3. Umbruch 4.4..2005 - Online Pot

The development of Sativex ® – a natural cannabis-based medicine 241
As part of GAP and GMP, the BRM must conform to a specification. The
specification for BRM includes tests for identification, extraneous matter and
identification and assay for cannabinoids and cannabinoic acids, confirmatory
thin-layer chromatography (TLC) and loss on drying. Additionally, BRM is
tested for aflatoxins and microbial bioburden. The growing parameters
employed have been selected to minimize the conditions that would be expected
to result in microbial and fungal spoilage.
Extraction
Cannabinoids are present in the plant as the corresponding carboxylic acid and
it is necessary to decarboxylate material before extraction. The conditions for
efficient decarboxylation have been optimized to maximize decarboxylation
and minimize oxidation. The process is time- and temperature-dependent and
a criterion of not less than 95% efficiency was adopted for BRM used in subsequent
manufacture of botanical drug substance (BDS; whole-plant extract).
Development work has shown that efficient extraction can be carried out
using patented extraction technology. The conditions of the extraction have
been carefully assessed during development and are essential to ensure the
optimum conditions and hence the correct composition of the extract produced.
The extraction produces a whole-plant extract, from which the BDS is
prepared.
The whole-plant extract is subject to further processing (covered by intellectual
proprietary rights) to remove unwanted materials from the extract. The
exact content of the BDS is defined by a specific BDS specification. BDS is
transferred to sealed, stainless steel containers and stored at –20 ± 5 °C to
maintain stability.
A schematic diagram of the process flow from cultivation to final processing
and quality-control release of the pharmaceutical product is detailed in
Figure 2.
BDS content
Using any defined BRM, a corresponding BDS may be created using the above
GW proprietary process. The contents of the BDS will depend on the genetically
defined content of the BRM, and the technology used to extract the active
constituents. Thus, BDSs may be produced which have defined levels of principal
cannabinoids, other cannabinoids and other non-cannabinoid constituents.
Thus a series of individual BDSs may be described.
Each BDS contains a cannabinoid fraction and a non-cannabinoid fraction.
GW describes its BDSs individually as each BDS generated has a unique composition.
The two BDSs used to generate Sativex ® are Tetranabinex ® ,an
extract of a chemically and genetically characterized cannabis plant, contain-