PHARMACEUTICALS have to comply with different , stricter regulations . Even with the same or similar chemistry and manufacturing lineage , many in the pharmaceutical industry treat drug molecules as a cut above the products of the fine chemical industry , even when it has continued to use its manufacturing practices , methods and equipment inefficiently . 8 Since the 1970s , environmental issues have become more important and environmental control regulations have been adopted . As a result , some in the chemical and pharmaceutical industries took the necessary steps to minimise effluent and emissions using the technologies available . With the introduction of the Hatch- Waxman Act , generic drug use expanded in developed countries . To manufacture them , many companies entered the business in developing countries where the labour costs are significantly lower and the environmental laws were relatively lenient . 9 Pharma manufacturing , for branded and generic drugs , has followed its own business and manufacturing technology model . Because the industry was so profitable , it did not need to innovate environmentally . This has resulted in high emissions . The industry still lags in terms of innovation and has minimal concern for global warming . As Table 1 shows , APIs and finished dose formulations ( FDFs ) only need to be produced in very small quantities . Theoretically , both can be produced in a single plant but this
Table 3 - Annual API need for selected drugs is usually not the case . Due to the production volume , multiple plants would be needed for the formulations shown . Many can be made continuously , but due to traditions and regulatory encumbrances , they are batch operations .
Drugs are generally sold at a high mark-up and for huge profits ( Table 2 ). Even if formulators increased their margins many times over , it would have a minimal impact on the selling price of the tablet to the patient . 10 Tables 3 and 4 illustrate the number of plants that produce API and FDFs for three specific drugs . Their average yearly volumes are based on certain assumptions . With the number of plants producing the API and formulating the drug , plus the simplicity of the chemistries , they are being produced in equipment that is available in most plants . Any good chemist or a chemical engineer can modify the process chemistry of these or any other APIs or FDFs to fit them into the existing equipment . cGMP would require cleaning the equipment to avoid cross-contamination . The number of plants producing the same APIs and formulating them in the existing equipment generally negates any value of economies of scale . 11 With the number of plants producing these three products , each will be a batch process . This suggests that no plant will use its equipment efficiently and might even have less than optimum yield . Asset utilisation would generally follow the norms of pharmaceutical industry , i . e . < 50 %.
Omeprazole Metoprolol Modafinil Population 7,800,000,000 7,800,000,000 7,800,000,000 Global need , % 14 1 0.06 # People 1,092,000,000 78,000,000 4,680,000 Mg needed / day 40 50 200 Tablets used # days / year . 50 365 365 Total mg needed / day 43,680,000,000 3,900,000,000 936,000,000 API need Kg / Year . 2,184,000 1,423,500 341,640 Current number of API Sites 94 29 51 Current number of FDF Sites 768 70 338
In addition , cleaning between batches to meet cGMP requirements means high use of solvents and reuse adds to global warming . With profitability assured , existing operations have not hitherto had any need to worry about this . In order to make any dent on its E-factor , pharmaceutical manufacturing will have an arduous task as it will have to tackle its current business model , manufacturing methods , the regulatory bodies and pharmacy benefit managers ( PBMs ) and rest of the supply chain .
Manufacturing & regulations
Pharmaceutical manufacturing has two components : APIs and formulations . The former is easier to simplify as most synthesis are conducted in solvents . Flow and stoichiometry can be readily controlled and managed . Most formulations , however are combinations of solid and liquid blending to produce a consistent and uniform quality product that can be converted to a dose . Current shortrun batch processes would have to be converted to continuous blending and tabletting processes , which are yet to be developed . It is best for them to be done at the formulating company and not at equipment vendors . Any blending developed in the lab or the pilot plant would require commercial scale-up . This could be a challenge and would require time to perfect each process . If short runs are not converted to continuous manufacture , solvent cleaning would still be required between product switches and no real impact could be made on the E-factor . If pharma companies can deal with manufacturing technologies , they will still have to address their business model and comply with regulations . For the business model to change would mean reducing the number of sites and manufacturing products differently . This will not sit well with many companies , as some will have to go out of business if they cannot reduce their emissions .
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