The Evolution of a Breakthrough: From Ideation to Finished Product

We thought it would be useful to take you through what product development actually looks like at Marie Veronique, from the initial idea all the way through formulation and launch. It’s increasingly rare for skincare companies to develop and make their products in-house, but we believe it matters enormously for both quality and efficacy. When you hand everything over to a third-party lab, you’re also handing over sourcing, formulation, manufacturing, and often much of the decision-making that happens along the way. You miss a lot of the magic that comes from having the same people, with the same ethos and intentions, working together throughout the process. For us, keeping that process close means more conversation, more iteration, and ultimately more integrity in the finished product.

Marie Veronique, R and D Chief:

Of course everything starts with an idea, and in skin care it was clear to me a few years ago that senolytics would be a promising avenue to explore. Using them in topicals to address one of the major hallmarks of skin aging, cellular senescence, is a simple enough concept.

We know that as we age, we accumulate senescent cells (SCs), that is, cells that no longer divide but refuse to die. They aren’t getting the message—actually, one of their survival strategies is to simply ignore messages telling them to go away. Instead, they engage in behaviors that are eerily reminiscent of human tactics we deplore—SCs hang about in gangs, sending nasty pro-inflammatory messages from their senescence-associated secretory phenotype, or SASP for short, headquarters.

SASP directives increase skin inflammation, which becomes chronic, leading to a condition called inflammaging. In the skin, skinflammaging damage shows up in the form of wrinkles, age spots and sagging. 

I had long been interested in a class of bioflavonoids that act as powerful senolytics; that is, they can preferentially target senescent cells for elimination. The only problem with bioflavonoids is that they are very unstable; in fact, they are even more unstable than Vitamin C and retinol, which, as senomorphic agents, do wonders to retard skin aging.  

It got me thinking about encapsulation as a solution. Other people had done this with resveratrol, Vitamin E and epigallocatechin gallate (1), but I wanted to take on the ultimate challenge and do the same for the most powerful senolytic in the flavonoid pantheon, namely fisetin.

The logical place to go was to the PSU team, headed by Dr. Jay Nadeau. They had helped us with retinol encapsulation in the past and were ready to work on a new project.  

Dr. Jay Nadeau, head of PSU team:

The PSU team used a novel Vitamin-E based, PEG-free encapsulating agent called Savie. Savie not only encapsulated the fisetin, but also provided additional antioxidant activity in cells as it was cleaved by enzymes (esterases) inside the cell into free Vitamin E. Before application onto cells, the fisetin-Savie complex was stable for many months (2).

That was a big breakthrough, but our work had only begun. An encapsulated fisetin led us to the next step, i.e., incorporating it into a finished product. Our principal scientist, Dr. Csaba Kotsmar, always up to the challenge, developed two products: one that used encapsulated fisetin in an aqueous solution (Senolytic Serum) and another that used free fisetin in an anhydrous solution (Senolytic Balm).

Dr. Csaba Kotsmar, Principal Scientist, Marie Veronique: 

The challenge on my end was taking the encapsulation chemistry developed in Jay’s lab and turning it into something we could actually make reproducibly in a skin care R&D and manufacturing environment. Academic laboratories have access to specialized reagents, suppliers and instrumentation that are not necessarily appropriate (or even available) for cosmetic manufacturing. 

As Jay’s group refined the encapsulation method, we worked closely with them to identify which properties of the raw materials and which processing parameters were truly essential. We then had to source suitable cosmetic-grade materials and reproduce the process in our own lab, initially at roughly the same small scale used at PSU and then at progressively larger scales. That required several iterations in raw material selection, processing conditions and equipment. Filtration was particularly challenging: separating and processing the colloidal fisetin nanocapsules was relatively straightforward with sophisticated university equipment, but we needed a method that could be performed efficiently at larger scale with equipment available in our lab, and ultimately be reproducible by our laboratory technicians. 

Throughout the process, scalability, robustness and cost had to be considered alongside the chemistry.

The two finished products then presented almost opposite formulation problems. For the water-based Senolytic Serum, getting highly hydrophobic fisetin uniformly dispersed, protected and chemically stable depended on successfully translating that encapsulation process into the finished formula. 

Once we solved that, developing the surrounding serum matrix felt almost easy by comparison. In the anhydrous Senolytic Balm, fisetin could instead be dissolved directly into the oil-based matrix, but chemical stability remained critical because fisetin is readily degraded by environmental stresses. We therefore designed both the antioxidant system and the manufacturing process around protecting it. Because the balm must be hot-poured, the process was engineered so that fisetin is introduced in a way that minimizes both its temperature exposure and the length of time it spends at elevated temperature.

The result of these two very different development paths was a water-based serum containing encapsulated, protected fisetin and an anhydrous balm designed to maintain the integrity of free fisetin. From a formulation and scale-up perspective, this was probably the most technically sophisticated project I have worked on at Marie Veronique.

Kristina Holey, Director of Skin Health, Marie Veronique: 

From there, we go back into R&D to talk through the format for the fisetin. This is where the conversation becomes much more collaborative between myself and the R&D team. We’re thinking about what makes the most sense for the customer: how the ingredient should be delivered, how we can optimize for efficacy, what format will best support the biology we’re trying to influence, and, importantly, how it actually works in a real routine. It’s not just a question of what we can formulate. It’s also a question of what makes the most sense for the person using it. Once we had prototypes for the Senolytic Balm and the Senolytic Serum, we tested them on a group of people, weighed the observations and comments, and finally settled on iterations that gave us the best results and also passed the tests required by the FDA. That’s where our regulatory head, Karina Kausch, comes in.

Karina Kausch, Head of Regulatory, Marie Veronique: 

Marie Veronique has our own internal standards when it comes to the ingredients used in our products. We follow the FDA's guidance, of course (there aren’t many for raw materials!), plus Canada and the European Union to ensure we are complying with international restrictions and prohibitions. On top of those requirements, we layer in our own ideas around avoiding petroleum-derived materials due to their lack of sustainability and the potential for undesired residual solvents or avoiding animal-derived materials unless they are truly the best option out there and we can ensure respect for the animals involved.

As Csaba noted, the ingredients used in a research setting are often very different from what is allowed within the personal care manufacturing industry. Where they can use reagent grade acetic acid, we are pushed towards using Vinegar as our acetic acid source. These difficulties and industry differences, coupled with our high standards, made this project challenging from the outset.

In addition to our sourcing standards, we go above and beyond the standard testing requirements for general personal care products. We test for irritation to both sensitive skin and eyes (non-animal!), ensure our preservative system is effective yet not detrimental to skin health, verify the potential allergenic responses to soy or gluten, and ensure we are complying with state regulations around heavy metals and dioxanes.

So, once we’ve successfully vaulted all the hurdles, we can release the product from R and D. 

Gretchen Auston Chevalier, SVP Operations, Marie Veronique: 

Once a formula has been approved by R&D and undergone evaluation and testing, it’s time to figure out how to make it consistently, at the scale we need, without compromising what made it special in the first place. A formula that works beautifully in a research lab doesn’t necessarily behave the same way when you’re producing a much larger batch, using different equipment, or preparing it for filling into final packaging. That transition from formulation to production is a critical part of the process.

We start with a pilot batch. This gives us the opportunity to evaluate how the formula behaves under actual manufacturing conditions. We look at everything from mixing and processing to texture, consistency, and stability. Are we getting the same results we saw in development? Are there adjustments needed to the process or equipment? We want to identify and work through those questions before moving into full-scale production.

Scale-up is where the science and the practical realities of manufacturing really come together. Mixing a small amount of a product is very different from mixing a much larger volume and seemingly small differences in processing can affect the finished product. Our job is to establish a process that is repeatable and reliable so that every batch meets our standards and delivers the experience we intended when we developed the formula.

One of the real advantages of developing and manufacturing in-house is that R&D, Quality and Operations can work through these challenges together. We can have conversations, make observations, and solve problems in real time rather than passing a formula between separate organizations and hoping nothing gets lost along the way. That collaboration is especially important to us because our goal isn’t simply to manufacture a product. It’s to preserve the integrity of the formula and the intention behind it, from the original concept through to the finished product in the hands of our customers. 

Kristina Holey:

The product then gets translated to the brand and marketing team, and we start talking in terms of what is interesting about the concept and what we want the user experience to be. This product was especially fun because, as a team, we wanted to exercise caution and be thoughtful before introducing something that was explicitly “longevity focused.” We believe in moving away from old-school language and the mentality of anti-aging. Instead, we want to be a resource for education and agency, helping people to understand their skin and helping them embrace aging processes that are as unique as they are. 

This product ended up being so inspiring that we built an entire campaign around the idea of “aging differently” as well as the idea of Skin Agency. We’ll be in NYC this late October hosting a panel around The Tyranny of Beauty, continuing the conversation about what we’re doing differently at all stages of product development and why that matters. For us, it’s about setting the bar higher than the industry standard, while staying grounded in integrity. Our goal is to make products that help people become the best expression of their unique selves, rather than making products designed to conceal their basic humanity.  

The point of all this, that I am sure has not escaped you by now,  is that it takes a team to make a product, and a great team to make great products. I want to thank Jay, Kristina, Csaba, Gretchen, and Karina for all their expertise, hard work and being on top of their game, always. - Marie Veronique Nadeau

Shop the Senolytic Series at the link below.