Solvent Selection and Substitution
As pharmaceutical manufacturers have known for some time, the easy solvent choices of the past (benzene, methylene chloride) may no longer be viable from either a safety or an environmental perspective. The normal solvent substitutions (mixed xylenes, ethyl acetate, etc.) all bring about their own sets of problems and are not at all without some of their own challenges from the perspective of employee exposure, flammability, or toxicity.
We at PROCESS are experienced with solution thermodynamics and vapor-liquid equilibria of various solvent combinations, and we can assist you in making more benign solvent choices for your active pharmaceutical ingredient (API) synthesis. Our extensive thermodynamic knowledge base can also be useful for multiple phase solvent extractions and final washes and workups.
Process Hazard Analyses
Experience is critical in achieving optimal results within a Process Safety Management (PSM) and Risk Management Program (RMP). Even if your facility may not be mandated to implement such programs, many of the key elements and the rigorous analysis of your process from a safety standpoint can benefit your bottom line in other ways.
Our engineers have performed over 200 PHAs on nearly 300 different processes for over 50 different companies throughout the U.S., Canada, and Puerto Rico. We have also performed over 20 compliance audits thus far. We have performed process safety work in Refining, Petrochemicals, Chemicals, Pulp & Paper, and the Nuclear industry.
PROCESS has a wide range of experience using many of the commercially available software packages for documenting Process Hazard Analyses (PHAs). We also have experience using in-house database programs developed by our customers at the plant or corporate level. This experience means we can quickly and easily apply our knowledge regardless of the software your facility uses.
Our extensive experience in designing processes for safely handling hazardous reagents or products can assist you in developing and operating a safe manufacturing process. We have experience with gaseous hydrogen, Grignard reagents, methylating agents (dimethyl sulfide, methyl iodide), Raney nickel catalysts, hydrazine, diazomethane, strong acids, oxidizing agents, etc.
FDA 483 Resolutions
Have you had recent FDA audits where you are left with puzzling or problematic 483 issues or concerns? PROCESS may be able to help, especially with those issues related to systematic process deficiencies. As an example, the FDA frequently finds deficiencies in areas such as your United States Pharmacopeia (USP) water supply—frequently caused by weak initial design or installation. PROCESS can help by performing hydraulic analyses of the Clean Steam and Purified Water systems to support your process.
Inventory Management and Control
The efficient FDA-compliant warehouse is a result of careful attention to process design and operation. We can model and simulate flows of incoming quarantined materials awaiting acceptance testing, manufactured intermediates in various stages of completion, and Active Pharmaceutical Ingredients (APIs) awaiting final analysis and release.