DDD - topic 2: FDA Drug Development Process

5 steps of drug development process

1. discovery and development

2. preclinical research

3. clinical research

4. FDA review

5. FDA post-market safety monitoring

discovery and development

this step is where research for a new drug begins in the laboratory

preclincial research

this step is where drugs undergo laboratory and animal testing to answer basic questions about safety

clinical research

this step is where drugs are tested on people to make sure they are safe and effective

FDA review

this step is where FDA review teams thoroughly examine all of the submitted data related to the drug or device and make a decision to not approve it

FDA post-market safety monitoring

this step is where FDA monitors all drug and device safety once products are available for use by the public

discovery

at this stage, thousands of compounds may be potential candidates for development as a medical treatment

discovery

this is where new insights into a disease process allows researches to design a product to stop or reverse the effects of the disease

discovery

this is where many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases

discovery

this is where existing treatments may have unanticipated effects

discovery

this is where new technologies (ex. new ways to target medical products to specific sites) may be

development

this is where experiments is done on identified compounds to know how it is absorbed, distributed, metabolized and excreted as well as its potential benefits, mechanism of action, dosage, and adminstration

development

this is where experiments is done on identified compounds to know its side effects, variated effects, drug interactions and effectiveness comparison

2 types of preclinical research

1. in vitro

2. in vivo

good laboratory practices (GLP)

this is required by the FDA for researchers as defined in medical product development regulations for preclinical laboratory studies

21 CFR part 58.1: Good Laboratory Practice for Nonclinical Laboratory Studies

the GLP regulations are found in

preclinical studies

these studies are not very large but must provide detailed information on dosing and toxicity levels

clinical research

it refers to studies or trials that are done in people

new drug process (IND)

A process that must be done before clinical research begins

clinical trials

researchers design _____ to answer a specific research question related to a medical product

protocol

clinical trials follow a specific study plan called _____ that is developed by the researcher or manufacturer

4 clinical trial phases

1. phase 1

2. phase 2

3. phase 3

4. phase 4

phase 1

this phase involves 20-100 healthy volunteers or people w/ disease

phase 1

this phase involves several months of study

phase 1

the purpose of this phase is safety and dosage

phase 1 studies

this phase is closely monitored and gathers information about how a drug interacts with the human body. researchers adjust dosing schemes based on animal data

phase 1 studies

this phase is where researchers answer questions related to how it works in the body, side effects w/ increased dosage, effectiveness and administration (min/max risk & benefits)

70

in phase 1, approximately ____% of drugs move to the next phase

phase 2

this phase involves several hundreds of people with disease

phase 2

this phase involves several months to 2 years

phase 2

the purpose of this phase is efficacy and side effects

phase 2

this phase is where researchers administer the drug to a group of patients with the disease.

phase 2 studies

this phase is not large enough to show whether the drug will be beneficial

phase 2 studies

this phase provides researchers with additional safety data. this data is used to refine research questions, develop research methods, and design new phase 3 research protocols

33

in phase 2, approximately ___% of drugs move to the next phase

phase 3

this phase involves 300-3000 volunteers with disease

phase 3

this phase involves 1-4 years of study

phase 3

the purpose of this phase is efficacy and monitoring of adverse reactions

phase 3 studies / pivotal studies

this phase is designed to demonstrate whether or not a product offers a treatment benefit to a specific population

phase 3 studies

this phase provides most of the safety data, are larger and longer in duration, and results are more likely to show long-term or rare side effects

25-30

in phase 3, ____ - ____ % of drugs move on to the next phase

phase 4

this phase involves several thousand volunteers with the disease

phase 4

the purpose of this phase is safety and efficacy

phase 4 trials

this phase is carried out once the drug or device has been approved by FDA during post-market safety monitoring

investigational new drug

drug developers / sponsors must submit an _____ application to FDA before beginning clinical research

project manager

this FDA IND review team member coordinates the team’s activities throughout the review process, and is the primary contact for the sponsor

medical officer

this FDA IND review team member reviews all clinical study information and data before, during, and after the trial is complete

statistician

this FDA IND review team member interprets clinical trial designs and data and works closely with the medical officer to evaluate protocols and safety and efficacy data

pharmacologist

this FDA IND review team member reviews preclinical studies

pharmakineticist

this FDA IND review team member focuses on the drug’s absorption, distribution, metabolism, and excretion processes.

pharmakineticist

this FDA IND review team member interprets blood-level data at different time intervals from clinical trials, as a way to asses drug dosages and adminisration scheduels

chemist

this FDA IND review team member evaluates a drug’s chemical compounds. they analyze how a drug was made and its stability, quality control, continuity, the presence of impurities etc.

microbiologist

this FDA IND review team member reviews data submitted, if the product is an antimicrobial product, to asses response across different classes of microbes

30

the FDA review has ___ days to review the original IND submission

FDA approval

this process protects volunteers who participate in clinical trials from unreasonable and significant risks in clinical trials

2 ways FDA responds to IND applications

1. approval to begin clinical trials

2. clinical hold to delay or stop investigation

developer

they are responsible for informing the review team about new protocols, as well as serious side effects seen during the trial. this information ensures that the team can monitor the trials carefully for signs of any problems

new drug application (NDA)

this tells the fully story of a drug. its purpose is to demonstrate that a drug is safe and effective for its intended use in the population studied

6-10

the FDA review team has ___ to ___ months to decide to approve the drug or not upon receiving the [complete] NDA

FDA inspectors

they travel to clinical study sites to conduct a routine inspection

FDA

they look for evidence of fabrication, manipulation, or withholding data

project manager

they assemble all individual reviews and other documents

action package

this document becomes the record for FDA review

[FDA] review team

they are the ones that issue a recommendation

senior FDA official

they are the ones that make a decision [for approval]

labeling

it is where FDA must work with the applicant to develop and refine prescribing information. it accurately and objectively describes the basis for approval and how best to use the drug

FDA advisory committee

the FDA consults this committee for additional consideration

patient representative

advisory committee include a _____ that provides input from patient perspective

supplemental application

developers must file ____ if they wish to make any significant changes from the original NDA

FDA

they regulate prescription drug advertisements and promotional labeling

patent protected

new drugs are _____ when approved for marketing. only the sponsor has the right to market the drug exclusively

bioequivalence studies, Abbreviated New Drug Application

instead of clinical trials for generic drugs, manufacturers conduct ____ studies and file ____

this is a gateway for reporting problems with medical products and learning about new safety

Medical Product Safety Network

this monitors the safety and effectiveness of medical devices

350

FDA recruits ____ healthcare providers throughout the US to report any medical device problems

MedSun newsletter

this newsletter gives consumers important information about medical device safety

Sentinel Initiative

under this, FDA is developing a new national system to more quickly spot possible safety issues. the system will use a very large existing electronic health databases