By: Richard Kwasny, Ph.D., Senior Consulting Engineer, Fauske & Associates, LLC (FAI)
We will be publishing four articles on the topic of safer scale-up for batch and semi-batch reactions. This initial article is on desktop reviews and preliminary hazard analysis.
Thermal runaway incidents continue to occur in batch production facilities in the chemical and pharmaceutical industries. Serious incidents can result in death, injury, capital loss, and business interruptions. Despite the best efforts of the chemical/pharmaceutical industries to be responsible, major incidents cast a negative light on this industry as a whole. In order to prevent incidents from occurring there is a need for all R&D, process development, and batch production facilities to have an effective process safety strategy in place including sound safety-management systems. Prior to scale-up, it is critical to have a clear understanding of the reactivity of all process chemicals as well as the energetics of both desired reaction(s) and undesired reactions, defining worst-case scenarios, characterizing the resulting adverse reaction, and understanding how to mitigate the process safety impact. A partial flowchart detailing these steps is shown in Figure 1. Processes that cannot be adequately controlled must be redesigned if possible or utilize less hazardous material.
Figure 1 Flowchart of a Preliminary Hazard Assessment
This article attempts to provide guidelines that can be used as a basis for developing and designing safer new processes. It can also be used to identify process safety information gaps when existing processes undergo periodic reviews, as required in part by OSHA Process Safety Management 1910.119, Hazard Communication 1910.1200, and the General Duty Clause.
Causes of Thermal Runaway Reactions
Studies have determined that thermal runaway reactions occur due to the following four reasons:
1. Insufficient understanding of the process chemistry and the energy/kinetics for the desired reactions
2. Improper design of the heat transfer capacity required at the plant level
3. Insufficient understanding of the adverse reaction and controls including plant-safety back-up systems, as well as adequate emergency venting
4. Inadequate written batch procedures and poor operator training.Never assume a chemical is not hazardous because of a low-hazard rating. Many incidents involve materials that have NFPA hazard ratings of 0 and 1. It is best to develop a proper testing program to identify and characterize all reactive materials and reaction mixtures under a variety of process conditions. If your company does not have a testing facility, FAI will be pleased to work with you to identify and conduct appropriate tests. Subsequently, a process hazard analysis can then be used to assign appropriate controls and safeguards to reduce risk of an adverse event. It is important to remember to update the process safety information, as a process undergoes changes during its lifecycle. The interim process-safety information reports can then serve as a reference for technology-transfer purposes as the process scales from R&D, kilolab, pilot plant to commercial-production stage. Once the process has been set, the final process safety report can then be used by a variety of end users either in-house or by outsource facilities. When developing safety documentation, it is important to keep in mind that it must comply with company policies and procedures as well as country and local regulations.
Desktop Reviews and Screening Tests
The following items should be considered in relation to a process safety hazard evaluation.
- Decision to Scale-Up
When management wants to scale-up a chemical reaction in an existing facility, the amount of information available can vary significantly. Therefore, it is essential to review the desired process and inform the organization if there are any issues that need to be addressed. Therefore, there is a need for a preliminary hazard assessment based on a balanced equation of the desired chemistry.
Preliminary Hazard Assessment:
• Develop an inventory of all process materials including but not limited to:
o Starting and product substrates
• Identification of material properties, hazards, and other potential problematic issues:
o Physical properties
o Health hazards
o Flammability and static properties
o Thermal stability of materials including the potential for shock sensitivity and explosion propagation
o Review the molecular structure of the reaction materials for highly reactive functional groups
o Conduct preliminary screening testing using differential scanning calorimetry (DSC) to identify thermal instability in the starting and final substrates
o Vapor phase reactivity
o Material of construction issues (catalytic, corrosion, compatibility, and so forth)
o Special hazards (oxidizers, pyrophoric, water-reactive, and so forth)
o Conduct a literature search for the above mentioned information and work with production/ process engineers to better
understand process limitations
o Estimate the heat of reaction using estimation techniques
o Quantitate the non-condensable off-gases to estimate volume and rate
o Interpret the potential hazards with respect to the process temperature and pressure including other critical issues
Initial Evaluation of the Reaction
Once we have all of the above mentioned information, we are in a better position to determine if there are any potential issues that would prevent scale-up.
For example, if the reaction involved a simple crystallization for the formation of a substrate salt with no off-gassing and a calculated adiabatic temperature rise that could be easily controlled through available agitation/heating/cooling of the reaction mass, then probably no additional testing is needed. However, for quality purposes we may need a more quantitative heat balance if there is crash crystallization. Then we could perform reaction calorimetry for this purpose.
There are times when the desired and quench reactions involve reactive functional groups that may become unstable. Therefore, the use of a preliminary hazard analysis will facilitate identification of problematic reactions that under
certain circumstances can be a potential hazard or become one if we lose control of the reaction. There are several ways in which this can occur; one is through a thermal runaway reaction, a fire, or process deviations due to misoperations such as mischarging, and so forth.
Quantification of the Desired Reaction
If we have a potentially problematic reaction then, the next step is to quantify the amount and rate at which heat is generated. Similarly, if there is off-gassing, we would require quantification of the evolved gas rate to ensure the process vent
capacity is adequate.
Therefore, the second article in this series will deal with how to characterize the desired reaction, as needed, based on issues encountered in the preliminary hazard assessment. Subsequent articles will include quantification of the adverse
reaction and case studies.
In the meantime, consider signing up for FAI University's Relief System Design Course. Unlike other emergency vent sizing courses, this curriculum highlights simplifed calculation methods capable of giving safe - but not overly conservative - relief system designs, with an emphasis on reactive chemistries and the role of two-phase flow. Attendees will participate in group workshops and complete an independent quiz at the end of the course in order to ensure comprehension of the material.
1. Hendershot, D. C., “A Checkl ist for Inherently Safer Chemical Reaction
Process Design and Operation,” Center for Chemical Process Safety
International Conference and Workshop on Risk and Reliability, 2002.
2. Kwasny, R. S., “Hazard Assessment Strategies for Reduction Reactions,”
London Southbank University, UK, 1999.
3. Barton, J. and Rogers, R., “Chemical Reaction Hazards,” Second edition,
Gulf Publ ishing, 1997.
4. Bretherick, L., “Bretherick’s Handbook of Reactive Chemical Hazards,”
Seventh edition, Butterworth Heinemann, 2008.
5. Stoessel, F., “ Thermal Safety of Chemical Processes: Risk Assessment and
Process Design,” Wiley-VCH , 2008.
6. Merritt, C. W., 2004. “Chemical Process Safety at a Crossroads,”
Environmental Health Perspectives, 112:a332-a333. doi:10.
1289/ ehp.112-a332, 2004.