Monograph Regulation of Weight Control Products for Over-The-Counter (OTC) Use Joint Nonprescription Drugs Advisory Committee and Endocrine and Metabolic Drugs Advisory Committee Meeting Arlene Solbeck, M.S. Senior Regulatory Review Scientist Division of Nonprescription Regulation Development Center for Drug Evaluation and Research

2 Joint NDAC/EMDAC Meeting January 23, 2005 Overview What is an OTC monograph? What is the current status of the monograph for OTC weight control ingredients/products established in 1982?

3 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs OTC Drug Review initiated in 1972 > 100,000 OTC drug products that contained > 700 active ingredients Active ingredients reviewed by therapeutic categories

4 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs Category I: GRASE (Generally Recognized as Safe and Effective) Category II: not GRASE Category III: data insufficient to determine if safe and effective; more data needed Advisory Review Panel

5 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs Category I: GRASE Category II: not GRASE Category III: cannot determine if safe and effective ANPR

6 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs ANPR TFM Comments

7 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs TFM Comments Data FM

8 Joint NDAC/EMDAC Meeting January 23, 2005 OTC Monographs Summary Regulatory pathway for marketing of GRAS/GRAE OTC ingredients and drug products –Public process –Active ingredient specific –Pre-approval not required

9 Joint NDAC/EMDAC Meeting January 23, 2005 Weight Control Products For Over-The Counter Use Panel’s Report (ANPR) January 26, 1982 Advisory Review Panel on OTC Miscellaneous Internal Drug Products

10 Joint NDAC/EMDAC Meeting January 23, 2005 Weight Control Drug Products – Definition and Use Definition of weight control drug product (January 26, 1982) –An agent which reduces appetite Indication statements –Helps control appetite –Helps curb appetite –For appetite control to aid weight reduction –An aid for effective appetite control to assist weight reduction –Helps you eat less, weigh less –Appetite depressant in the treatment of obesity (excess weight) –An aid in the control of appetite –An aid to diet control in conjunction with a physician’s recommended diet –For use as an aid to diet control

11 Joint NDAC/EMDAC Meeting January 23, 2005 Panel’s Definition of “Obesity” Target population –Adult “obese” persons free of known underlying organic diseases Panel’s definition of obesity (1982) “ An increase in body weight beyond the limitation of skeletal and physical requirements as the result of an excessive accumulation of fat in the body; that physical state in which body weight in relation to height and body build is more than 10 percent above the ideal weight determined from the Metropolitan Life Insurance Company table of desirable weights”

12 Joint NDAC/EMDAC Meeting January 23, 2005 Duration of Use Duration of use –Temporary (3 months) –In conjunction with a diet –3 months enough time to establish new eating habits –Labeling to state: “This product’s effectiveness is directly related to the degree to which you reduce your usual daily food intake. Attempts at weight reduction which involve the use of this product should be limited to periods not exceeding three months, because that should be enough time to establish new eating habits.”

13 Joint NDAC/EMDAC Meeting January 23, 2005 Efficacy Criteria Efficacy Studies –12 week treatment period –Average weight loss: PLACEBO TEST 1 lb / week 12 lbs / treatment period 1.5 lbs / week 18 lbs / treatment period

14 Joint NDAC/EMDAC Meeting January 23, 2005 Ingredients 113 reviewed 2 recommended for Category I –Phenyl propanolamine hydrochloride (PPA) –Benzocaine 111 ingredients recommended for Categories II and III by Panel 111 ingredients classified as “not generally recognized as safe and effective” (nonmonograph) –TFM: 1990 –FM: 1991

15 Joint NDAC/EMDAC Meeting January 23, 2005 Current Status of Category I Ingredients Phenylpropanolamine hydrochloride (PPA): –FDA published a proposed rule to reclassify PPA from Category I to Category II (nonmonograph) based on safety concerns (2005) Benzocaine: –Final rulemaking in progress that will address the adequacy of available efficacy data for benzocaine for weight reduction

16 Joint NDAC/EMDAC Meeting January 23, 2005 Panel’s Report - Summary Panel’s recommendations: –OTC weight control drug products reasonable for temporary use (3 months) for assistance in weight reduction in “obese” population in conjunction with a diet Panel recognized that a diet and other behavioral changes are integral components of weight control Uncertain whether there will continue to be any active ingredients in the weight control monograph recognized as safe and effective for that intended use.