September 3, 2024 2:00 - 5:00

This hands on decision-making exercise will permit you and your fellow sourcing managers to work through a realistic sourcing scenario in small groups of 6-8 persons led by a facilitator. Timelines, budget, chemistry, interpersonal relationships within and outside your pharmaceutical company will all be explored. At the end each group will present its decisions to the whole workshop group for comment and comparison.

There has never been an opportunity for CMC management to work through an extensive exercise like this – this will be a real learning experience!

A biotech company has recently identified an early development candidate and subsequently secured 4.5 million funding to file an Investigational New Drug (IND) application with the FDA and to initiate a Phase 1 clinical trial study. The focus of this workshop will be to study how to develop a successful overall development plan for production of sufficient formulated active pharmaceutical ingredient (API) to supply all the IND enabling studies as well as the Phase I clinical trial.

The nominated developmental candidate has shown excellent in vivo pharmacology, an excellent safety margin and all PKDM parameters within accepted standards. Your chemistry group has only standard bench hoods and their largest reaction flask is five liters; they have reached their maximum capacity in preparing a few 100g batches to compile the developmental data package. This new chemical entity (NCE) has an eight step synthesis from commercially available starting materials that introduces an asymmetric carbon center in step 3. The S(-) enantiomer is about three orders of magnitude more active than the R(+) and the racemic mixture is shipped to a CRO at step 4 for preparative supercritical fluid chromatography using a chiral stationary phase. The desired S(-) enantiomer is returned with >98% enantiomeric excess in 42% yield. The final API contains a basic nitrogen that gives the compound good aqueous solubility below pH 6.8 and based on this information an ideal formulation will need to be developed for both the IND enabling studies and Phase 1 clinical trial. Also, the clinical trial will be conducted in Europe and it will be important to ensure that the final drug product will be either formulated in the EU or if conducted in the US to develop a plan to have the product shipped to the EU for the clinical trial.

You need to provide an overall development plan for production of sufficient active pharmaceutical ingredient (API) to supply all the IND enabling studies as well as the Phase I clinical trials. Your plan will include the design the IND studies as well as the compilation all the information for the preparation of the CMC and the IND filing.

Activities:

• Break out into small group
• Designate a spokesperson (who will later present your plan to the entire group)
• Identify your strategic plan
• Develop the necessary elements of the plan
• At the conclusion of the discussion, the spokesperson will offer a description of your plan. Please include your approach to the problem, your rationale, and a description of the elements of risk and your choices to minimize the risks.
• Discussion Leaders will be available for consultation, and will help to provide input during the breakout session and at the conclusion of the workshop provide their proposed strategies for a successful development program too.

Workshop Leaders:

Deb Minor
President
Drug Discovery Alliances

Sean Bradley
Vice President of Business Development
GL Chemtec International

James Kanter
Principal
K2 CMC

Michael Humora
Director
Apex Scientific Inc