Lecture 3 - Legislation and Drug Development

‭Harris-Kefauver Amendments (1962)‬ ‭●‬ ‭Impetus:‬ ‭○‬ ‭Response to the thalidomide tragedy in Europe‬ ‭○‬ ‭Thalidomide was teratogenic and widely used in pregnant pts‬ ‭●‬ ‭Focus:‬ ‭○‬ ‭Sought to strengthen all aspects of‬‭drug regulation‬‭to protect populations from‬ ‭wasting money and endangering their health‬ ‭○‬ ‭Drugs provided to the public had to be‬‭proven safe‬‭and effective‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭The first act to demand that drugs are effective and beneficial before marketing‬ ‭○‬ ‭Required that all drugs introduced from 1932-1962 undergo‬‭testing‬‭; any drug that‬ ‭failed to prove useful would be‬‭withdrawn‬ ‭○‬ ‭Established rigorous procedures for testing new drugs‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Ensured safety before adverse effects occurred‬ ‭○‬ ‭Established manufacturing practices used today by pharmaceutical companies and‬ ‭FDA approval‬ ‭○‬ ‭Quality of clinical research became held to a higher standard (increased use of‬ ‭randomized control trials)‬ ‭Food, Drug, and Cosmetic Act (1938)‬ ‭●‬ ‭Impetus: More than 100 people died after using an antibiotic containing sulfanilamide‬ ‭and diethylene glycol‬ ‭●‬ ‭Focus: Congress required that all new drugs undergo safety training, which would have to‬ ‭be reviewed and approved by the FDA‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Drugs were made safer and had to go through‬‭more testing‬‭for approval‬ ‭○‬ ‭Drugs could no longer contain any‬‭lethal combinations‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Requires patient transparency through labeling on products‬ ‭○‬ ‭Allows the FDA to take action against drug products that may be deemed unsafe‬ ‭Prescription Drug User Fee Act (1992)‬ ‭●‬ ‭Impetus: Drugs were taking years to be approved due to under-staffing, leaving pts‬ ‭without medicine‬ ‭●‬ ‭Focus: To‬‭shorten drug review times‬‭and create‬‭revenue‬‭for the FDA‬ ‭●‬ ‭Key changes: The FDA started to collect fees from pharmaceutical companies for drug‬ ‭applications‬ ‭Food & Drug Administration Modernization Act (1997)‬ ‭●‬ ‭Impetus: AIDs epidemic and the need for cancer drugs‬ ‭●‬ ‭Focus: Creating change to FDA regulations in all four areas of importance for healthcare‬ ‭professionals‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Passing drugs for‬‭serious illness‬‭faster for market‬‭availability‬ ‭○‬ ‭Making patients aware of drug‬‭discontinuance‬‭at least‬‭six months prior‬ ‭○‬ ‭Database for clinical trial participants provides more informed decision-making‬ ‭about new drugs‬ ‭○‬ ‭Journal articles were made available to prescribers by drug companies to promote‬ ‭off-label use‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Helps pts to gain access to new drugs and information faster than before‬ ‭○‬ ‭Pts can prepare for drug discontinuation by finding other sources before cutting‬ ‭off access‬ ‭Best Pharmaceuticals for Children Act (2002) & Pediatric Research Equity Act (2003)‬ ‭●‬ ‭Impetus: Drugs were not tested in children before going onto the market, so there was no‬ ‭way to predict how drugs would affect them‬ ‭●‬ ‭Focus: To improve the‬‭safety and effectiveness‬‭of‬‭drugs used on children‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭The BPCA allowed manufacturers to‬‭re-evaluate‬‭the‬‭safety of drugs within six‬ ‭months of them being on the market‬ ‭○‬ ‭The PREA allowed the FDA to require‬‭pediatric clinical‬‭trials‬ ‭FDA Amendments Act (2007)‬ ‭●‬ ‭Impetus: Expansion of the FDA’s mission to rigorously monitor a drug after approval,‬ ‭ensuring its safety‬ ‭●‬ ‭Focus:‬ ‭○‬ ‭To ensure the safety of a drug after its public release‬ ‭○‬ ‭The effects of a drug could be seen in a‬‭larger population‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Requirement of‬‭post-marketing safety studies‬‭(phase‬‭IV trials)‬ ‭○‬ ‭Updated safety information on drug labels‬ ‭○‬ ‭Restriction of drug distribution if safety concerns became present‬ ‭●‬ ‭Today’s impact: Sooner discovery of adverse drug effects‬ ‭ omprehensive Addiction and Recovery Act (2016) & Substance-Use Disorder Prevention‬ C ‭that Promotes Opioid Recovery and Treatment for Patients and Communities Act (2018)‬ ‭●‬ ‭Impetus:‬ ‭ ‬ ‭Nationwide opioid epidemic‬ ○ ‭○‬ ‭Lack of access to proper treatment‬ ‭○‬ ‭Deaths due to overdose‬ ‭ ‬ ‭Focus:‬ ● ‭○‬ ‭Providing grants and efforts for prevention,‬‭rehabilitation‬‭,‬‭treatment, and recovery‬ ‭○‬ ‭Law enforcement and criminal justice reform to reverse overdose‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Prevent and treat addiction to opioids‬ ‭○‬ ‭Increase‬‭education‬‭on drug use‬ ‭○‬ ‭Increase and expand medication-assisted treatment‬ ‭○‬ ‭Improve‬‭prescription drug monitoring‬‭programs‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Authorized $181 million yearly in federal funding for the continued epidemic‬ ‭○‬ ‭Distribution of naloxone has increased to fight/reverse opioid overdose rapidly‬ ‭Controlled Substances Act (1970)‬ ‭●‬ ‭Impetus: Need to regulate addictive substances to combat the rising incidence of drug‬ ‭abuse in the 1960s‬ ‭●‬ ‭Focus:‬ ‭○‬ ‭Setting rules for the creation and distribution of drugs with potential for abuse‬ ‭into classifications/schedules‬ ‭○‬ ‭Schedules I‬‭(high potential for abuse)‬‭to V‬‭(lower‬‭potential for abuse)‬ ‭■‬ ‭I: No accepted medical use (unsafe)‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Companies could no longer sell/manufacture dangerous drugs without‬‭regulation‬ ‭○‬ ‭Addictive drugs were highly confined to‬‭solely medical‬‭purposes‬ ‭○‬ ‭Increased‬‭penalties‬‭against drug-related offenses‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Narcotics are illegal for recreational use‬ ‭○‬ ‭The distribution of drugs is a high offense‬ ‭○‬ ‭Hospitals are still given access to opioids‬ ‭○‬ ‭CSA was passed later, which banned OTC medicines that can make meth‬ ‭Family Smoking Prevention and Control Act (2009)‬ ‭●‬ ‭Impetus: Cigarettes are responsible for about one in five deaths in the U.S. yearly‬ ‭●‬ ‭Focus: Protecting consumers from harmful nicotine products and being more transparent‬ ‭about their effects‬ ‭●‬ ‭Key changes:‬ ‭○‬ ‭Restricting advertisements and prohibiting‬‭marketing‬‭toward youth‬ ‭○‬ ‭Revising and making prominent‬‭warning labels‬ ‭ ‬ ‭Disclosing all ingredients in nicotine products‬ ○ ‭○‬ ‭Restricting harmful‬‭additives‬ ‭ ‬ ‭Today’s impact: Levels of nicotine in cigarettes have been reduced to less addictive levels‬ ● ‭Federal Pure Food and Drugs Act (1906)‬ ‭●‬ ‭Impetus: Adulterated food practices in the meat industry‬ ‭●‬ ‭Focus:‬ ‭○‬ ‭Regulating the sale of‬‭food and drugs‬‭for commerce‬ ‭○‬ ‭Prohibited any‬‭ingredients‬‭that posed a health hazard‬ ‭●‬ ‭Key changes: Gave the government authority to seize misbranded foods and punish‬ ‭violators with up to a $500 fine or imprisonment‬ ‭●‬ ‭Today’s impact:‬ ‭○‬ ‭Foundation of the‬‭FDA‬ ‭Hazardous Drug Exposure‬ ‭●‬ ‭The National Institute for Occupational Safety and Health regulates safety‬ ‭●‬ ‭Drug meets criteria if:‬ ‭○‬ ‭Carcinogenic‬ ‭○‬ ‭Teratogenic‬ ‭○‬ ‭Reproductive toxicity‬ ‭○‬ ‭Organ toxicity (at low doses)‬ ‭○‬ ‭Genotoxicity‬ ‭○‬ ‭New drugs similar to others that meet this criteria‬ ‭Drug Development‬ ‭●‬ ‭Randomization:‬‭Randomizing which subjects receive‬‭the drug or does not‬ ‭●‬ ‭Control:‬‭A group that receives a‬‭placebo‬‭to compare‬‭the drug’s effects to‬ ‭●‬ ‭Blinding:‬‭The subject and/or researcher do not know‬ ‭who is receiving the drug and who is receiving the‬ ‭placebo‬ ‭Drug Names: Three Types‬ ‭●‬ ‭Chemical name‬ ‭●‬ ‭Generic name‬ ‭●‬ ‭Brand/Trade name‬ ‭ uestion:‬‭On average, how long does it take for the‬ Q ‭development and testing of a new drug?‬ ‭a.‬ ‭3-5 years‬ ‭b.‬ ‭5-8 years‬ c‭ .‬ 8‭ -10 years‬ ‭d.‬ ‭10-15 years‬ ‭Stages of New Drug Development‬ ‭●‬ ‭Pre-clinical testing: Animals or animal models‬ ‭○‬ ‭Testing for toxicity, pharmacokinetics, and possible useful effects‬ ‭●‬ ‭Investigational New Drug (IND) status‬ ‭●‬ ‭Clinical testing/trials: People‬ ‭○‬ ‭Phase I (healthy volunteers)‬ ‭■‬ ‭Testing for metabolism, pharmacokinetics, and biologic effects‬ ‭○‬ ‭Phase II (patients)‬ ‭■‬ ‭Testing for therapeutic utility and dosage range‬ ‭○‬ ‭Phase III (patients)‬ ‭■‬ ‭Testing for safety and effectiveness‬ ‭○‬ ‭Conditional approval of New Drug Application (NDA)‬ ‭○‬ ‭Phase IV (post-marketing surveillance)‬ ‭Limitations of Drug Trials‬ ‭●‬ ‭Effectiveness in‬‭pediatric and geriatric‬‭populations‬ ‭○‬ ‭Not included in clinical trials due to safety concerns‬ ‭○‬ ‭Metabolize drugs differently‬ ‭●‬ ‭Lack of female,‬‭pregnant‬‭mothers, and minorities in‬‭clinical trials‬ ‭●‬ ‭Insufficient representation of the population‬ ‭●‬ ‭Inability to detect/predict all possible adverse effects‬ ‭○‬ ‭In different people‬ ‭○‬ ‭Contraindications (other drugs, food, activity, etc.)‬