ERI Home IRR Home Last updated 8/11/04
[Note: Two asterisks indicate a provisional conclusion that will be expanded into more detailed narrative. Three asterisks indicate an additional topic area, not yet boiled down to a conclusion, that is being prepared for incorporation into the document.]
The products of the pharmaceutical industry must be extremely well characterized and highly refined. Its production processes must therefore be tightly controlled. Much of the environmental impact from the sector's processes relates back to this premium on control.
[batch production; "campaign" structure; multitude of different processes]
[large volumes of processing aids]
Environmental impacts and risks
Effects of existing and future regulations on impacts
The pharmaceutical sector is assigned the four digit NAICS category 3254. At the six digit level. four subcategories are recognized. There are also four SIC codes assigned to the sector, but the split is slightly different. The breakdown is outlined in the table below. More exact definitions can be deduced from the U.S. Census Bureau web page covering these codes.
| NAICS | SIC | ||
| 325411 | Medicinal and Botanical Manufacturing | 2833 | Medicinal Chemicals and Botanical Products |
| 325412 | Pharmaceutical Preparation Manufacturing | 2834 | Pharmaceutical Preparations |
| 2835 | In-Vitro and In-Vivo Diagnostic Substances (except in-vitro diagnostic) | ||
| 325413 | In-Vitro Diagnostic Substance Manufacturing | 2835 | In-Vitro and In-Vivo Diagnostic Substances (in-vitro diagnostic substances) |
| 325414 | Biological Product (except Diagnostic) Manufacturing | 2836 | Biological Products, Except Diagnostic Substance |
Basically, the split means the following:
The numbers of establishments involved primarily in each of the four SIC categories is given in the 1997 Economic Census as follows:
| NAICS | Description | No. of Estab. |
| 325411 | Medicinal and Botanical Manufacturing | 338 |
| 325412 | Pharmaceutical Preparation Manufacturing | 838 |
| 325413 | In-Vitro Diagnostic Substance Manufacturing | 227 |
| 325414 | Biological Product (except Diagnostic) Manufacturing | 364 |
Not surprisingly, most of the environmental impacts from the sector comes from manufacturers in the first two categories, who are more apt to carry out large-scale processes. But even within a given category, a facility that specializes in purifying vitamins from natural sources might look very different from another facility that carries out chemical syntheses, or from one that relies on cultures of microorganisms. An understanding of the specific impacts associated with a particular facility is probably best approached by a consideration of the specific types of processes carried out in the facility.
A useful breakdown of the process types used in the pharmaceutical sector is provided in the EPA's The Technical Development Document for the Effluent Guidelines for the pharmaceutical sector. (Note: the description below uses the basic framework provided in the reference, but takes a somewhat different view of how the processes interrelate. Some very useful details provided in the reference have not been included below. The reader should consult the original source to round out the picture.) Four process types are identified:
The difference between fermentation and extraction may become less clear cut with continuing advances in genetic engineering and tissue culture. The point of view reflected in the EPA source document emphasizes the difficulties involved in extraction, such as the need to process large quantities of material to extract small quantities of the desired product, and the need to separate the desired isomers from chemically similar, but pharmacologically different substances. The process engineer undoubtedly considers the growth of microorganisms in a tank to be a much more controllable situation than the harvesting of plant or animal tissue grown "in the wild", so that point of view makes perfect sense in terms of twentieth century technology. In the future, however, one might envision cultures of higher animal or plant tissue, disconnected from its parent organism, producing materials for extraction in a process that will seem more closely related to a fermentation tank. Or the organism itself can become the tank -- production of pharmaceuticals in genetically engineered cows and goats, and recovery of the product from the milk, is already at an advanced stage of development.
Environmental concerns do not appear to be exactly prominent on the sector's radar screens. A 115 page document, Pharmaceutical Industry Profile, 2002 from PhRMA, the leading trade organization for the sector, contains detailed discussions of a wide range of public policy matters, strongly oriented toward health issues, of course, but touching also on intellectual property, innovation incentives, and extensive industry data. The word "environment" appears once in the publication, in reference to "the regulatory environment" for drugs. The sector is unquestionably well-tuned into many aspects of corporate responsibility, but environmental impact does not seem to have captured a great deal of its attention.
** The major environmental impacts from processes carried out by the pharmaceutical industry stem from the use of solvents as reaction media and as aids for separation and purification processes. The solvents may be emitted directly into the atmosphere as VOCs (often as HAPs), or may appear in wastewater. Sources of the latter include solvent residues from separative operations involving both a water and a solvent phase, as well as solvents captured in wet scrubbers.
** A secondary impact from pharmaceutical operations is dusts generated by grinding and polishing operations.
Air emissions data for certain key criteria pollutants (ozone precursors) are available from the National Emission Trends (NET) database (1999), and hazardous air pollutant emissions data are available from the National Toxics Inventory (NTI) database (1996 is the most recent year for which final data are available). For the pharmaceutical sector's SIC codes (2833, 2834, 2835, and 2836), the total emissions for volatile organic compounds (VOC), nitrogen oxides (NOx) and hazardous air pollutants (HAPs) are as follows (in tons per year):
| SIC | Subsector | VOC | NOx | HAP |
| 2833 | Medicinals And Botanicals | 5,410 | 8,118 | 630 |
| 2834 | Pharmaceutical Preparations | 7,997 | 6,558 | 4,287 |
| 2835 | Diagnostic Substances | 20 | 17 | 18 |
| 2836 | Biological Products, Except Diagnostic | 57 | 46 | 10 |
| Total, pharmaceutical subsectors | 13,484 | 14,739 | 4,945 |
The total emissions from the pharmaceutical sector are relatively small in comparison with other sectors with the chemical industry (an order of magnitude below that of SIC 2869, Industrial Organic Chemicals, Not Elsewhere Classified, for example, which includes the commodity chemical manufacturers)
*** Would be interesting to compare the ratio of hazardous air pollutants (HAPs) emitted by an industry to its volatile organic compound (VOC) emissions. This would provide a measure of the extent to which a sector might benefit from substitution of more benign materials (either as processing aids, or as products).
** A set of risks unique to this sector are associated with the nature of biological materials. Some substances can be physiologically significant at extremely low doses (for example, if they affect regulatory systems on a cellular level). Trace quantities of product excreted in patients' urine, for example, can be identified in environmental samples. This problem will be compounded with the introduction of genetically engineered organisms into standard pharmaceutical manufacturing practice. The possibility of the release of "trace quantities" of potentially self-replicating "substances" will necessitate a revision in our current notions of contamination thresholds. This applies not only to self-standing organisms, which is problematic enough, but to much smaller entities. Genetic modifications are packaged in free-standing loops of DNA ("plasmids"). There does not appear to be any credible evidence that "infection" of wild-type microorganisms by free-floating plasmids has ever occurred, but experience has shown that we underestimate the creativity of the microbial world at our peril.
A NESHAP for Pharmaceuticals Production was finalized in 1998, and has been subsequently amended.
Existing Effluent Guidelines relating to the pharmaceutical sector are found in the Code of Federal Regulations, Title 40, Chapter 1, Subchapter N, Part 439 - Pharmaceutical Manufacturing Point Source Category.
Supporting documentation, including a very useful set of process descriptions contained in the Technical Development Document, may be found collected on an EPA index page for this rule.
** The EPA Technical Development Document for effluent guidelines for the pharmaceutical industry makes reference (p. 3-40) to an effort involving both EPA and the Food and Drug Administration (FDA) to encourage pollution prevention. This would presumably include the problem of triggering an expensive requirement for amendment of FDA approval conditions when instituting process changes (such as the substitution of safer solvents). The Technical Development Document was produced in 1995 -- it would be interesting to see if these efforts have continued, and have borne fruit.
There is an OECA Sector Notebook on the pharmaceutical sector available at http://www.epa.gov/compliance/resources/publications/assistance/sectors/notebooks/pharma.pdf . The Sector Notebooks almost always contain particularly useful summaries of the processes carried out by the subject sectors. In this case, for some reason, that aspect of the coverage was not given much priority, and the process description section consists largely of a set of excerpts from a different EPA publication (the Technical Development Document for the Effluent Guidelines). Unfortunately, there is some valuable framework material in the latter document that does not come out in the Sector Notebook's somewhat patchy excerpts. The reader seeking a cogent process description would do better going directly to the source document. The Technical Development Document for the Effluent Guidelines for the pharmaceutical sector may be found at http://www.epa.gov/waterscience/guide/pharm/techdev.html
Trade orgs
Pharmaceutical Research and Manufacturers of America (PhRMA) http://www.phrma.org/
Other data sources include