Pharmaceutical Times

Current Good Manufacturing Practice for Einished Pharmaceuticals, Time Limitations on Production, (1998), CER, Title 21, Part 211, Volume 4, Section 211.111. 

Holden P. The role of the Medical Department. Pharmaceutical Times November 1992 12. 

A third reason, which partly explains the reluctance, is the pressure of time. Fine chemicals generally have a much shorter lifecycle than bulk chemicals and, especially in pharmaceuticals, time to markef is crucial. An advantage of many time-honored classical technologies is that they are well-tried and broadly applicable and, hence, can be implemented rather quickly. In contrast, the development of a cleaner, catalytic alternative could be more time consuming. Consequently, environmentally (and economically) inferior technologies are often used to meet market deadlines. Moreover, in pharmaceuticals, subsequent process changes are difficult to realise owing to problems associated with FDA approval. 

Creer J (1989) Business intelligence—relevance to the pharmaceutical industry. Pharmaceut Times 18-20. 

The development of a new drug is both a time-consuming and a cost-intensive process. It takes 12 to 15 years and costs up to 800 million to bring a new drug to the market. As measured by the market capitalization, the pharmaceutical companies play a pivotal role in the global economy. In February 2003 Pfizer was ranked at position five worldwide, with a market capitalization of 163 billion. Ranking third as far as the market capitalization in Europe is concerned was GlaxoSmithKline, with a current value of 101 billion. Novartis was number five in Europe with 82 billion. 

At the time, I was so fascinated by the potential of our organofluorine compound-based pharmaceutical research that, to learn more about... 

Memfield s concept of a solid phase method for peptide synthesis and his devel opment of methods for carrying it out set the stage for an entirely new way to do chem ical reactions Solid phase synthesis has been extended to include numerous other classes of compounds and has helped spawn a whole new field called combinatorial chemistry Combinatorial synthesis allows a chemist using solid phase techniques to prepare hun dreds of related compounds (called libraries) at a time It is one of the most active areas of organic synthesis especially m the pharmaceutical industry... 

Approximately 500,000 Americans suffer strokes each year. Many of the 80% that survive suffer paralysis and impaired vision and speech, often needing rehabiUtation and/or long-term care. Hence, whereas treatment using rt-PA is likely to be expensive (costs are 2200/dose for treating heat attacks), the benefits of rt-PA could outweigh costs. In the case of heart attacks, the 10 times less expensive microbiaHy derived streptokinase can be used. There is currentiy no competing pharmaceutical for treatment of strokes (18,19). Consequentiy, the cost of manufacture of rt-PA may not be as dominant an issue as would be the case of other types of bioproducts. 

The behavior of drops in the centrifugal field has been studied (211) and the residence times and mass-transfer rates have been measured (212). PodbieHiiak extractors have been widely used in the pharmaceutical industry, eg, for the extraction of penicillin, and are increasingly used in other fields as weU. Commercial units having throughputs of up to 98 m /h (26,000 gal/h) have been reported. 

Other than fuel, the largest volume appHcation for hexane is in extraction of oil from seeds, eg, soybeans, cottonseed, safflower seed, peanuts, rapeseed, etc. Hexane has been found ideal for these appHcations because of its high solvency for oil, low boiling point, and low cost. Its narrow boiling range minimises losses, and its low benzene content minimises toxicity. These same properties also make hexane a desirable solvent and reaction medium in the manufacture of polyolefins, synthetic mbbers, and some pharmaceuticals. The solvent serves as catalyst carrier and, in some systems, assists in molecular weight regulation by precipitation of the polymer as it reaches a certain molecular size. However, most solution polymerization processes are fairly old it is likely that those processes will be replaced by more efficient nonsolvent processes in time. 

Quantitative mass spectrometry, also used for pharmaceutical appHcations, involves the use of isotopicaHy labeled internal standards for method calibration and the calculation of percent recoveries (9). Maximum sensitivity is obtained when the mass spectrometer is set to monitor only a few ions, which are characteristic of the target compounds to be quantified, a procedure known as the selected ion monitoring mode (sim). When chlorinated species are to be detected, then two ions from the isotopic envelope can be monitored, and confirmation of the target compound can be based not only on the gc retention time and the mass, but on the ratio of the two ion abundances being close to the theoretically expected value. The spectrometer cycles through the ions in the shortest possible time. This avoids compromising the chromatographic resolution of the gc, because even after extraction the sample contains many compounds in addition to the analyte. To increase sensitivity, some methods use sample concentration techniques. 

In the United States, through the NDA review process, pharmaceutical companies that seek FDA approval for new dmg products are assessed user fees by FDA to gain faster approval, by virtue of the U.S. Prescription Dmg User Fee Act of 1992. These assessments are used to increase the new dmg review staff of the FDA, which has agreed to reduce the NDA review time to 12 months by 1997 (6). 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Saccharin is the most economical sweetener available. It is 300 times (8% sucrose solution sweetness equivalence) more potent than sugar and its price in 1996 was about 6.05/kg, ca 0.02/(kg-sweet unit). Sugar, on the other hand, was ca 0.77/kg, which is 39 times more expensive than saccharin on equal sweetness basis. Consequentiy, the low cost and high stabiUty of saccharin render it the sweetener of choice for dentifrices (qv), other toiletry products, and pharmaceuticals (qv). 

Process Economics. Relative economics of various ceU culture processes depend heavily on the performance of the ceU line in a system and on the cost of raw materials, particularly the medium. Models are usuaUy developed for the various processes using productivity data obtained from smaU-scale experiments (see Pilot AND MiCROPLANTs). Often, for high value products, the process which ensures the shortest time to market may be the process of choice because of other economic criteria. This is especially tme for pharmaceuticals (qv). RehabUity concerns also often outweigh economic considerations in choosing a process for a high value product. 

Mono- and dichlorotoluenes ate used chiefly as chemical iatermediates ia the manufacture of pesticides, dyestuffs, pharmaceuticals, and peroxides, and as solvents. Total annual production was limited prior to 1960 but has expanded greatly siace that time. Chlorinated toluenes ate produced ia the United States, Germany, Japan, and Italy. Siace the number of manufacturers is small and much of the production is utilised captively, statistics covering production quantities ate not available. Worldwide annual production of o- and -chlorotoluene is estimated at several tens of thousands of metric tons. Yearly productions of polychlorotoluene ate ia the range of 100—1000 tons. 

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