Fast to IND (INDiGO)

SSCI, Inc., an Aptuit Company along with Aptuit sites at Riccaron Scotland and Kansas City, Missouri is once again taking a bold, new step to engineer a better drug development process. Our Fast-to-IND service will substantially reduce time to first-in-man clinical trials while improving consistency of results and product knowledge, the two backbones of quality.

Fast-to-IND reduces time from API to IND submission to 25 weeks or less for appropriate compounds. These reductions are achieved by merging traditional preformulation, drug substance, drug product, clinical supplies and analytical method development silos into a single unit managed by a veteran, dedicated project manager and staffed by professionals with experience spanning the development process.

The Fast-to-IND approach is based on a novel discipline we call development science, and centers on four primary elements: Eliminating artificial barriers between drug substance (API) and drug product development, merging these into a single track, called clinical supplies. This approach streamlines the pre-IND process down to only three development tracks: (a) Preclinical toxicology; (b) Clinical supplies; and (c) IND preparation. These tracks operate in parallel to reduce time to clinical trials. Modern approaches such as amorphous dispersions to increase the solubility and bioavailability of the test compound. (3) Utilizing quality-by-design strategies in the earliest stages and throughout the development cycle. This will enable the facile implementation of such strategies for successful drug candidates at each stage. (4) Establishing information for patent filings even during this early timeframe and maintaining the seamlessness and integrity of data throughout.

General Plan

The diagram below outlines how the Fast-to-IND process works and approximate time frames for various parallel development tracks.

The chart is divided into three tracks: Preclinical, Clinical supplies, and IND preparation. The preclinical program includes a rigorous preclinical study involving 28 day tox studies as well as a complete battery of additional tests, designed and implemented with an eye toward the requirements for successful IND submission – with non GMP material timelines can be further reduced. The clinical supplies module includes a significant planning component where the type of dosage form for clinical supplies is determined based on the solubility of the API, as well as methods development. Finally, there is an IND preparation segment during which the IND will be prepared. All of this is intended to be accomplished in 25 weeks. This plan is based on the assumption that the client is able to provide us with 1 kg of GMP drug substance on day one – a capability we are also able to resource.

Formulation Approaches

The first approach involves amorphous dispersion in capsules. This approach will increase exposure for the estimated 80% of NCEs with solubility problems. A typical amorphous formulation will be a dispersion of the drug in a polymer. The second approach involves filling a capsule with crystals of the drug. Such a product is the simplest formulation and greatly reduces development time. An automated powder filling device will be used to prepare both of these drug products. The third formulation is a powder in a bottle formulation that is intended to be dissolved just prior to administration. If needed, we will help develop the vehicle for dissolution or use the client’s preferred solvent.

Quality Overall Summary

Our approach was developed based on the latest FDA standards for quality. These concepts are briefly summarized in the wheel below. In INDiGO our work on our clients’ behalf focuses on the inner part of the wheel. As shown on the wheel, step 1 is product design as described in the formulation approaches section. A process is then designed to produce the product. Quality by design elements are at the heart of the process design, and extensive measures are taken to ensure stability, for example. The process is monitored using sophisticated analytical equipment including in-line Raman probes. This information will be provided in a report suitable for submission to the FDA.

Intellectual Property

Information needed for patent filings is also provided as a standard part of the Fast-to-IND offering.

Unique Aspects of Our Fast-to-IND Service

• Integrated preclinical toxicology, clinical supplies and regulatory documentation and IND preparation support services.
• Fast turnaround times, reducing time to submission.
• Quality by design approach.
• Best possible approaches for poorly soluble drugs including amorphous dispersion in capsule.
• Intellectual property support elements.