As a CDMO that specializes in the development of liquid and solid dose delivery systems, at PL Developments/Avéma Pharma Solutions, we envision a future where drug development takes center stage in the growing gummy industry—mirroring the explosive growth witnessed in the supplement market. If you observe the nutritional space, the trend of products transitioning from traditional forms like tablets, capsules, and soft gels to gummies has seen a massive compound annual growth rate (CAGR) exceeding 10%. We believe this momentum will soon extend into the over-the-counter (OTC) drug market and also into Rx drugs.

However, developing gummies for OTC or Rx drugs is no simple task. Unlike the relatively straightforward process of creating a two-piece capsule or a standard tablet, making a gummy requires a fine balance between art and science. To succeed in this market, you need a combination of expertise in confectionery, gummy formulation, and drug development subject matter experts to navigate the challenges ahead.

Beyond Supplements and Candy

There are two primary methods of gummy manufacturing: depositing into a fixed mold or using a starch-based mogul system. While starch moguls are commonly used by confectionery companies, there are some inherent limitations in this approach, with cross contamination being a primary concern. In a starch-based system, the gummies are dried in the molds, which are then the powdered starch reconditioned and then re-used. If you make different products with that starch, the starch poses a risk of cross-contaminating batches. This is fine if you’re making candy, but not acceptable for products subject to FDA approvals.

To offer a gummy drug delivery system, starchless production, which PLD uses, is the best option. In a starchless system, the slurry is deposited into a fixed mold where a chemical reaction in the formulation causes the gummy to solidify immediately. This allows the gummy to be quickly released from the mold so it can be dried in individual drying suites, freeing up the line to run a different product without fear of contamination. It’s our investment in the physical infrastructure, coupled with expertise in gummy manufacturing, that ensures the gummies meet the stringent standards required for FDA approval. Our New York facility is fully compliant with CFR 111, 210 and 211 and GDUFA requirements to produce supplements, OTC and Rx gummies.

Overcoming Manufacturing Challenges

Even starchless gummy production comes with a unique set of challenges, particularly as we move beyond supplements. One of the biggest hurdles is controlling the extreme moisture and heat during the manufacturing process. Stabilizing APIs under these conditions and ensuring the integrity of the formulation remains intact throughout the manufacturing process, is no small feat, especially given the trend away from gelatin-based gummies towards pectin, a plant-based alternative. This shift introduces its own set of complexities, as pectin reacts chemically with acids in the formulation. Managing the pH balance in these products becomes critical to ensuring the stability and quality of the final gummy—not just during the manufacturing process but also its shelf life.

Here’s where working with a CDMO that has extensive experience in developing drug delivery systems is advantageous. To solve this riddle, we drew on the company’s years of experience on the dietary supplement side as well as stabilizing APIs on the drug development side.

We also established a dedicated R&D center at our Miami headquarters, focused exclusively on gummy development. This facility works in tandem with our teams developing liquids, tablets, capsules, and soft gels, creating a synergy that allows us to tackle gummy-specific challenges like API stabilization and taste masking.

This facility also houses our small-scale pilot plant. Here, we create small batches of new gummy formulations, ensuring they meet our rigorous quality standards before moving to large-scale production. This bench-to-pilot-to-commercial process ensures a smooth transition from concept to market, enabling us to address any formulation challenges early in the development phase.

These resources have been key to developing a product that can control both pH, the bricks, and the viscosity of the product, to ensure that what we deposit is a good, solid product coming off the line.

Providing Uniform, Consistent Dosage

When it comes to formulating gummies with active ingredients, another hurdle is the amount of active load a gummy can support. Typically, a gummy can carry around 10-15% of its overall weight in active ingredients, depending on the formulation. At PLD, we’ve dedicated significant resources to developing intellectual property that allows us to increase the active load in our gummies without compromising taste or texture. This is a continuous effort as we push the boundaries of what’s possible in gummy drug formulation.

Of course, to maintain consistency in dosage, it’s also important that each gummy is the same weight. In a typical gummy manufacturing facility, there can be ae 10-15% variance in the weight that’s deposited in the mold. We have fine-tuned our manufacturing processes so deposit accuracy is in the low single digits.

Another challenge is ensuring product uniformity. Each gummy needs to provide an accurate, consistent dose of the API. This comes down to blending methods. While traditional gummy manufacturers typically use one or two blending methods, we have developed a proprietary four-way blending technique using equipment that we have designed and customized. This ensures that every batch of gummies—whether drawn from the top, bottom, left, or right of the mixing kettle—exhibits consistent content uniformity. You get the same API dose in every gummy.

Making Gummies Look and Taste Good – but Not Too Good

Once you have a stable gummy with the content uniformity, you get to the “fun” parts of gummy manufacturing—such as flavor and color.  We’ve developed a variety of base candy formulations to address the diverse needs of the growing gummy market. Among these are sugar-free, tapioca-based, and glucose syrup/pectin-based formulations, all of which have been extensively tested with different APIs.

After you’ve achieved stability across these various formulations, it’s important the gummy tastes good. Some APIs, though present in minimal quantities, are very bitter. At the beginning, we chose to tackle one of the toughest APIs for taste masking—caffeine. It’s notoriously difficult to work with, but through extensive research and development, we’ve effectively masked its bitter taste. This effort has helped us refine our approach for other challenging APIs.

From black coffee to cherry lemonade, our flavor portfolio spans a wide range of profiles. Thanks to our years of experience in both liquid and gummy development, we can meet virtually any flavor demand. But the other side of the coin is making sure that the gummies don’t taste too good, as that could lead to overconsumption. There is a fine line that needs to be addressed when taste masking, and one that’s already on the FDA’s radar screen.

Regulatory Challenges: Navigating Safety and Packaging

As the gummy space evolves into OTC drug territory, we’re facing a complex regulatory landscape. Recently, the FDA held a conference in October 2023, addressing “candy-like OTC drugs,” which emphasized not only formulation concerns, like formulation and content uniformity, but also safety and efficacy. A key topic was the need to distinguish gummy drugs from candy-like products to minimize the risk of accidental overdoses, especially in children. They noted that the introduction of melatonin gummies has already spiked an increase in calls to poison control centers.

The FDA recommended that gummies for drugs should avoid bright, candy-like colors and flashy shapes that could appeal to children. While gummies offer an excellent delivery system for people who struggle with swallowing traditional tablets or capsules, it’s essential to balance their appeal with safety considerations. This includes revisiting packaging strategies to ensure products are clearly labeled and stored in child-resistant containers. Currently, PLD/Avéma packages gummies in traditional packers, but we are exploring trends like resealable gusset bags to meet evolving consumer preferences and FDA regulations.

Let’s talk about new product approvals with the FDA. At least one Investigational New Drug application has been approved, although no NDAs have been approved so far. There are a couple of products out there on the confectionery side that are emerging in this space. Pepto Bismol and Alka Seltzer have pan chew-like products, Dulcolax has fruit chews and there are diphenhydramine and acetaminophen products available. There’s probably a bit more FDA approval that needs to happen to open up and unlock this space, but it’s definitely coming. CDMOs need to be prepared to offer expertise with OTC drug manufacturing and packaging along with the FDA approval process to enable their customers a successful product launch.

At PLD, we continue to push the boundaries of what’s possible in gummy formulation, from increasing active loads to improving stability, safety, and efficacy. As we move forward, we are committed to leading the gummy space with innovative solutions that make drug delivery more accessible and enjoyable for consumers, while maintaining the rigor and compliance that the pharmaceutical industry demands. With a production capacity of over 1.2 billion doses annually, PLD and Avéma have the infrastructure to meet large-scale demand. Our packaging facility in Westbury supports this output, ensuring that we can manage both production and packaging in-house, further enhancing efficiency.

By leveraging our existing infrastructure and focusing on high-quality, FDA-compliant gummy drug development, we’re ready to lead the charge in this exciting and evolving space.

Learn more at www.avemapharma.com