Prof. Moustafa M. Mohamed Vice dean Dr. Safa Ahmed El- askary

1. Development and Regulation of Medical Products(MEDR-101) Prof. Moustafa M. Mohamed Vice dean Dr. Safa Ahmed El-askary Faculty of Allied Medical Science Pharos University in Alexandria

2. Lecture (5) Prescription Drug Labeling

3. Objectives • Event History leading to FDA regulation of drug labeling • Laws that regulate prescription drug labeling and promotional materials • Scope of labeling components and their content • Significance of promotional labeling and DTC Advertising and why FDA regulates these materials • Current topics in prescription drug labeling • Where to find current information related to prescription drug labeling

4. Prescription Drug Labeling • Essential scientific information needed for safe and effective use • Informative, accurate, not promotional or misleading • Based on human experience, whenever possible • Animal data when necessary for safe and effective use

5. Drug Labeling Law • Federal Register • Legal newspaper published daily, contains current federal agency regulations, proposed rules, and Executive orders. • Code of Federal Regulations (CFR) • CFR codifies final rules published in Federal Register • Divided into titles an subparts representing broad areas subject to Federal regulation • Updated yearly and issued quarterly • Code of Federal Regulations: About • 21CFR201:Drug Labeling - Title 21-Drugs, Subpart 201-Labeling • Labeling Requirements for Prescription Drugs and Insulin • Laws • Laws Enforced by the FDA

6. Labeling Components • Professional Labeling • Immediate Container/ Outer package • Patient Product Information • Medication Guide • Promotional Labeling • DTC Advertising

7. 1.Professional Label • Description • name, dosage form, ingredients, sterility, class, structure) • Animal pharmacology • Clinical Pharmacology • Clinical Studies • Indications and Usage • Contraindications • Warnings • Precautions • General precautionary information • Drug interactions; carcinogenicity, mutagenesis, fertility; • Pregnancy/ nursing mothers; • Special Populations

8. Example Professional Label Professional Labeling: Isotrentinoin

9. 2.Container/Package Labels • Statement of identity • Established name, Ingredients • Net quantity of contents • Weight, measure, numerical count, combination • Statement of usual dosage • “See package insert” • Expiration date • Name and place of business of manufacturer, packer, or distributor

10. 3.Patient Product Information (PPI) • Extension of professional labeling for the patient • Distributed to patients when dispensed and includes Important information in consumer-friendly language • May describe benefits, risks, how to recognize risks, dosage and administration • May Include Special Notices (Boxed Warnings) • Required for certain drugs • oral contraceptives (21 CFR 310.501) • estrogens (21 CFR 310.515) • progestational drug products (21 CFR 310.516) • Voluntary for other drugs

11. Example PPI Patient Product Information

12. 4.Medication Guides • Serious and significant public health concern • Significant risk:benefit issue(s) that may affect patients’ decisions to use, or continue to use the product • Patient compliance (i.e., adherence to directions for use) is crucial to drugs safety/ effectiveness • Where additional information could help prevent serious adverse effects • Where drug would used primarily in an outpatient setting without supervision of health professional

13. 4.Medication Guide(s) • Brand name • What is the most important information I should know about (name of drug)? • What is (name of drug)? • Who should not take (name of drug)? • How should I take (name of drug)? • What should I avoid while taking (name of drug)? • What are the possible or reasonably likely side effects of (name of drug)? • Additional headings

14. Example Medication Guide Accutane Medication Guide

15. FDAMA & Off-Label Use • The Food and Drug Modernization Act of 1997 (FDAMA) - FDAMA Homepage

16. Off-Label Use: Pre- & Post-FDAMA Pre- • “On-Label” Indications are listed in FDA approved labeling, however, FDA does not dictate the medical practice • Drug sponsors may not discuss, promote or distribute materials that encourage “off-label” use • Promotion of “Off-label” use by sponsors would: • Diminish use of evidence-based medicine • Expose patients to unidentified risk or harm Post- • Firms may distribute information related to new (unapproved) use of approved drug, prior to FDA approval, if: • Reprint or copy of a peer-reviewed scientific or medical journal article, or reference publication, about a clinical investigation • Is not false or misleading and does not pose a significant risk to the public health • Manufacturer must submit copy to FDA (DDMAC) 60 days prior to dissemination

17. 5.Promotional Labeling • Direct-to Consumer (DTC) promotion for purpose to enhance patient awareness of disease states, available therapies, potential side effects • Includes magazines, newspapers, broadcast (TV/radio), internet dissemination/ advertising of drug information to physicians and patients • May be product-claim, reminder or help-seeking advertisements • New form of product labeling with specific regulation by DDMAC

18. 6.DTC Regulation • Before 1980, No DTC promotion • 1983 – Voluntary Moratorium • 1985 – Policy Statement, Sufficient Safeguards • 1990’s – Promotional Message/ Brief Summary (AEs) • Mid 1990s – “Reminder Ads” • 1997 – FDA Draft Guidance

19. DDMAC • Division of Drug Marketing, Advertising and Communication (DDMAC) • Regulates DTC promotional labeling • Ensures truthful, balanced and accurate communication of drug information to the public • Post-Hoc evaluation, most recommendations to “Stop or Discontinue” due to false, misleading or unbalance representation

20. DDMAC Authority • Untitled Letters– notice of violation • Warning Letters – More serious violations • Injunctions and Consent Decrees • Criminal Investigation or Prosecution • Product Seizure

21. Thanks