"Clinical Research"

Question to addressed: FDA Regulatory Oversight - Too much? Too little? Your thoughts

Additional websites that I was provided for this project along with the attached files:
https://www.sciencedirect.com/science/article/pii/S2590156719300246?via%3Dihub


https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/new-drug-development-and-review-process
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The FDA has provided considerable regulatory input for drug/industry management of pharmaceutical development. What are your thoughts on the depth and breadth of the FDA's regulations? Be specific as you consider their regulations, use of the QMS, and industry requirements.

How would you, in a research environment, adapt/adopt the FDA regulations?

Clinical Studies Development (CRM 722) Clinical Studies Development Module 3: Regulatory Oversight – the FDA 1 Objectives Describe the FDA format for drug development oversight Identify key points related to FDA regulatory oversight Explain the CRM responsibility for FDA oversight 2 What Does the FDA Regulate Foods Dietary supplements Bottled water Food additives Shares responsibility with USDA for meat, poultry and eggs Drugs Prescription drugs (generic and brand name) OTC drugs Biologics Human vaccines Blood & blood products Cellular and gene therapies Tissue/tissue products Allergenics Medical Devices Simple products e.g., tongue depressors Complex technologies, e.g., pacemakers Dental devices Surgical Implants Radiation Producing Electronics Microwaves X-ray, laser products Cosmetics (moisturizers, nail polish) Veterinary Products Pet and livestock foods/feeds Drugs and devices Tobacco Products – all types 3 What Doesn’t the FDA Regulate Vaccines for animal diseases Some but not all flea and tick products EPA regulates others Cat litter Pet toys and bedding Pharmacies! The FDA regulates the drugs The pharmacies are regulated by their state board of pharmacy 4 Keep this image in mind….. 5 FDA Regulatory Processes Applications prior to clinical trials Investigational new drug (IND) application Investigator IND Treatment IND Emergency IND Access to Investigational Drugs Group C drugs (aka Treatment INDs) Applications post clinical trials New drug application (NDA) Safety Efficacy Packaging Quality 6 New Drug Applications Review types Standard No advancement in disease treatment Must be completed within 10 months of application Priority New drug with significant improvement over current treatments in an unmet medical need illness Must be completed within 6-months Accelerated Meaningful increase in therapeutic benefit for a serious or life-threatening illness Surrogate endpoints used Phase IV CTs must be performed to demonstrate clinical benefit Fast Track Treats a serious or life-threatening illness Pharmaceutical company in continuous conversations with FDA r/t drug approval “Rolling submission” 7 Off-Label Use Use of an approved drug/treatment for any purpose other than what it has been approved for For a disease/illness other than what the drug was approved for Alternate dosage/frequency than originally approved for Treating a child when the original drug was for adults only 8 12% 40% Consider this!! For every 50,000 – 5 million compounds screened 1000 will be considered worthy of moving forward 10 will be tested in CTs Multiple research studies suggest that between 12 and 40% of physicians write prescriptions for off-label use 9 5 mill 1000 10 Summary Many steps take place during the product lifecycle management process Pre and post research applications are required by the FDA – take note of what types are required for your study/project The FDA regulations focus on the safety, efficacy, quality, and risk of drug development 50K – 5 million drugs are submitted; 1000 considered worthy – 10 enter the clinical trial phase Off-label drug use is a method of using a drug for other than what it was developed for 10 2/21/2021 CISN - Drug Development - The Regulatory Process https://cisncancer.org/research/drug_development/regulatory_process.html 1/5 You Are Here: Home > Cancer Research > Drug Development > The Regulatory Process The Regulatory Process Researchers and other scientists involved in the drug development process, including drug companies, government agencies such as the National Cancer Institute (NCI), and academia, must receive regulatory approval from the Food and Drug Administration (FDA) to test drugs in humans and make them available for public use. The FDA reviews specific types of applications from study sponsors. By law, the FDA must review all test results from tests of new treatments to ensure that products are safe and effective for specific uses. "Safe" does not mean that the treatment is free of possible adverse side effects; rather, it means that the potential benefits have been determined to outweigh any risks. This was determined by the testing process begun well before the first person used the treatment, with preliminary research and animal testing. This section explains more about the types of research, costs, time required, FDA applications, and types of FDA review involved in the drug development process. Application Needed Before A Clinical Trial Application Needed After A Clinical Trial Types of FDA review Other Issues Applications Needed Prior to Starting a Clinical Trial 1. Investigational New Drug Application (IND) If a treatment seems to be promising in lab tests, the Drug Company or sponsor must apply for FDA approval to test it in human clinical trials. This application is called an Investigational New Drug (IND) application. The FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk. If the application is approved, the candidate drug usually enters a Phase 1 clinical trial. The application must include: Safety Information - results of animal pharmacology and toxicology studies. Section Index What We KnowAbout Cancer How Cancer isStudied ● Drug Development New Treatments Research Advocacy http://cisncancer.org/ https://cisncancer.org/research/index.html https://cisncancer.org/research/drug_development/overview.html https://cisncancer.org/search.html http://cisncancer.org/personalized_medicine/index.html http://cisncancer.org/diagnosed/index.html http://cisncancer.org/cancer101/index.html http://cisncancer.org/survivorship/index.html http://cisncancer.org/research/index.html http://cisncancer.org/research/research_section_index.html https://cisncancer.org/research/what_we_know/overview.html https://cisncancer.org/research/how_cancer_is_studied/overview.html https://cisncancer.org/research/drug_development/overview.html https://cisncancer.org/research/new_treatments/overview.html http://cisncancer.org/advocacy/research_advocacy.html http://cisncancer.org/advocacy/index.html http://cisncancer.org/inspiration/index.html http://cisncancer.org/resources/index.html http://cisncancer.org/advocacy/webinars/webinars.html http://cisncancer.org/eTraining/free_e-Training.html 2/21/2021 CISN - Drug Development - The Regulatory Process https://cisncancer.org/research/drug_development/regulatory_process.html 2/5 Manufacturing information - pertaining to the chemical composition, manufacturing methods, stability and controls used. Clinical protocols and investigator information - detailed protocols for proposed clinical studies and information on the qualifications of clinical investigators. There are three IND types: An Investigator IND - submitted by a physician who both initiates and conducts the investigation, and under whose immediate direction the investigational drug is administered or dispensed An Emergency Use IND - authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND A Treatment IND - for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions Although it may take 6 months or more to prepare an application, once the IND is submitted, the FDA has only 30 days to respond. During this time, the FDA has an opportunity to review the IND for safety to make sure that research subjects will not be exposed to unreasonable risk. 2. Access to Investigational Drugs (faster route than traditional IND process) Group C Drugs (also called Treatment INDs) In the 1970's, researchers from the NCI became concerned about the lag time between the date when an investigational drug was found to have anti-tumor activity and the time that drug became available on the market. Working with the FDA, the NCI established the Group C classification system to allow patients access to certain investigational drugs. Group C drugs are provided to properly trained physicians who have registered using a special form to assure that their patients qualify under guidelines or protocols for the drug. Each Group C drug protocol specifies patient eligibility, drug use, and how information about the patients' use of the drug should be reported. Group C designation (now called Group C/Treatment INDs) speeds new drugs to patients who need them most. The process also allows the NCI to gather important information on the safety and activity of the drugs as they are used in the "real world" prior to their final FDA approval. Group C drugs are always provided free of charge, and the Centers for Medicare and Medicaid Services provides coverage for care associated with Group C therapy. Application Needed After Clinical Trials The process of new drug development has many stages. In the United States, until a drug has been approved by the FDA, it can usually be obtained only through several mechanisms: enrollment in a clinical trial studying the drug, an expanded access program, or special exemption/compassionate use programs. 1. New Drug Application (NDA) http://cisncancer.org/latina_navigator_training/index.html http://cisncancer.org/contact/donate.html 2/21/2021 CISN - Drug Development - The Regulatory Process https://cisncancer.org/research/drug_development/regulatory_process.html 3/5 If the treatment or drug makes it through the clinical trials process - that is, if the studies show the treatment is safe and effective - the sponsor may submit another application to the FDA. In the case of drugs, it's a New Drug Application (NDA); for biologics, it's a Biologics License Application (BLA). The application must include the following: Safety data Efficacy (does it work) data documented through clinical trials Chemical makeup How the drug or biologic is made, processed, and packaged Quality control standards An FDA Advisory Board Committee analyzes the data in the application to assess if a specific indication (standard use) is worthy of approval for public use. For more information on the regulatory process go to: FDA U.S. Federal Food and Drug Administration - New Drug Application (NDA) Types of FDA review for a New Drug Application (NDA) Although the approval process is long and arduous, the FDA has tried to cut through the some of the red tape by providing several different approval routes. Standard Review Priority review Accelerated review Fast Track Review Standard Review Standard reviews are given to NDA's that do not represent an advance in the treatment for a disease. A standard review must be completed within 10 months of the application. Priority Review A priority review is granted for a new drug that, if approved, would be a significant improvement over current treatment options for a disease fulfilling an unmet medical need. While a standard review must be completed in 10 months, a priority review must be completed in 6 months. Drugs that receive a priority review designation are often approved in much less than 6 months. Gleevec was approved in 8 weeks in June 2001, and Eloxatin was approved in 7 weeks in August 2002. Accelerated Approval To be considered for accelerated approval, a drug must treat a serious or life threatening illness and provide a meaningful increase in therapeutic benefit to patients over existing treatments. Accelerated approval uses surrogate endpoints that measure treatment effects that may correlate with clinical benefit. As an example, tumor shrinkage that occurs when using a drug may or may http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/default.htm 2/21/2021 CISN - Drug Development - The Regulatory Process https://cisncancer.org/research/drug_development/regulatory_process.html 4/5 not correlate with increased survival. However, even though a new drug may be approved with an accelerated approval, the drug company must conduct Phase IV clinical trials to demonstrate meaningful clinical benefit, such as prolonging patients' lives or improving their quality of life. Generally, any accelerated approval drug receives a priority review. Fast Track A drug may receive a fast-track designation if it is intended to treat a serious or life-threatening condition and demonstrate the potential to address an unmet medical need. Fast tracking actually has little effect on the patient's access to the drug. It means that the drug company is engaged in continuous discussions with the FDA about the drug's development