Process Mass Intensity

The Green Chemistry Institute (GCl) Pharmaceutical Roundtable has used the Process Mass Intensity (PMl) [12], defined as the total mass used in a process divided by the mass of product (i.e. PMl = E factor -i- 1) to benchmark the environmental acceptability of processes used by its members (see the GCl website). The latter include several leading pharmaceutical companies (Eh Lilly, GlaxoSmithKline, Pfizer, Merck, AstraZeneca, Schering-Plow, and Johnson Johnson). The aim was to use this data to drive the greening of the pharmaceutical industry. We believe, however, that the E factor is to be preferred over the PMl since the ideal E factor of 0 is a better reflection of the goal of zero waste. 

Different variahons on E factor have been proposed and used in the pharma-ceuhcals industry (for example, mass intensity, mass productivity [6], and process mass intensity [21]). Each of these has the aim of greening pharmaceutical processes by highlighting the amount of material used in a process, either when... 

At the end of the day, however, these metrics are essentially similar, and their beauty is their simplicity in concept, practical use, and understandability by different audiences whether they are academics or industrial scientists, laboratory or development scientists, or senior management in global corporations. If you reduce your mass intensity (or process mass intensity or E factor) there is a very high probability that your process will be greener. 

With new technical processes, the determination of the process mass intensity (PMl = total mass in a process (kg)/mass of product (kg)) and considerations of possible adverse effects on the environment usually form part of the process evaluation (Green Chemistry). On grounds of modem environmental protection legislation, in many cases environmentally friendly procedures are reckoned better than older processes, which have a greater polluting effect on the environment (Fig. 1.8). [16,17]... 

Figure 15.6 Example output of the process mass intensity and life cycle assessment tool developed by the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable. The data presented in the columns provide the metrics for steps 1,2, 3, and the total of the synthesis. Some of the instructions in the tool are included as an illustration.

Mass intensity takes into account the aeld, reaction stoichiometry, solvents, and reagents in a reaction mixture as well as in the reaction workup and purification steps. It does not include any process water used. For a multiple step process, process mass intensity is used instead where the mass inputs include everything from step one to the last step. The ideal PMI is 1 when no waste is produced and all materials are integrated into the product. 

W. Cue Berkeley used this and similar data for the calculation of MI (or PMI, process mass intensity) and waste produced during the different phases of drug diseovery and came to the conclusion that overall early research (200-2000 t) and preclinical (150-1500 t) investigation produce more waste than in e.g. clinieal phase 1 (40-400 t) development. 

---