Law Lecture 2.2

Drug and/or Cosmetic

https://www.fda.gov/drugs/information-healthcare-professionals-drugs/definition-drug-april-2017

FDA Enforcement (of FDCS:)

Injunction (can cause violators to cease illegal activity through an "injunction" = authoritative order Criminal Action (can institute criminal proceedings which can result in fines, imprisonment, or both) Seizure of Products (can issue warning letters for minor violations of this act...this would be the first step.)

DSHEA permits Nutritional or Structure/ Function Claims (403(r)(6))

1. Benefiting a classical nutrient deficiency disease (Ex Vit D and Rickets) 2. Affects the structure/function of the body 3. Characterizing the mechanism by which a Dietary Supplement acts to maintain the structure or function 4. Statements of general well-being "Label must contain disclaimer. "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.""

National Drug Code Number

10 digit three segment code (4-4-2, 5-3-2, 5-4-1) First segment identifies the manufacturer or distributor, second identifies the strength, dosage form, and formulation; and the third package size and type of drug Billing and Claims submissions require an 11 digit NDC number Picture on slide telling what is what

What is a device and how does it differ from a drug?

A device does not achieve its principle purpose through chemical action and is not dependent on being metabolized to achieve its principle purpose. "An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, recognized by USP or NF. Some devices are combination products (therapeutic and diagnostic products that combine drugs, devices, and/or biological products...these products present challenges for regulation because they are usually regulated by different agencies.) that also contain drug for example; drug eluding stents, IUD- Mirena releases levonorgestrel. (=>hybrid category) (Another example is insulin pump. )

Adulteration

Adulteration provisions focus on both facility and product. A pure drug may (Key Word! = these provisions in the law are intended to regulate the facility or the means of production rather than the product itself...2 reasons for this approach: 1. much easier for FDA to inspect a relatively few manufacturing plants than thousands of drug products produced by plants. 2. the health and safety risk to the public is much low if the FDA can prevent adulteration rather than wait and remove product.) be considered adulterated on the basis of conditions at the facility. (prepared, packed, or stored, contaminated container) • Drug is considered adulterated if its strength, quality, or purity differ from the label. • Drug is considered adulterated if its strength, quality, or purity differ from compendia standards, unless clearly stated on label (Pharmacies can violate adulteration provisions. Ex. pharmacy counts tablets on a dirty tray or tray where residue of previous drug remains...pharmacy repackages products in contaminated containers...pharmacy stores inventory in room with inadequate temp control • Manufacturers need to comply with CGMP or the product can be considered adulterated. • CGMP is a set of regulations or standards that manufacturers must follow to ensure that the drug is safe and meets purity requirements. • Manufacturers are registered with FDA and inspected for compliance with CGMP • Failure to manufacture a product in a tamper resistant container when required by law is adulteration and misbranding.

Federal Food and Drug Administration (FDA)

Agency within the Department of Health and Human Services (DHHS) Authority for administering the FDCA (US Code 21 U.S.C. 301.) Core functions include Offices of; Medical Products and Tobacco Foods and Veterinary Medicine Global Regulatory Operations and Policy Operations

How does a food differ from a drug? (Definition of food is intentionally vague)

Depends on the intended use. • Something is a food if it is used for its ordinary purpose and in an ordinary manner. • Legal Categories (might categorize them as a drug) Special dietary foods (recognized under FDCA - include but not limited to those supplying a dietary need that exists by reason of a physical, physiological, pathological, or other condition...includes condition of disease, convalescence, pregnancy, lactation, infancy, allergic hypersensitivity to food, being under/overweight or need to control Na+ intake) Medical Foods (Ex special infant formulas, caloric supplements (Ensure)) • "Nutriceuticals" and "functional" foods not specifically defined by law (regulated by FDA) (Substances that would provide healthier medical benefits which could include prevention or treatment of disease...Ex cereals, fruits, veggies) • Nutrition Labeling and Education Act allows foods to contain health claims if approved by FDA by regulation or "significant scientific agreement" test. (Functional foods: foods fortified or enhanced with dietary supplements....Ex energy drinks with k??? or ginseng added)(Medical Foods - foods formulated for internal nutrition under the supervision of a physician that are intended for special dietary management of a disease or condition which has distinctive nutritional requirements that are established by medical evaluation...*Specially Formulated, not naturally occurring...They provide nutritional requirements that could not be obtained from normal diet...Ex. Osmolite or Jevity)

Dietary Supplements "FDA regulates both finished dietary supplement products and dietary ingredients...they regulate dietary supplements under a different set of regulations that are covered by conventional foods and drug products...under DSHEA"

Dietary Supplement Health and Education Act of 1994 (DSHEA) ü Created a new category of food called "dietary supplements". ü "Dietary Supplements" do not require premarket approval (FDCA defines dietary ingredients as:)Defined as a vitamin, mineral, herb, or other botanical; amino acid, or substance used to supplement the diet by increasing total dietary intake. ( or a concentrate, metabolites, constituent, extract or combination of above substances) "Manufacturers of dietary supplements and dietary ingredient are prohibited from marketing products that are adulterated or miss branded which means these firms are responsible for evaluating the safety and the labeling of their products before marketing to ensure they meet requirements of DSHEA and FDA" "FDA is responsible for taking action against any adulterated or misbranded dietary supplement products after it reaches the market ***FDA does NOT approve dietary supplements...it approves drugs not dietary supplements"

True or False? The primary purpose of drug labeling is to give patients information they need to take medications properly.

FALSE! "Although patients may obtain useful information from prescription drug labeling, its primary purpose is to give healthcare professionals the information they need to prescribe drugs appropriately."-FDA Introduction to the Improved FDA Prescription Drug Labeling

Mission Statement

FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

Product Recalls (way of removing adulterated or misbranded products and interstate commerce happens voluntarily by manufacturer or by FDA request or FDA mandate if necessary)

FDAAA (passed in 2007) gives FDA limited authority to recall certain products such as medical devices, biological products, and foods. Does not include drugs. • Three classes of drug recalls Class 1: issued when there is a reasonable probability that the product will cause serious adverse health consequences or death Class 2: occur when the product may cause temporary or medically reversible adverse health consequences but the probability of the consequences is remote Class 3: apply to products that are not likely to cause adverse health consequences • Manufactures responsible for notifying the seller and the seller is responsible for notifying the consumer (Manufacturer recalls may be delivered via telephone, letter, telegram, sales representative, etc. ...FDA requires that written notices for class 1 and 2 and some class 3 recall be sent in 1st class mail with an envelope and letterhead marked in red (preferably) "Urgent Drug Recall") • Pharmacists are responsible for knowing product recalls (Furnishing a recalled product may violate FDCA because product is likely adulterated or misbranded)

What does FDA regulate? (FDA is responsible for protecting public health by assuring foods with few exceptions meat from livestock, poultry, and some egg products are safe, wholesome, sanitary, and properly labeled...ensure cosmetics and dietary supplements are safe and properly labeled...Regulate tobacco products and advance public health by helping to speed product innovations

Foods; including dietary supplements, bottled water, food additives, infant formulas, other food products Drugs; prescription drugs (brand name and generic), non-prescription (over-the-counter) drugs Biologics; vaccines, cellular and gene therapy, blood products, etc. Medical Devices; simple, complex (pacemakers), dental, surgical implants and prosthetics Cosmetics; skin care products, color additives Other; veterinary, tobacco, electronic products, oncology "FDA approves new drugs and biologics FDA approves food additives in food for people FDA approves color additives used in FDA-regulated products FDA approves animal drugs and food additives for use in food for animals"

Cosmetic or Drug?

Just pictures

Evidence a Product is a Drug

Labeling ( claims stated on label made by manufacturer, does manufacturer promote for particular use or treat or prevent a disease or affect structure or function of body?) • Advertising ("product restores hair growth, reduces cellulite, treats varicose veins, regenerates cells...generally drug claims) • Nature of the product (May be established through products reputation...why is consumer buying the product, and what does consumer expect it to do...inclusion of ingredient that has well known use like fluoride in toothpaste)

Prescription Drug Labeling Resources

Lots of pictures (Ex from FDA website) (DailyMed: Good for finding info about prescribing sponsored by the NIH)

Labeling may also include Instructions for use or medication guides

Lots of pictures (Medication Guide: Accompanies the drug)

Drug Safety Communications

Picture

Prescription Drug Lablein

Prescription drugs are labeled for the healthcare professional, not the patient. (With the exception of Medication Guide or Patient Instructions) Regulations specify information requirements of the commercial label. (includes info such as name and address of manufacturer, packer, or distributor, name of product, quantity, % of each active ingredient... will also contain Rx only legend: "Caution federal law prohibits dispensing without a prescription" Unit dose labeling is subject to different information requirements. (Can be found on FDA website) New package insert requirements include a "Highlights" section at the beginning, a table of contents, "Full prescribing information", and a "patient counseling information" section.

Pregnancy Warnings

Prior to June 30, 2015 the labeling system required that drugs that were potentially risky during pregnancy would be placed into five categories; A, B, C, D, X. 2014 regulation replaced the prior system. For drugs approved after June 30, 2015, labeling requires the inclusion of three subsections; Pregnancy, Lactation, and Females and Males of Reproductive Potential. Drugs that were approved prior to June 30, 2015 will be gradually phased into the new labeling standards.

Rationale for Federal Drug Regulation

Protection of the public against adulterated and misbranded drug products • Necessity of balancing "Direct regulation" and "Indirect regulation" (less formal way of regulating...allows consumers/patients to have more choice or to take more risk and not be as protected Ex. Use of OTC and herbal supplements...They regulate by publishing guidance documents) • Rulemaking authority from Section 707 of FDCA "The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation's food supply, cosmetics, and products that emit radiation. FDA also has responsibility for regulating the manufacturing, marketing, and distribution of tobacco products to protect the public health and to reduce tobacco use by minors."

Eucrisa (cristabole) ointment 2% Anacor Pharmaceuticals

Too much on this slide for me to know how to type. (She went on to explain why they advertise this...expectation of the consumer is that this treats eczema....therefore, this fits the definition of a drug.)

Health or Disease Claims for Foods

Unlike drugs, supplements are not intended to treat, diagnose, prevent, or cure diseases. That means supplements should not make claims, such as "reduces pain" or "treats heart disease." Claims like these can only legitimately be made for drugs, not dietary supplements. (www.fda.gov) The Nutrition Labeling and Education Act of 1990 does allow foods to contain health claims if approved by FDA regulation or the "significant scientific agreement" test. "The agency has concluded that, based on the totality of the scientific evidence, there is significant scientific agreement among qualified experts to support the relationship between soluble fiber in whole oats and CHD. Therefore, FDA has decided to make the subject of the health claim ''soluble fiber from whole oats'' and has concluded that claims on foods relating the consumption of soluble fiber from whole oats to reduced risk of heart disease are justified. " "Manufacturers must submit considerable evidence to support the claim to obtain FDA approval Example: oatmeal helps reduce cholesterol"

www.Recalls.GOV

Your Online Resource for Recalls (Patients can self report on MedWatch) Just a big picture

Nonprescription Drug Labeling

• "User friendly format" (pharmacologic category, principle intended use, cautions, warnings, adequate directions for use and "Drug Facts" panel. • Pharmacists who relabel or repackage must conform to the same labeling requirements as manufacturer. (OTC = safe and effective drugs for self medication by consumers) • "Professional labeling" can be published by manufacturers for conditions not appropriate for lay diagnosis or treatment. • Some drugs exist as both OTC and prescription, (ex. prilosec, ibuprofen) depending on the indication for use (some indications can be labeled with adequate directions for use).

Labels and Labeling

• 'Labeling means all labels (any info that is required on the container or wrapper itself) and other written, printed, or graphic matter upon any article or any of its containers or wrappers, or accompanying such articles.' 201 (m); 21 U.S.C. 321 (m) (package insert is example of labeling b/c it "accompanies" the drug) • Labeling includes labels. • Courts have defined the word accompanying. (to determine if misbranding has occurred) • If the written, printed, or graphic matter is not labeling, it is advertising. • Physician Labeling Rule in January 2006, revised the content and format of prescribing information to this PLR format to enhance the safe and effective use of drugs. 21 CFR 201.57

What is a Drug?

• Articles recognized in USP or homeopathic pharmocopeia • Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease. • Articles (other than food) intended to affect the structure or function of the body. • Definition is intentionally broad to include almost anything with an intended therapeutic purpose or purpose of altering the structure or function of the body.

Health and Disease Claims

• DSHEA only permits DS manufacturers to make health claims if either the FDA approves the claim or by regulation of the "significant scientific agreement" test. • Pearson v. Shalala, held that dietary supplement manufacturers could make health claims not approved by the FDA, provided they are not false or misleading and accompanied by a disclaimer. • FDA now allows qualified and unqualified health claims.

Cosmetics

• Definition: generally includes topical articles intended for cleansing, beautifying, promoting attractiveness, or altering appearance. • A cosmetic can become a drug if the seller makes a health or structure/function claim. (For cosmetics, the standard is "will a reasonable customer be mislead.") • "Ignorant, unthinking consumer" standard likely applied • FDCA prohibits the distribution of cosmetics that are adulterated or misbranded in interstate commerce. (Dandruff is a health condition) "Some products may be both a cosmetic and a drug if a product has two intended uses. An antidandruff shampoo treats dandruff and cleanses the hair. Some moisturizers and makeup contain sunscreen and make sun-protection claims. These products must comply with requirements for both drugs and cosmetics."

Safety Issues

• FDA can only remove a DS on the basis of the product being adulterated, defined as presenting "significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling." Example: Ephedrine alkaloid DS •Dietary Supplement and Nonprescription Drug Consumer Protection Act requires manufacturers to report serious adverse events.

Drug and/or Device

• Historical approach of the FDA prior to the Medical Device Amendments was to declare devices as drugs when necessary. • Definition of device excludes articles that achieve their purpose through chemical action and metabolism. • Whether a device containing drugs is a drug or device is dependent on various factors. (Some devices can contain drugs...Drug Eluting Stent) • Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products.

Misbranding

• Misbranding focuses on representations made by the manufacturer on the label or labeling. • Labeling cannot be false or misleading (including pharmaco-economic information) (When dangerous to health when used in a dosage or a manner or frequency or duration prescribed, recommended or suggested on the labeling and it does not comply with the color additives provision (section 705 of FDCA) • Labeling must include a list of active ingredients, quantity, inactive ingredients in alpha order (Label fails to tell name and place of business of manufacturer, packer, or distributor) • Labeling must contain "adequate directions for use" by children and others for whom use might be dangerous (Directions under which a lay person can use the drug safely and for the intended purposes) • Prescription drugs are exempt for the "adequate directions for use" (package inserts) requirement if they contain "adequate information for use" (inaccurate statement of the quantity or contents in terms of weight, measure or humerical count is different) • If a drug imitates another drug it is considered misbranding) (establishment is not registered with the FDA) (Any required warning wording is not properly disp)

Drug Recalls

• Most effective way to protect the public from a potentially harmful product • A Recall is a voluntary action taken by a company to remove a defective drug product from the market • Drug recalls may be conducted on a companies own initiative or by FDA request • FDA's Role in a recall; 1. oversee a company's strategy 2. assess the adequacy of the recall 3. classify the recall • Alerting the public (Not all recalls are an FDA gov or in news media. Public notification is generally issued when a product that has been widely distributed or poses a serious health hazard is recalled. *If company does not issue public notice, FDA may do so if necessary to protect patients.)

Prohibited Acts

• Most prohibited acts under the FDCA involve misbranding or adulteration • Violation of FDCA is subject to strict liability (if a pharmacy purchases a misbranded or adulterated drug and doesn'tknow it, then sells to patient, the pharm violated this act) Good faith excuse is applicable (if pharmacist who sales the drug in good faith will not be subject to any penalties if they furnish the FDA with info about the sources of supply) • Applicable to pharmacies -The receipt and subsequent delivery of an adulterated or misbranded drug (§301(c) ) -Doing any act that causes a drug to be counterfeit (§301 (i) (3)) -Adulteration, mutilation, etc of the labeling. (§301 (k) ) "Pharmacists can be held responsible if they do not investigate potential violations and conduct themselves using due diligence which is the standard to make sure they are not violating the FDCA...they need to ensure the integrity of the drug distribution system It is illegal for pharmacist to make, dispense, or hold for sale a counterfeit drug Pharmacies that repackage drugs or reliable them put into unit doses, they must pay really close attention to making sure that the label conforms to FDA specifications for unit doses"

DSHEA Implications for Pharmacists

• Product selection • Education of patients as opposed to promotion of products-Benefit vs. Risk (decision ALWAYS) • Restrictions regarding the display of Dietary Supplements publications (<They can't be in the same area as the dietary supplements)

Black Box Warnings

• Required in labeling when use of a drug may lead to death or serious injury. • Adverse reaction so serious in proportion to the potential benefit (fatal, life-threatening, permanently disabling) • Serious adverse reaction that can be prevented or reduced in frequency or severity by appropriate use of the drug. (patient selection, careful monitoring, avoiding concomitant therapy, addition of another drug to manage risk, avoiding use in specific clinical situations) • FDA approved with restrictions to ensure safe use-"Risk Evaluation and Mitigation Strategies" or REMS • Required for 450 prescription drugs. (FDA admits Black Box warning are pretty ineffective.)

Functions of the FDA

• Rulemaking or regulations Title 21 of the Code of Federal Regulations (CFR) (Congress delegates authority to the FDA to develop regulations based on the laws set forth by FDCA and other laws that FDA operates under... .FDA uses process called "notice and comment rulemaking" => allows public input for a proposal legislation before FDA issues a final regulation => allows stakeholders, experts and public to have a voice... FDA laws are fed laws but not part of the FDCA • Issue Guidance documents, but these do not have the force of law. 21 CFR 10.115 (less formal way of regulation...Guidance documents describe agency's current thinking on a regulatory issue but don't have the face of law..."Good Guidance Practice Regulation" • Incorporates advice from standing advisory committees of outside experts (They make recommendations about whether drugs and devices should be approved.

Official Compendia "In part A of definition of a drug it recognizes compendium such as the US Pharmacopeia as a legal source of drug standards..."

• The USP (U.S. Pharmacopeia)is published by the USPC Sets uniform standards USPC (U.S. Pharmacopeia Convention) works closely with FDA but it is a private organization (for a drug) • HPUS (Not a government agency) Publishes standards for homeopathy products by HPCUS, a private organization Role and legal authority of HPUS • Pursuant to FDCA, if a drug is recognized in the USP or the HPUS the drug product must meet all standards of the compendia.(If it does NOT, ten it is considered misbranded or adulterated.)