Regulatory Affairs Exam

DHHS Department of Health and Human Services FDA protects public health by assessing safety and efficacy in Foods Dietary Supplements cosmetics veterinary drugs medical devices biologics tobacco products statute law or amendment to a law passed by congress regulation rule issued by federal agency CFR code of federal regulations Virus-toxin law/biologics control act required licensing vaccine manufacturer inspections premarket approval of vaccines, serums, and antitoxins Food and Drugs Act prohibited marketing adulterated and misbranded food and drugs Food, Drug, and Cosmetic Act strengthened safety and labeling requirements required FDA to confirm product safety Durham-Humphrey Amendment required medications that could be habit forming or dangerous without oversight to be dispensed with a Rx Kefauver-Harris Amendment companies required to demonstrate drug product efficacy and safety FDA given authority to oversee drug advertising Food and Drug Administration Modernization Act fast-tracking drugs and biologics for life-threatening diseases imposes risk evaluation and migration strategies (REMS) Expansion of clinical trial registry data- 1 / 12 2007- FDA Amendments Act base new office of chief scientist percent FDA advisory committee members conflict of interest 2012 FDA safety and Innovation Act expanded user fees from Rx to generic drugs and biosimilars 1976 Medical Device Amendments divided devices into 3 classifications based on risk required FDA premarketing approval of high risk devices Hatch-Waxman Act allows generic drug product approval based on bioequivalence Abbreviated New Drug Application ANDA Patient Protection and Affordable Care Act FDA can approve biosimilar and interchangeable biologic products Family Smoking Prevention and Tobacco Control Act FDA authority to regulate tobacco FDA budget 4.74 billon FDA organization and structure led by commissioner: nominated by president and confirmed by senate Scott Gottlieb CBER Center for biologic evaulation and research CDRH Center for Device and Radiological CDER center for drug evaluation and research CTP center for tobacco products GO office of global regulatory operations office of global regulatory operations and and policy polcy Laws, Regs, and Guidance Federal Statues begin as a bill introduced by legislative branch bill undergo scrutiny via committees and public hearings 2 / 12 an approved bill is presented to the present to veto or sign into law requires FDA to keep public informed and give them right to participate in the Administrative Procedures Act of 1946 rulemaking process by commenting on proposed rules Pure Food and Drug Act prohibited misbranded and adulterated foods, drinks, and drugs from interstate commerce Sherley Amendment prohibits labeling medicines with false therapeutic claims intended to defraud Public Health Service Act of 1944 FDA gets authority over biological products such as vaccines and serums licensing of new biological products through application process Food Additives Amendment delineates substances added to food products generally recognized as safe (GRAS) marketing approval requires manufacturer to prove a product is safe for human consumption kefauver-harris amendment supply proof of effictiveness and safety Francis Kelsey joined FDA in 1960 President's award for distinguished federal civilian service refused to authorize thalidomide: serious birth defects Medical Device Amendments established 3 classes of medical devices GMP good maufactoring practice Orphan drug act orphan drug is a drug for disease which are rare <200k guarantees developer 7 years of market exclusivity safe medical device act of 1990 3 / 12 must report device related deaths semi-annual reports to FDA post market surveillance device manufacturers required to pay Medical Device User Fee and Modern- FDA fees ization Act generic drug and biologics industries as well Food and Drug Modernization Act of 1997 FDAMA additional authority for monitoring drug and biologic postmarket studies allowed "notice of change" for changes not affecting design or safety Food Safety Modernization Act of 2011 Food-borne illnesses new enforcement authorities preventative controls reauthorized user fees Food and Drug Administration and Innouser fees to fund review of generic and vation Act biosimilar biologics Drug Quality and Security Act compounding quality act outsource facilities must comply with GMPs ICH international conference on harmonization US code official compilation of codified laws by subject, why CFR is the official compilation of regulations How many titles is CFR divided into 50 titles that are divided into chapters chapters divided into parts 21 CFR parts 1-100 administrative issues and protection of human subjects 21 CFR 100s foods (not covered in this chapter except for dietary supplements 21 CFR 200s labeling, CGMPs, controlled substances 4 / 12 21 CFR 300s drugs for human use 21 CFR 500s drugs for animal use 21 CFR 600s biologics 21 CFR 700s cosmetics 21 CFR 800s medical devices 21 CFRs 1000s-1400s contain many miscellaneous tops but 1270 human tissues intended for transplantation and 1271 human cells and tissue FDA regulates more than _____ marketed drugs and medical devices 150,000 at any time, more than ______ investigation new drugs are being developed 3,000 SOPPs standard operating procedures and policies Biologic made of natural resources (human or animal or microorganism) to treat diseased or medical conditions ex. vaccine, blood, human cells BLA biologics license application request for permission to introduce biologic product into interstate commerce NDA new drug application PHS public health service Affordable care act created an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar biosimilar product approved based on showing its highly similar to FDA approved biological product FD&C ACt Biosimilar User Fee act of 2012 authorizes FDA to assess and collect fees for 5 / 12 biosimilar biological products during IND phase new drug use combination of approved drugs ingredients change new intended use dosage, method, duration change Drugs are considered new if PDUFA II formal process for meetings was established Prescription Drug User Fee Act in 1997 different types of meetings A,B,C meetings can be requested at any time for any reason SPA special protocol assessment 45 days of receipt, FDA evaluates certain protocols and determines whether they meet requirements OOPD office of orphan products develoment Fast Track Designation designed to facilitate the development and expedite the review of new drugs intended to treat serious or life-threatening conditions breakthrough therapy designation allow sponsor increased FDA communication and attention goal is to expedite the development and review of potential new medicine if intended to treat serious or life-threatening disease Generating Antibiotics Incentives Now Act GAIN act provides incentives for the development of antibacterial and antifungal drugs qualified infectious disease product (QIDP_ eligible for fast track designation application is not request for approval it is a request for exemption from federal law 6 / 12 Initial IND requires NDA or BLA to be approved by FDA prior to distributing drug 30days NDA drugs gain entry into market sufficient data for FDA to decide whether or not benefits outweigh the risk PAI pre approval inspection determine whether the methods used in manufacturing and the controls are adequate prei-approval activities 120 day safety report after submitting NDA PTO patent and trademark office 505(b) (2) NDA similar to traditional NDA and ANDA used for changes in drug dosage, ingredients, new combo DESI drug efficacy study implementation evaluated 3k+ products Orange book RLD (reference listed drug) and provides info on patents and expiration dates ANDA must contain patent certification info development time is short requires same post approval reporting as NDA Branded and authorized generics "authorized generic" is a drug product where there is licensing agreement between innovator and generic approved in the same manner as generics generic can be added to the original NDA as a supplement GDUFA generic drug user fee amendment designed to speed access to safe and effect generic drugs and reduce cost industry pay user fees 7 / 12 DIetary Supplemets may be vitamins, minerals, herbs, or other botanicals, amino acids, or enzymes Do not require premarket FDA approval DSHEA Dietary supplement health and education act define dietary supplements and ingredients over-the-counter OTC marketed for use by consumer without healthcare professional prescription-to-OTC switch over the counter marketing of former prescription drug product for same administration original NDA-sponsor plans to market a new product whose active substance indication or dosage form Medical device amendments 1976 made devices more distinct from drugs safety & effectiveness requirements for device established IDE IDE investigation device exemption SMDA safe medical devices act extended adverse device incident reporting required device tracking defined HDE FDA recall authority HDE Humanitarian device exememption Device Classes Class I: lowest risk Class III: greatest risk The class determines premarket submission Premarket Approval ensures class III devices are safe and effective class III support life, prevent impairments in health 8 / 12 HUD Humanitarian Use Device similar to PMA exempt from PMA effectiveness <4k individuals per year PMA premarket approval application required for class III devices Premarket Notification 510(k) sponsors of class I,II,III devices must submit a 510(k) exemption when PMA is not required some class I are exempt substantial equvilance FDA determines in 90 days can be marketed once FDA sends letter If not... submit another 510)k) submit PMA etc. De novo classification also known as evaluation of automatic class III designation if sponsor receives NSE may request FDA make risk-based classification NSE not substantially equivalent IDE allows investigation device to be used in a clinical study to collect safety and effectiveness data required to support PMA Clinical studies are conducted most often to support PMA Establishment Registration involved in the production and distribution of medical devices required to register with FDA provide FDA with location of medical device manufacturing facilities RFD request for designation may obtain a formal agency determination of a combination products primary mode of action Citizen petitions 9 / 12 formal written request to FDA asking agency to take or refrain from taking an administrative action suitability petitions allowing the sponsor to file an abbreviated application for a human or animal drug whose active ingredient, dosage, differ from approved drug Type A meetings meetings to address a stalled development program Type B meetings prior to submission of the IND end-of-phase conclusion of phase-2 Type C meeting any other product development or guidance meeting not included in Type A or B pre-submissions opportunity to obtain feedback and advice prior to submitting IDE PDP product development protocol submission issue meeting held at sponsors request to dicuss deficiencies PMA Day-100 Meetings discuss the PMAs review status FDA will conduct interim review of the application to identify deficiencies Advisory Committee Meeting subject matter experts provide recommendations and advice to agencies Public regulatory hearting obtain additional information before making decision or taking regulatory action Board of Inquiry alternative to a formal evidentiary hearing review issues Evidentiary Hearing occurs when specifically provided by law, mandated by congress or ordered by FDA 10 / 12 Advisory Committee Meetings begin with call to order introduc panel statement regarding conflict of interest review issues public hearing questions Three-step approach analysis content development testing strategy Leveraging advocacy third party advocates key leaders and medical experts breifing book 100-150 pgs clinical section of NDA no new data Core presentation 45-90 minutes clear, concise Q&A book answers should be clear well-organized organized by topic crsis difficult or dangerous situation that needs serious attention Types of crises market change employee misconduct environmental events Submission failures end of development cycle if not successful, company must expend additional resources to respond Recalls prepared to address product recalls efficiently to avoid risk of patient injury finacial crsis sale deficiencies, economic slowdowns or stock market crashes internal communication include written and verbal communications between any and all company departments and employees 11 / 12 Full disclosure most important rule during a crisis fully disclose all facts CMT crisis management team as soon as the scope of crisis is identified CMT should be designated and assembled leadinging and monitoring activities creating internal crisis plan communicating applicapable information Fact Sheet what do we know? when did we know it? what are we doing? question sheet what do we need to do? who will get answers? when will we have those answers? Investigation should include such activities as root cause analysis and CAPA collection of clinical data animal testing engineering reviews risk assessment External communications regulatory authorities comprehensive plan regulatory authories critical to inform FDA as soon as possible about potential harm Public communications crisis management often require communication with external stakeholders support patients nad physcicians 5Ps prior planning prevents poor performance 12 / 12