Prof. Moustafa M. MohamedProf. Moustafa M. MohamedVice deanVice dean

Dr. Safa Ahmed El-askaryDr. Safa Ahmed El-askary

Faculty of Allied Medical ScienceFaculty of Allied Medical SciencePharos University in AlexandriaPharos University in Alexandria

Development and Regulation Development and Regulation of Medical Productsof Medical Products

((MEDR-101MEDR-101))

Lecture (5)

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

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

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

1. Professional Labeling

2. Immediate Container/ Outer package

3. Patient Product Information

4. Medication Guide

5. Promotional Labeling

6. DTC Advertising

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

Professional Labeling: Isotrentinoin

1. Statement of identity1. Established name, Ingredients

2. Net quantity of contents1. Weight, measure, numerical count, combination

3. Statement of usual dosage1. “See package insert”

4. Expiration date

5. Name and place of business of manufacturer, packer, or distributor

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

Patient Product Information

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

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

Accutane Medication Guide

The Food and Drug Modernization Act of 1997 (FDAMA) - FDAMA Homepage

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-Pre-““On-Label” Indications are On-Label” Indications are listed in FDA approved listed in FDA approved labeling, however, FDA labeling, however, FDA does not dictate the does not dictate the medical practicemedical practice

Drug sponsors may not Drug sponsors may not discuss, promote or discuss, promote or distribute materials that distribute materials that encourage “off-label” useencourage “off-label” use

Promotion of “Off-label” Promotion of “Off-label” use by sponsors would:use by sponsors would:

Diminish use of Diminish use of evidence-based evidence-based medicine medicine

Expose patients to Expose patients to unidentified risk or harmunidentified risk or harm

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

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

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

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

Thanks