academic researchers directly. Even though our current model still gets funding to the academic researchers, it makes those rare parents and the rare disease foundations the central player in the space. We empower them with knowledge related to drug development, and we empower them with funding and resources, and we engage with them for a prolonged period. It's not just a quick boot camp; it's not a weekend course. We're working with these foundations, oftentimes in excess of 16 months, perhaps two years, to really help them solve all the challenges that will come up inevitably during their drug development campaign.”

Katakowski and Deanna Portero, VP, Partnerships & Innovation, Orphan Therapeutics Accelerator, gave a presentation titled, 

“A Novel Pathway for Ultra-Rare Disease Treatment Development, Commercialization and Access”

 at INTERPHEX 2025, in which they discussed approaches to advancing treatments for ultra-rare diseases. PharmTech Group sat down with Katakowski to discuss how organizations like the RTW Foundation work to advance the development of treatments for rare diseases.

INTERPHEX 2025 was held in New York City from April 1–3.

Click the video above to watch part one of PharmTech’s interview with Joe Katakowski.

Joe Katakowski is director of Research at the RTW Foundation

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In part two of Pharmaceutical Technology® Group's discussion with Joe Katakowski, director of Research at the RTW Foundation, the work of organizations like RTW Foundation in promoting the development of treatments for ultra-rare diseases is discussed. 

Nitrosamine Impurities inscription on wooden chips with stethoscopes on white background. Nitrosamine Impurities in certain drugs and pharmaceutical products concept. | Image credit: ©Debalina - stock.adobe.com

Nitrosamines occurring in pharmaceuticals became a developing problem in 2018, and regulatory agencies have been working with pharmaceutical companies since to mitigate the risk of these cancer-causing chemicals in drug products (1). In January 2025, FDA posted “Determining Recommended Acceptable Intake Limits for 

-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach” in the Spotlight on CDER Science on the FDA.gov website (2).

® spoke with Josh Hoerner, general manager of Purisys, which specializes in a small volume custom synthesis and specialized controlled substance manufacturing, to gain his perspective on FDA’s recommendations for acceptable intake limits for 

What are nitrosamine drug substance-related impurities (NDSRIs)?

 NDSRIs are nitrosamine impurities that share structural similarities with the API and are generally unique to each API. These impurities are considered more complex and require more sophisticated testing methods to detect and quantify. The presence of NDSRIs is considered a higher risk, especially when the impurity forms as a result of the API’s chemical structure or the processes used during production.

The advanced testing conducted to determine the presence of NDSRIs involves sophisticated and sensitive mass spectrometry (MS) technology, including Triple Quadrupole Technology, which enables liquid chromatography-tandem mass spectrometry (LC-MS/MS). A high-sensitivity, low-level quantitation technology is particularly advantageous for detecting nitrosamines and other impurities that must remain within low permissible levels (based on safety data, a comparator, or the CPCA Potency score).

 What can you tell us about the recommendations FDA published in January 2025 for the development and application of carcinogenic potency categorization approach to nitrosamines? 

 Safety data (e.g., animal carcinogenicity data) for many potential NSDRIs or comparators are not readily available. FDA worked with the Nitrosamine International Technical Working Group (NITWG) to develop a methodology called the Carcinogenic Potency Categorization Approach (CPCA). The approach is based on a training set of 81 nitrosamines to establish five potency categories (1 high–5 low), reflecting carcinogenic risk. Essentially, the CPCA applies the knowledge that the α-hydroxylation mechanism of metabolic activation and the associated number of α-hydrogens as well as associated activating and deactivating features, drives nitrosamine potency. This allows a potency score for a potential NDSRI to be calculated along with the associated an AI to be calculated without direct safety data. Using this framework, a drug product manufacturer can then assess their drug products for NDSRIs below the [acceptable intake] and ensure patients are not exposed to levels exceeding or approaching the [acceptable intake].

What makes determining acceptable intake so challenging?

 There is a lack of direct safety data on NDSRIs and comparator compounds to establish a basis for potency. Prior to the CPCA framework, one might default to higher [acceptable intake] limits such as the 1500 ng/day, whereas those with higher potency scores have higher carcinogenicity risk, and therefore, should be controlled to lower [acceptable intake] levels.

What can pharma manufacturers do to manage the nitrosamine risk?

 There are two key guidelines included in the FDA-published compliance recommendations that define the framework for nitrosamine assessment and control:

Risk assessment and control of nitrosamine formation

. Manufacturers should evaluate and control two types of nitrosamine impurities:
--Small-molecule nitrosamines (structurally different from the API)
--NDSRIs, structurally similar to the API.

. Risk assessments should determine if nitrosamines are likely present, followed by testing. If testing shows nitrosamine impurity is present at a level 10% above the acceptable intake limit for that specific nitrosamine, FDA recommends that manufacturers develop specifications to keep nitrosamine levels within limits.

A comprehensive approach includes an initial paper-based assessment of technical risks (e.g., chemistry, solvents, excipients), followed by testing according to USP [

] General Chapter 1469.11. Risk ratings (low, medium, high) are assigned based on the likelihood of nitrosamine formation, with secondary amines posing the highest risk.

Manufacturers should partner with experienced CDMOs [contract development and manufacturing organizations] that offer a comprehensive solution for testing, synthesis, and risk assessment to ensure compliance with these complex requirements.

FDA. FDA Statement on the FDA’s Ongoing Investigation into Valsartan and ARB Class Impurities and the Agency’s Steps to Address the Root Causes of the Safety Issues. Press Release. Jan. 25, 2019.

FDA. Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach. Spotlight on CDER Science. FDA.gov. Jan. 10, 2025.

Articles

Josh Hoerner, general manager of Purisys, provides his perspective on FDA’s recommendations for acceptable intake limits for N-nitrosamine impurities.

N-Nitrosamine Impurities and FDA’s Recommendations for Acceptable Intake Limits

INTERPHEX 2025: Challenges in Ultra-Rare Disease Treatment Development

At INTERPHEX 2025, which was held in New York City from April 1–3, Joe Katakowski, director of Research at the RTW Foundation, and Deanna Portero vice-president, Partnerships & Innovation, Orphan Therapeutics Accelerator, gave a presentation titled, “

A Novel Pathway for Ultra-Rare Disease Treatment Development, Commercialization and Access”,

 in which they discussed approaches to advancing treatments for ultra-rare diseases. PharmTech Group sat down with Katakowski to learn more about the RTW Foundation and its work to advance the development of treatments for ultra-rare diseases and the challenges faced by those involved in these efforts.

“[Ultra rare disease] is the most difficult space in which I've worked in preclinical drug development ever. [R]are disease foundations have challenges [to] getting access to the same resources and expertise that drug development companies would have; that's mainly due [to] their small patient population sizes,” Katakowski says. “Rare disease is defined as fewer than 200,000 individuals affected by a disorder in the [United States]. Ultra rare is [a] made-up term. I use that term to describe any rare disease that's too small to attract any commercial attention from biotech[s] or [the] pharmaceutical industry, and so there are really no prospects towards the traditional drug development avenues, such that the only way you can get a drug developed is if the parents form a foundation and become de facto drug developers themselves.”

The ultra-rare disease community must work withing the same regulatory structure despite not having the same access to resources as pharmaceutical companies and biotechs, according to Katakowski. “They can't seek the same investment opportunities from venture capital groups or other investment firms, so they have to self-fund these efforts through fundraising, through their own foundations. So, they have limited resources and finances at their disposal to develop these drugs, and they are sort of expected to develop them in the same regulatory structure and environment as other biotech and pharma developers,” he explains.

Click the video above to watch part one of PharmTech Group’s interview with Joe Katakowski.

Joe Katakowski is director of Research at the RTW Foundation.

The Pharmaceutical Technology® Group sat down with Joe Katakowski, director of Research at the RTW Foundation about the challenges involved in the development of treatments for ultra-rare diseases. 

INTERPHEX 2025: Beta Bags and Sterile Manufacturing

Sterile manufacturing environments require that items be brought into the environment in a sterile manner. Traditionally, items would be taken through a transfer door into the sterile environment through a stainless-steel canister. Beta bags are a more flexible single-use method. To learn more about beta bags, the 

 Group spoke with Chris Gooding, general manager at CRL Solutions, during INTERPHEX 2025, which is being held in New York City from April 1–3.

According to Gooding, products that need to be transferred to a sterile environment come in different sizes that require different sterilization methods, which has resulted in the development of new methods for transfer. Beta bags can be made longer or for different sterilization methods, therefore, making them convenient.

The beta bag is really [designed] out of convenience for transferring either supplies, tools, or equipment into a sterile environment through an RTP [rapid transfer port] or a transfer door ... as opposed to the previous method, [which] would be a stainless-steel canister, but it was limited on the size and the depth and a number of different things,” Gooding says. “The bag allows it to be sized differently. It's much less expensive and is ultimately disposable after use.”

Click the video above to watch the interview.

Chris Gooding is the General Manager for Central Research Laboratories (CRL), headquartered in Red Wing, Minn. Chris has been the GM of CRL for five years. Prior to that, he worked in various leadership roles for many different manufacturing companies. CRL has 80 years of experience in the development of remote-handling systems, including telemanipulators, transfer systems, glove ports, and waste drum transfer systems. CRL's solutions promote operator safety and efficiency when performing various tasks in life sciences and nuclear applications around the world. For more information about CRL Solutions and its network of partners, visit 

The Pharmaceutical Technology® Group sat down with Chris Gooding, general manager at CRL Solutions, to learn more about how beta bags assist in the transfer of supplies and equipment into a sterile environment.

INTERPHEX 2025: Continuous and Controlled Freeze-Drying

Regulatory uncertainty has been a challenge to the implementation of continuous freeze-drying in the pharmaceutical industry, according to Thomas De Beer, co-founder and CEO of RheaVita. “The pharmaceutical industry is highly regulated, which makes it pretty difficult to innovate—[maybe] not difficult, but it makes it slow to innovate, especially new manufacturing technologies,” De Beer says in an interview with Pharmaceutical Technology® Group at INTERPHEX 2025. “And along with that, let's say, regulatory uncertainty. You also have the mindset of people within the pharmaceutical industry, they know that there is regulatory uncertainty to innovate, so their mindset is a bit oriented to that regulatory hesitance. However, on the other hand, there are also opportunities.”

The highly regulated nature of the pharma industry may make it difficult to innovate; however, regulators can often be the instigation for innovation. “They published several guidelines on process analytics and process analytical technology, but also on continuous manufacturing,” De Beer says. “And you see that this indeed stimulated the industry to innovate in pharmaceutical manufacturing, to leave the conventional batch wise manufacturing approach and to focus on continuous manufacturing. And at the same time, you see also new types of drug products coming up. And these new types of drug products, they become more and more complex. They require more flexible manufacturing. This also helps to stimulate innovation.”

RheaVita is exhibiting at Stand 2967 at INTERPHEX 2025, which is being held in New York City from April 1–3. De Beer's presentation, "

Revolutionizing Pharma: Continuous Manufacturing and GMP-Ready Freeze-Drying for Scaled Innovation

" is scheduled for Thursday, April 3 at 9:15AM.

Thomas De Beer, co-founder and CEO of RheaVita

Thomas De Beer graduated in pharmaceutical sciences in 2002 at the Ghent University in Belgium. He obtained his PhD at the same university in 2007. For his PhD research, he examined the suitability of Raman spectroscopy as a process analytical technology tool for pharmaceutical production processes. Within his PhD research period, he worked four months at University of Copenhagen in Denmark, Department of Pharmaceutics and Analytical Chemistry (Prof. Jukka Rantanen). After his PhD, he was an FWO-funded post-doctoral fellow at the Ghent University (2007-2010). Within his post-doc mandate, he worked nine months at the Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics from the Ludwig-Maximilians-University in Munich, Germany (Prof. Winter and Prof. Frieβ). In February 2010, he became professor in Process Analytics & Technology at the Faculty of Pharmaceutical Sciences from the university of Ghent. His research goals include bringing innovation pharmaceutical production processes (freeze-drying, hot-melt extrusion, continuous from-powder-to-tablet processing, etc.). More specifically, De Beer contributes to the development of continuous manufacturing processes for drug products such as solids, semi-solids, liquids and biologicals (continuous freeze-drying of unit doses). De Beer is also director of Ghent University’s Center of Excellence in Sustainable Pharmaceutical Engineering (CESPE) which was founded in 2016. In 2018, De Beer became co-founder and CEO at RheaVita, which provides a continuous freeze-drying technology for the pharmaceutical market.

Pharmaceutical Technology® Group sat down with Thomas De Beer, co-founder and CEO of RheaVita, to talk about his presentation at INTERPHEX 2025, “GMP-ready Continuous & Controlled Pharmaceutical Freeze-Drying”.

INTERPHEX 2025: AI and Automation in Pharma

Automation is being utilized in the areas of quality, throughput, and operator autonomy within the pharmaceutical industry, according to Peter Sarvey, head of Sales for Automation NTH, and the cost of using automation has decreased in the past two years. Meanwhile, the accuracy of these tools is increasing.

The use of artificial intelligence (AI), which has been used in the “vision side” of automation according to Sarvey, is also increasingly starting to be used in the inspection side of manufacturing.

“When we have a lot of part variation, we're not just programming pick and place, or motion based on preset points. So, we move to an area, and then we use the AI vision to tell us, where is that exact part or how much has that part changed? So, it actually allows the automation to move more seamlessly,” Sarvey says. “And then the other side of that is on the inspection side of things. There are a lot of inspections that previously were done manually, because it's not a simple pattern match for if this medical device or this pharmaceutical component is a reject. Now we can teach the AI what a good part looks like, what a bad part looks like, and then over time, shift that area too, all in the nature of increasing throughput and decreasing yield loss.”

® Group spoke with Peter Sarvey at INTERPHEX 2025, which is being held in New York City from April 1–3. Automation NTH can be found at Stand 3061.

Peter Sarvey is Head of Sales for Automation NTH, a specialist in semi-automated and fully automated solutions for a broad array of manufacturing applications, including pharmaceuticals and medical device production. With a focus on next-gen robotics and controls, the company’s services include custom automation, equipment optimization and automation consulting. 

Pharmaceutical Technology® Group spoke with Peter Sarvey, head of Sales for Automation NTH, at INTERPHEX 2025 about the growing use of automation and artificial intelligence in the pharmaceutical industry.