Botanical applications

Collects information, maintains a database of botanical applications, and performs periodic analysis on the status of botanical new drug development. 

To implement the Botanical Guidance, a new set of review processes for botanical applications have been delineated in a new CDER MAPP (MAPP 6007.1 for Review of Botanical Drug Products). 

These review processes for botanical applications have been tested in CDER with approximately 100 submissions. Collaborations between BRT and the new drug divisions have been smooth and productive. 

As of April 30, 2004, there are a total of 203 botanical drug applications in CDER, including 167 investigational new drug (IND) applications and 36 pre-IND consultations. At least 75% of the total botanical applications were submitted after 1999, and about two per month were received by the Agency recently. 

As provided in the Botanical Guidance, clinical studies have been permitted for many botanical preparations prior to a complete set of conventional animal toxicity testing. The decisions were not difficult for submissions with substantial and well-documented history of past human use. But some other applicants had not presented an adequate summary of the past human experiences and had failed even to document well-known toxicity of the herbal ingredients. Between these two extremes, how to adjust the requirements of animal toxicity data and substitute that with large quantity but poor quality of human experiences is another big challenge to the regulatory agency in the review of botanical applications. 

For these reasons, integrating all the background information into the overall safety assessment for botanical applications has been difficult and required active participation of the BRT. 

There is a voluminous literature, chiefly of botanical interest, dealing with the effects of the application of colchicine to plants of economic importance such as tobacco, cotton,wheat and rice. ... 

The application of linear discriminant analysis of the 16 amino acids foimd in Spanish honeys established both botanical and geographical differences (Perez Arquillue and Herrera Marteache, 1987). Gas chromatography (GC) analyses of free amino acids showed obvious differences when honey samples from the UK, Argentina, Australia, and Canada were compared (Gilbert et al., 1981). Pawlowska and Armstrong (1994)... 

The United States Pharmacopeial Convention, Inc. (USP) in 2000 issued the USP criteria for levels of evidence for botanical articles [117]. While issued for botanicals, the criteria have application to all therapeutic agents. The USP criteria rank evidence from I to IV, with Level I being the strongest. Within Level I, the randomized controlled clinical trial is ranked highest, followed by meta-analysis and epidemiological studies. Level II consists of the same designs, but with methodological flaws. Level III includes inconclusive studies, and Level IV is anecdotal evidence. 

Khan, M.A. and Ungar, I. A. (1986). Inhibition of germination in Atriplex triangularis seeds by application of phenols and reversal of inhibition by growth regulators. Botanical Gazette 142 148-151. 

Hawes CR. Applications of high voltage electron microscopy to botanical ultrastructure. Micron 1981 12 227-257. 

Harvey DMR. Applications of x-ray microanalysis in botanical research. Scanning Electron Microsc 1986 HI 953-973. 

Is the BCS that was developed with reference to chemically characterized and well-defined synthetic drug substances relevant for application and or adoption to botanical preparations (8) If one assumes, as is reasonable, that bioavailability of the active component(s) in a botanical dosage form depends on both solubility and permeability, the solubility of the botanical extract could be controlled through appropriate formulation technology and dissolution testing. The applicability of the BCS to botanical preparations will certainly be increasingly researched, debated, and discussed in the coming years. 

In the broad domain of plant biology, the same general principles hold. A tremendous volume of scientific work of a fundamental nature needs to be done and can be done without any more than the usual attention to variability. The moment, however, one becomes interested in applications, biochemical individuality is likely to come into play and needs to be given due attention. We have not used any illustrations of individuality from the botanical field, but this does not mean that they do not exist. 

Starch is isolated from plant sources by various methods (Ratnayake and Jackson, 2003 Zobel, 1992). The method of starch isolation depends on the nature and composition of the raw material source. Most food starches are isolated and purified on a commercial scale and then used as ingredients by food manufacturers. Commercial food starches are generally classified based on both botanical origin and functionality. With the increasing availability of modified starches prepared for specific food applications, starch manufacturers tend to emphasize and market starch with a secondary focus on botanical source. In fact, for food... 

The analysis of soils and plant material are common examples used to demonstrate ICP applications. Dahlquist and Knoll(43) compared the preparation and ICP analyses of botanicals (16 elements) and soils (11 elements) with few exceptions the ICP values for the CII botanicals were in excellent agreement with the assigned values, and the soil analyses were in excellent agreement with FAA analyses of soil digests. )ones( 4) reported the analysis of 17 elements in plant material and soils but confirmation of the two analyses was not given. Alder, et. aJ.(75) describe the unique analysis of ammonia-nitrogen in soils by gas evolution into an ICP no interferences were observed from the concomitants evaluated and acceptable recoveries were obtained. Irons et. al.(76) compared the ICP analyses of 13 elements in NBS orchard leaves and bovine liver to the data obtained by FAA and energy dispersive x-ray. 

The haemoglobinization of human leukaemic cell lines by alkaloids demonstrated through in vitro means that these compounds are biologically very active. Alkaloids are therefore a promising botanical to be used in future applications. 

Other interesting applications arise from studies concerning vegetable-derived foods, where the differentiation is carried out according to the botanical variety or cultivar of the plant involved (Beullens et ah, 2008 Dias et ah, 2008 Kantor et ah, 2008 Rudnitskaya et ah, 2006b). In other cases, the attention is focused onto the geographical origin (Buratti et ah, 2004 Cosio et ah, 2006 Oliveri et ah, 2009). 

Modification, which involves the alteration of the physical and chemical characteristics of the native potato starch to improve its fimctional characteristics, can be used to tailor it to specific food applications. The rate and efficacy of any starch modification process depend on the botanical origin of the starch and on the size and structure of its granules. This also includes the surface structure of the granules, which encompasses the outer and iimer surface depending on the pores and channels, which cause the development of the so-called specific surface (Juszczak, 2003). Potato starch modification can be achieved in three different ways physical, conversion, and chemical (derivatization) (Table 10.6). 

In view of the multiplicity of CYPs and the many possible botanical-drug interactions, highly efficient clinical study designs using CYP probe cocktails have been explored. Following successful application to St. John s wort, other botanicals that have been evaluated in this fashion include echinacea (42), saw palmetto (43), garlic (39), peppermint oil, and ascorbyl palmitate (44). The results are summarized in Table 1. Curbicin, a botanical... 

There can exist no standardization regime that would be universally applicable to all medicinal botanical products. Ideally, the formulated product should be chemically assayed for an active constituent, using an analytical method appropriate for the given compound class, and also biologically assayed for in vitro and/or in vivo activity, using assay(s) relevant to the intended use of the product. 

To implement the new Guidance, the CDER established a new Botanical Review Team (BRT) dedicated to the review of botanical specific issues in new drug applications (NDAs). A new Manual of Policies and Procedures... 

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