21 CRF 312 Flashcards
Explain the role of the FDA in the approval process for new drugs, medical devices, and biological products.
All new drugs, biologics and devices must FIRST be approved by the FDA before they are marketed to the public.
Briefly describe the ICH E6 guideline and its relevance in conducting clinical trials according to Good Clinical Practice (GCP) standards.
The ICH E6 guideline is compromised of standards relating to all aspects of conducting clinical research about drugs and biologics on research on human subjects. Such as study design, IRB/IEC approval, PI and sponsor responsibilities, etc.
GCP is a set of standards for designing, conducting, monitoring, reporting, documenting, etc in clinical studies involving human subjects. It ensures that the rights and wellbeing of the participants while also ensuring that the trial data is credible and accurate.
Who are sponsor-investigators, and what responsibilities do they have in seeking FDA approval for investigational drugs or devices?
Sponsor-investigators are investigators who not only conducts the drug investigation, but also initiates the approval process with the FDA (typically done by a sponsor). They have the combined responsibilities of a sponsor AND an investigator
Outline the steps involved in the Investigational New Drug (IND) application process, and why is it necessary before conducting human clinical trials? Discuss timelines.
What happens if the FDA finds issues? What happens if they don’t?
The IND application is part of the pre-clinical phase of drug development. Steps:
1. Drug is developed/created in a lab
2. Animal and tissue studies are done to study its toxicity, safety, efficacy (limited but still need to show that it has the potential to work), dose)
~3-6 years
3. IND application is submitted by sponsor/ sponsor-investigator to FDA for approval. FDA has to review the safety and potential of benefit as well as all other supporting date within 30 days of receiving the IND.
If there are concerns, they will place the clinical operations on HOLD until those concerns are resolved.
If they don’t find any and it has been more than 30 days, it is assumed that the FDA did not find any issues and the investigation and proceed as stated in the plan.
What is the section(s) of the FDA that conducts review and approval of INDs + NDAs?
CDER = center of drug evaluation and research
CBER = centre of biologics evaluation and research
In summary/general terms, what information must be included in an IND application, according to the U.S. Food, Drug, and Cosmetic Act?
- data from all pre-clinical studies including information on pharmacologies (kinetics, dynamics), bioavailability in animal studies, known side effects + toxicity, potential of benefit/efficacy, dosing on animals, IBs, protocols
- Also needs to propose the general investigational plan for the different phases with human subjects
Summarize the timeline of drug development, highlighting key phases from preclinical studies to postapproval surveillance.
Pre-clinical phase: obtain preliminary information from drug development + animal/tissue studies about the drugs safety, toxicity, pharmacologies and potential benefit/efficacy and route of administration. Takes around 3-6 years.
Sponsor submits IND (6 months to 2 yrs) and the FDA has 30 days to review it.
Phase 1 (clinical): administer the drug product to health volunteers OR patients (if the toxicity does not make it suitable for volunteers (e.g. cancer drugs)). Around 20-80 people are usually part of this.
MAIN PURPOSE = SAFETY. Need to know about side effects, pharmacological aspects (kinetics, dynamics, bioavailability), metabolism, excretion, dosing.
Phase 2: administer drug to patients with condition/disorder. Typically hundreds of patients are part of this phase. Controlled studies.
MAIN PURPOSE = EFFICACY + SHORT TERM RISKS AND SIDE EFFECTS.
Phase 3: large scale study on thousands of patients. Assessing a larger population and obtaining additional information about risks + benefits.
MAIN PURPOSE: Safety + efficacy in a large population.
Total time for these =7-8 years
Sponsor and FDA meet to discuss NDA —> sponsor submits NDA to FDA and they have 60 days to decide whether or not to file it for review.
FDA reviews drug labeling to ensure appropriate information is on vials for physicians and community
FDA audits manufacturing facility
If all goes well, NDA is approved :)
Post-approval phase/Phase 4:
FDA continues to monitor the drug, especially for unanticipated SAEs. Requests for frequent safety reports from sponsor
Medwatch = online report tool that physicians and patients can report side effects.
FDA must notify public and applicable members of important new side effects of drug.
Could suspend drug or limit its use until more information is found OR could withdraw approval (very rate).
Define bioavailability, controlled clinical trial, and placebo in the context of clinical trials.
Differentiate between pharmacodynamics and pharmacokinetics.
Bioavailability = the rate at which the drug is available at the desired location or target
Controlled clinical trial = a clinical trial where one group is receiving the investigational drug product and the control group is receiving a placebo/standard treatment or nothing
Pharmacodynamics = the effect that the drug has on the body
Pharmacokinetics = the effect that the body has on the drug
Who is responsible for submitting an NDA? What is the purpose of submitting it?
The sponsor and to obtain FDA approval to market the product
What is the fast track approval process. For what type of studies is it used for? How does the submission of data from a sponsor work?
The fast track process is meant for investigational drugs that are for serious or life threatening diseases or that meet un-met medical needs. The sponsor can submit data on a roll-out method.
What is a CRO (contract research organization?
A CRO is an individual or a company that is contracted to take on some of the sponsor’s obligations (e.g. protocol development, monitoring, preparing materials and documents for submission to the FDA)
What is the difference between the sponsor and an investigator?
The sponsor initiates the drug development process and submits the IND to the FDA. They do not conduct the investigation.
An investigator conducts all aspects of the investigations. They do not submit the IND to the FDA UNLESS, they are a sponsor-investigator.
