From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 76
a signal of therapeutic effect. Thus the study design, formulation and dose determination/
selection are critical. Once the IND is completed, the manufacturer must file an NDA.
As of May 2006, there were 229 IND submissions pending approval at FDA’s Center
for Drug Evaluation and Research. Just one NDA has been approved.7
In late 2006, one manufacturer compiled all of the onerous but necessary data needed
for submission. MediGene, a company headquartered in Munich, received approval
to market Veregen, an ointment for genital warts. The drug substance in Veregen is
Kunecatechins, a partially purified fraction of the water extract of green tea leaves from
Camellia sinensis O Kuntze, and is a mixture of catechins and other green tea components.
Each gram of the ointment contains 150 mg of Kunecatechins in a water-free ointment
base. Two Phase 3 randomized double-blind studies were performed to investigate the
product’s safety and efficacy. The experimental group comprised 397 patients, and 207
patients served as controls.8
Final Thoughts
I spoke to one FDA reviewer to ascertain why there had been a change of heart for
approving herbal medicines. He could not cite anything specific, but felt the passage of
Public Law 102-170 in 1991, providing an NIH office to evaluate unconventional medical
practices, and consumer pressure similar to that responsible for enacting the 1994 Dietary
Supplement Health and Education Act played a major role, as did an editorial in the New
England Journal of Medicine published in 2002.9 The editorial cited the need for regulatory
safeguards to ensure the safe use of botanical medicines.
References
1. Zamiska N. “Dueling therapies: Is a shotgun better than a silver bullet?” The Wall Street Journal Online, 2
March 2007.
2. Chiu YY. “Quality control and quality assurance of botanicals,” presented at the conference for
Complementary and Alternative Medicine, 22–24 August 1999.
3. Manual of Policies and Procedures 6007.1, Review of Botanical Drug Products. US Department of Health and
Human Services, Food and Drug Administration, Center for Drug Evaluation and Review. 7 June 2004.
4. Siegel EB. “Chemistry, manufacturing, and control requirements of the NDA and ANDA,” in Guarino RA,
New Drug Approval Process 4th Ed. Marcel Dekker, New York, 2004.
5. Ibid.
6. Guidance for Industry: Botanical Drug Products, US Department of Health and Human Services, Food and Drug
Administration, Center for Drug Evaluation and Review, Division of Drug Information. Rockville, MD. June
2004.
7. Vaccari LA. “Current regulation of botanical drugs in the United States,” presented at the 42nd Annual
Meeting, Drug Information Association, Philadelphia, PA, 18–22 June 2006.
8. Veregen Package Insert included in NDA 21-902 assessed April 2007.
9. Marcus DM and Grollman AP. “Botanical medicines—the need for new regulations.” NEJM
2002 347(25):2073-76.
Published in Regulatory Focus, January 2009. Copyright © 2009 Regulatory Affairs Professionals Society.
a signal of therapeutic effect. Thus the study design, formulation and dose determination/
selection are critical. Once the IND is completed, the manufacturer must file an NDA.
As of May 2006, there were 229 IND submissions pending approval at FDA’s Center
for Drug Evaluation and Research. Just one NDA has been approved.7
In late 2006, one manufacturer compiled all of the onerous but necessary data needed
for submission. MediGene, a company headquartered in Munich, received approval
to market Veregen, an ointment for genital warts. The drug substance in Veregen is
Kunecatechins, a partially purified fraction of the water extract of green tea leaves from
Camellia sinensis O Kuntze, and is a mixture of catechins and other green tea components.
Each gram of the ointment contains 150 mg of Kunecatechins in a water-free ointment
base. Two Phase 3 randomized double-blind studies were performed to investigate the
product’s safety and efficacy. The experimental group comprised 397 patients, and 207
patients served as controls.8
Final Thoughts
I spoke to one FDA reviewer to ascertain why there had been a change of heart for
approving herbal medicines. He could not cite anything specific, but felt the passage of
Public Law 102-170 in 1991, providing an NIH office to evaluate unconventional medical
practices, and consumer pressure similar to that responsible for enacting the 1994 Dietary
Supplement Health and Education Act played a major role, as did an editorial in the New
England Journal of Medicine published in 2002.9 The editorial cited the need for regulatory
safeguards to ensure the safe use of botanical medicines.
References
1. Zamiska N. “Dueling therapies: Is a shotgun better than a silver bullet?” The Wall Street Journal Online, 2
March 2007.
2. Chiu YY. “Quality control and quality assurance of botanicals,” presented at the conference for
Complementary and Alternative Medicine, 22–24 August 1999.
3. Manual of Policies and Procedures 6007.1, Review of Botanical Drug Products. US Department of Health and
Human Services, Food and Drug Administration, Center for Drug Evaluation and Review. 7 June 2004.
4. Siegel EB. “Chemistry, manufacturing, and control requirements of the NDA and ANDA,” in Guarino RA,
New Drug Approval Process 4th Ed. Marcel Dekker, New York, 2004.
5. Ibid.
6. Guidance for Industry: Botanical Drug Products, US Department of Health and Human Services, Food and Drug
Administration, Center for Drug Evaluation and Review, Division of Drug Information. Rockville, MD. June
2004.
7. Vaccari LA. “Current regulation of botanical drugs in the United States,” presented at the 42nd Annual
Meeting, Drug Information Association, Philadelphia, PA, 18–22 June 2006.
8. Veregen Package Insert included in NDA 21-902 assessed April 2007.
9. Marcus DM and Grollman AP. “Botanical medicines—the need for new regulations.” NEJM
2002 347(25):2073-76.
Published in Regulatory Focus, January 2009. Copyright © 2009 Regulatory Affairs Professionals Society.