Volume Usage Projection

Introduction to Update Quantity Projection

In 1992 this author attempted to estimate the production, sales, and demand of four different categories of Cyclodextrin’s – the natural Cyclodextrin’s (alpha, beta, gamma); the chemically modified Cyclodextrin’s (hydroxypropyl BCyclodextrin primarily); the naturally modified Cyclodextrin’s (glucosyl and maltosyl BCyclodextrin); and the mixed natural Cyclodextrin’s (mixtures of Cyclodextrin’s, maltodextrins and glucose syrups).

The following abbreviations will be used throughout the remainder of the report.

NCyclodextrin	Natural Cyclodextrin (alpha, beta, gamma)
ACyclodextrin	Alpha Cyclodextrin
BCyclodextrin	Beta Cyclodextrin
GCyclodextrin	Gamma Cyclodextrin
CMCyclodextrin	Chemically modified Cyclodextrin
HPB	Hydroxypropyl BCyclodextrin
HPG	Hydroxypropyl GCyclodextrin
HPA	Hydroxypropyl ACyclodextrin
RAMEB	Randomly methylated BCyclodextrin
DIMEB	2,6 di-o-methyl BCyclodextrin
NMCyclodextrin	Naturally modified Cyclodextrin
G1B	Glucosyl BCyclodextrin
G2B	Maltosyl BCyclodextrin
G1A	Glucosyl ACyclodextrin
G2A	Maltosyl ACyclodextrin
G1G	Glucosyl GCyclodextrin
G2G	Maltosyl GCyclodextrin
MNCyclodextrin	Mixed natural Cyclodextrin

The tonnage demand projections turned out to be hopelessly optimistic; the 1992 report projected a worldwide demand for all Cyclodextrin’s in 1999 to be more than 40,000 tons annually – the 1999 estimate of production capacity for all Cyclodextrin’s is 2500 – 3000 tons annually. Probably the biggest reason for the overestimation is the accumulation of error caused by considering the growth for each of the Cyclodextrin’s in each of the categories. If only BCyclodextrin and HPBCyclodextrin are considered, the demand estimate for 1999 drops to 15-16,000 tons – still too high.

Other reasons for the overestimation are:

(1)

GRAS status in the US for BCyclodextrin was not achieved until late 1997, therefore the great demand projected for the Food industry could not even begin to develop until 1998

(2)

The pharmaceutical company working hardest to achieve regulatory acceptance of HPB in commercial formulation also ran into many production delays with its major Cyclodextrin containing offering; instead of having several commercial products containing Cyclodextrin’s on the market by 1995, only one product was approved in the US for marketing by early 1998.

(3)

The major Japanese manufacturer of Cyclodextrin’s, NSK, had restrictions put on its sales of HPB to non-Japanese companies by its major Japanese customers. NSK was also reluctant to increase its production of the mixed natural Cyclodextrin’s that make up the bulk of its Cyclodextrin production to accommodate non-Japanese demand for these products. It is not unlikely that this reluctance to increase Cyclodextrin production was motivated by lack of financial resources at the time given that NSK was acquired by Mitsubishi Corporation in 1997.

(4)

Another significant Japanese manufacturer of Cyclodextrin’s, Ensuiko Sugar Refining Co., LTD spun off its Cyclodextrin producing unit as a private company, BICO, to improve the financial performance of the parent company. Ensuiko had chosen to specialize in the naturally modified derivatives of Cyclodextrin’s.

(5)

The major French manufacturer of Cyclodextrin’s, Roquette Freres, was dissuaded from considering expansion of its Cyclodextrin producing capacity by a restrictive, exclusive supply agreement with a major European pharmaceutical company that didn’t expire until 1995. Roquette also dismantled a small Cyclodextrin sales force it had assembled in the US in the mid 90’s.

(6)

The only manufacturer of Cyclodextrin’s in Germany, Wacker Chemie, decided to slow its time-table for expansion of Cyclodextrin production as a result of:

	(a)	A patent issued to a US government researcher describing the hydroxyalkylation of BCyclodextrin was licensed to a European pharmaceutical company and was perceived by Wacker to prohibit its manufacture of that CMCyclodextrin. Wacker therefore discontinued sales of HPB for several years.
	(b)	Disillusionment at the outcome of a patent opposition it filed in 1989 against the European Janssen patent covering the use of HPB with drugs.
	(c)	An internal decision to develop its own proprietary position for GCyclodextrin and derivatives.

(7)

American Maize, the only manufacturer of bulk Cyclodextrin’s in the US until 1999, continued its policy of minimal information dissemination about Cyclodextrin containing products; the development of new industrial and consumer products with Procter and Gamble Co., Rohm & Haas, and 3M Co. was kept under close wraps. The fact that American Maize did not want to tackle the problems of getting FDA approval for the use of Cyclodextrin’s with drugs stemmed from its lack of experience with pharmaceuticals; unfortunately, the partner it picked to guide it in that area further soured it against moving decisively into the pharmaceutical arena. American Maize also had a frustrating regulatory experience with a low-cholesterol egg product using BCyclodextrin that it was helping to develop with a German company and its Minnesota affiliate.

These setbacks in the development of commercial Cyclodextrin- containing products in the hands of the largest manufacturers, i.e. the organizations supposedly best equipped to develop such products, was viewed by the major new product developers around the world as evidence that Cyclodextrin’s were not yet ready to be included in major products; no matter how well they worked, the practical matter of development time and cost were still perceived to be unfavorably skewed by regulatory and patent issues.

Fortunately as a result of the following events

(1)	GRAS confirmation in 1997 for the use of BCyclodextrin in foods in the US
(2)	First FDA approved drug to contain HPB marketed in the US in 1998
(3)	Wacker Chemie brings a Cyclodextrin manufacturing plant on-line in the US in 1999
(4)	Procter & Gamble Co. includes Cyclodextrin’s in two major consumer products – one, an existing product, Bounce® and a new product, Febreze™
(5)	Monograph for BCyclodextrin appears in USP-NF in 1995

This author believes that Cyclodextrin’s have entered into the fourth stage of its life cycle – commercialization. Using Dr. Jozsef Szejtli’s description of the first three stages, this author respectfully suggests the following extension –

1891 – 1935	Cyclodextrin’s discovered; structure and characteristics only incompletely elucidated
1936 – 1970	Chemical structure and characteristics well studied and described
1970 – 1998	Plant scale manufacturing; active product application research and development; a few pioneering commercial products.
1998 -	Quantifiable production, demand, and sales of products containing Cyclodextrin’s justifying status as global industry