From Bench to Bedside: Regulatory Bodies Flashcards
What are the Steps for the Discovery of Drugs and their Development Process?
Step 1: Have something to discover
Step 2: Pre-clinical Study
Step 3: Clinical Studies
Step 4: Regulatory Review
Step 5: Post-Marketing Activities
What happens during the first step of Drug Development Process?
You need to have something to discover (isn’t limited to drugs, can be health product/device, or etc.)
What happens during the Pre-Clinical Studies?
Show proof of MECHANISM (exactly how it’s working), can’t move on if you’re still proving how it works.
- doesn’t have to be done on just animals, humans are just less common
What happens during the Clinical Studies?
Between all 4 phases, the difference is the number of humans involved and their demographics; Phase 1 has a smaller pool of people and increases with each phase.
Takes 6-7 years
What happens during Regulatory Review?
A new drug submission from start to finish in Canada can take about 6 months - 2 years for Health Canada to approve. However for USA, 4 years.
What happens during Post-Marketing Activities?
Phase 4 of Clinical Studies; you look at post-marketing changes, and this is where companies engage in unethical behaviour; substituting one compound for another, or adding more fillers as to not sell the same amount of compounds. This usually leads to then have these products not being allowed to be sold.
What are the regulatory bodies reviewing?
Safety, Effectiveness & Quality
- this usually is assessed during the preclinical studies
How are drugs and medications authorized for sale in Canada?
Drugs and other medications are authorized for sale after they’ve successfully gone through the drug review process
Does everything sold under Canada have to go through the drug review process?
No; so if Health Canada wants, they can pull it off of shelves and put a fine to that business
Who oversees the drug review process for drugs and medications to be authorized for sale in Canada?
Health Canada; specifically within Health Canada: Health Product and Food Branch (FEDERAL AGENCY)
What does Health Canada review when it comes to drugs and medications to be authorized for sale in Canada?
Safety, effectiveness and quality
How long can the rug review process last?
6 months - 2 years
What is considered to be a drug?
- Prescriptions & nonprescription pharmaceuticals
- Biologically derived products such as vaccines
- Blood derived products
- Products produced through biotech.; tissues & organs; disinfectants and radiopharmaceuticals
Anything not listed is a Health Product!!
What is the difference between prescription vs nonprescription?
Prescriptions are restricted; doesn’t say anything about the safety, effectiveness and quality of it.
What policy determine the list of what is considered to be a drug?
Food and Drugs Act
- This is on the Federal Level by Health Canada
What is part of the Canadian regulatory framework?
- Acts
- Regulations
- Guidelines
- Policies
What is acts?
Food & Drug Act
This is authorized by Health Canada, and they see the development and marketing of drugs
What is regulations?
Food & Drugs Regulations, and Medical Devices Regulations
How does Food & Drugs act work specifically for FDR and MDR?
Oversees the development of everything that gets sold in Canada. Each of these regulations are siloed for whatever that thing is (e.g. if it’s a prescription drug or not, it will go under the FDR, if it’s a medical device, it goes under medical device regulations)
What is guidelines within the Canadian regulatory framework?
They are usually general on what must be done, in terms of how regulations are interpreted.
What is policies?
More general in terms of how we interpret those regulations. more loose and fine-tuned to the province, as each province has their own regulatory bodies that interpret these regulations.
What factors determine the timeframe of drug discovery and development process?
- Accelerated Review Process from Health Canada
- HPFB can provide faster authorization for health conditions that are serious, life-threatening, or severely debilitating diseases (Alzheimer’s, cancer, AIDS, and etc.)
How can the HPFB provide faster authorization of a drug?
- Priority Review
- Notice of Compliance with Conditions
How does Priority Review work?
This applies to drugs that show substantial evidence of clinical effectiveness at the end of the clinical trial phases
What does the Notice of Compliance with conditions apply to?
Drugs with promising evidence of criminal effectiveness throughout the clinical trial phases; they show good evidence of effectiveness, but need more to show in terms of efficacy or not. Approval would be granted to a manufacturer to market and sell that drug in Canada with the condition that the manufacturer execute additional studies to confirm the drug’s benefit and safety.
What is the purpose of Health Canada’s partnership with initiative like Project Orbis?
Designed to give cancer patients faster access to promising cancer treatments, alongside the US FDA
Which products are eligible for Project Orbis?
Include oncology products that are either new active substances or new indications for previously approved drugs.
What criteria are Project Orbis submissions expected to meet?
“FDA Priority Review” and Health Canada PR or NOC/c criteria
Why is Canada focusing on increasing the approval of cancer treatments?
To provide more options for patients, particularly for diseases like endometrial carcinoma where there’s very little treatment in Canada that doesn’t go through experimental therapies. For that reason, Canada is focusing on increasing the products that’re approved so they can be funded by the public infrastructure.
Who regulates medical devices classified under Health Canada’s regulations?
Health Canada
What are the 2 parts of Health Canada’s Medical Device Regulations (MDR) based on classification rules?
Part 1: Medical devices other than in vitro diagnostic devices
Part 2: In vitro diagnostic devices
What is time 0 of the Clinical Trial Phases?
Discovery (can be product, medical device, or anything that you’re trying to market)
What is the difference between Phases 1-3 of Clinical Trials?
Population; with each phase, the number of patients increases.
Who provides oversight for clinical trial applications in Canada?
Hospitals, not Health Canada
Where does the initial approval for clinical trials typically occur?
Typically occurs at the regional level, mainly through hospitals.
What ensures the safety of patients during clinical trials?
The clinical board, hospital board, and ethics review board have a say in ensuring the safety of patients during clinical trials.
What is the process for final approval of clinical trials in Canada?
Final approval of clinical trials in Canada occurs at the federal level through Health Canada.
What happens once all data from clinical trials is obtained?
A new drug submission is submitted to Health Canada for review, including preclinical, clinical, and discovery data.
Who has a say into the patients being recruited for Phase 1-3? Why?
The clinical board, hospital review board, and the ethics review board. This is to ensure the safety of the patients.
What happens after completing all 3 phases of clinical trials?
A new drug submission is made to Health Canada.
What data is included in the new drug submission to Health Canada?
Data on safety and efficacy, including preclinical, clinical and discovery data
Who reviews the data submitted to Health Canada for drug approval?
Health Canada
What is the primary focus of Phase 1 in clinical trials?
To assess safety during the translation from animal models to humans
What is being measured in terms of safety during Phase 1 trials?
Safety is assessed by measuring both primary and side effects of the drug, as well as interactions with factors such as food, lifestyle, and demographics.
Why is so important to assess interactions during Phase 1 trials?
To assess interactions during Phase 1 trials because humans are diverse, and factors like food, lifestyle, and demographics can influence how individuals respond to a drug.
Who are investigational drugs typically tested on in Phase 1 clinical trials?
They’re typically tested on a small group of healthy individuals in Phase 1 clinical trials
What is the primary purpose of Phase 1 clinical trials?
To determine the pharmacokinetics/pharmacological action of the drug, find a safe dosage range, and identify adverse drug reactions.
When might investigational drugs be tested on populations other than healthy individuals in Phase 1 trials?
May be tested on populations other than healthy individuals in Phase 1 trials when it’s not ethically acceptable to test on healthy individuals
How does Phase 2 of clinical trials differ from Phase 1?
Phase 2 builds on Phase 1 by increasing the population size and focuses on testing both safety and effectiveness of the drug, with a primary focus on effectiveness.
What is the typical population size for Phase 2 clinical trials?
Usually several hundred individuals
What is the primary purpose of Phase 2 clinical trials?
To obtain data on the effectiveness of the drug, further assess its safety, and determine the best dosage.
How do Phase 1 and Phase 2 clinical trials relate to each other?
While both phases assess safety and effectiveness, Phase 2 builds upon Phase 1 by increasing the population size and focusing more on effectiveness.
What is the typical location for Phase 3?
Often conducted in a country different from where Phases 1 & 2 were conducted, although this isn’t always the case
Why might it be beneficial to conduct Phase 3 in a different location?
Allows for a assessment of safety & effectiveness in different demographics, providing more comprehensive data on the drug’s performance
What is the primary purpose of Phase 3?
To confirm the drug’s effectiveness, monitor side effects, compare it to other treatments, and gather additional safety data.
How does the population size in Phase 3 compare to 1 & 2?
Phase 3 trials typically involve even larger groups of patients, usually in the thousands, compared to Phases 1 & 2.
What is the purpose of Phase 4?
To gather more information on the best ways to use a drug, and to assess its long-term benefits and risks to the population
When are Phase 4 trials conducted in relation to drug approval?
After a drug has been approved and marketed
Why might changes to a drug’s claims or composition require regulatory review?
To ensure safety, effectiveness, and ethical marketing practices
What happens if a drug is to be used outside the terms of its market approval?
a Clinical Trial Application may need to be submitted to Health Canada to obtain a No Objection Letter
How do companies manage the need for regulatory review for small changes to drugs?
They may use pipelines to develop multiple iterations of a drug simultaneously, allowing for efficient regulatory review and approval
Why are rodents commonly used in preclinical studies?
Due to their high sample sizes and relatively low variability, allowing for a clearer understanding of the drug’s mechanism of action
What is the typical duration of clinical studies?
Can last 6-7 years, but this may be extended due to recruitment challenges and attrition
How long does regulatory review typically take?
1/2 - 2 years and is based on detailed safety and efficacy data
How long do post-marketing activities typically continue?
Continue for the lifetime of the drug/device
What is the primary expense in drug development?
Goes towards discovery and preclinical stages
How much of the budget typically goes toward salaries?
75% of the budget, covering researchers’ salaries and other personnel expenses
Why’s it common to contract molecular services to other labs or companies?
One lab may not have all the necessary tools, and contracting out services allows for access to specialized expertise and equipment
How does replicating studies in 3rd party labs impact regulatory approval?
Can accelerate regulatory approval by reducing bias and increasing confidence in the results.
Why are patients not paid for their participation in clinical trials?
They aren’t paid to prevent selection bias in clinical trials.
