*2.1. Catalogue of Pharmaceutical VOCs in China*

Medicines in China are mainly produced in six ways, biological fermentation, chemical synthesis, extraction, coagulation preparation, bioengineering, and treatment of traditional Chinese medicine [4,14]. The different methods produce varying levels of pollution, with the order of emitted VOCs being biological fermentation > chemical synthesis > extraction > bioengineering > treatment of traditional Chinese medicine > coagulation preparation [15]. All these processes can be plagued by the need for high volumes of solvents, the consumption of large quantities of complex organic precursors, or the production of volatile byproducts. Some of the volatile organic compounds used or produced in these processes may be released into the atmosphere, which causes air pollution. The released VOCs primarily include alkanes, alcohols, ketones, aromatic hydrocarbons, halohydrocarbons, amines, esters, ether, aldehyde, carboxylic acid, and sulfur containing organic compounds [4,11,12,14,15].

Biological fermentation is often used to produce antibiotics, vitamins, and amino acids, via processes which include fermentation, separation, purification, and refinement [16,17]. The primary source of emitted VOCs are the solvents used in these processes, especially in the separation and purification steps. Additionally, H2S is also produced as a byproduct in some fermentation processes.

The chemical synthesis technology is usually used for the production of medicine which can be used for prevention, cure, and diagnosis of the disease [18,19]. It contains the units to synthesize intermediates from raw materials, modify the structure of intermediates, purify the products, and dry the final products. The VOCs from this process comprise solvents and unreacted intermediates, which are more complex and often harder to be eliminated than those produced from the biological fermentation. These VOCs include heptane, toluene, xylene, methanol, n-propyl alcohol, isopropanol, phenol, aminomethane, dimethylamine, aminobenzene, cyclohexylamine, triethylamine, butyraldehyde, acetone, chloroform, chlorobenzene, etc.

Extraction involves the use of physical, chemical, and biological methods to separate a substance from a mixture. In the case of the pharmaceutical industry, extraction is carried out to separate organic compounds of interest from liquid solvents [16,20]. As a result, extraction processes require a large supply of solvents, including toluene, naphtha, methanol, ethanol, isopropanol, phenol, acetone, ether, acetic ether, diethylamine, dichloromethane, dichloloethane, chloroform, etc. VOCs are released during extraction mainly from the organic solvents used within the process.

The bioengineering method is a new way to produce some new medicines, via processes such as cloning antibodies, genetic engineering drugs, and genetic engineering vaccines [21]. The VOCs released from this process are similar to those of biological fermentation. These VOCs come from the solvents used within the process and as byproducts of certain reactions. They include n-hexane, methanol, ethanol, formaldehyde, acetaldehyde, formic acid, propanediol, acetone, aminoehtyl alcohol, acetonitrile, acetic acid, acetocaustin, N, N-dimethylformamide, phenol, butanone, 4-methyl-2-pentone, n-propyl alcohol, isopropanol, n-pentanol, isopropyl ether, isobutyl aldehyde, etc.

Another process of pharmaceutical production is the manufacture of traditional Chinese medicines or certain Chinese patent drugs [22]. As this is a traditional process which involves the use of only limited organic solvents to treat the natural animals and plants, the production of VOCs is limited. Hence, this process only emits a spot of VOCs, SO2, and smoke.

Coagulation preparation involves the formation of larger particle agglomerates from fine particle suspensions. In the synthesis of pharmaceuticals, it is the process of mixing the active ingredients with helper constituents (often called coagulants) to produce a drug which has the desired particle size. The physical nature of the coagulation process means that the waste produced via this method is primarily a solid particle with little notable VOC production [4,14–16,22].
