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

2. Lecture (5)

3.  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.  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.  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 Code of Federal Regulations: About  21CFR201 :Drug Labeling - Title 21-Drugs, Subpart 201-Labeling ▪ Labeling Requirements for Prescription Drugs and Insulin Labeling Requirements for Prescription Drugs and Insulin  Laws  Laws Enforced by the FDA Laws Enforced by the FDA

6. 1. Professional Labeling 2. Immediate Container/ Outer package 3. Patient Product Information 4. Medication Guide 5. Promotional Labeling 6. DTC Advertising

7.  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. Professional Labeling: Isotrentinoin

9. 1. Statement of identity 1. Established name, Ingredients 2. Net quantity of contents 1. Weight, measure, numerical count, combination 3. Statement of usual dosage 1. “See package insert” 4. Expiration date 5. Name and place of business of manufacturer, packer, or distributor

10.  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. Patient Product Information

12.  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.  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. Accutane Medication Guide

15.  The Food and Drug Modernization Act of 1997 (FDAMA) - FDAMA HomepageFDAMA Homepage

16. 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 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 Diminish use of evidence- based medicine Expose patients to unidentified risk or harm Expose patients to unidentified risk or harm

17.  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.  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.  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.  Untitled Letters– notice of violation  Warning Letters – More serious violations  Injunctions and Consent Decrees  Criminal Investigation or Prosecution  Product Seizure

21. Thanks