1/25 Federal Regulation of Medications
Prescription Drug Labels and Labeling *** usually more specific to state uNewer package insert requirements include a______ section at the beginning, a table of contents, _____ organized to give prominence to most important information, and a _____ section.
"Highlights" "Full Prescribing Information" "Patient Counseling Information" **** As noted earlier, prescription drugs are labeled for the healthcare professional, not the patient.
Drug Manufacturer Controversial Practices uProducing ______ u30-month stay from ANDA approval awarded when a patent holder sues for ______ uFiling of _____, often for product changes and attempts to shift market share to new product ____ payments (pay-for-delay agreements) - brand will pay generic company to not make product
"authorized generics" - when a brand name gets authority for generic of their own drug patent infringement secondary patents Exclusion
Dietary Supplement and/or Drug? DSHEA. (Dietary Supplement Health and Education Act) uCreated a new special category of food called _______ which do NOT require _____ approval u _____ defined as a vitamin, mineral, herb, or other botanical, amino acid, or substance used to supplement the diet by increasing total dietary intake
"dietary supplements" (DSs) premarket DS
21st Century Cures Act and New Drug Approval •It encourages the consideration of novel clinical trial designs and the incorporation of _____ into the decision-making process. •The law also creates or amends four pathways or programs for drugs that treat serious or life-threatening diseases that affect ______ or diseases with significant public health risk.
"real-world evidence" smaller populations including facilitating the development and approval pathway for GENETICALLY TARGETED drugs that meet unmet medical needs; creating a program for the approval of antimicrobial resistant drugs ("SUPERBUGS") for limited populations; expanding the ORPHAN DRUG program; and reauthorizing the FDA voucher program for RARE PEDIATRIC diseases.
In class slidgo questions
...
New Drug Application (NDA) •The FDA has _____ days to act on a completed NDA, but delays are common. •Approval is based on proof of ____ & _____, the ______ process, and ____ ratio.
180 safety and efficacy manufacturing risk-benefit
Drug Efficacy Study Implementation (DESI) •Initiated to evaluate the efficacy of drugs approved between _____ •The FDA created the ANDA for generic drugs approved between _____
1938 and 1962 1938 and 1962.
National Drug Code Number •10-digit three segment code (____, ____, or ____) •The first segment identifies _____; the second identifies ______; and the third identifies _____ •Billings and claims submissions require an _____ NDC number
4-4-2, 5-3-2, or 5-4-1 manufacturer or distributor strength, dosage form, and formulation package size and type of drug 11-digit
Pregnancy Warnings •The labeling system prior to June 30, 2015 required that drugs potentially risky during pregnancy be placed into one of five categories: ______ •A 2014 regulation replaces the above system. For drugs approved after June 30, 2015, labeling will require the inclusion of three subsections to describe risks: ___, ___, ___ •Drugs approved prior to June 30, 2015 will be gradually phased into the new labeling standards.
A, B, C, D, X. "Pregnancy," "Lactation," and "Females and Males of Reproductive Potential." *** now all drugs have to include all 3 sections
Controversies for Healthcare Practitioners •______ of generics to the parent and each other •Whether a drug without _____ for a particular indication could be prescribed and dispensed for that indication
Bioequivalence market exclusivity
uRequired in labeling when use of a drug may lead to death or serious injury uRequired for many prescription drugs
Black Box Warnings
Adulteration uA product is adulterated unless manufacturer complies to ______. u _____ is an exhaustive set of standards directed at manufacturers. uThe failure to manufacture a product in a _____ container when required by law is adulteration AND ALSO MISBRANDING
CGMP (Current Good Manufacturing Practices) CGMP tamper-resistant
New Drug Application (NDA) Process IND Investigational New Drug Application uThe sponsor must receive approved Notice of ______ for a New Drug in order to SHIP drug in interstate commerce to CONDUCT phase 1, 2, and 3 clinical studies. uThe FDA may terminate testing at any time under ______ criteria; the decision is not subject to _____ uThe FDAAA requires _____ sponsors to publish summary information regarding phase 1 trials on a public registry.
Claimed Investigational Exemption risk-benefit appeal or judicial review. NDA
Federal Food and Drug Administration (FDA) - came from FDCA •Housed under the _____ •Authority for ADMINISTERING the ______ •FDA _____ appointed by president with confirmation of Senate
Department of Health and Human Services (DHHS) FDCA (Food Drug and Cosmetic Act) secretary
•The goal is to institute new policies aimed at bringing more competition to the drug market, most notably improving the efficiency of the generic drug approval process. •Policies designed to bring complex generic drugs to market more quickly •Guidance also released to streamline the ANDA process for all generic drugs
Drug Competition Action Plan
Drug Quality and Security Act (2013) - QUALITY focused on compounding Title 1: _______ Act- New England Compounding Center uPut in place requirements for "outsourcing facilities" also call 503A pharmacies???????
Drug Compounding -The FDA has designated 503A compounding pharmacies as those that compound according to prescriptions - NOT patient specific -somewhere in between manufacturer and pharmacy 503A Compounding Pharmacies (aka "traditional compounding pharmacies) provide individual physician-prescribed drug products. 503B drug products are readily available for ambulatory surgery centers, hospitals, and other healthcare systems. 503A drug products are designated for home use only
Drug Quality and Security Act (2013) u ________ Act (DSCSA) "Track and Trace" Provides a national requirement for electronic track and trace system for prescription drugs from raw ingredient to patient
Drug Supply Chain Security -NOV 2023 pharmacy level will take place
Established 2 classes of drugs: prescription and over-the-counter before this needed an prescription
Durham-Humphrey Amendment help accessing drugs - drug help -DH
Office of Medical Products and Tobacco - the one we tend to hear from the most The Office of Medical Products and Tobacco coordinates and leads scientific and regulatory evaluations and interpretations for drugs, biologics, medical devices, and tobacco products, and includes: •Center for Drug ____ & _____ •Center for _____ Evaluation and Research •Center for Devices and _____ Health •Center for _____ Products •______ Center of Excellence •Office of Special _____ Programs •_____ Affairs Staff
Evaluation and Research (CDER) Biologics Radiological Tobacco Oncology Medical Patient
Product Recalls •The FDAAA established _____ to order drug recalls for certain products, but not drugs. •Three classes of _____ •______ responsible for notifying seller; ______ responsible for notifying consumers, if necessary •Pharmacists responsible for knowing of ______
FDA authority recalls Manufacturers, seller product recalls
•Following deaths by sulfanilamide elixir in 1937, new drugs must be proven SAFE prior to marketing •ESTABLISHED the FDA
Food Drug & Cosmetic Act
Order of studies
INDA - can't be shipped without this P123 NDA (comes to market) P4 (after on the market)
Misbranding uIf drug cannot be labeled with "adequate directions for use," it must contain "adequate _____ for use." uIt is misbranding if a drug _____ another drug.
INFORMATION - package insert??? In addition to the statements of all conditions, purposes, or uses, "adequate" labeling of a drug must include: The quantity or dosage for each intended use and for persons of different ages and physical conditions The frequency of administration or application The duration of administration or application The time of administration or application (in relation to meals, onset of symptoms, or other factors) The route or method of administration or applicationThe preparation necessary for use (e.g., shaking, dilution) imitates Identical in shape, size, and color Similar or virtually identical in gross appearance Similar in effect to controlled substances
Informed Consent • ______ required in all three phases •Research subjects required to know risks, possible benefits, and ______ treatment • _______ approval required in some settings
Informed consent alternative courses of Institutional Review Board (IRB)
FDA Enforcement Authority - similar to BOP • _____ action against the violator to cause it to cease its illegal activity • _____ action against violators, resulting in fines, imprisonment, or both • _____ of products seize any adulterated or misbranded food, drug, or cosmetic in interstate commerce • _____ letters to the violator as a first step when such an action would adequately serve the public interest
Injunction Criminal Seizure Warning
•Required new drugs to be proven SAFE and EFFECTIVE for their clinical use •Increased safety requirements and established good manufacturing practices (GMP) •Gave FDA authority over prescription drug advertising
Kefauver-Harris Amendment I'm safe & effective have good practices & advertise myself
Prescription Drug _____ Act (1987) uBans _____ uProhibits sale, trade or purchase of _____ samples uRequires storage, handling, and record keeping requirements for ______ samples uProhibits the _____ of prescription drugs purchased by hospitals or healthcare facilities and donated drugs
Marketing: reimportation prescription drug prescription drug resale
Drug and/or Device? •The historical approach of the FDA prior to the ______ Amendments was to declare devices as drugs when necessary. •The definition of _____ excludes articles that achieve their purpose through chemical action and metabolism. •Whether a device containing _____ is a drug or device is dependent on various factors.
Medical Device device drugs The FDA has stated that many factors may determine whether a product is a device or a drug: Is the product intended to deliver drugs to the patient, but is not prefilled by the manufacturer (e.g., an empty implantable infusion pump)? Is the drug component included solely to make the product safer (e.g., a surgical drape impregnated with antimicrobial agents)? Is the drug component intended to have a therapeutic effect (e.g., an intrauterine contraceptive device that releases a hormone)?
Risk Evaluation and Mitigation Strategy (REMS) •The FDAAA granted the FDA authority to require REMS as a condition for approval of an _____ or _____ when the FDA believes it necessary to ensure benefits outweigh risks. •Under REMS authority, the FDA can require a variety of procedures ranging from ______ to limiting the drug to specified _____ for dispensing.
NDA postmarket Medication Guides settings
New Drug Approval •The FDA will not accept a GRASE application and requires a _____.
New Drug Application (NDA)
Nonprescription Drug Labeling uProfessional ____ labeling may be published by manufacturers for indications not appropriate for lay diagnosis or treatment. uDrugs that are both _____ exist when some indications can be labeled with adequate directions for use and some cannot.
OTC For example, the allowed OTC labeling indications for antacids include "heartburn," "sour stomach," "acid indigestion," and so forth. The professional labeling includes indications for "the symptomatic relief of hyperacidity associated with the diagnosis of peptic ulcer, gastritis ..." ( OTC and prescription For example, meclizine is sold OTC for the indications of nausea, vomiting, and dizziness associated with motion sickness. The drug is sold by prescription with the added indication of being possibly effective for vertigo associated with diseases affecting the vestibular system.
process approves drugs on the basis of therapeutic category and conformance to a monograph rather than on a drug-by-drug basis like prescription drugs.
OTC Drug Review This system, which continues today for post-1962 OTC products, evaluates OTC products on the basis of therapeutic category rather than individually and classifies products through rulemaking rather than on a case-by-case basis. The agency took this approach for several reasons. First, there were between 100,000 and 500,000 OTC drug products on the market, many of which were not approved by the NDA; reviewing each of these products would overwhelm the FDA's resources. Second, litigation to remove unsafe or ineffective individual OTC products would be prohibitively time- consuming and expensive. Third, nearly all the OTC drugs were prepared from only 200 or so active ingredients.
Corporate Officer Liability: " _____ Doctrine" Affirmative duty of corporate officers to be aware of and correct violations
Park if you're the VP of company and people are cutting corners you are responsible Finding the defendant liable under the FDCA, the Court stated that the act imposes a duty not only to seek out and correct violations, but also to implement procedures to ensure that violations will not occur. This requirement on corporate officers may be demanding and onerous, stated the Court, but no more so than the public has a right to expect in light of the effect on the public health and well- being. These two decisions collectively are known as the "Park Doctrine" and establish that corporate officials can be personally prosecuted without proof they acted intentionally or with negligence and even if they had no knowledge of the offense.
Implications of DSHEA for Pharmacists •______ selection •______ of patients as opposed to promotion of products •Restrictions regarding the display of DS _______
Product Education publications If possible, pharmacists should steer patients to products conforming to United States Pharmacopeia (USP) or National Formulary (NF) standards, or at least products in which manufacturers can attest to quality and uniformity standards. DSHEA permits pharmacists to display certain publications, such as articles, book chapters, books, and abstracts of peer-reviewed scientific publications, used in conjunction with the sale of dietary supplements. To conform to the law, however, these publications must be reprinted in their entirety; must not be false or misleading; must be presented with other publications, if available, about the product in order to present a balanced view; must be physically separate from the actual product; and must not have appended to them any information by sticker or other method.
Prohibited the adulteration and misbranding of foods and drugs in interstate commerce
Pure Food and Drug Act food and drugs were entering market adulterated
Functions of FDA • ____ making •Issue _____ documents •Incorporate _____ from standing advisory committees of outside experts
Rule (when congress passes law can be regulated by FDA) guidance advice
•Similar to extinct "paper NDA" Used to file for: •New indications for approved drugs •Generic approvals that do not qualify under ANDA
Section 505(b)(2) NDAs Examples of products eligible for the 505(b)(2) approval process include but are not limited to the following: Change in the route of administration. Conversion to lower or higher strength. Change in the route of administration of dosage form or dosage regimen. Change in the formulation
Official Compendia •Pursuant to FDCA, if a drug is recognized in ____ or ____, the drug product must meet all standards of the compendia
USP or HPUS Under the FDCA, a drug recognized in the USP-NF or HPUS must meet all compendium standards or it will be considered misbranded or adulterated. Similarly, a drug is considered misbranded or adulterated if it is not recognized in the USP-NF or HPUS, yet purports to be so recognized.
What Is a Drug? •Articles recognized in the ____ or _____ •Articles intended for use in ..... •Articles other than ____ intended to affect the structure or function of the body (Part C) •Definition is intentionally _____ to include almost anything with an intended therapeutic purpose or purpose of altering the structure or function of the body
USP or homeopathic pharmacopeia diagnosis, cure, mitigation, treatment, or prevention of disease (Part B) food broad
Official Compendia USP •Published by the ____ •Sets _____ standards •USPC works closely with the _____, but is private
USPC United States Pharmacopeial Convention uniform FDA
Nonprescription Drug Labeling - now standardized u ______ format including pharmacological category or principal intended use, cautions and warnings, adequate DIRECTIONS for use, and "Drug Facts" panel uPharmacies that _____ must conform to the same labeling requirements as manufacturers.
User-friendly relabel or repackage
Postmarket Drug Safety Information for Patients and Providers uThe FDAAA required the FDA to develop and maintain _____ for patients and providers including labeling, safety information, REMS, guidance documents, etc. uThe FDAAA also established ______ designed to detect early signs of a drug's risk
a website Sentinel Initiative Under the Sentinel Initiative, the FDA has developed a new electronic system that enables it to query a broad array of information data sources, such as electronic health record systems and insurance claims databases, to identify possible postmarket adverse events. The FDA has partnered with the Centers for Medicare & Medicaid Services (CMS) to analyze Medicare Part D claims data, and also will partner with the Veterans Administration as well as an array of private healthcare organizations to analyze their data.
Safety Issues •The FDA can only remove a DS on the basis of the product being ______, defined as presenting "significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling." •Example: ______ DS •The Dietary Supplement and Nonprescription Drug Consumer Protection Act requires manufacturers to report ______.
adulterated ephedrine alkaloid (cardiac events) serious adverse events
Rationale for Federal Drug Regulation •Protection of the public against ____ & ____ drug products •Necessity of balancing ____ & ____
adulterated and misbranded "direct regulation" and "indirect regulation" The 1906 law was an example of "indirect regulation." Its purpose was to help people make their own decisions by providing accurate and useful information through appropriate labeling. The 1938 act not only reinforced the indirect regulation by expanding the labeling requirements, but it also introduced an important piece of "direct regulation" by keeping off the market those drugs that have not met government safety standards. This type of regulation is direct because it makes decisions for people rather than helping them to make decisions for themselves. The 1951 and 1962 amendments increased direct regulation by mandating prescriptions for certain drugs and requiring proof of efficacy as well as safety for drug approval. At present, most of the drugs available cannot be used unless the government has certified them as safe and effective and another person (an authorized prescriber) has decided to permit their use. It is also perhaps no coincidence that the past decade has witnessed an unprecedented number of drugs switched from prescription status to OTC status. This may signal the beginning of a trend away from direct regulation and back toward indirect regulation, empowering patients to participate actively in healthcare decisions rather than passively accepting therapies decided on by others.
Applicable to pharmacies •The receipt and subsequent delivery of an ____ or _____ drug (Section 301(c)) •The doing of any act which causes a drug to be _____ (Section 301(i)(3)) •The alteration, mutilation, etc. of the _____ (Section 301(k))
adulterated or misbranded counterfeit labeling *** as long as providing available information, purchasing through appropriate channel
Phase 4 Studies uThe FDAAA Food and Drug Administration Amendments Act empowered the FDA to require manufacturers to conduct phase 4 studies when _____
adverse event reporting or active surveillance is inadequate
Dietary Supplements Containing Drugs uDSHEA excludes an article as a DS if it was ______ uThe ______ case establishes that DSs cannot be specially manufactured to concentrate the natural drug ingredient.
approved as a drug prior to being marketed as a DS Pharmanex
New Drug Approval •No person may introduce a "new drug" into interstate commerce unless ______. •"New drug" is defined as a drug that is not ______ for use under the conditions recommended in the drug's labeling and has been used for a material extent and time for conditions recommended in labeling.
approved by the FDA generally recognized by qualified experts as safe and effective (GRASE)
Drug Efficacy Study Implementation (DESI) •The ANDA only requires evidence of ______ and _____ methods rather than proof of safety and efficacy. •The U.S. Supreme Court ruled that generic drugs are _____
bioequivalence manufacturing new drugs and subject to FDA approval
Supplemental New Drug Application (SNDA) uSNDA generally required when a manufacturer makes any _____ u ____ categories of SNDA uA _____ SNDA allows the sponsor to make the change before FDA approval and is important for labeling changes.
change in an approved drug or in its production Three "change being effected (CBE)" For changes in any part of the production, ranging from the synthesis of the drug to the manufacturing processes of the drug to most of the labeling of the drug, a "prior approval" supplement is required, whereby the agency must approve the change before the sponsor can implement it. For certain types of labeling changes, such as those that strengthen warnings or dosage and administration information or for certain changes in manufacturing methods, facilities, and controls, a "change being effected" (CBE) supplement may be allowed. The CBE supplement allows the sponsor to implement the change before the FDA approves it. For labeling changes, however, the regulation requires that the change must reflect "newly acquired information" that strengthens a contraindication, warning, precaution, or adverse reaction, and then only if there is sufficient evidence of a causal association. The final category of supplemental NDA allows very minor changes, such as editorial changes in labeling or changes in container size to merely be reported in the annual report that the sponsor must file to the FDA.
Prescription Drug Labels and Labeling uRegulations specify information requirements of _____ label. u _____ labeling is subject to different information requirements.
commercial Unit dose
Health or Disease Claims for Foods •A health claim for a food made by a manufacturer could result in the product being ______ •The Nutrition Labeling and Education Act of 1990 and subsequently FDAMA allow foods to contain health claims if approved by the FDA by regulation or by the _____ test. •Manufacturer must submit considerable _____ to support the claim to obtain FDA approval.
considered a drug - Cheerios: lowering cholesterol had to submit evidence, ended up changing label "significant scientific agreement" evidence
Drug and/or Cosmetic? uThe definition of _____ generally includes topical articles intended for cleansing, beautifying, or altering appearance. uA _____ can become a drug if the seller makes a health or structure/function claim. u"Ignorant, unthinking _____" standard likely applied uSome products can be both ____ & ____.
cosmetic cosmetic consumer cosmetics and drugs (acne medication in soap)
Special Food Categories Legal categories •Special _____ foods •_____ foods Publicly conceived categories •____ & ____ foods
dietary special dietary foods include but are not limited to those supplying a special dietary need that exists by reason of a physical, physiological, pathological, or other condition, including but not limited to the condition of disease, convalescence (recovery from illness), pregnancy, lactation, infancy, allergic hypersensitivity to food, underweight, overweight, or the need to control the intake of sodium. Examples of products in this category include infant formulas, artificial sweeteners, and caloric supplements. Medical Examples of medical foods include foods formulated without the amino acid phenylalanine for phenylketonuria; and folic acid, B6, B12 combination products for hyperhomocysteinemia. Medical foods must be specially formulated, not naturally occurring, and must provide nutritional requirements that would be impossible for the patient to meet through a normal diet. Nutraceuticals and functional foods category of nutraceuticals would include any substance that may be considered food or part of food and that provides health or medical benefits, including the prevention and treatment of disease. Such products would include nutrients; genetically engineered foods; some cereals, soups, and beverages; and many fruits and vegetables because they contain such health-related isolates as vitamins, minerals, and omega-3 fatty acids. Advocates of this product classification contend that the current system deters the development of a substantial number of beneficial food-related products because the FDA could regard the products as drugs. Another related category of product some would like distinguished by law is one called "functional foods." These include foods or nutraceuticals that have been fortified or enhanced, often with a dietary supplement such as drinks with ginseng or kava kava added and foods fortified with calcium. Probiotics are yet another example of products that would likely fall into this category. Probiotics are defined as live microorganisms that when administered in adequate amounts produce healthy results. Currently, the law does not recognize any category of articles as nutraceuticals or functional foods. However, many products that might be considered nutraceuticals or functional foods are regulated as dietary supplements and would likely be exempted from parts of the drug definition (discussed later). There is a contentious history between the FDA and food manufacturers who have made health claims for their products. One controversy arose in the 1980s when studies at the time indicated that the ingestion of psyllium might lower cholesterol levels. Cereal manufacturers whose products contained fibrous psyllium thus proclaimed the value of their products in reducing cholesterol levels. The FDA believed that these claims made the products drugs and warned the cereal manufacturers. OTC drug manufacturers who produced psyllium laxatives also were concerned but for a different reason— their products were regulated as drugs and because of this, they could not promote their products as effective for lowering cholesterol without being charged for misbranding. Thus, they felt the cereal manufacturers had an unfair advantage if the FDA allowed them to label their products with the health claim.
Nutritional or Structure/Function Claims •The label must contain a ______.
disclaimer
Misbranding uLabeling must not be false or misleading, including healthcare ______ information. uLabeling must include a listing of _____ ingredients and quantity and listing of _____ ingredients in alpha order. uLabeling must contain "adequate _____ for use" and "adequate _____ against use" by children and others for whom use might be dangerous.
economic (pricing ect) active, inactive directions, warnings
Drug Price Competition and Patent Term Restoration Act (PTRA) of 1984 Statutorily created the ANDA, _____ generic approval Concessions to innovator drug companies included: u _____ extensions u ____ exclusivity
expediting Patent Market The PTRA (Hatch-Waxman amendment; P.L. 98-417) came to the aid of generic drugs by statutorily creating the ANDA, which had been the FDA's policy for pre-1962 generic drugs. As discussed earlier, an ANDA allows a sponsor to streamline the approval process because it does not have to conduct clinical studies to establish safety and efficacy. Rather, the sponsor needs only to submit sufficient information to demonstrate that the generic contains the same active ingredient, route of administration, dosage form, and strength as the pioneer drug; is bioequivalent to the pioneer drug; and has acceptable manufacturing methods and control procedures. The FDCA establishes a presumption that if the products are bioequivalent, then the generic drug is as safe and effective as the innovator drug.
Adulteration uAdulteration provisions focus on both the ____ & _____ uA drug is adulterated if its ____, ____ or _____ differs from compendia standards, unless plainly stated on label. uA drug is adulterated if its ____, _____ or _____ DIFFERS FROM LABEL.
facility and the product. - a pure drug may be considered adulterated on the basis of the facility. strength, quality, or purity - SO PURE QUEEN strength, quality, or purity
Health or Disease Claims •Pearson v. Shalala, however, held that DS manufacturers could make _____ not approved by the FDA, provided they are not false or misleading and accompanied by a disclaimer.
health claims
Official Compendia HPUS •Publishes standards for _____ products by the HPCUS, a private organization •Role and _____ authority of HPUS
homeopathy legal The other official compendium stated under the FDCA is the Homeopathic Pharmacopoeia of the United States (HPUS), which has been in continuous publication since 1897. The HPUS defines homeopathy as the "art and science of healing the sick by using substances capable of causing the same symptoms, syndromes, and conditions when administered to healthy people" However, the FDA has not applied the drug approval laws to homeopathic drugs and has chosen not to require proof of the safety and efficacy of these products. As a result, no drug products currently marketed and labeled as homeopathic have received FDA approval.
Drug Rating and Classification System •A priority classification system rates new drugs by chemical type and therapeutic potential; this determines _____ •A number designates ____ type, and a letter (S, P, or O) designates _____ potential
how quickly the drug will move through the IND/NDA process. chemical therapeutic FDA uses the letters P for priority or S for standard (replacing the A, B, and C letter ratings used before 1992) or O for orphan drug
Generic Drug Labeling Controversies •Whether FDA can approve an ANDA for a generic when the labeling will not include one or more of the _____ contained on the innovator drug product's labeling •Whether generic drug manufacturers should be required to change labeling to reflect a known _____
indications - should a new indication on brand name automatically be put on generic product adverse effect
Food or Drug? Generally depends upon _____ Food definition not very helpful in itself u(1) articles used for food or drink for man or other animals u(2) chewing gum u(3) articles used for components of any such article
intended use
New Drug Application (NDA) •Applicant may _____ a rejected NDA, but success is very unlikely.
judicially appeal *** remember can't appeal during testing phase
Labels and Labeling uThe term labeling includes _____. u_____ is defined as written or printed or graphic matter "accompanying" the article. uCourts have defined _____. uIf the written, printed, or graphic matter is not labeling, it is _____.
labels Labeling accompanying advertising The term "label," as the definition indicates, refers to information required on the container or wrapper. The term "labeling" has a far broader application. Although the term labeling includes the label, it also applies to the information "accompanying" the drug such as the package insert. The legal interpretation of the word accompanying can be important in establishing whether misbranding has occurred. If the literature is deemed to accompany the product, it is labeling. If it is deemed not to accompany the product, it is advertising. The line between labeling and advertising is not always a clear one, leading to controversies.
Postmarketing Surveillance •Required of _____ after NDA approval •Must submit to FDA reports of serious _____ and any new information of safety and efficacy
manufacturer adverse drug reactions
Postmarket Labeling uThe FDAAA gave the FDA the authority to require ______ to add safety information or warnings postmarket.
manufacturers
Prohibited Acts •Most prohibited acts involve ____ or _____. •Violation of _____ is subject to strict liability - _____ excuse applicable
misbranding or adulteration FDCA - Good faith the violations are of a STRICT LIABILITY nature. In other words, the commission of any of the listed offenses violates the FDCA, regardless of the person's intentions or knowledge. Under § 301(c), for example, a pharmacist who unknowingly and innocently receives an adulterated or misbranded drug and subsequently sells it to a consumer has violated the act. Section 303(c) of the act, however, provides that a pharmacist who sells the drug in good faith will NOT be subject to any penalties, if on request the pharmacist furnishes the FDA with information about the source of supply.
Nutritional or Structure/Function Claims DSHEA permits four types of nutritional support claims: •Benefiting a classical _____ disease •Describing role of the DS in affecting the _____ of the body •Characterizing the mechanism by which a DS acts to maintain the _____ •Statements of general ____
nutrient deficiency structure/function (Ca2+ builds strong bones) structure or function well-being (Vitamin C supports immune system)
Patent Considerations of ANDA •The generic manufacturer must make one of four types of patent certifications. ---> •A ______ certification contends that the parent drug's patent is invalid or will not be infringed by the generic company. The ANDA applicant must notify _____ holder. If holder sues, _____ is enjoined for 30 months, unless a court rules otherwise. The generic company receives 180 days of _____ if it prevails under a paragraph IV certification.
paragraph IV patent FDA market exclusivity *** 6 months of market exclusivity for first generic (why not a big price drop until other generics can be made) In order to ultimately obtain approval for an ANDA, the generic manufacturer must make a patent certification. The law provides four types of certification a generic applicant can make relevant to the patent of the reference drug: (I) That the NDA holder did not file information on the patent to the FDA(II) That the patent already had expired(III) The date that the patent will expire(IV) That the patent is invalid or will not be infringed by the manufacture, use, or sale of the generic applicant's drug If the applicant submits a paragraph I or II certification, the FDA will approve the ANDA provided all other requirements of the application are met. If a paragraph III certification is filed, the approval will likely be effective on the patent expiration date. If, however, a paragraph IV certification is filed, the process gets considerably more complicated. The applicant must notify the patent owner and NDA holder, citing the factual and legal bases for why the applicant believes the patent is invalid. If the patent owner sues the generic applicant, the FDA is automatically enjoined from approving the ANDA for 30 months, unless a court issues a final ruling that the patent is invalid prior to the end of the 30-month expiration period. To encourage generic manufacturers to challenge patents, because to do so is very costly, the law awards 180 days of marketing exclusivity to the first generic applicant to file an ANDA containing a paragraph IV certification. Of course, the generic applicant, if sued by the patent holder, must obtain a favorable court decision on the patent issue to obtain this exclusivity.
Food or Drug? Congress likely intended the meaning of food in the exclusion from _____ of drug definition to apply to food used for its ordinary purpose and in an ordinary manner. In def of "drug" u(1) recognized in USP u(2) intended to diagnose, cure, mitigate, treat or prevent disease u(3) article (other than food) intended to affect structure or function of the body of main or animal
part C f) The term "food" means (1) articles used for food or drink for man or other animals, (2) chewing gum, and (3) articles used for components of any such article (§ 201(f); 21 U.S.C. § 321(f)).(g) (1) The term "drug" means (A) articles recognized in the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any articles specified in clause (A), (B), or (C).
21st Century Cures Act and New Drug Approval Passed in 2016 •Objectives include streamlining and adding flexibility to the drug development and approval process and creating a more _____ approach to the process.
patient-focused
Paper NDA •The FDA lacked authority to allow ANDAs for ______, so it created the "paper NDA." •The paper NDA was not very effective.
post-1962 generics Although the FDA would accept ANDAs for generic drug equivalents marketed between 1938 and 1962, it did not accept ANDAs for generic equivalents marketed after 1962. The FDA held the position that it lacked statutory authority to do so. Recognizing the inconsistency of allowing ANDAs for pre- 1962 generic drugs but requiring NDAs for post-1962 generic drugs, the FDA compromised by implementing what it called a "paper" NDA policy in the late 1970s. Under this policy, a generic drug manufacturer would not have to duplicate the actual research establishing the safety and efficacy of the innovator drug, as a full NDA would require. Rather, the generic drug manufacturer could submit evidence of its drug's safety and efficacy on the basis of the published scientific data generated from the innovator manufacturer's studies.
Three classes of recalls Class I recalls are issued when there is a reasonable _____ that the product will cause serious _____ consequences or ____. Class II recalls occur when the product may cause temporary or medically ______ adverse health consequences, but the probability of serious adverse consequences is _____. Class III recalls apply to products that are ______ to cause adverse health consequences.
probability, adverse health, death reversible, remote not likely
Health or Disease Claims •The FDA now allows ____ & ____ health claims.
qualified and unqualified Qualified health claims (QHCs) are supported by scientific evidence, but do not meet the more rigorous "significant scientific agreement" standard required for an authorized health claim. To ensure that these claims are not misleading, they must be accompanied by a disclaimer or other qualifying language to accurately communicate to consumers the level of scientific evidence supporting the claim. The Pearson decision ultimately produced a profound change in how the FDA evaluates health claims. The agency now essentially allows two types of health claims, unqualified and qualified, for both foods and dietary supplements. Unqualified health claims (those requiring no disclaimer) are allowed if authorized by the agency by means of a regulation, because the dietary supplement met the significant scientific agreement test. Qualified health claims (those that must contain a disclaimer as pursuant to Pearson) may be made when the claim does not meet the significant scientific agreement test and the claim would be misleading without the qualification. Qualified claims will be allowed only when there is more evidence for the claim than against it. The qualified claim must be truthful and not misleading and itmust appropriately indicate the level of scientific support, for example,"Scientific evidence suggests but does not prove" or "Some evidence showsthe nutrient may be beneficial, but there is insignificant scientific evidence top rove the effect."
Health or Disease Claims •DSHEA only permits DS manufacturers to make health claims if either the FDA approves the claim by _____ or by the significant ______ test.
regulation scientific agreement
Approved Drugs as New Drugs An approved drug can become a new drug under certain conditions: uAddition of new _____ uNew _____ of approved drugs uChange in _____ of ingredients uNew _____ use uDosage, method, or duration of administration or application is _____
substance combination proportion intended changed
Nutritional or Structure/Function Claims •Claims must be substantiated as ____ and not.
truthful and not misleading
Evidence a Product Is a Drug ____ ____ ____
uLabeling uAdvertising uNature of product Luke Adores Nature
Structure of FDA National headquarters and extensive field force: Five offices under commissioner: •Office of ____ & _____ Medicine •Office of _____ Regulatory Operations and Policy •Office of _____ Products and ____ •Office of _____ •Office of Policy, Planning, Legislation and ____
•Office of Foods and Veterinary Medicine •Office of Global Regulatory Operations and Policy •Office of Medical Products and Tobacco •Office of Operations •Office of Policy, Planning, Legislation and Analysis
