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.
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 expenses for both registration and travel and for time away from the work site.
Topics in the two-day short course (presented in-house twice in 2018)
- Speeding process development Increased heat transfer burden as vessel size increases leads to extended operations using external cooling. Batch, semi-batch, and continuous processes. Discussion of over 20 processing operations, comparing those that are commonly used or easy to implement in the laboratory to those used on scale. Key attitude: the process scientist does what needs to be done in order to meet the timeline.
- Safety Anticipate safety concerns: controlling the generation of heat and gases, and health and environmental issues. Functional groups, oxygen balance, and elements of control. Scale-up should occur after suitable safety testing. Using safety evaluations to facilitate operations. (This section does not discuss the details of hazard evaluations.)
- Route selection Time-efficient vs. cost-effective routes, discovery vs. manufacturing routes. The clear advantages of convergent routes and locating a resolution early in a route. Greatest impact on cost of goods is to minimize number of steps. Brief discussion on cost of goods calculations.
4-5. Reagent selection & solvent selection Characteristics of the ideal reagent. The importance of balancing the equation in developing processes. Discussion of selected oxidants, reductants, biocatalysis, and PTC. Considerations for choosing solvents: heterogeneous vs. homogeneous reaction conditions, solvents rarely used on scale, ICH limits, azeotroping. The often unappreciated reactivity of dichloromethane. Impurities in common solvents and denaturants in EtOH.
- Practical considerations for scale-up Safe operating conditions are mandatory. Reaction concentrations, additions on scale, micromixing and mesomixing. Some guidelines for designing processes for pilot plants and manufacturing sites. How full to fill your reactors, and charging reactors. Scale-up rule of thumb: double processing time for every 10 × scale-up (and run extended use-tests in the lab before scaling up).
- Water Influence of water as a solvent, cosolvent, and impurity.
- In-process controls and reaction duration IPCs ensure reliable yield and quality for good financial return, and ensure compliance with processing filed with regulatory bodies. Over 20 techniques that can be used for IPC, including PAT.
- Process optimization by minimizing impurities Goals of process optimization change as a candidate is developed. Monitoring pH and agitation. Harmful and beneficial impurities. Decomposition of catalysts. The “snapshot” as diagnostic tool. Discussion of selecting factors for DoE studies.
- Work-up conditions Streamlining work-ups. Inverse quenching. Safety considerations of work-up. Techniques to remove metal catalysts, e.g., Pd and Ru.
- Purification, crystallization and isolation Characteristics of reliable crystallizations and crystallization tips. Developing processes through CIDR and CIAT. Presence and detection of polymorphs and pseudopolymorphs. Details of finding the second polymorph in ritonavir.
- Final product form and impurities ICH guidelines. Nelfinavir mesylate as example. How to control GTIs in the API.
- Continuous operations Benefits of continuous operations for scaling up some fast reactions, and examples of photochemistry, static mixers, and others. Continuous operations provide many options for scale-up. The primary drivers for developing continuous operations are safety, quality, economics, and throughput. Continuous operations are feasible for reactors, separators, and crystallizers. Continuous operations may dramatically increase the efficiency of extraction and decrease the amount of solvent needed. Pharma is rediscovering what Chem Es knew decades ago. Many opportunities here.
- Scale-up, process implementation, & troubleshooting The importance of purity assessment, mass balances and simple operations to guide scale-up optimization. Process validation begins before process implementation.Trouble-shooting: is the problem due to operations, equipment used on scale, or some other factor? Trouble-shoot in layers, from the end.
Problem sets Working through real-life problems. With each session.
Cost: $1100 for public two-day course (lodging not included)
Course notebook: Each participant receives a bound copy of the slides, detailed and thoroughly referenced.
No public presentation planned for 2019.
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!
