Short Courses


 






Short courses are designed for chemists and engineers who want insights into generating rugged, practical, cost-effective processes for the preparation of active ingredients and intermediates. Approaches are drawn from instructor’s experience, recent examples from industry, and literature data.  Problem-solving sessions using real-life examples reinforce course principles.  The course provides a jump-start for those beginning industrial process R & D, and gives updates and new ideas for experienced researchers.

Example: Thursday, May 22, 2014 in Boston An interactive dinner course on “Refining API Process Development for Efficiency” to provide chemists – both new to the field and experienced – with tactical approaches for better control of scale-up. This was scheduled as part of the Cambridge Healthtech meeting Efficient Process Chemistry.  Contents:

1. Safety Considerations to Enable Process Development
Reactions that are highly exothermic or generate gases can be difficult to scale up safely, but these considerations and others can be applied for successful scale-up. Successful scale-ups, including cryogenic alkylations, Curtius rearrangements and some continuous operations, will be discussed.

2. Tips to Anticipate and Avoid Scale-Up Problems
The laboratory is the first place to avoid difficulties that could arise from future scale-up, such as the generation of impurities from extended processing or the presence of isomeric in purchased chemicals. We will discuss some “war stories” from scale-ups.

3. Approaches for Controlling Mutagenic Impurities (Genotoxins) in APIs:
Functional groups can flag a compound as a potential mutagenic impurity. A stepwise approach can be used to set limits on such impurities, but knowing the toxicity of a compound is the most powerful approach. The ACE approach (Avoid, Control, Eliminate) can be used to minimize the impact of impurities, including mutagenic impurities.

 

 Example: Two-day short course.  The two-day short course Practical Process Research & Scale-Up focuses on research and development of chemical processes for the pharmaceutical and fine chemicals industries.  Participants learn tips and approaches for rapid, reliable scale-up to the kilo lab, pilot plant, and beyond.

Presenting the short course in-house allows researchers to identify and focus on skills and challenges unique to your company.  In-house courses provide a considerable savings in both registration and time away from the work site.

Topics in the Two-Day short course (September 2013)

Day 1

Introduction.  The whys and hows of process R&D.   Driving forces for developing processes.   Heat and mass transfer on scale extend operations in batch processing.  Liability of unsafe operations increases on scale: design safety into processes early in development.  Batch, continuous, and semi-continuous operations as used in industry. Guidelines for making tox batches. Key attitudes: exploit observations, green chemistry, teamwork, fit-for-purpose.

Route selection. Greenest route / shortest route / best route: depends on timelines.  Where and when to concentrate efforts to optimize process development.  Factors affecting cost of goods (COG) estimates.

Reagent selection. Reactivity, toxicity, selectivity, ease of workup.  Selected examples of oxidation, reduction, C-C bond & peptide bond formation.  PTC reactions & guidelines for process development.

Solvent selection. Solvents used and avoided on scale. Polarity and azeotropes. Best solvents accelerate reactions and simplify workups. Solvent impurities, e.g., peroxides.  Reactions of CH2Cl2, 1,2-dichloroethane, acetonitrile, and others.  “Green” solvents.  Water as solvent.

Running the reaction. Applying guidelines for pilot plant introduction for successful process development in the lab.  Benefits of homogeneous & heterogeneous reactions, and scale-up considerations; mixing problems. Inverse & extended additions.  “Snapshots” to identify details critical for scale-up.  Determining when continuous processing is necessary for scale-up.

Water as a process consideration. Avoid surprises: water may be necessary or harmful.

Problem sets

Case studies: aztreonam, sitagliptin

Day 2

In-process controls. In-process data are crucial for developing good processes.  Designing practical IPCs for each stage of operations.  Sampling & external analyses or on-line (PAT).

Optimizing reaction conditions. Minimizing impurities.  Beneficial & harmful impurities in catalytic reactions.  Importance of controlling pH.  How much data is needed for scale-up.

Work-up. Safety considerations.  When to use inverse quenches.  Solubility considerations for work-up.  Streamlining workups.  The benefits of direct isolation.  Removing metal ions, e.g., Pd & Ru.

Crystallization and final product considerations. Five modes of crystallization. CIAT & CIDR processes.  Some considerations to control particle size.  Guidelines for developing a good crystallization in the lab.

Final form. Salt selection & polymorphs. Controlling API impurities, e.g., solvents.  Genotoxins.

Scale-up concerns and process implementation. Tips for kilo lab scale-up. Implementing the scale-up run and trouble-shooting.  Working long-distance through CROs.  Continuous processing to make more material in select cases.

Problem sets

Case studies: aprepitant, eniluracil

Cost: $1100 for two-day course (lodging not included)

Course notebook: Each participant receives a bound copy of the slides, detailed and thoroughly referenced.

Site: Princeton, New Jersey USA


To register, click on button below:

Public courses can be customized for in-house presentation.  Participants invariably bring different backgrounds to the course, and find the resulting discussions extremely valuable.  The in-house course also allows researchers to identify and focus on skills and challenges unique to your company.  Contact me for a detailed quotation.

If you wish further information please fill out the contact fields below. If you do not wish to register through PayPal please pre-register here. Instructions for class fees and final registration will be mailed to you. Thank You!

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