Biotechnology-derived products

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-... 

Basic Principles for Preclinical Safety Evaluation of Cellular and Gene Therapies. For biotechnology-derived products in general... 

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... 

Biotechnologically-derived products that achieve highly specific receptor targeting (refer to toxicology studies) ... 

The need for DDSs is possibly the greatest in the case of biotechnologically derived products that cannot be orally absorbed, such as peptides, proteins, and oligonucleotides. 

Biotechnology-derived products have led to renewed interest in establishing reference standards based on the same bulk of material. Thus a single formulation, assay, and reference standard may be the fact worldwide. This situation can become complex such as with insulin where both biotechnology-derived insulin and animal-source insulin are in the marketplace at the same time. 

Articulating the three concepts for harmonization was particularly important. Prospective and retrospective clarify the distinction between work required to avoid conflict when establishing standards for pharmacopeial articles for which standards do not exist, or where few standards exist among the pharmacopeias, from work required to reconcile differences among well-established standards for articles that may have been in the pharmacopeias for considerable time. Prospective harmonization was inaugurated for biotechnology-derived products. Retrospective harmonization focused on pharmaceutical excipients and analytical tests and methods. Forward harmonization expresses a philosophy and environment for harmonization consistent with advances in pharmaceutical analysis. 

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. 

Interpharmacopeial Open Conference on Harmonization of Biotechnology-derived Products Standards Verona April 1993... 

Proceedings of Interpharmacopeial Open Conference on Standards for Biotechnology-derived Products, Pharmeuropa (Special Edition), 1993. 

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. 

In many cases, biotechnology-derived products may have many components that have biological activity. The aim should be to devise controls that monitor the various components so as to retain a consistent potency and purity. For example, the USP monograph for erythromycin [9] indicates that the principal component is erythromycin A and that the percentage of erythromycin A, erythromycin B, and erythromycin C is not less than 85.0% and not more than 100.5%. Within these parameters, the relative ratios of erythromycins A, B, and C may change. This is not always the case for biotechnology-derived products, however. For example, the USP monograph for amoxicillin [10] allows for only one active component. 

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... 

For some compounds, such as biologicals and biotechnology derived products, continuous treatment is not appropriate and a specific dosing regimen adapted to the activity of the test compound will need to be devised. 

Table 1 Examples of Biotechnology-Derived Products Continued)...

---