Biologic Approvals

Biotechnology as a promising source of new and more efficient targeted therapeutics has been with us since the mid-1980s. While (as one should expect) some of the early promises have not quite been met, biotechnology has turned out to be a valuable source of new and valuable therapeutics. Table 12.1, summarizing the first 15 years of biologic approvals, demonstrates this (Malinowski, 1999 Maulik and Patel, 1997). 

Figure 1.1 R D spending versus the number of NMEs and biologies approved by the US Food and Drug Administration (FDA). (Reprinted with permission from Pharma 2020 The vision Which path will you take , PricewaterhouseCoopers, 2007.)...

Figure 10.2 FDA approvals for new APIs, 1995-2005. Source www.fda.gov CDER Drug and Biologic Approvals.)...

As other recombinant proteins and monoclonal antibodies came under development, the CBER held primary responsibility for this review, with the CDER retaining responsibility for hormones such as insulin and HGH. However, in 2003 all therapeutic proteins were transferred from the CBER to the CDER. This reassignment of review responsibility did not impact the legal classification of these protein products, such that the Center for Drug Evaluation and Research assumed responsibility for the review and approval of biologies approved under Section 351 of the PHSA. 

Giezen TJ, Mantel-Teeuwisse AK, Straus SM, Schellekens H, Leufkens HG, Egberts AC (2008) Safety-related regulatory actions for biologicals approved in the United States and the European Union. JAMA 300 1887-1896... 

Gauvin DV, Baird TJ (2008) A functional observational battery in non-human primates for regulatory-required neurobehavioral assessments. J Pharmacol Toxicol Methods 58 88-93 Giezen TJ, Mantel-Teeuwisse AK, Straus SM et al (2008) Safety-related regulatory actions for biological approved in the United States and the European Union. JAMA 300 1887-1896 Golozoubova V, Brodersen TK, Klastrup S et al (2014) Repeated measurements of motor activity in rats in long-term toxicity studies. J Pharmacol Toxicol Methods 70 241-245. doi 10.1016/j. vascn.2014.06.007... 

US Food and Drug Administration. CDER new molecular entity (NME) drugs and new biologic approvals in calendar year 2004. Further information available at http //www.fda.gov/cder/rdmt/ nmecy2004.htm (accessed November 2007)... 

Health Safety. PET fibers pose no health risk to humans or animals. Eibers have been used extensively iu textiles with no adverse physiological effects from prolonged skin contact. PET has been approved by the U.S. Eood and Dmg Administration for food packagiug and botties. PET is considered biologically iuert and has been widely used iu medical iaserts such as vascular implants and artificial blood vessels, artificial bone, and eye sutures (19). Other polyester homopolymers including polylactide and polyglycoHde are used iu resorbable sutures (19,47). 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

Biomedical and Biotechnology. The use of mictocapsules for a variety of biomedical and biological appHcations has been promoted for many years (50,51). Several biomedical mictocapsule appHcations ate in clinical use or have approached clinical use. One appHcation is the use of air-fiUed human albumin mictocapsules as ultrasound contrast agents. Such mictocapsules, caUed mictobubbles, ate formed by ultrasonicating 5% albumin solutions to produce 4—10-)J.m diameter air-fiUed capsules (52). When injected the capsules act as a useful transpulmonary echo contrast agent (53) that has been approved for use in humans by the U.S. FDA. 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

Incineration in an approved combustion plant is the preferred method of disposal. Wastewater from succinic acid processes is suitable for biological degradation by activated sludge (188). Polymeric sorbents (189) and ferric chloride treatment processes (190) can also be used for wastes containing... 

In 1998, the FDA approved fibrin sealant for three specific indications. These include hemostasis at the time of cardiac surgical operations [8] (Fig. 2) as well as at the time of operative procedures to treat splenic trauma. The application of the fibrin sealant which consists of normal biologic components in the body s clotting cascade creates a localized clot which further enhances inherent clotting ability. Although approved for these specific hemostatic indications only, fibrin sealant is useful as a hemostat in a wide variety of off-label clinical situations as well [9,10]. These include such applications as hemostasis for liver trauma or resection [11], vascular anastomoses [12], tonsillectomy [13], peripheral joint replacement [14], dental extractions [15], and bum debridement [16]. 

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