Accelerating Proof of Concept involves combining an accelerated CMC development program with a well planned clinical trial. In many cases, the solid form chosen for the IND is simply scaled-up to prepare supplies for phase II. In some cases the IND clinical supplies will be sufficient for phase II and different doses must be prepared. In other cases a new formulation is prepared for phase II. The clinical trials are planned by Improved Pharma's consultants and fully integrated with the accelerated CMC program.
Poorly soluble compounds
Improved Pharma has extensive experience with poorly soluble materials. Improved Pharma will usually use amorphous dispersions, cocrystals, or salts to improve solubility.
Stability
During the solid form screening, extensive stability studies under accelerated and forced degradation studies are performed. These studies focus on both chemical and physical stability of the solid form. Improved Pharma has a strategy using a minimum of experiments to obtain information on the stability of clinical supplies. These stability studies are used to select the form for manufacture into clinical supplies.
API Synthesis
Improved Pharma's external partners/subcontractors have outstanding experience and capability in synthesizing APIs. Typically, these collaborators synthesize enough API during the exploratory phase to allow form screening and selection of the best form for IND and POC clinical supplies.
Solid State Chemistry & Formulation
Improved Pharma provides an expert assessment of the API and drug product and determines the risk for solid state conversions. Improved Pharma uses its superior expertise in solid state chemistry to design a solid form screening and selection process based on the structure and known properties of the starting drug. This process is carried out during the scale up of the synthesis. Then, the selected form is manufactured. This form is fully characterized and used to formulate the material for both the preclinical studies and the clinical supplies in Phase I and II.
IND
The IND is prepared during the 12 month development process. The software program FPOC is used to "fill out" templates. Amendments for Phase II are also prepared using this strategy.
Proof of Concept
The proof of concept clinical trials are designed by Improved Pharma's network of external experts. The clinical trial design will depend on the disease indication and the mechanism of action of the drug. Improved Pharma will work closely with the client or its external experts to design the proper trial and provide clinical supplies.
Clinical Supplies Manufacture
Clinical supplies are manufactured by filling the selected form into a capsule or bottle. For Phase II, simplified formulations are designed if needed. Improved Pharma's extensive experience with stability allows an optimum formulation to be discovered rapidly.
COA from US Firm
Improved Pharma has the capability of carrying out the synthesis of the API at foreign firms. However, our current plan is to manufacture drug product in the US and issue a Certificate of Analysis from that firm.
Molecular Basis of Manufacture
Manufacturing clinical supplies by filling a known solid form into capsules or a bottle is the ultimate in the molecular basis of manufacturing. The structure of the form is known and well characterized. In this case the molecular structure of the solid is used to control he release rate.
Preclinical Studies
Preclinical studies are performed at one of Improved Pharma's third party providers. Because of their importance, only the best providers are included in Improved Pharma's network. The preclinical studies are carried out on the most soluble, stable solid form to insure maximum exposure of the animals.
FPOC
FPOC is a template-based software tool that provides instantaneous feedback on the progress of a project. This allows fast, informed decision making. FPOC also contains a stability prediction module that facilitates decision making in cases where development is difficult due to stability problems. FPOC is currently under development.
