By Rachelle H.B. Fishman

Special To BioWorld Today

Validation and optimization of biological activities of pharmaceuticals and nutraceuticals derived from botanical sources is a growing business.

The FDA has shown heightened interest in this area and has recently established two working groups under the botanical subcommittee of the Center for Drug Evaluation and Research (CDER) to develop regulatory guidelines for approval of botanical medicines as pharmaceuticals.

This is a new area for the FDA, which previously has not approved pharmaceutical versions of multicomponent botanical extracts.

As publicly stated by CDER staff, there are dozens of investigational new drug (IND) applications that have been filed with the FDA for products that would be considered "botanicals." Due to confidentiality rules, only an IND sponsor may discuss the contents or disclose the existence of an IND.

There are various approaches to standardizing and patenting botanical products. One approach, from PharmaPrint Inc., was developed over 20 years at the University of Southern California School of Medicine, in Los Angeles, by Tasneem A. Khwaja. He is a cofounder of PharmaPrint and chief scientific officer.

"[PharmaPrint's] process ensures that herbal products made from plant extracts have consistency and standardization similar to typical single molecule pharmaceuticals, and provides that consistency in every bottle just as you would expect with any other drug you buy," said urologist Peter Walther, head of the division of urology at the Scripps Research Institute, in La Jolla, Calif.

Saw Palmetto Aimed At Prostatic Hyperplasia

Walther is the lead investigator in tests of PharmaPrint's saw palmetto treatment, which in December began Phase II trials. The study is a double-blind, placebo-controlled dose-ranging examination at four medical centers in 48 men with benign prostatic hyperplasia (BPH).

Elliot Friedman, president and CEO of PharmaPrint, said, "The PharmaPrint process enables the identification and quantification of the bioactives within plant extracts that are believed to provide therapeutic or other health benefits."

Instead of selecting a single molecule from a plant suggesting bioactivity, Khwaja showed it is possible to identify sets of molecules with bioactivity and to evaluate them against specific bioassays.

If found to have acceptable efficacy, specific molecular components are isolated and their concentration levels determined. These components are then tested for bioactivity and disease-specific biological effects. The most active components are chemically identified and a precise standard by weight, bioactivity and specific biological effect is established. The standards for each active component comprise the "PharmaPrint," also known as the fingerprint, for the medicine.

If any active component is out of specification in a batch of the manufactured pharmaceutical, then either the batch is discarded or the proportion is adjusted by balancing the components to achieve maximal therapeutic effect with minimal toxicity.

"The PharmaPrint technology combines drug screening capabilities with biologically driven fractionation, enabling identification and quantification of bioactive molecules within plant sources believed to provide therapeutic or other health benefits," said Clive Taylor, chairman of the department of pathology and laboratory medicine at the University of Southern California School of Medicine. Taylor also serves on PharmaPrint's scientific advisory board.

PharmaPrint has filed applications with the U.S. Patent and Trademark Office (PTO) for a broad process patent covering a method for making high quality botanicals and for use of this method to manufacture 11 specific botanical compositions. Two patents have been accepted and the others are pending.

The company is focusing its development efforts on certain plants and plant extracts that are widely used throughout the U.S. and Europe to treat a variety of diseases and physical conditions, starting with saw palmetto for BPH. PharmaPrint expects that its botanical products will need to meet the same standards for toxicity, dosage tolerance, efficacy and manufacturing as traditional pharmaceutical products.

To help fund these programs, PharmaPrint completed its second public offering in February, raising more than $27 million through the sale of 2.6 million shares.

The company received $2.5 million up-front in an exclusive marketing agreement with American Home Products, of Madison, N.J., for seven nutraceutical products, including saw palmetto for BPH, St John's wort for depression and valerian for insomnia. *