FDA Handouts - Exam 1

FDA

Food and Drug Administration

• established under FDCA

• agency within department of health and Human Services (HHS) Commissioner - Acting-Sara Brenner, M.D., MPH

Food, Drug, and cosmetic Act (FDCA)

FDA is established under what act?

there’s no federal regulation on sale of drugs

What happened before the 20th century?

Food and Drugs Act of 1906

What act was under President Teddy Roosevelt?

FDA of 1906

• Forbade interstate and foreign commerce in adulterated and misbranded food and drugs

• offending products could be seized and condemned (destroys)

• offending persons could be fined and jailed

  authority based on the interstate commerce clause of constitution

  Drug had to meet standards of strength and purity

  • Set by USP - United States Pharmacopoeia OR by manufacturer based on label

(sum: a law that was aimed to protect people by ensuring that food/drugs were safe and labeled → gave gov the power to seize unsafe products, punish violators, and set quality standards for drugs)

1937 Disaster

Sulfanilamide

• Miracle drug used to prevent infection when sprinkled on wound

• manufacturer turned it into liquid for sore throats - mixed it with diethylene glycol (antifreeze)

• No clinical tests done prior to marketing; 107 died and there was public outcry

(there wasn’t any mechanism to look at the product)

FDA of 1938

Assumption: all drugs are to some degree harmful if used improperly

• All drugs must be tested for safety (& if cause/effect disease)

• labels must contain adequate directions for use

• warnings about the habit forming properties of certain drugs were required

• drugs marketed before date grandfathered in

Durham Humphrey Amendment

(1951) defined the kinds of drugs that can’t be safely used without medical supervision and restricted their sale to prescription by a licensed practitioner

Kefauver-Harris Amendment

(1962)

• Thalidomide scare - a sleeping pill found to cause birth defects in babies form in western Europe kept off the market by a medical officer at the FDA

• Amendment passed to ensure drug efficacy and greater drug safety

• For first time drug manufacturers required to prove to the FDA the effectiveness of products before marketing them

Medical Device Amendments

(1967) passed to ensure safety and effectiveness of medical devices including diagnostic products. require manufacturers to register with the FDA and follow quality control procedures. Some products must have pre-market approval others must meet performance standards before marketing

Orphan Drug Act

(1983) enabled FDA to promote research and marketing of drugs needed for treating rare diseases

• 7 year period of market exclusivity

• Tax credits to 50% for research and development expenses

• definition - affects less than 200,000 people or drug company can’t recover costs of development

Drug Price Competition and Patent Term Restoration Act

1984 (Hatch-Waxman)

Expedites the availability of less costly generic drugs by permitting the FDA to approve applications to market generic versions of brand-name drugs without repeating the research done to prove them safe and effective. Brand name companies can apply for up to 5 years additional patent protection

Prescription Drug User Fee Act

(1992) - requires drug and biologics

manufacturers to pay fees for product applications and supplements and other services. the act also requires FDA to use these funds to hire more reviewers

Dietary Supplement Health and Education Act

(1994)

establishes specific labeling requirements, provides a regulatory framework and authorizes FDA to promulgate good manufacturing practice regulations for dietary supplements

Food and drug Administration Modernization Act (FDAMA)

(1997)

Reauthorizes the Prescription Drug User Fee Act (PDUFA) and mandates wide ranging reforms including measures to accelerate review of devices, regulate advertising of unapproved uses of approved drugs and devices and regulate health claims for foods

• allows manufacturers to disseminate peer reviewed journal articles about off label use provided company files within a specified time frame a supplemental application based on research to establish safety and efficacy

• gave a special exemption to ensure continued availability of compounded products prepared by pharmacists

• increases patient access to experimental drugs

• allows expanded database on clinical trials accessible to patients (manufacture has to agree to be included)

• provides a method of notifying patients if a drug needed for treatment is no longer going to be produced

Public Health Security and Bioterrorism Preparedness and Response Act

(2002)

• protect the safety and security of human drugs, biologics, medical devices, veterinary drugs and other FDA regulated products

• reauthorized PDUFA

New commitments-more ambitious and comprehensive improvements in the regulatory process

• strengthen and improving the review and monitoring of drug safety

• greater interaction between agency and sponsors during the review of drugs for serious and life-threatening

• developing principles for improving first cycle review

• fees authoritized be dedicated toward expediting drug development process and the process for the review of human drug applications

• where FDA required manufacturer to do post-marketing studies, failure to comply with the timetable will be posted on the FDA website and clinicians who prescribe the drug will be informed of the failure

Medical Device User Fee Modernization Act

(2002) Applied same time of structure to devices as it did to prescription drugs utilizing user fees from the industry

Animal Drug User Fee Act

(2003) Applied same type of structujre to animal drugs as prescription drugs and medical devices. Fees from industry pay for additional testing

Pediatric Research Act

(2003)

• Gives the FDA additional authority to require pediatric studies of pharmaceutical products when studies are needed to ensure the safe and effective use of products in children

• best Pharmaceuticals for Children Act (BCPA) of 2002 - extended marketing exclusivity for FDA requested studies

Dietary Supplement and Nonprescription Drug Consumer Protection Act

(2006)

• added serious adverse event reporting for nonprescription drugs

• added serious adverse for dietary supplements

• prohibited transaction falsification of serious adverse event reports

• tightened regulations regarding importation of both product groups

Food and drug Administration Amendments ACT (FDAAA)

(2007)

• reauthorized PDUFA and the Medical Device User Fee and Moderization Act

• Reauthorizes the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act

• allows the FDA to review DTC television ads voluntarily submitted

• expands FDA’s implementation of guidance for reviewers

• allows FDA to develop guidelines on clinical trial design

• helps move the agency and the industry toward an all electronic environment

• streamlines the device inspection program by allowing accredited outside firms to conduct routine inspections for GMP

• focuses FDA’s device inspection resources on high-risk products and production facilities

• calls upon FDA to set up an electronic survelliance system for using E health records and electronic health data sources to perform surveillance for adverse events

• expands the existing govenment database on clinical trials

• allows FDA to add warnings to labels and require post marketing studies

Family Smoking Prevention and Tobacco Control Act

• gives FDA the ability to regulate the tobacco industry and to stop tobacco companies from aggressively marketing to children

• requires FDA review new tobacco products before they can go to the market unless similar to products marketed before Feb 15, 2007

• allows FDA to enforce restrictions on advertising and promotion of menthol and other cigarettes to minors

Biologics Price Competition and Innovation Act of 2009 (BPCI Act)

• Part of the Patient Protection and Affordable Care Act

• Abbreviated licensure pathway for biological products demonstrated to be biosimiliar or interchangeable with an FDA approved biological product

Biologics

defn: large, complex molecules produced in living species (microorganisms, plant cells, animals cells) using recombinant DNA

• used to treat, prevent, cure diseases and medical conditions (therapeutic proteins, vaccines, blood, blood components or derivatives, allergenic products, monoclonal antibodies)

Biosimilars

• Has no clinically meaningful difference in terms of safety, purity, potency, same type of sources, administrated in the same, strength, dosage, potential treatment effects, and potential side effects of reference product

• Interchangeable-biosimilar substituted for reference product without intervention of prescribing healthcare provider (if state law allows)

FDA FOOD Safety Modernization Act 2010

• FDA now has a legislative mandate to require comprehensive, prevention based controls across the food supply, including imported foods

• regulations will also deal with inspection and compliance issues

• they also have mandatory recall authority in this area

Food and Drug Administration Safety and Innovation Act (FDASIA)

Signed July 9, 2012

• gave FDA the authority to collect user fees for innovator drugs, medical devices, generic drugs and biosimilar biological products

• promoted innovation to speed patient access to safe and effective products

• increased stakeholder involvement in FDA processes

• enhanced the safety of the drug supply chain

Drug Quality and Security Act 2013

• outlines steps to build an electronic interoperable system to identify and trace certain prescription drugs as distributed in US

• enhances FDA’s ability to help protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated or otherwise harmful

• establishes national licensure standards for wholesale distributor and 3rd party logistics providers and requires them to report information to the FDA annually

21st Century Cures Act - 2016

• designed to help accelerated medical product development and bring new innovations and advances to patients who need them faster and more efficiently

• regenerative medicine advanced therapy- offers a new expedited option for certain eligible biologic products

• breakthrough devices program-designed to speed review of certain innovative medical devices

• create one or more intercenter institutes to help coordinate activities in major disease areas -Onocology Center of Excellence

FDA Restoration Act (FDARA) - 2017

• enhanced review of transparency and communication

• promoting innovation through enhanced communication

• ensuring sustained success of breakthrough therapy program

• early consultation on the use of new surrogate endpoints

• advancing development of drugs for rare diseases

• advancing development of durg-device and biologic-device combination products

• enhancing the use of real world evidence (RWE) for use in regulatory decision making

• capturing the patient voice in drug development

• advancing the use of complex innovative trial design and model informed drug development

• enhancement and modernization of the FDA drug safety system

Cares Act 2020

• March 27, 2020 - The Coronavirus Aid, Relief Economic Security Ace (CARES) was signed into law as the 3rd major initiative to address COVID-19. (1-Coronavirus Preparedness and Response Supplemental Appropriations Act - March 6, 2020; 2-Families First Coronavirus Response Act - March 18, 2020)

• The CARES Act Includes: paid sick leave, insurance coverage for coronavirus testing and nutrition assistance

• there were provisions to address drug, device, equipment and supply shortages/stockpiles

• there were amendments to the FDCA, to expedite approval, review, and inspections of drugs and devices and institute new user fees

• it clarified tests for detection or diagnosis of virus would be covered without cost sharing by private insurance and Medicare. Medicaid programs must cover such tests

• expanded coverage of telehealth

• reauthorized programs to strengthen rural health

• included 242+ billion dollards for health and health-related activities

Prescription Drug User Fee Reauthorization Act of 2022

• As PDUFA VI was about to expire, Congress reauthorized the user fees without conditions. The senate and the House had different bills and could not come to consensus. It was hoped that conditions would be added later

• it provides for the continued, timely review of new drug and biologic license application

• reauthorized:

  • PDUFA VII

  • GDUFA III

  • BsUFA III

  • MDUFA V

• Things that were in negotiation but did not make it into the bill:

  • A) Regulation of:

    • 1. in vitro clinical tests

    • 2. Cosmetics

    • 3. Dietary supplements

  • B)

    • 1. Accelerated approval reforms

    • 2. Generic drug labeling

    • 3. Development of rare disease endpoints

    • 4. Agency inspection activities (from both House and Senate versions)

Omnibus Bill

Later agreement included:

1. New authority to regulate cosmetic products (Management of Cosmetics Regulation Act)

2. Authority to encourage diversity in clinical trial enrollment

Food and Drug Omnibus Reform Act of 2022 (FDORA )

Included a request for manufacturers of critical food to

• develop, maintain and implement, as appropriate, a redundancy risk management plan

  • this request was generated by an infant formula shortage

• The plan must identify and evaluate risks to the supply of food and identify mechanisms by which manufacturers would mitigate the impact of supply disruptions, through alternative production sites, alternative suppliers and stockpiling of inventory

• effective 12/29/22

• Critical food-infant formula or medical food as defined in the Orphan Drug Act

modernization of Cosmetics Regulation Act (MoCRA )

On average people use 6-12 cosmetic products daily

• makeup

• nailpolish

• shaving cream

• perfume

• haircare products

• deodorant

defn: Article intended to be rubbed, poured, spinkled or sprayed on, introduced into or otherwise applied to the human body for cleansing, beautifying, promoting attractiveness or altering appearance

• also includes component parts in the definition

• does not require premarket approvavl by FDA

This legislation is the most significant expansion of FDA authority to regulate since 1938

• adverse event

• serious adverse event

• facility

• responsible person

New FDA authority

• records inspection

• records access

• mandatory recall authority

New Industry Requirements

• adverse event reporting (within 15 business days) using MedWatch

• comply with GMP (good manufacturing practices) at facilities

• registration of facilities (every 2 years) and product listening

Exemptions - small businesses

From GMP requirements, registration, product listing

Unless products:

• contact with eye muscus membrane

• are injected

• are for internal use

• alter appearance for more than 2 hours

the label must contain information:

• domestic address

• phone number

• electronic contact info such as a website

yet to be done:

• FDA must establish regulations about fragrance allergenics

• FDA must establishes GMPs based on national and international standards

• FDA must establish regulations about standarized testing for asbestos in talc products

• FDA must report on PFAS in products (per and polyfoloralkyl) substances

• Draft guidance on registration and listing issued 12/19/23

adverse event

health related event associated with use of cosmetic that is adverse

serious adverse event

results in death, a life-threatening experience, inpatient hospitatlization, persistent or significant disability, birth defect, infection or significant disfigurement or requires medical or surgical intervention

facility

establishment (including importers) that manufacture or process cosmetics distributed in US

responsible person

manufacturer, packer, distributor of cosmetics whose name appears on the label

Drug

4 defintions:

1. Articles (items) recognized in official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the US, official National Formulary, or any supplement

2. intended for use in diagnosis of disease, or other conditions, or in cure, mitigation, treatment or prevention of disease in man or animals

3. intended to affect structure or function of the body of man or animal (except food)

4. component parts are also drugs; biologics that are therapeutic come under this heading

Generic Drug

this drug is the same as a brand name drug in dosage, safety, strength, how it is taken, quality, performance, and intended use

• it is tested to assure it can be substituted. FDA bases evaluation of suitability “therapeutic equivalence” on scientific evaluation

food

3 defn:

1. articles used for food or drink for man or other animals

2. chewing gum

3. articles used for components of any such article

biologic

Large complex molecules produced in living species (microorganisms, plant cells, animal cells, human cells)

• using recombinant DNA

• used to treat, prevent, or cure diseases and medical conditions

therapeutic biologic

vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissue, and recombinant therapeutic proteins

• they are isolated from natural sources-human, animal, or microorganism

biosimilar

product has no clinical meaningful difference in terms of safety, purity, potency, sources, administered in teh same way, same strength, dosage, potential treatment effects and potential side effects with referenced product

device

an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or similar or related article

a) recognized in the official National formulary, or USP or supplement

b) intended for use in diagnosis of disease or other conditions, or in cure, mitigation, treatment or prevention of disease in man or animals

c) intended to affect structure or function of the body of man or animals

d) includes components, parts or accessories . it doesn’t achieve its primary intended purpose through chemical action within the body of man or metabolized for achivement of primary intended purposes

→ does not include software functions

cosmetic

article intended to be rubbed, poured, sprinkled or sprayed on, introduced into or otherwise applied to the human body for cleansing, beautfying, promoting attractiveness or altering appearance

→ includes component parts; it does not include soap

combination product

a) A product comprised of 2 or more regulated components (drug/device, biologic/device, drug/biologic, or drug/device/biologic) physcially, chemically, or otherwise combined or mixed and produced as a single entity

b) 2 or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device adn biologic products or biologic and drug products

c) a drug, device, or biologic product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved, independently specified drug, device, or biologic, where both are required to achieve the intended use, indication, or effect and upon approval the labeling of the approved product would need to change

d) any inverstigational drug, device, or biologic that according to its proposed labeling is for use only with another individually specificed investigational drug, device, or biologic where both are now required to achieve intended use, indication or effect

Presently the FDA recognizes 9 specific types of combination products

Department of Health and Human Services (HHS)

a federal agency responsible for protecting public health and providing essential human services. It oversees various divisions that focus on healthcare research, safety, drug regulation, and public health. (includes AHRQ, FDA, NIH, SAMHSA)

Agency for Healthcare Research and Quality (AHRQ)

(what’s this? - which agency under Division of HHS)

Goal: Improve the quality, safety, efficiency, and effectiveness of healthcare in the United States.
✅ Key Functions:

• Conducts research on healthcare outcomes and patient safety.

• Develops guidelines and tools to help healthcare providers and patients.

Food and Drug Administration (FDA)

(what’s this? - which agency under Division of HHS)

✅ Goal: Ensure the safety and effectiveness of drugs, medical devices, food, cosmetics, and other consumer products.
✅ Key Functions:

• Approves new drugs and medical devices.

• Monitors the safety of food and cosmetics.

• Regulates tobacco products and dietary supplements

National Institutes of Health (NIH)

(what’s this? - which agency under Division of HHS)

✅ Goal: Conduct medical research to improve public health.
✅ Key Functions:

• Funds and conducts biomedical research.

• Develops new treatments and therapies.

• Supports research on preventing and treating diseases.

Substance Abuse and Mental Health Services Administration (SAMHSA)

(what’s this? - which agency under Division of HHS)

✅ Goal: Improve mental health and address substance use disorders.
✅ Key Functions:

• Provides funding for mental health and addiction treatment.

• Develops programs to promote mental health awareness and prevention.

• Supports research and data collection on substance abuse and mental health

Federal Register

✅ Goal: Publish official government rules, regulations, and public notices.
✅ Key Functions:

• Provides public access to government regulations and notices.

• Allows for public comments on proposed rules.

• Ensures transparency in the rulemaking process