Roundtable Part 2: What are some general challenges when developing oral solid dosage products?

Karry: Some of the challenges that we need to overcome if we want to develop or manufacture solid dosage forms. is actually the API solubility. With poor API solubility, you either have to use high amounts of excipients or enabling technologies. Now these enabling technologies may be hot melt extrusion, spray drying, etc. but the problem is that they also lead to further problems with regard to, for example, the cohesiveness of an API with high cohesion comes with poor flow, which then leads to problems with blending uniformity.

Kane: One of the biggest challenges the industry faces is poor solubility and bioavailability of small molecules coming out of drug discovery. It is very important to solve this challenge at a very early stage in clinical so that we optimize the dose and its absorption profile and early clinical studies in pre-clinical animal models and then go into first in humans. Once this problem barrier is crossed, then we have opportunities to optimize the formulation in older solid dosage forms take it to a clinical proof of concept rapidly, and confirm that the drug works in the indication that is being sought. Another challenge that the industry faces in order solid dose delivery is confirming the proof of efficacy and proof of concept in patients in clinical trials in phase one and phase two. It is important to address the formulation and process challenges early on and ensure that the drug product is stable and scalable to late-stage development through the clinical phases and to commercially visible dosage form. Bringing speed and efficiency in drug product development early on helps our partners bring their medications to clinical trials confirm efficacy results and then scale it up appropriately to phase 2, phase 3, and towards filing and approval.

Kallelis: There are a number of technical challenges with respect to developing oral solid dose products, But I will say in addition to that, it’s right now the business challenge is significant in the United States. That being the severe price erosion on generics, the downward pressure on pricing for pharmaceutical drugs in general to the consumers in this political climate, that’s requiring it. At the same time, we have to maintain a high level of compliance with the FDA and the Drug Enforcement Agency, and that compliance level is quite expensive. So how do you operate an organization with a significant overhead that is at the same time calling for very low-cost products? And this is the biggest challenge we’re facing today, along with other HMOs in this space.

Labella: I think what we see a lot of times in our area is that a formulation is not fully developed or vetted before it’s brought to us. And a lot of times we have to make some changes or tweaks to a formulation or a process in order to make it robust and actually work well in our facility. We’ve had a number of challenges recently and have been able to overcome those problems with minor changes. You know, when people bring stuff to us, it’s expected to work, but not to change anything in the formulation or process. Sometimes that’s not possible. So minor changes that are within the regulatory realm are typically needed in order to facilitate robustness or manufacture durability of certain products and formulations.

Bejaoui: Developing OSD products can pose various challenges for pharmaceutical companies. Some common challenges include formulating the drug to ensure stability and bioavailability, selecting appropriate excipients to enhance drug dissolution and absorption, and ensuring the dosage form is easy to swallow for patients of all ages. Additionally, developing oral solid dosage products that can be manufactured on a large scale while maintaining consistent quality and efficacy can also be a challenge. overall, these challenges require careful consideration and expertise to overcome in order to develop effective and patient-friendly oral solid dosage products.

Hulvat: I think some of the general challenges in the development of oral drug products have not changed over the years. Their time budget API. We never have enough of all three. Developing a new drug product with speed and flexibility is a challenge. Whether it’s an oral drug product an injectable or other technologies.

Selling: when developing a small molecule or solid product, there are several different challenges that formulators, must consider. First is probably the molecule characterization, understanding how the molecule can be formulated into a different type of capsule or a pill, for example, and thinking about how physical character, sticks of the API, and ingredients that go into the product can ultimately be pulled together into the product There’s also bioavailability and solubility challenges that come with formulating and developing oral solids. Those with a great scientific team also can oftentimes be overcome by, you know, some of the technologies that are deployed in development labs around the world. the other challenge with developing in formulating products is actually the manufacturing of the product itself. The first challenge that we often have to overcome is around scalability of the product as you take a product through the different phases of development, it goes from phase 1 to 3. Then when you get to actual commercial production, you have to make sure your process in equipment is aligned to handle the scalability to different batch sizes and different quantities that need to be produced for the ultimate market. The second challenge is just the quality of the product. As you go to the different batch sizes and scalability, the quality and stability of the product is something that’s critical and often needs to be replicated batch after batch in order to ensure the highest standards for an oral solid product. two other challenges with manufacturing are the regulatory environment. You need to be able to comply with the guidelines and the dossier. The FDA approval process is quite detailed and making sure that you’re complying with those guidelines with each and every step of the production process is critical. So the final challenge with manufacturing today is working in a cost-constrained environment. There are very detailed costs of goods and targets that need to be achieved and with each of the various steps and quality support that’s needed for the product, we’re thinking continually how do we how do we produce the most cost-effective product in order to pass those savings along ultimately to the wholesalers and then finally to the patients who are taking the medicine?

Robert Sedlock, Director of Natoli Scientific, Natoli: Some of the challenges with developing oral solid dosage products is the proper training following best practices. For example, USP Chapter 1062 is on tablet characterization methods. It’s a series of studies and tests to really understand your material and where its failure points are.

Is it scalable? What type of deprivation properties do you have? Is a plastic, brittle, elastic?

Understanding all these things will allow you to develop a robust product that’s scalable to high-speed manufacturing. For example, is your product a direct compression product? Is it dry granulation? Is it wet granulation? Understanding all the unit ops and these different methods is very important for consistency and scalability.