Bill Murray says masked kiss led to sexual misconduct allegation that shut down movie

Arts & Culture, Film & TV

Bill Murray said a masked kiss in 2022 on the set of a movie led to sexual misconduct allegations that eventually shut down the film, an incident the famed actor says still bothers him and feels he was “barbecued” for.In 2022, a female staff member working on the film set for “Being Mortal” accused the “Ghostbusters” and “Groundhog Day” star of behaving inappropriately with her. The film, directed by Aziz Ansari, was eventually shelved by Searchlight Pictures.“I don’t go too many days or weeks without thinking of what happened in ‘Being Mortal,’” the 74-year-old actor told The New York Times in an interview published Saturday. He explained that he had known the woman who made the complaint, and the incident involved him kissing her as they were both wearing face masks that were part of Covid-19 protocols. Murray and the woman eventually reached a settlement, Deadline reported. The woman was never identified by anyone affiliated with the movie and has not come forward to comment on the matter.When asked to discuss what unfolded, Murray said, “I tried to make peace. I thought I was trying to make peace. I ended up being, to my mind, barbecued.”“But someone that I worked with, that I had had lunch with on various days of the week — it was Covid, we were all wearing masks, and we were all stranded in this one room listening to this crazy scene. I dunno what prompted me to do it. It’s something that I had done to someone else before, and I thought it was funny, and every time it happened, it was funny,” Murray said. “I was wearing a mask, and I gave her a kiss, and she was wearing a mask,” he explained. “It wasn’t like I touched her, but it was just, I gave her a kiss through a mask. And she wasn’t a stranger.” He said the incident still “bothers me.””Because that movie was stopped by the human rights or ‘H & R’ of the Disney corporation, which is probably a little bit more strident than some other countries’. It turned out there were pre-existing conditions and all this kind of stuff. I’m like, what? How was anyone supposed to know anything like that? There was no conversation, there was nothing. There was no peacemaking, nothing,” Murray said. “It went to this lunatic arbitration, which, if anyone ever suggests you go to arbitration: Don’t do it. Never ever do it. Because you think it’s justice, and it isn’t,” he continued. The veteran comedian and critically acclaimed actor, who has a long history of alleged bad behavior on movie sets, said he thinks the whole experience was “stupid.” “You can teach an old dog new tricks. But it was a great disappointment, because I thought I knew someone, and I did not. I certainly thought it was light. I thought it was funny,” he said. “To me it’s still funny, the idea that you could give someone a kiss with a mask on. It’s still stupid. It’s all it was.”

Scientists Develop Process Using Molecules in the Cell to Identify Environmental Signals

Science and Health

An effort involving Rutgers researchers could have applications for disease detection and environmental monitoringScientists have transformed RNA, a biological molecule present in all living cells, into a biosensor that can detect tiny chemicals relevant to human health.

Research by Rutgers University-New Brunswick scientists centers on RNA, a nucleic acid that plays a crucial role in most cellular processes. Their work is expected to have applications in the surveillance of environmental chemicals and, ultimately, the diagnosis of critical diseases including neurological and cardiovascular diseases and cancer.

“Imagine that people will go to the hospital and give a sample of cells from their own bodies for regular check-ups,” said Enver Cagri Izgu, an assistant professor in the Department of Chemistry and Chemical Biology in the Rutgers School of Arts and Sciences and the corresponding author of the study. “And there will be some technology involved in transforming their cells into sensor cells without changing their frame and physiology. Those cells would then be returned to the person’s body, and the body will never have the issue of rejecting because it’s their own cells. Those cells will have the ability to talk to us and generate signals about whether we have traces of toxic chemicals or the beginnings of disease within us.”

In the journal Angewandte Chemie International Edition, Izgu and his team reported how they implemented RNA within bacterial cells in such a way that these cells, and even their daughter cells, were able to detect distinct chemicals. Such substances to be detected can be short-lived inorganic chemicals central to many physiological processes, both in healthy and disease states. RNA normally would not interact with these types of chemicals, and it would be exceedingly challenging to sense them through complex genetic circuits. 

(From left) Sarah Cho and Liming Wang, graduate students in the Department of Chemistry and Chemical Biology, assess data for a research study headed by Assistant Professor Enver Cagri Izgu.

Enver Izgu

Friends of the Library to host spring book sale this week

Arts & Culture, Books

MOOSE JAW — Book lovers in Moose Jaw will have another chance to browse a wide selection of used books while supporting their local library at the upcoming Friends of the Library book sale.

The sale, which takes place twice each year, is scheduled to run at the Moose Jaw Public Library during regular business hours on Friday, April 11, and Saturday, April 12.

Proceeds from the sale will help support the library and enhance its range of programming.

“We have one sale every spring and fall, and they are to raise money for the library to purchase things that aren’t covered in their budget,” explained Rae Trites, publicity chairperson for Friends of the Library.

“We help support book clubs, children’s programs in the summer, and anything that they need.”

The sale will feature a variety of used books donated by the public, as well as books removed from the library’s collection. Visitors can expect to find titles across all genres, including fiction, mystery, non-fiction, and children’s books. In addition to books, the sale will also include items such as magazines and CDs.

“If you can believe it, there are still CDs out there,” Trites said with a laugh.

The Friends of the Library also maintains a used book and puzzle cart near the library’s circulation desk, with items available for purchase year-round. While the upcoming book sale will not include a dedicated puzzle space, Trites noted that a separate event for purchasing puzzles is being planned for later in the year.

Any books that remain unsold after the sale will be passed along to another organization to ensure they are either resold or recycled responsibly.

Friends of the Library is a volunteer-based, non-profit organization formed in 1989 that operates with the stated purpose of promoting and supporting the Moose Jaw Public Library.

Trites expressed her gratitude for the continued support during each sale.

“We appreciate the support of the community to help the library, and we want to thank them for their participation in our book sales,” she said. “There’s quite a wonderful community of people who come (down to the sale each time it runs).”

Book donations are still being accepted right up until the start of the sale. If you wish to contribute, donations can be dropped off at the library’s front service desk.

To learn more or to apply as a Friends of the Library member, visit MooseJawLibrary.ca/Friends-Of-The-Library.

The Moose Jaw Public Library is located at 461 Langdon Crescent and can be reached online at MooseJawLibrary.ca, by calling 306-692-2787, or by emailing [email protected].

Welcoming Science: CGIAR Week-Long Focus on Innovation for Food, Climate-Secure Future

Science and Health

Africa, Biodiversity, Civil Society, Climate Action, Climate Change, Development & Aid, Economy & Trade, Editors’ Choice, Environment, Featured, Food and Agriculture, Food Security and Nutrition, Food Sustainability, Global, Headlines, Human Rights, Humanitarian Emergencies, Natural Resources, Poverty & SDGs, Sustainable Development Goals, TerraViva United Nations, Trade & Investment Food and Agriculture

CGIAR and the Kenyan Agricultural and Livestock Research Organization (KALRO) have convened the very first CGIAR Science Week, April 7 to 12, 2025. Credit: Joyce Chimbi/IPSNAIROBI, Apr 7 2025 (IPS) – The world’s leading scientists and decision-makers in agriculture, climate, and health are meeting in Nairobi this week to promote innovation and partnerships towards a food, nutrition, and climate-secure future. As current agrifood systems buckle under multiple challenges, nearly one in 11 people globally and one in five people in Africa go hungry every day.
Recognizing the urgency of these challenges, CGIAR and the Kenyan Agricultural and Livestock Research Organization (KALRO) have convened the very first CGIAR Science Week, April 7 to 12, 2025, at the UN Complex. In this regard, a high-level opening plenary session today underscored an unwavering commitment to international agricultural research.
During the opening plenary, CGIAR’s Executive Managing Director Ismahane Elouafi told the audience that the food crisis was depressing. “We are faced with one of the food shortage crises in history… We have seen emerging conflicts in so many parts of the world. We have also seen climate change that is accelerating and showing us how bad it is in different parts of the world.
“And this is bad for all of us, but imagine how bad it is for a woman that doesn’t have food for her kids.”
However, this is where science comes to the fore.
“This week marks a pivotal moment in our shared journey towards transforming global agriculture and food systems. CGIAR is unwavering in our commitment to advancing groundbreaking agricultural science that is sustainable, inclusive, and rooted in the belief that research, innovation, and collaboration are the keys to overcoming the complex challenges facing agri-food systems today,” Elouafi said.
There was a lot of emphasis on the role of youth and ensuring they were part of the solution, especially in the global South.
Elouafi welcomed students to the Science Week and said she hoped they would remain committed to the South.
“Go to agriculture, because we all need food, and you could be the solution in the future,” she said.
“And in all honesty, I used to introduce myself as a girl from the South that made it to the North… and it was a success… I want, really,  the kids in the south to go out saying, ‘I’m a girl from the South and I am staying in the South.’”
While officially opening the science conference, Kenya’s Prime Cabinet Secretary Musalia Mudavadi said it was a privilege to represent the President, who is “himself a scientist. In fact, the first scientist president that Kenya has had. The theme of this year’s assembly is timely, considering the unprecedented environmental and food security challenges that the world faces today.”
“The only way forward is through scientific research and on the stakeholders of our country. I am proud to be a member of the National Coalition of Colonists, providing employment for over 60 percent of our population, significantly contributing to national armament and ensuring food security for millions of people.”
“The sector faces immense challenges, from climate change and extreme weather conditions, land deprivation, soil infertility, food insecurity and malnutrition, post-harvest losses, unlimited access to technology, financing, and investments, and of course, confidence. This Science Week is a defining moment. It gives us an opportunity to engage in how to mitigate these challenges.”
As major and connected global challenges threaten the sustainability of food, land, and water systems, global and regional leaders in research, policy, and development say tackling these disruptions requires continued strengthening of collaborative efforts and strategic partnerships towards agri-food systems that are sustainable, resilient, inclusive, and can nourish both people and planet.
A Council of the Wise, a panel session graced by distinguished personalities in Africa, spoke about issues such as politics, policy, and science, and the place of women and youth in transforming agrifood systems. Ameenah Gurib–Fakim, Former President of Mauritius, asked, “Where are the women in Africa in agriculture? What I’m going to say next is not a political statement; it is a fact. Women feed Africa. Where is the technology? Where is the empowerment for our African girls and women?”
“How do we empower them with the technologies? How do we empower them with the capacity to go and open their bank account? How do we empower them to access land? These are issues we have to tackle. Because after all, African food is produced mostly by smallholder farmers, and many of them are women. So, looking at the challenges across Africa, we really have to look at it through the gender lens.”
Ibrahim Assane Mayaki, Former Prime Minister of Nigeria and African Union Special Envoy for Food Systems, spoke about population growth and the challenges facing agrifood systems. “In the 60s, the total population of the African continent was about 300 million and we had relative subsistence. Today, we are 1.5 billion people. And in between, between the 60s and today, a lot of things have happened. Progresses and improvements have been made. We have seen food and agriculture strategically implemented, continentally, regionally, and nationally.”
“We have seen our networks of research, science, and innovation really get a significant momentum. But the demographics have beaten the games that we are playing. So, the conclusion that needs to be drawn from that picture is that we need to accelerate. And… we need to do more with less. We know the challenges in terms of productivity, production, land, immigration, and climate. We have the technical answers. The question now is how do we add political solutions to these technical solutions, the scientific solutions, and the innovative solutions? We need political solutions.”
Towards this end, experts and participants from around the globe will explore transformative solutions to the complex challenges facing agri-food systems, such as water scarcity, biodiversity loss, and extreme weather events. Recognizing their intersection while also reflecting on past successes and lessons learned in embracing solutions centered on inclusivity, partnership, and innovation.
There is an emphasis on sustained global investment in innovation, technology, and science as the most effective tools to deliver food, nutrition, and climate security for all, and more so, the most vulnerable people and communities who are increasingly burdened by heightened food insecurity, poverty, and social inequality as unprecedented multiple, complex challenges converge.
Mohamed Beavogui, former Prime Minister, the Republic of Guinea, said that responses to the food and nutrition challenges have not been adequate. Lands are degrading fast. “To date, we are still using about 20 kilograms of fertilizer per hectare while others are using more than 137 kilograms per hectare. Yet, climate change is giving us chaotic rains, droughts, and floods.”
“We do not have, on the ground at least, the right resources. And then, our farmers lack finance, access to technology, etc. And moreover, those who are living between agriculture and the ground, women, are excluded. But there is good news, and a lot of good news; there is a lot of innovation everywhere you look and we need to move it from the lab to the land to the plate.”
Importantly, agricultural research and science is a means to economic stability and gender equality. Given the enormity of the task at hand, the CGIAR is positioning the week as a platform to enhance regional and global partnerships with an aim to scale scientific innovations and solutions but also to reinforce local community-bred practices that work.
Goodluck Ebele Azikiwe Jonathan, Former President of Nigeria who holds a doctorate degree in hydrobiology, spoke of the critical need to have leaders who are aware of the usefulness of science. Stressing that science is a mindset that focuses on problem-solving and that this mindset is a key issue towards solving the challenges facing humanity today.
“In Africa, our leaders spend more time thinking about how to get to leadership and hold on to leadership than thinking about the people. We have to spend more time thinking about the people. Even when the President is not a scientist, they can put the right people, experts and competent people, in the right places. It is about the President having the political will and commitment to move the country forward and adopt science and technology to solve agricultural problems.”
Overall, the Science Week is an opportunity to use the best science, innovation, research, and existing knowledge within communities to draw the most effective roadmap into a future where agrifood systems and interconnected issues of climate change, environment, biodiversity, and water can harmoniously converge to produce the best possible outcomes for both planet and humanity.IPS UN Bureau Report,

 

Welcoming Science: CGIAR Week-Long Focus on Innovation for Food, Climate-Secure Future

Science and Health

Africa, Biodiversity, Civil Society, Climate Action, Climate Change, Development & Aid, Economy & Trade, Editors’ Choice, Environment, Featured, Food and Agriculture, Food Security and Nutrition, Food Sustainability, Global, Headlines, Human Rights, Humanitarian Emergencies, Natural Resources, Poverty & SDGs, Sustainable Development Goals, TerraViva United Nations, Trade & Investment Food and Agriculture

CGIAR and the Kenyan Agricultural and Livestock Research Organization (KALRO) have convened the very first CGIAR Science Week, April 7 to 12, 2025. Credit: Joyce Chimbi/IPSNAIROBI, Apr 7 2025 (IPS) – The world’s leading scientists and decision-makers in agriculture, climate, and health are meeting in Nairobi this week to promote innovation and partnerships towards a food, nutrition, and climate-secure future. As current agrifood systems buckle under multiple challenges, nearly one in 11 people globally and one in five people in Africa go hungry every day.
Recognizing the urgency of these challenges, CGIAR and the Kenyan Agricultural and Livestock Research Organization (KALRO) have convened the very first CGIAR Science Week, April 7 to 12, 2025, at the UN Complex. In this regard, a high-level opening plenary session today underscored an unwavering commitment to international agricultural research.
During the opening plenary, CGIAR’s Executive Managing Director Ismahane Elouafi told the audience that the food crisis was depressing. “We are faced with one of the food shortage crises in history… We have seen emerging conflicts in so many parts of the world. We have also seen climate change that is accelerating and showing us how bad it is in different parts of the world.
“And this is bad for all of us, but imagine how bad it is for a woman that doesn’t have food for her kids.”
However, this is where science comes to the fore.
“This week marks a pivotal moment in our shared journey towards transforming global agriculture and food systems. CGIAR is unwavering in our commitment to advancing groundbreaking agricultural science that is sustainable, inclusive, and rooted in the belief that research, innovation, and collaboration are the keys to overcoming the complex challenges facing agri-food systems today,” Elouafi said.
There was a lot of emphasis on the role of youth and ensuring they were part of the solution, especially in the global South.
Elouafi welcomed students to the Science Week and said she hoped they would remain committed to the South.
“Go to agriculture, because we all need food, and you could be the solution in the future,” she said.
“And in all honesty, I used to introduce myself as a girl from the South that made it to the North… and it was a success… I want, really,  the kids in the south to go out saying, ‘I’m a girl from the South and I am staying in the South.’”
While officially opening the science conference, Kenya’s Prime Cabinet Secretary Musalia Mudavadi said it was a privilege to represent the President, who is “himself a scientist. In fact, the first scientist president that Kenya has had. The theme of this year’s assembly is timely, considering the unprecedented environmental and food security challenges that the world faces today.”
“The only way forward is through scientific research and on the stakeholders of our country. I am proud to be a member of the National Coalition of Colonists, providing employment for over 60 percent of our population, significantly contributing to national armament and ensuring food security for millions of people.”
“The sector faces immense challenges, from climate change and extreme weather conditions, land deprivation, soil infertility, food insecurity and malnutrition, post-harvest losses, unlimited access to technology, financing, and investments, and of course, confidence. This Science Week is a defining moment. It gives us an opportunity to engage in how to mitigate these challenges.”
As major and connected global challenges threaten the sustainability of food, land, and water systems, global and regional leaders in research, policy, and development say tackling these disruptions requires continued strengthening of collaborative efforts and strategic partnerships towards agri-food systems that are sustainable, resilient, inclusive, and can nourish both people and planet.
A Council of the Wise, a panel session graced by distinguished personalities in Africa, spoke about issues such as politics, policy, and science, and the place of women and youth in transforming agrifood systems. Ameenah Gurib–Fakim, Former President of Mauritius, asked, “Where are the women in Africa in agriculture? What I’m going to say next is not a political statement; it is a fact. Women feed Africa. Where is the technology? Where is the empowerment for our African girls and women?”
“How do we empower them with the technologies? How do we empower them with the capacity to go and open their bank account? How do we empower them to access land? These are issues we have to tackle. Because after all, African food is produced mostly by smallholder farmers, and many of them are women. So, looking at the challenges across Africa, we really have to look at it through the gender lens.”
Ibrahim Assane Mayaki, Former Prime Minister of Nigeria and African Union Special Envoy for Food Systems, spoke about population growth and the challenges facing agrifood systems. “In the 60s, the total population of the African continent was about 300 million and we had relative subsistence. Today, we are 1.5 billion people. And in between, between the 60s and today, a lot of things have happened. Progresses and improvements have been made. We have seen food and agriculture strategically implemented, continentally, regionally, and nationally.”
“We have seen our networks of research, science, and innovation really get a significant momentum. But the demographics have beaten the games that we are playing. So, the conclusion that needs to be drawn from that picture is that we need to accelerate. And… we need to do more with less. We know the challenges in terms of productivity, production, land, immigration, and climate. We have the technical answers. The question now is how do we add political solutions to these technical solutions, the scientific solutions, and the innovative solutions? We need political solutions.”
Towards this end, experts and participants from around the globe will explore transformative solutions to the complex challenges facing agri-food systems, such as water scarcity, biodiversity loss, and extreme weather events. Recognizing their intersection while also reflecting on past successes and lessons learned in embracing solutions centered on inclusivity, partnership, and innovation.
There is an emphasis on sustained global investment in innovation, technology, and science as the most effective tools to deliver food, nutrition, and climate security for all, and more so, the most vulnerable people and communities who are increasingly burdened by heightened food insecurity, poverty, and social inequality as unprecedented multiple, complex challenges converge.
Mohamed Beavogui, former Prime Minister, the Republic of Guinea, said that responses to the food and nutrition challenges have not been adequate. Lands are degrading fast. “To date, we are still using about 20 kilograms of fertilizer per hectare while others are using more than 137 kilograms per hectare. Yet, climate change is giving us chaotic rains, droughts, and floods.”
“We do not have, on the ground at least, the right resources. And then, our farmers lack finance, access to technology, etc. And moreover, those who are living between agriculture and the ground, women, are excluded. But there is good news, and a lot of good news; there is a lot of innovation everywhere you look and we need to move it from the lab to the land to the plate.”
Importantly, agricultural research and science is a means to economic stability and gender equality. Given the enormity of the task at hand, the CGIAR is positioning the week as a platform to enhance regional and global partnerships with an aim to scale scientific innovations and solutions but also to reinforce local community-bred practices that work.
Goodluck Ebele Azikiwe Jonathan, Former President of Nigeria who holds a doctorate degree in hydrobiology, spoke of the critical need to have leaders who are aware of the usefulness of science. Stressing that science is a mindset that focuses on problem-solving and that this mindset is a key issue towards solving the challenges facing humanity today.
“In Africa, our leaders spend more time thinking about how to get to leadership and hold on to leadership than thinking about the people. We have to spend more time thinking about the people. Even when the President is not a scientist, they can put the right people, experts and competent people, in the right places. It is about the President having the political will and commitment to move the country forward and adopt science and technology to solve agricultural problems.”
Overall, the Science Week is an opportunity to use the best science, innovation, research, and existing knowledge within communities to draw the most effective roadmap into a future where agrifood systems and interconnected issues of climate change, environment, biodiversity, and water can harmoniously converge to produce the best possible outcomes for both planet and humanity.IPS UN Bureau Report,

 

An Exclusive Spectroscopy Interview on Flow Imaging Microscopy in Collaboration with the American Association of Pharmaceutical Scientists (AAPS), Part 2

Science and Health

IntroductionIn Part 2 of this two-part interview, we continue to speak with Austin Daniels, application scientist for Yokogawa Fluid Imaging Technologies, about the subject of flow imaging microscopy (FIM).Flow imaging microscopy (FIM) offers a more comprehensive approach, capturing high-resolution images and quantitative data on particle size, shape, and composition in pharmaceutical preparations. Instruments like FlowCam enable detailed characterization, distinguishing protein aggregates from contaminants and monitoring process stability. Recognized in regulatory guidelines such as USP and , FIM enhances compliance and quality control in biotherapeutic development (1–16).In Part 2 of this interview, we continue to discuss the advantages of FIM over traditional techniques, its role in regulatory compliance, and real-world applications for improving biologic safety and efficacy. Join us as we explore the impact of this innovative technology on subvisible particle characterization.How does FIM address challenges in low-volume or high-viscosity formulations while meeting USP and particle limits?FIM instruments help with low-volume formulations simply by not requiring a ton of volume relative to many other particle analysis techniques. FIM measurements only require around 100 μL to perform and get consistent measurements. This can still be a lot of volume to spend on a single measurement, but as it’s much lower than traditional particle analysis techniques like light obscuration (LO) it can allow scientists to capture subvisible particle measurements as part of their formulation development. It’s important to note that FIM can also process larger volumes using a similar standard operating procedure (SOP), meaning that the technique can also process very large volumes as well depending on the available volume and experiment goals.With regards to viscosity, there is an interesting quirk to how FIM instruments perform concentration measurements that help the technique be robust to viscosity changes. To measure concentrations, the number of particles that are detected is normalized to the volume imaged during the measurement rather than the total volume that passes through the flow cell. The volume analyzed is based on the number of times the flow cell was imaged and the volume sampled per image. Handling concentration calculations this way makes the technique robust to small errors in flow rate—the main concern viscosity poses for particle measurements. While I would still recommend diluting a very viscous sample to ensure that the sample flows through at the recommended flow rates, the technique can provide reasonable measurements on most typical biotherapeutics regardless of their viscosity.How does FIM offer an advantage in monitoring silicone oil droplets compared to LO or membrane microscopy (MM)?The main advantage of FIM for monitoring silicone oil droplets is the ability to analyze them using one analytical technique instead of two. Neither LO nor MM are ideal for monitoring silicone oil droplets but for completely different reasons. LO measurements detect silicone oil droplets in a sample but are unable to distinguish them from other particle types that may be in the sample and thus cannot provide a concentration or size distribution for these particle types. MM captures particle morphology info, but silicone oil droplets are removed during membrane filtration and thus not detected. To get a measurement of the silicone oil content with these techniques, researchers must use both methods to analyze a sample and take the difference in the measured concentrations. Since FIM can distinguish between silicone oil droplets while still counting them, it can be used in isolation and capture a reasonable estimate of a sample’s silicone oil content.How does FIM differ from LO in sensitivity to particle types, like protein aggregates, and how does this impact USP compliance?FIM primarily differs from LO in its sensitivity to transparent particle types. LO measurements depend on both the size and refractive index of the particles and will generally report smaller particle sizes the more translucent a particle appears. This often results in LO underestimating the concentration and size of particles in a sample, particularly biologics that contain a high concentration of translucent particles. FIM measurements are not impacted by these issues to the same extent, resulting in higher particle concentrations and sizes relative to LO.When thinking about USP compliance, it is important to remember that the pharmacopeia limits were set with the limitations of LO in mind. Many researchers are often surprised to see FIM and related particle techniques report much higher particle concentrations than are allowed via USP . However, that only means that LO is missing particles in a sample and not necessarily that the sample is not USP compliant. The sample only fails to meet pharmacopeia guidelines if it has more particles than are allowed via USP when tested by a compendial method. That said, regulators are aware of the limitations of the compendial methods and the current subvisible particle limits.How does FIM’s particle morphology analysis help identify sources of particles and enhance control in line with USP and ?Both USP and motivate the need to monitor particle type and source as part of a robust particle control strategy. For , this comes from a need to distinguish between extrinsic and intrinsic particles in a drug product (which often need to be prevented or minimized) from inherent protein aggregate particles in a protein therapy (which cannot be completely prevented). It also helps researchers better characterize protein aggregate particles in general which is necessary given their potential to impact patient safety. FIM is one of the many techniques cited in this chapter to help formulation scientists with this effort.For USP , the ability of FIM to help determine particle source is the primary cited reason the technique was included in the chapter—otherwise, the chapter solely focuses on methods compendial to USP . FIM allows researchers to capture this information without using MM and the measurement bias it can introduce. This feature also makes FIM a good “referee” method between the two compendial methods, providing particle type/source information that can help scientists interpret the results from the compendial methods (for example presence of silicone oil droplets in a sample).How does FIM track protein aggregation, particularly under stress conditions, and how does it compare to traditional methods?FIM tracks protein aggregation the way most particle analyzers do—by tracking changes in particle concentrations and size distributions following different stress conditions. One of the advantages of this approach relative to legacy methods like LO is simply the accuracy and sensitivity of the method. This often helps researchers identify if even subtle changes in how a sample is formulated or handled can impact the stability of the protein. This data can sometimes help researchers find differences in protein aggregation that sometimes don’t show up via other analytical techniques like size-exclusion chromatography (SEC) and high-performance liquid chromatography (HPLC).The other main advantage is the ability to track changes in the types of aggregates that are formed under different stress conditions. Some studies have shown that different stress conditions generate protein aggregates whose morphology is characteristic of the stress at their root cause. With appropriate study design, this data can help researchers glean information about the mechanisms of aggregation that are occurring in different samples.How does FIM help identify aggregation mechanisms in biologics and guide formulation improvements to minimize risks?As discussed previously, the concentration, size, and morphology data FIM provides can help researchers identify even subtle changes in aggregation mechanisms between formulations and stress conditions. It can also give some general insights into aggregation mechanisms under certain conditions.Knowing the sources of instability in a protein formulation can help formulation scientists be more methodical in designing formulation changes to mitigate known instabilities. Imagine we noticed a significant change in aggregate concentrations following an agitation stress. We might decide to try changes like adding surfactants or increasing the fill volume to address the issue as these changes will often mitigate aggregation via shaking stresses.Can FIM be used to control visible particles?Yes! While FIM is most typically used as a subvisible particle monitoring tool, some FIM instruments are also able to measure visible particles. This can be a helpful orthogonal technique to visual inspection for monitoring visible particles. FIM is a destructive measurement and thus cannot be used as a primary lot release test for visible particles. In exchange, FIM provides more consistent detection and enumeration of visible particles, including gray zone particles that are too small to be consistently observed via visual inspection. It also provides particle images that can be used to determine the root cause of visible particles that may appear in samples. This makes FIM a useful method to screen for visible particles during drug product development or as secondary destructive testing as part of lot release testing in a similar fashion as it is used for subvisible particle monitoring.How does integrating FIM into training programs improve operator qualification and visual inspection accuracy for visible particles in therapeutics?FIM can be used as an orthogonal technique for visual inspection, providing more sensitive and quantitative visible particle measurements albeit in a destructive fashion. This data can help validate visual inspection processes, allowing scientists to quantify the number of particles detected via visual inspection against the actual number of visible particles in a sample. This can help researchers develop processes and training strategies that catch as many visible particles as possible, greatly reducing the number of withheld units and helping minimize the risk of complaints and recalls in the clinic.FIM has also been used to develop better particle standards for visual inspection by groups at the US National Institute of Standards and Technology (NIST) and other organizations. These efforts have mostly focused on making particles that mimic visible protein aggregates, one of the most challenging yet important particles for inspectors to detect. Using these standards in training kits as part of operator training and qualification may help inspectors find these particles more reliably, potentially reducing their number in the final drug products. These standards may also make visual inspection processes more consistent between organizations, ensuring that these improvements can be implemented by any organization developing parenteral therapies.What future potential or new applications do you envision for FIM going forward?The main potential I see in FIM is in its use as a lot release test for subvisible particles. FIM has replaced LO and MM throughout much of biotherapeutic development for its greater accuracy and access to morphology information. These features make it equally valuable in a quality control context. While I don’t think it will be added to USP any time soon, I think it is likely to happen once the technology becomes more mature and methods for using the image data are more established.I also think there is a lot more that scientists can do with the image data that FIM provides. Several labs have started to explore what can be done with cutting-edge image analysis approaches like artificial intelligence in recognizing different particle types in samples using FIM data. FIM is unlikely to completely replace forensic methods for identifying particles in samples—the technique only has access to morphology data that can be encoded in a brightfield microscopy image. However, as image analysis tools become more powerful and commonplace I think there is a lot of untapped potential for FIM as a tool to screen samples for different particle types.Application-wise, I am most excited to see what FIM can do in the context of cell therapies. Cell therapies pose unique challenges from a quality control strategy since the active ingredient is a subvisible particle. As some researchers have found, FIM can be a useful way to get around this issue, letting researchers distinguish between cells that are supposed to be there and other particle types that are not.Likewise, FIM can also process much bigger cell assemblies as well that can be useful to monitor. This not only includes cell clusters but even larger assemblies like organoids that have applications outside of parenteral therapy development.Supplemental DefinitionsFlow Imaging Microscopy (FIM)Flow Imaging Microscopy (FIM) is a technique used to analyze particle size, morphology, and distribution in liquid suspensions. It captures images of particles as they flow through a microscope system, providing high-resolution data on particle shape, size, and concentration.Light Obscuration (LO)LO is a method for measuring particle size and concentration in suspensions. It works by detecting changes in light transmission through a sample as particles pass through a sensing zone. The extent of light blockage correlates with the size of the particles, offering a quantitative measurement.Electron Microscopy (EM)EM uses a beam of electrons instead of light to form an image. This technique provides high-resolution images of biological and non-biological samples, revealing fine details at the nanoscale, including cellular structures and molecular components.Membrane Microscopy (MM)MM is a particle analysis technique that involves using membrane filtration to remove the background buffer of a sample, then using microscopy to image and analyze particles on the membrane filter. It provides particle morphology information in addition to some particle concentration and size data.USP Methods Summary: – Subvisible Particulate Matter in Therapeutic Protein InjectionsThis method provides guidelines for detecting and quantifying subvisible particles in therapeutic protein injections using LO. It applies to protein formulations administered by injection and ensures product safety by limiting particulate contamination. – Particulate Matter in InjectionsThis monograph defines the requirements for detecting and quantifying particulate matter in injectable drug products using LO or MM. It outlines acceptable levels of subvisible particles in injectable medications to ensure patient safety. – Detection of Subvisible Particulate Matter in Injectable Drug ProductsSimilar to , this method focuses on assessing subvisible particles in ophthalmic drug products. It emphasizes techniques such as LO for determining particle size and distribution in these critical formulations. – Particulate Matter in Parenteral Drug ProductsThis chapter focuses on protein therapies. It details various methods researchers can use to characterize protein aggregates and other subvisible particles, including flow imaging microscopy, Raman Spectroscopy, and electron microscopy. – Determining the Amount of Subvisible Particles in Parenteral Drug ProductsThis method outlines how to assess subvisible particle contamination in parenteral drug products. It includes guidelines for using light obscuration, flow imaging microscopy, and other validated techniques to detect particles and ensure product safety.References(1) Molina, S. A.; Davies, S. J.; Sethi, D.; et al. Particulates Are Everywhere, but Are They Harmful in Cell and Gene Therapies? Cytotherapy2022, 24(12), 1195–1200. DOI: 10.1016/j.jcyt.2022.07.014(2) Rosenberg, A. S. Effects of Protein Aggregates: An Immunologic Perspective. AAPS J.2006, 8(3), E501–E507. DOI: 10.1208/aapsj080359(3) Kotarek, J.; Stuart, C.; De Paoli, S. H.; et al. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated with Severe Adverse Postmarketing Events. J. Pharm. Sci.2016, 105(3), 1023–1027. DOI: 10.1016/S0022-3549(15)00180-X(4) Shibata, H.; Harazono, A.; Kiyoshi, M.; Ishii-Watabe, A. Quantitative Evaluation of Insoluble Particulate Matters in Therapeutic Protein Injections Using Light Obscuration and Flow Imaging Methods. J. Pharm. Sci.2021, 000. DOI: 10.1016/j.xphs.2021.09.047(5) Calderon, C. P.; Daniels, A. L.; Randolph, T. W. Deep Convolutional Neural Network Analysis of Flow Imaging Microscopy Data to Classify Subvisible Particles in Protein Formulations. J. Pharm. Sci.2018, 107(4), 999–1008. DOI: ht10.1016/j.xphs.2017.12.008(6) Rosenberg, A. S. Effects of Protein Aggregates: An Immunologic Perspective. AAPS J.2006, 8(3), E501–E507. DOI: 10.1208/aapsj080359(7) Kotarek, J.; Stuart, C.; De Paoli, S. H.; et al. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated with Severe Adverse Postmarketing Events. J. Pharm. Sci.2016, 105(3), 1023–1027. DOI: 10.1016/S0022-3549(15)00180-X(8) Srivastava, A.; Mallela, K. M. G.; Deorkar, N.; Brophy, G. Manufacturing Challenges and Rational Formulation Development for AAV Viral Vectors. J. Pharm. Sci.2021, 110(7), 2609–2624. DOI: 10.1016/j.xphs.2021.03.024(9) Gambe-Gilbuena, A.; Shibano, Y.; Krayukhina, E.; Torisu, T.; Uchiyama, S. Automatic Identification of the Stress Sources of Protein Aggregates Using Flow Imaging Microscopy Images. J. Pharm. Sci.2020, 109(1), 614–623. DOI: 10.1016/j.xphs.2019.10.034(10) Wright, J. F.; Le, T.; Prado, J.; et al. Identification of Factors That Contribute to Recombinant AAV2 Particle Aggregation and Methods to Prevent Its Occurrence During Vector Purification and Formulation. Mol. Ther.2005, 12(1), 171–178. DOI: 10.1016/j.ymthe.2005.02.021(11) Saggu, M.; Bou-Assaf, G. M.; Bucher, R.; et al. Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products. J. Pharm. Sci.2024, 113(5), 1401–1414. DOI: 10.1016/j.xphs.2024.01.002(12) Chisholm, C. F.; Nguyen, B. H.; Soucie, K. R.; Torres, R. M.; Carpenter, J. F.; Randolph, T. W. In Vivo Analysis of the Potency of Silicone Oil Microdroplets as Immunological Adjuvants in Protein Formulations. J. Pharm. Sci.2015, 104(11), 3681–3690. DOI: 10.1002/jps.24573(13) Mazaheri, M.; Saggu, M.; Wuchner, K.; et al. Monitoring of Visible Particles in Parenteral Products by Manual Visual Inspection—Reassessing Size Threshold and Other Particle Characteristics That Define Particle Visibility. J. Pharm. Sci.2024, 113(3), 616–624. DOI: 10.1016/j.xphs.2023.10.002(14) Liu, F.; Hutchinson, R. Visible Particles in Parenteral Drug Products: A Review of Current Safety Assessment Practice. Curr. Res. Toxicol.2024, 7(June), 100175. DOI: 10.1016/j.crtox.2024.100175(15) Telikepalli, S. N.; Carrier, M. J.; Ripple, D. C.; et al. An Interlaboratory Study to Identify Potential Visible Protein-Like Particle Standards. AAPS PharmSciTech2023, 24(1). DOI: 10.1208/s12249-022-02457-9(16) Amara, I.; Germershaus, O.; Lentes, C.; et al. Comparison of Protein-Like Model Particles Fabricated by Micro 3D Printing to Established Standard Particles. J. Pharm. Sci.2024, Article in Press. DOI: 10.1016/j.xphs.2024.04.011About the IntervieweeDr. Austin Daniels is an application scientist for Yokogawa Fluid Imaging Technologies. He received his Ph.D. in Chemical and Biological Engineering from the University of Colorado. His research focused on flow imaging microscopy and similar subvisible particle imaging techniques combined with artificial intelligence-driven image analysis tools. These methods were used to compare protein aggregates generated via different stress conditions in biotherapeutics. Currently, he is working on exploring and improving applications for flow imaging microscopy in biotherapeutics development and beyond.About the InterviewerJerome Workman, Jr. serves on the Editorial Advisory Board of Spectroscopy and is the Executive Editor for LCGC and Spectroscopy. He is the co-host of the Analytically Speaking podcast and has published multiple reference text volumes, including the three-volume Academic Press Handbook of Organic Compounds, the five-volume The Concise Handbook of Analytical Spectroscopy, the 2nd edition of Practical Guide and Spectral Atlas for Interpretive Near-Infrared Spectroscopy, the 2nd edition of Chemometrics in Spectroscopy, and the 4th edition of The Handbook of Near-Infrared Analysis. Author contact: JWorkman@MJHlifesciences.com ●

An Exclusive Spectroscopy Interview on Flow Imaging Microscopy in Collaboration with the American Association of Pharmaceutical Scientists (AAPS), Part 2

Science and Health

IntroductionIn Part 2 of this two-part interview, we continue to speak with Austin Daniels, application scientist for Yokogawa Fluid Imaging Technologies, about the subject of flow imaging microscopy (FIM).Flow imaging microscopy (FIM) offers a more comprehensive approach, capturing high-resolution images and quantitative data on particle size, shape, and composition in pharmaceutical preparations. Instruments like FlowCam enable detailed characterization, distinguishing protein aggregates from contaminants and monitoring process stability. Recognized in regulatory guidelines such as USP and , FIM enhances compliance and quality control in biotherapeutic development (1–16).In Part 2 of this interview, we continue to discuss the advantages of FIM over traditional techniques, its role in regulatory compliance, and real-world applications for improving biologic safety and efficacy. Join us as we explore the impact of this innovative technology on subvisible particle characterization.How does FIM address challenges in low-volume or high-viscosity formulations while meeting USP and particle limits?FIM instruments help with low-volume formulations simply by not requiring a ton of volume relative to many other particle analysis techniques. FIM measurements only require around 100 μL to perform and get consistent measurements. This can still be a lot of volume to spend on a single measurement, but as it’s much lower than traditional particle analysis techniques like light obscuration (LO) it can allow scientists to capture subvisible particle measurements as part of their formulation development. It’s important to note that FIM can also process larger volumes using a similar standard operating procedure (SOP), meaning that the technique can also process very large volumes as well depending on the available volume and experiment goals.With regards to viscosity, there is an interesting quirk to how FIM instruments perform concentration measurements that help the technique be robust to viscosity changes. To measure concentrations, the number of particles that are detected is normalized to the volume imaged during the measurement rather than the total volume that passes through the flow cell. The volume analyzed is based on the number of times the flow cell was imaged and the volume sampled per image. Handling concentration calculations this way makes the technique robust to small errors in flow rate—the main concern viscosity poses for particle measurements. While I would still recommend diluting a very viscous sample to ensure that the sample flows through at the recommended flow rates, the technique can provide reasonable measurements on most typical biotherapeutics regardless of their viscosity.How does FIM offer an advantage in monitoring silicone oil droplets compared to LO or membrane microscopy (MM)?The main advantage of FIM for monitoring silicone oil droplets is the ability to analyze them using one analytical technique instead of two. Neither LO nor MM are ideal for monitoring silicone oil droplets but for completely different reasons. LO measurements detect silicone oil droplets in a sample but are unable to distinguish them from other particle types that may be in the sample and thus cannot provide a concentration or size distribution for these particle types. MM captures particle morphology info, but silicone oil droplets are removed during membrane filtration and thus not detected. To get a measurement of the silicone oil content with these techniques, researchers must use both methods to analyze a sample and take the difference in the measured concentrations. Since FIM can distinguish between silicone oil droplets while still counting them, it can be used in isolation and capture a reasonable estimate of a sample’s silicone oil content.How does FIM differ from LO in sensitivity to particle types, like protein aggregates, and how does this impact USP compliance?FIM primarily differs from LO in its sensitivity to transparent particle types. LO measurements depend on both the size and refractive index of the particles and will generally report smaller particle sizes the more translucent a particle appears. This often results in LO underestimating the concentration and size of particles in a sample, particularly biologics that contain a high concentration of translucent particles. FIM measurements are not impacted by these issues to the same extent, resulting in higher particle concentrations and sizes relative to LO.When thinking about USP compliance, it is important to remember that the pharmacopeia limits were set with the limitations of LO in mind. Many researchers are often surprised to see FIM and related particle techniques report much higher particle concentrations than are allowed via USP . However, that only means that LO is missing particles in a sample and not necessarily that the sample is not USP compliant. The sample only fails to meet pharmacopeia guidelines if it has more particles than are allowed via USP when tested by a compendial method. That said, regulators are aware of the limitations of the compendial methods and the current subvisible particle limits.How does FIM’s particle morphology analysis help identify sources of particles and enhance control in line with USP and ?Both USP and motivate the need to monitor particle type and source as part of a robust particle control strategy. For , this comes from a need to distinguish between extrinsic and intrinsic particles in a drug product (which often need to be prevented or minimized) from inherent protein aggregate particles in a protein therapy (which cannot be completely prevented). It also helps researchers better characterize protein aggregate particles in general which is necessary given their potential to impact patient safety. FIM is one of the many techniques cited in this chapter to help formulation scientists with this effort.For USP , the ability of FIM to help determine particle source is the primary cited reason the technique was included in the chapter—otherwise, the chapter solely focuses on methods compendial to USP . FIM allows researchers to capture this information without using MM and the measurement bias it can introduce. This feature also makes FIM a good “referee” method between the two compendial methods, providing particle type/source information that can help scientists interpret the results from the compendial methods (for example presence of silicone oil droplets in a sample).How does FIM track protein aggregation, particularly under stress conditions, and how does it compare to traditional methods?FIM tracks protein aggregation the way most particle analyzers do—by tracking changes in particle concentrations and size distributions following different stress conditions. One of the advantages of this approach relative to legacy methods like LO is simply the accuracy and sensitivity of the method. This often helps researchers identify if even subtle changes in how a sample is formulated or handled can impact the stability of the protein. This data can sometimes help researchers find differences in protein aggregation that sometimes don’t show up via other analytical techniques like size-exclusion chromatography (SEC) and high-performance liquid chromatography (HPLC).The other main advantage is the ability to track changes in the types of aggregates that are formed under different stress conditions. Some studies have shown that different stress conditions generate protein aggregates whose morphology is characteristic of the stress at their root cause. With appropriate study design, this data can help researchers glean information about the mechanisms of aggregation that are occurring in different samples.How does FIM help identify aggregation mechanisms in biologics and guide formulation improvements to minimize risks?As discussed previously, the concentration, size, and morphology data FIM provides can help researchers identify even subtle changes in aggregation mechanisms between formulations and stress conditions. It can also give some general insights into aggregation mechanisms under certain conditions.Knowing the sources of instability in a protein formulation can help formulation scientists be more methodical in designing formulation changes to mitigate known instabilities. Imagine we noticed a significant change in aggregate concentrations following an agitation stress. We might decide to try changes like adding surfactants or increasing the fill volume to address the issue as these changes will often mitigate aggregation via shaking stresses.Can FIM be used to control visible particles?Yes! While FIM is most typically used as a subvisible particle monitoring tool, some FIM instruments are also able to measure visible particles. This can be a helpful orthogonal technique to visual inspection for monitoring visible particles. FIM is a destructive measurement and thus cannot be used as a primary lot release test for visible particles. In exchange, FIM provides more consistent detection and enumeration of visible particles, including gray zone particles that are too small to be consistently observed via visual inspection. It also provides particle images that can be used to determine the root cause of visible particles that may appear in samples. This makes FIM a useful method to screen for visible particles during drug product development or as secondary destructive testing as part of lot release testing in a similar fashion as it is used for subvisible particle monitoring.How does integrating FIM into training programs improve operator qualification and visual inspection accuracy for visible particles in therapeutics?FIM can be used as an orthogonal technique for visual inspection, providing more sensitive and quantitative visible particle measurements albeit in a destructive fashion. This data can help validate visual inspection processes, allowing scientists to quantify the number of particles detected via visual inspection against the actual number of visible particles in a sample. This can help researchers develop processes and training strategies that catch as many visible particles as possible, greatly reducing the number of withheld units and helping minimize the risk of complaints and recalls in the clinic.FIM has also been used to develop better particle standards for visual inspection by groups at the US National Institute of Standards and Technology (NIST) and other organizations. These efforts have mostly focused on making particles that mimic visible protein aggregates, one of the most challenging yet important particles for inspectors to detect. Using these standards in training kits as part of operator training and qualification may help inspectors find these particles more reliably, potentially reducing their number in the final drug products. These standards may also make visual inspection processes more consistent between organizations, ensuring that these improvements can be implemented by any organization developing parenteral therapies.What future potential or new applications do you envision for FIM going forward?The main potential I see in FIM is in its use as a lot release test for subvisible particles. FIM has replaced LO and MM throughout much of biotherapeutic development for its greater accuracy and access to morphology information. These features make it equally valuable in a quality control context. While I don’t think it will be added to USP any time soon, I think it is likely to happen once the technology becomes more mature and methods for using the image data are more established.I also think there is a lot more that scientists can do with the image data that FIM provides. Several labs have started to explore what can be done with cutting-edge image analysis approaches like artificial intelligence in recognizing different particle types in samples using FIM data. FIM is unlikely to completely replace forensic methods for identifying particles in samples—the technique only has access to morphology data that can be encoded in a brightfield microscopy image. However, as image analysis tools become more powerful and commonplace I think there is a lot of untapped potential for FIM as a tool to screen samples for different particle types.Application-wise, I am most excited to see what FIM can do in the context of cell therapies. Cell therapies pose unique challenges from a quality control strategy since the active ingredient is a subvisible particle. As some researchers have found, FIM can be a useful way to get around this issue, letting researchers distinguish between cells that are supposed to be there and other particle types that are not.Likewise, FIM can also process much bigger cell assemblies as well that can be useful to monitor. This not only includes cell clusters but even larger assemblies like organoids that have applications outside of parenteral therapy development.Supplemental DefinitionsFlow Imaging Microscopy (FIM)Flow Imaging Microscopy (FIM) is a technique used to analyze particle size, morphology, and distribution in liquid suspensions. It captures images of particles as they flow through a microscope system, providing high-resolution data on particle shape, size, and concentration.Light Obscuration (LO)LO is a method for measuring particle size and concentration in suspensions. It works by detecting changes in light transmission through a sample as particles pass through a sensing zone. The extent of light blockage correlates with the size of the particles, offering a quantitative measurement.Electron Microscopy (EM)EM uses a beam of electrons instead of light to form an image. This technique provides high-resolution images of biological and non-biological samples, revealing fine details at the nanoscale, including cellular structures and molecular components.Membrane Microscopy (MM)MM is a particle analysis technique that involves using membrane filtration to remove the background buffer of a sample, then using microscopy to image and analyze particles on the membrane filter. It provides particle morphology information in addition to some particle concentration and size data.USP Methods Summary: – Subvisible Particulate Matter in Therapeutic Protein InjectionsThis method provides guidelines for detecting and quantifying subvisible particles in therapeutic protein injections using LO. It applies to protein formulations administered by injection and ensures product safety by limiting particulate contamination. – Particulate Matter in InjectionsThis monograph defines the requirements for detecting and quantifying particulate matter in injectable drug products using LO or MM. It outlines acceptable levels of subvisible particles in injectable medications to ensure patient safety. – Detection of Subvisible Particulate Matter in Injectable Drug ProductsSimilar to , this method focuses on assessing subvisible particles in ophthalmic drug products. It emphasizes techniques such as LO for determining particle size and distribution in these critical formulations. – Particulate Matter in Parenteral Drug ProductsThis chapter focuses on protein therapies. It details various methods researchers can use to characterize protein aggregates and other subvisible particles, including flow imaging microscopy, Raman Spectroscopy, and electron microscopy. – Determining the Amount of Subvisible Particles in Parenteral Drug ProductsThis method outlines how to assess subvisible particle contamination in parenteral drug products. It includes guidelines for using light obscuration, flow imaging microscopy, and other validated techniques to detect particles and ensure product safety.References(1) Molina, S. A.; Davies, S. J.; Sethi, D.; et al. Particulates Are Everywhere, but Are They Harmful in Cell and Gene Therapies? Cytotherapy2022, 24(12), 1195–1200. DOI: 10.1016/j.jcyt.2022.07.014(2) Rosenberg, A. S. Effects of Protein Aggregates: An Immunologic Perspective. AAPS J.2006, 8(3), E501–E507. DOI: 10.1208/aapsj080359(3) Kotarek, J.; Stuart, C.; De Paoli, S. H.; et al. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated with Severe Adverse Postmarketing Events. J. Pharm. Sci.2016, 105(3), 1023–1027. DOI: 10.1016/S0022-3549(15)00180-X(4) Shibata, H.; Harazono, A.; Kiyoshi, M.; Ishii-Watabe, A. Quantitative Evaluation of Insoluble Particulate Matters in Therapeutic Protein Injections Using Light Obscuration and Flow Imaging Methods. J. Pharm. Sci.2021, 000. DOI: 10.1016/j.xphs.2021.09.047(5) Calderon, C. P.; Daniels, A. L.; Randolph, T. W. Deep Convolutional Neural Network Analysis of Flow Imaging Microscopy Data to Classify Subvisible Particles in Protein Formulations. J. Pharm. Sci.2018, 107(4), 999–1008. DOI: ht10.1016/j.xphs.2017.12.008(6) Rosenberg, A. S. Effects of Protein Aggregates: An Immunologic Perspective. AAPS J.2006, 8(3), E501–E507. DOI: 10.1208/aapsj080359(7) Kotarek, J.; Stuart, C.; De Paoli, S. H.; et al. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated with Severe Adverse Postmarketing Events. J. Pharm. Sci.2016, 105(3), 1023–1027. DOI: 10.1016/S0022-3549(15)00180-X(8) Srivastava, A.; Mallela, K. M. G.; Deorkar, N.; Brophy, G. Manufacturing Challenges and Rational Formulation Development for AAV Viral Vectors. J. Pharm. Sci.2021, 110(7), 2609–2624. DOI: 10.1016/j.xphs.2021.03.024(9) Gambe-Gilbuena, A.; Shibano, Y.; Krayukhina, E.; Torisu, T.; Uchiyama, S. Automatic Identification of the Stress Sources of Protein Aggregates Using Flow Imaging Microscopy Images. J. Pharm. Sci.2020, 109(1), 614–623. DOI: 10.1016/j.xphs.2019.10.034(10) Wright, J. F.; Le, T.; Prado, J.; et al. Identification of Factors That Contribute to Recombinant AAV2 Particle Aggregation and Methods to Prevent Its Occurrence During Vector Purification and Formulation. Mol. Ther.2005, 12(1), 171–178. DOI: 10.1016/j.ymthe.2005.02.021(11) Saggu, M.; Bou-Assaf, G. M.; Bucher, R.; et al. Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products. J. Pharm. Sci.2024, 113(5), 1401–1414. DOI: 10.1016/j.xphs.2024.01.002(12) Chisholm, C. F.; Nguyen, B. H.; Soucie, K. R.; Torres, R. M.; Carpenter, J. F.; Randolph, T. W. In Vivo Analysis of the Potency of Silicone Oil Microdroplets as Immunological Adjuvants in Protein Formulations. J. Pharm. Sci.2015, 104(11), 3681–3690. DOI: 10.1002/jps.24573(13) Mazaheri, M.; Saggu, M.; Wuchner, K.; et al. Monitoring of Visible Particles in Parenteral Products by Manual Visual Inspection—Reassessing Size Threshold and Other Particle Characteristics That Define Particle Visibility. J. Pharm. Sci.2024, 113(3), 616–624. DOI: 10.1016/j.xphs.2023.10.002(14) Liu, F.; Hutchinson, R. Visible Particles in Parenteral Drug Products: A Review of Current Safety Assessment Practice. Curr. Res. Toxicol.2024, 7(June), 100175. DOI: 10.1016/j.crtox.2024.100175(15) Telikepalli, S. N.; Carrier, M. J.; Ripple, D. C.; et al. An Interlaboratory Study to Identify Potential Visible Protein-Like Particle Standards. AAPS PharmSciTech2023, 24(1). DOI: 10.1208/s12249-022-02457-9(16) Amara, I.; Germershaus, O.; Lentes, C.; et al. Comparison of Protein-Like Model Particles Fabricated by Micro 3D Printing to Established Standard Particles. J. Pharm. Sci.2024, Article in Press. DOI: 10.1016/j.xphs.2024.04.011About the IntervieweeDr. Austin Daniels is an application scientist for Yokogawa Fluid Imaging Technologies. He received his Ph.D. in Chemical and Biological Engineering from the University of Colorado. His research focused on flow imaging microscopy and similar subvisible particle imaging techniques combined with artificial intelligence-driven image analysis tools. These methods were used to compare protein aggregates generated via different stress conditions in biotherapeutics. Currently, he is working on exploring and improving applications for flow imaging microscopy in biotherapeutics development and beyond.About the InterviewerJerome Workman, Jr. serves on the Editorial Advisory Board of Spectroscopy and is the Executive Editor for LCGC and Spectroscopy. He is the co-host of the Analytically Speaking podcast and has published multiple reference text volumes, including the three-volume Academic Press Handbook of Organic Compounds, the five-volume The Concise Handbook of Analytical Spectroscopy, the 2nd edition of Practical Guide and Spectral Atlas for Interpretive Near-Infrared Spectroscopy, the 2nd edition of Chemometrics in Spectroscopy, and the 4th edition of The Handbook of Near-Infrared Analysis. Author contact: JWorkman@MJHlifesciences.com ●

Public Health Nightmare: CDC Shuts STI Lab, Fires Its Scientists

Science and Health

RFK Jt. Photo: sweejak via Flickr CC, Gonorrhea bacteria – Medical Illustrator: Alissa Eckert, CDC via Unsplash ” data-medium-file=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?resize=600%2C388&ssl=1″ data-large-file=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?fit=800%2C572&ssl=1″ class=”size-full wp-image-245737″ src=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?resize=800%2C572&ssl=1″ alt width=”800″ height=”572″>RFK Jr. Photo: sweejak via Flickr CC, Gonorrhea bacteria – Medical Illustrator: Alissa Eckert, CDC via Unsplash The Centers for Disease Control and Prevention (CDC) fired dozens of employees who…

Public Health Nightmare: CDC Shuts STI Lab, Fires Its Scientists

Science and Health

RFK Jt. Photo: sweejak via Flickr CC, Gonorrhea bacteria – Medical Illustrator: Alissa Eckert, CDC via Unsplash ” data-medium-file=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?resize=600%2C388&ssl=1″ data-large-file=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?fit=800%2C572&ssl=1″ class=”size-full wp-image-245737″ src=”https://i0.wp.com/www.metroweekly.com/wp-content/uploads/2025/04/CDC-fires-entire-lab-working-on-STI-infections-RFK-Jt.-Photo-sweejak-via-Flickr-CC-Gonorrhea-bacteria.-Medical-Illustrator-Alissa-Eckert-CDC-via-Unsplash.jpg?resize=800%2C572&ssl=1″ alt width=”800″ height=”572″>RFK Jr. Photo: sweejak via Flickr CC, Gonorrhea bacteria – Medical Illustrator: Alissa Eckert, CDC via Unsplash The Centers for Disease Control and Prevention (CDC) fired dozens of employees who…