Safety matrix process review

In 2002 FDA and Fiealth Canada asked the Institute of Medicine s Food and Nutrition Board (FNB) to formulate an expert committee to review and identify gaps in methods currently used to assess the safety of ingredients new to infant formulas. The committee was asked to identify tools to evaluate the safety of these ingredients under intended conditions of use in term infants. This charge included determining the data needed to demonstrate the safety of a component already present in human milk, that is, the effect of the matrix, and the utilization of preclinical and clinical studies and postmarket monitoring in the safety assessment process. FDA also asked the committee to apply its recommendations to the recent addition of LC-PUFAs as new ingredients in infant formulas, and others as appropriate. 

Experience has shown that reactive chemistry hazards are sometimes undetected during bench scale and pilot plant development of new products and processes. Reactive chemistry hazards must be identified so they can be addressed in the inherent safety review process. Chemists should be encouraged and trained to explore reactive chemistry of "off-normal operations. Simple reactive chemicals screening tools, such as the interactions matrix described in Section 4.2, can be used by R D chemists. 

Additionally process safety requires teams. Teams are often brought together to perform PHAs or hazard identifications, PSSRs, or to review MOC plans. Teams are sometimes used to write and/or review operating procedures. Teams facilitate bringing together the SMEs assigned to a task. Here SMEs can interact to be sure all aspects of the task are addressed. Further peer review teams may be used to ensure that nothing important is overlooked, misinterpreted, or miscalculated. These team activities are consistent with a matrix structure. 

First, the importance of learning lessons from past process safety incidents is highlighted in Section 3.2. The subsequent section presents preliminary hazard review procedure, risk matrix, what-if method, plot plan and layout review, pressure relief system review and fire safety design aspects. Section 3.4 presents PHA techniques and procedures hazards and operability analysis (HAZOP), failure modes and effects analysis (FMEA), instrumented protective system (IPS) design, fault trees, event trees, layer of protection analysis (LOPA) and finally SIS life eyele. The importanee of revision of PSI is highlighted in Seetion 3.5. 

Alternatively, coacervation or solvent extraction is often used to produce microspheres (Fig. 3). The protein and polymer emulsion is stirred with a nonsolvent for the polymer such as silicone oil, resulting in the formation of embryonic microspheres (for a review, see Lewis, 1990). The nonsolvent extracts the methylene chloride or ethyl acetate firom the polymer phase, causing precipitation of the polymer and entrapment of the protein in the polymer matrix. To remove the nonsolvent, a volatile second nonsolvent (e.g., heptane) is added, and the microspheres are allowed to harden in the nonsolvent. After repeated extraction with the volatile nonsolvent, the final microspheres are then dried. While this method offers the advantage of avoiding contact between the protein phase and an aqueous phase as in the solvent evaporation method, the additional solvents utilized in this process are often difBcult to completely remove and are a safety and toxicity concern. 

A safety design review process will not be effective until the participants in the review team have acquired knowledge of hazards and risks and agreed on the risk assessment methods and risk assessment matrix to be used. Chapter 7, A Primer on Hazard Analysis and Risk Assessment, serves as a basis for the education of team members. Also, a safety design review process can be successfiilly applied only if senior management has been convinced of its value. 

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