AdaptDose, an innovative platform that reduces product development time and costs by 30% or more

Transcription

1 WHITE PAPER January 2017 AdaptDose, an innovative platform that reduces product development time and costs by 30% or more Frontida BioPharm, Inc. Ron Connolly

2 CONTENTS ABSTRACT INTRODUCTION PROBLEM 1 PROBLEM 2 PROBLEM 3 CONCLUSION

3 Contract Manufacturing Oral dosage form manufacture and packaging of immediate release and controlled release tablets, capsules, powders, liquids and suspensions. Product Development Our experienced team can accelerate your drug product development from early phase to commercial launch in a variety of dosage forms. Focused on Highly Potent, DEAcontrolled, or difficult to formulate products. Analytical Services Fully staffed raw material and commercial product release GMP laboratories ready to support your development, stability and manufacturing projects. Are you searching for ways to get your product into clinical trials faster? Do you believe that you are wasting R&D resources at earlier stages of development making customized dosage forms for a specific clinical study that may never be used for a commercial product? Are you trying to formulate combination products with known chemical interactions? Frontida has a solution that increases the probability of utilizing the knowhow of early formulation efforts in later stages of development. Using our innovative capsule filling equipment and processing technology, plus mini-tablet and drug-layered beadlet manufacturing capabilities, Frontida can provide an adaptable, easily modified formulation even before knowing the therapeutic dose of your investigational new drug. Contact us to find out more about our adaptive formulation technology.

4 INTRODUCTION Considering the amount of efforts required to bring new products to the market, drug development scientists have significant concerns in balancing the development of robust formulations, costs, and time to clinical studies at earlier stages of clinical research. A common approach to try and limit the expenses of formulation development at Phase I and II is to create a simple oral liquid, API powder in capsule, or powder for constitution or injection. These formulations are often limited in stability or present challenges for bioavailability of the API. As a result, companies will develop another formulation for Phase II or III studies and commercial launch that have the desired dose, stability and enhanced bioavailability. Frontida s AdaptDose technology platform provides a tool that can eliminate the need to reformulate after Phase I and overcomes several technical hurdles in the development and scale up of (1) new molecules, (2) binary and tertiary mixtures of active ingredients, zero and first order drug release matrices, or (3) scalable clinical trial materials used in dose ranging or adaptive dose clinical studies. AdaptDose technology allows us to incorporate granules, beadlets / pellets, and mini-tablets into a single capsule without the step of mixing the different materials prior to filling, using our commercially engineered, accurate and high speed equipment (capable of fill speeds over 100,000 units per hour). Let s take a look at three common formulation challenges and how AdaptDose can be used to overcome these challenges.

5 Problem #1 You are entering a new drug candidate into clinical development, but are uncertain of your target exposure levels for the study. Do you resort to API powder-in-a-capsule, knowing that you need a viable product formulation shortly after your dose escalation studies? Answer: Frontida s formulation development team has successfully developed the use of mini-tablets as a streamlined, flexible oral solid dose platform that we call AdaptDose. Using this technology, we can develop a stable tablet formulation that is pressed into mini-tablets measuring 1.0 millimeter to 2.5 millimeters in size. We then utilize our uniquely engineered capsule filling equipment (equipped with visual and weight inspection systems) to precisely load the correct dose of mini-tablets into a single dose capsule. This technology enables us to quickly deliver customized doses of your investigational new drug for adaptive-design clinical studies, such as Dose Range Finding and Dose Escalation Studies at Phase I and II of clinical development. When the target doses are identified from the clinical research, Frontida s team can then utilize the already-developed formulation to efficiently create larger tablets of the target dosage strengths for Clinical Phase III and commercial production. Benefits: Frontida s AdaptDose technology eliminates the necessity of using an early-phase powder formulation, and corresponding stability data, that may result in limited utility for the product s lifecycle, saving tens of thousands of dollars and months of development effort. Mini-tablet technology allows us to create a variety of strengths required for clinical dose escalations (SAD and MAD studies) of the product in a format that can be used in future development efforts and clinical phases. You can then gain valuable know-how about the stability and utility of a tablet formulation for future efforts.

6 Problem #2 You have interest in developing a fixed-dose combination (FDC) of 2 or 3 Active Pharmaceutical Ingredients (APIs) for oral delivery, but are aware of a potential chemical interaction between the API s. How can you develop such a combination that avoids the interaction issues that you face? Answer: AdaptDose gives Frontida the ability to accurately combine multiple active ingredients into one capsule while avoiding the potential for interactions. How can we do so? By creating independent, single-api formulations with a protective barrier that can reduce the potential of interaction when the formulations are combined in a single unit dose. Because our capsule filling technology platform shortcuts the need to blend the formulations together prior to filling, we can quickly and successfully develop FDC products. Benefits: Frontida s AdaptDose technology serves as a platform to bring Fixed Dose Combinations to clinical studies and the market. The platform is so flexible that both small, clinical trial material batches and large commercial-scale production can be produced in the same equipment, reducing the amount of manufacturing studies and process validation efforts required. Once the clinical trials prove the combination to be effective, our clients can quickly launch the FDC product upon FDA approval, saving months, if not years, of process development and stability study efforts.

7 Problem #3 You want to combine different release mechanisms into one dosage unit in order to provide the benefits of a dual release system with the simplicity of one dosage unit. Do you resort to bi-layered tablets which eliminate the advantages of a multi-particulate capsule system while presenting manufacturing challenges characteristic of the bi-layer compression process? Do you resort to administering two capsules, each separately filled with different beads, which may result in decreasing patient compliance? Answer: Using AdaptDose we can design a combination of minitablets, beads, granules, or liquid with different release mechanisms, such as immediate-release, extended-release, or delayed-release into one dosage unit. The technology allows us to quickly create a combination of quick onset of action and/or extended or delayed therapeutic effect. The combination can be in any ratio to achieve the desired release profile with our uniquely engineered capsule filling equipment and processing technology. Furthermore, certain types of matrix that we can employ in this system can provide both immediate and delayed action, resulting in operational efficiencies and reduced costs. Benefits: Frontida s AdaptDose technology enables us to quickly deliver customized release profiles which can be used in clinical studies to validate delivery systems that can provide therapeutic doses over 24 hours and improve patient compliance. The release profiles can be easily modified based on the outcomes of the pharmacokinetic and therapeutic effects observed in the trial.

8 Conclusion: As demonstrated by these three scenarios, AdaptDose can serve as a unique, commercial ready technology that allows our clients to quickly create custom oral delivery systems, thereby reducing the time to market, improving the flexibility of system modifications during clinical studies, and decreasing the potential to reformulate the product. It is a platform that can also help companies to bring new Fixed Dose Combinations to clinical research and commercial quickly. If you wish to speak further about your specific application, our team would be happy to arrange a free consultation to determine if your product concept fits the AdaptDose platform. Contact us at the numbers listed below, or use our online form to arrange a consultation.

9 THANK YOU. FOR MORE INFORMATION CONTACT: RON CONNOLLY