FDA Topic - Public Health

• accurate listing of ingredients

• physician’s prescription NOT required

• no mandate for testing before marketing for safety and efficacy

What does Pure Food and Drug Act of 1906 state? (3)

1937

what year did this took place?

• Elixir Sulfanilamide mixed with diethylene glycol → 107 died

• Congress passed Food, Drug and Cosmetic Act

• Drugs must be proved to be safe for use as labelled

• Manufacturer responsible for presenting data to FDA re: safety

  • pre-market review

Food, Drug and Cosmetic Act (1938)

which act: 1938

• evidence that drug was not toxic

• did not mandate evidence for efficacy

• FDA had only 60 days to take action before drug could be marketed

Thallidomide

antiemetic agent and sedative

(1950s → affect pregnant women)

Diethylstilbesterol (1953 controlled study showed that it was ineffective → decided to market it anyway)

• risk of rare adenocarcinomas in young girls

promoted to prevent miscarriage

• what were the effects of exposure in utero??

Kefauver-Harris Amendments (1962)

• Drug manufacturers must provide substantial evidence of efficacy based on “adequate and well-controlled studies”

• established standards of evidence

• increased likelihood that drug worked

• 70% of drug claims could not be substantiated

• 1/3 of marketed drugs lacked even a single effect

• establish rigorous testing methods and analysis: regulatory science

• randomized controlled clinical trials carried out by drug sponsor

• rigorous review by experts at FDA

• promote innovation and progress in drug development

what are some FDA standards (4) ??

safety

• benefit is greater than risk

• adverse events, how severe, how prevalent

benefit

produces the effect intended

• measured by some outsome(s)

• must be retested if used for different application (e.g hydroxychloroquine for treating COVID)

• Balance between rigorous testing and timely release of innovative therapies

  • Kefauver Harris Amendments 1962 delineate the process for required testing and submission of applications to FDA

How much testing is enough?

• Preclinical

• Clinical

  • Phase 1

  • Phase 2

  • Phase 3

  • Submit results in New Drug Aplication for approval to market

What are the stages for testing new drugs?

submit results of testing in animals in an investigational new drug application to proceed to clinical trials in humans

Testing of New Drugs: what happens in preclinical?

• 20-6- healthy volunteers

• Pharmokinetics, pharmocogynamics of drugs in human body

• assess safety at varying doses

• preliminary evidence of efficacy

Testing of New Drugs: what happens in phase 1?

• Few hundred particpants with condition to be treated

• evaluation of adverse effects

• efficacy for intended purpose

• surrogate measures

• no control group

• not blinded

• not randomized

Testing of New Drugs: what happens in phase 2?

• several hundred to several thousand participants

• evidence that benefit.risk

• multiple sites and researchers

• placebo-controlled group vs. experimental group

• randomization

• blinding

• outcome measures

  • extension life expectancy physiological indicator of improved health

Testing of New Drugs: what happens in phase 3?

FDA Review Process

• Requires expert personnel - costly

• number of new drugs to be reviewed increases, review time increases

• prescription drug user fee act 1992

  • expedited review for fee paid by sponsor

  • concern about conflict of interest

• Breakthrough Therapies 2012

  • greater FDA attention to expedite development/approval of innovative drugs

Hatch Waxman 1984: Generic Drugs

• patented medications and exclusively

• generic drugs

• full clinical trials not required if they are identical in their active ingredients, dosage, route of administration and exhibit similar response (bioequivalence)

• Abbreviated New Drug Application

  • must present data that it produces same effects as patented drug

generic drugs

drugs of companies do not have research and development costs

2007 FDA Amendments Act

• Even large clinical trials contain narrow subset of patients

• in populations who will use drugs, heterogeneity, e.g. age

  • adverse events occuring at low frequency would not be observed (e.g. 1 event in 1,000000 cases)

  • new adverse effects can occur in diverse pop

• active postmarketing surveiliance

  • more difficult than clinical trials

• Contrinue to track adverse events

• aggregate data from millions of patients from data collected by insurers, gov agencies

• Public Health

• FDA: drug approval for marketing is one of its responsibilities

• post-marketing surveiliance

• oversight of advertising and promotion of drugs

• develop expertise in emerging areas of science

• control of during drug costs

FDA Responsibilities (name some)

1938, first regulation

(Year & main objective of FDA?)

Food, Drug, & Cosmetic Act

1962, effectiveness

(Year & main objective of FDA?)

Kefauver-Harris Amendments

1984, generics

(Year & main objective of FDA?)

Hatch-Waxman Act

1987, accelerated approval

(Year & main objective of FDA?)

Fast Track

1994, supplements considered food

(Year & main objective of FDA?)

DSHEA

1997, streamlining of regs

(Year & main objective of FDA?)

FDA Modernization Act

2016, FDA accel. processes

(Year & main objective of FDA?)

21st Century Cures Act

1906

when was was the first food and drug act?

Robert Califf

who’s the FDA commissioner?

Dr. Rochelle Walensky

Who’s part of the CDC Leadership ?

Debra Haalland

• oversees uses of land mass of US

• 1st native american to serve

• strong advocate for protections of public lands

WHo’s the secretary of Interior?

Medicare

health insurance for elderly and disabled Americans

Medicaid

joint federal-state program

2003

When did Medicare Prescription Drug Improvement and Modernization Act take place?

• EPA

• OSHA

• FEMA
  Office of Homeland Security

• Department of Agriculture

• Drug Enforcement Agency (DEA)

• Social Security Administration (SSA)

What Health-related Agencies are non-DHHS?

EPA

Administrator in President’s cabinet (DOI)

OSHA

Department of Labor

FEMA & Office of Homeland Security

which non-DHHS agencies are considered director in President’s cabinet ? (2)

Micheal Regan

EPA: Who’s the top North Carolina Environmental Protection regulator?

CDC

disease surveillance, outbreak prevention, health statistics

FDA

ensures drug/food safety, regulates medical products

NIH

conducts medical research

HRSA

supports healthcare for underserved populations

• study mandated by Congress

SAMHSA

focuses on substance abust & mental health services

CMS

administers Medicare & Medicaid

IHS

provides healthcare for Native American populations

Dr. Murthy

(who’s this)

• Surgeon general

• Gun violence, opiod, Ebola/Zika virus response

Dr. Marcella Nunez-Smith

(who’s this)

• Chair of COVID-19 equity task force

Dr. Fauci

(who’s this)

medical Advisor to President

Arati Prabhaka

(who’s this)

office of Science & Task Policy

Steve Ricchetti

(who’s this)

coordinator of COVID Response

assessment & assurance

Local health department consists of?? (2)

Federal

Consitutional Powers

State

powers not delegated to fed. gov., only states

• police powers, education, disease control, licensing healthcare professionals

Local Municipalities

enactment of specific programs addressing community needs

Local

Implement services

Provision of basic services:

• sanitation

• water safety

• public hospitals

International/Non-gov Orgs

WHO, Red Cross, and other orgs contribute to global health

Administrative laws

agencies are empowered to develop & enact specific rules and regulations

1906 Pure Food and Drug Act

(Which FDA)

required ingredient listing, but didn’t mandate safety testing ; Physician’s prescription NOT required

• Elixir Sulfanilamide mixed with diethylene glycol → 107 people died

Why did 1937 FDA passed?

1938 Food, Drug, and Cosmetic Act

Which act states :

• Evidence that drug was not toxic

• did NOT mandate evidence for efficacy

• FDA had only 60 days to take action before drug could be marketed

to prevent miscarriage

Diethylstilbesterol (DES) is promoted to???

1962 Kefauver-Harris Amendments

What states:

• Drug manufacturers must provide sustantial evidence of efficacy

• established standards of evidence

• increased likelihood that drug worked

Industry-Regulatory Relationship

Intensification of relationship between industry and regulatory agency, including conflicts of interest and user fees

External Expertise

Increasing reliance on external experts

FDA as both a protector and promoter of public health, balancing the interests of the pharmaceutical industry

What’s FDA’s Dual Role?

drug

Does FDA regulate cigarettes as a Food or drug?

food

Does FDA regulate dietary supplements as a Food or drug?