Drug products, biotechnology-derived

Efforts are under way to make the USP-NF more useful worldwide. Incorporation of monographs for multi-vitamin products, biotechnology-derived products, veterinary drugs, and botanicals and other dietary supplements help. The US AN and USP Dictionary of Drug Names has wide international applicability, thereby making it a repository of International Names Nomenclature (INN) and British Adopted Names (BAN), as well as U.S. Adopted Names (USAN). Pharmacopeial Forum now contains announcements of proposals from the Japanese Pharmacopeia and European Pharmacopeia for revision of standards for international harmonization. 

In this chapter, pharmaceutical and health-care products, such as prescription drugs, generic drugs, OTC products, animal health products, dietary supplements (vitamins and herbal drugs), and biotechnology-derived products, are discussed in relationship to the format of preformulation reports. Topics of the preformulation study are discussed in detail. Models for some of the reports are provided in the hope that the pharmaceutical development team will devise an individual report format based on particular needs and resources. Analytical techniques useful for preformulation and regulatory conformity or requirements relative to product registration processes are also enumerated. 

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

In light of recent experience with biotechnology-derived products, it is reasonable to expect that pharmacogenomics-based drugs will be expensive relative to traditional modes of treatment (Richmond et al., 1999). If the price of these innovations is viewed out of context from the consumption of other health care goods and services, the response may well be to reduce or deny access to these products. In an era of escalating health care cost, "inputs" to the production of health care, such as pharmaceuticals, physician visits, lab-... 

Biotechnological/Biological Products Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products Notice Draft Guidance on Specifications Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products Chemical Substances Notice... 

Lumpkin, M. (1996). Guidance for Industry Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including well-characterized, therapeutic, and biotechnology-derived products, http //www.fda.gov/cder/guidance/phasel.pdf... 

Prospective harmonization is particularly successful when dealing with biotechnology-derived products [14,15] because only a few manufacturers are involved. There should be no reason for the pharmacopoeias to arrive at different standards proposed for any particular medicine. This is in stark contrast to the situation where many manufacturers of drugs are no longer covered by patent protection. There is no possibility of harmonization of the some 4000 monographs for individual substances and preparations. 

In theory, all impurities should be eliminated. In practice, it is generally not economically feasible to totally eliminate all impurities. However, the levels of all impurities should be controlled to provide a consistent product. In most cases, only low levels of impurities should be allowed, but in rare cases, even quite high levels of impurities are tolerated. In some cases, for example, biotechnology derived products such as macrocyclic antibiotics, or extracts of a botanical source such as some dietary supplements, the drug substance or active component contains multiple compounds, all of which have biological activity. However, only organic impurities, which include residual solvents in the drug substance, are addressed in this chapter. 

For synthetic drug substances, purification is most often accomplished through crystallization. Preparative chromatography is currently more widely used for biotechnology-derived products than for synthetic drug substances... 

By 1991, more than 375 products had received orphan designation, and more than 40 orphan drugs were available In the US. Nine of the 15 biotechnology-derived drugs on the market have orphan drug status, as do 19 biotechnology-derived drugs under development. Some of these prod-... 

The field of pulmonary administration of biomacromolecules is just now in its infancy, and much promise is held in this field. By carefully examining the methods and types of delivery that are possible we may be able to better design easy to use and inexpensive methods for delivering biotechnology-derived products. This chapter was neither all-inclusive nor comprehensive, but was intended to be a starting point for the examination of pulmonary administration of biotechnology derived drugs. 

FDA, INDs for phase II and III studies of drugs, including specified therapeutic biotechnology derived products. Federal Register (Notices) 1999 64(76) 19543-19544. 

Center for Drug Evaluation and Research (CDER). Draft Guidance for Industry. INDsfor Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic Biotechnology-Derived Products CMC Content and Format, Feb. 1999. 

For biotechnologically derived products the acceptable levels of foreign proteins should be based on the sensitivity/selectivity of the test method, the dose to be given to a patient, the frequency of administration of the drug, the source, and the potential immunogenicity of protein contaminants [10]. Levels of specific foreign proteins range from 4 ppm to 1000 ppm. 

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