7 - Drug Approval Process Flashcards
Generally describe the steps and authorities involved in the process of drug discovery to market
- Molecule discovery
- Pre-clinical trials
- Clinical trials (phase 1, 2, 3)
- Therapeutic products directorate (TPD)
- Notice of compliance (NOC, NOC/C)
Generally describe the steps and authorities involved in the process of drug pricing and access
- CADTH common drug review (CDR)
- PMPRB
- Phase 4 trials, ADR surveillance
- Formulary decision (provincial)
What is tested in pre-clinical trials from a pharmaceutics point of view?
- Physicochemical characterization
- Impurity analysis
- Formulation
- Stability testing
What is tested in pre-clinical trials from a toxicology point of view?
- Cytotoxicity
- Hepatotoxicity
- CV safety pharmacology
- Maximum tolerated dose
Describe phase 1 of clinical trials
- Establish safe dosing range in humans
- Use normal, healthy volunteers (20-100)
- Lasts about 1 year
Describe phase 2 of clinical trials
- Efficacy trials in small population w/ the indicated condition
- Select optimal dose and observe for AEs
- Volunteer patients (100-500)
- Lasts 2-3 years
Describe phase 3 of clinical trials
- Extensive trials in large populations w/ the indicated condition (hundreds to thousands)
- Goal = verify efficacy of the drug by comparing the new drug to a control group (placebo or comparator)
- Lasts 1 to 5+ years
- Sample size is designed to have enough statistical powder to detect difference in the clinical outcomes of interest (NOT adverse effects)
Describe phase 4 of clinical trials
- Post-marketing trials of effectiveness and safety
- Surveillance of real-word effectiveness and long-term safety
- New indications for use
- Special disease-state and populations
- Drug interaction studies
What is Health Canada’s HPFB (health products and food branch)?
- National authority that regulates, evaluates, and monitors the safety, efficacy, and quality of therapeutic and diagnostic products available to Canadians
- HPFB also contains TPD (therapeutic products directorate) and BGTD (biologics and genetic therapies directorate)
What is the purpose of the TPD (therapeutic products directorate)?
Responsible for evaluating the safety, effectiveness, and quality of pharmaceutical drugs and medical devices available to Canadians
What is the purpose of the BGTD (biologics and genetic therapies directorate)?
Responsible for evaluating the safety, effectiveness, and quality of biological and radiopharmaceutical drugs (ex: blood and blood products, viral and bacterial vaccines, genetic therapeutic products, tissues, organs, xenografts)
What is the role of Health Canada in the drug approval process?
- Pre-clinical studies
- Clinical trial authorization (including clinical trial application or amendment)
- Submission review (including regulatory product submission, safety, efficacy, and quality review; and market authorization decision)
- Public access
- Post-market (including surveillance, inspection, and investigation and post-market changes)
What does TPD do?
- Clinical trial authorization, drug submission reviews, and post-market
- Reviews scientific info to assess safety, efficacy, and quality of Rx drugs or a medical device
- Benefit/risk product analysis
- Reviews clinical trial applications
- Special access program
- Provides Canadians w/ science-based medical info they need to make informed choices
- Monitors evolving safety of drugs in development through review of adverse reaction reports
What must be included in a new drug submission to TPD?
- Safety, efficacy, and quality
- Pre-clinical and clinical data
- Drug production
- Packaging and labelling
- Therapeutic claims
- ADEs
Describe the notice of compliance (NOC)
- Permits the sponsor (drug company) to market the drug
- Indicates the drug’s official approval in Canada
Describe the priority review process
- Faster review possible for promising drug products for life threatening/ severely debilitating illnesses (ex: cancer, AIDS, Parkinson’s)
- Effective tx of a disease or condition for which no drug is presently marketed in Canada
- OR, a significant increase in efficacy and/or significant decrease in risk such that the overall benefit/ risk profile is improved over existing therapies for a disease or condition that isn’t adequately managed by a drug marketed in Canada
Describe the NOC w/ conditions (NOC/C)
- Allows earlier market access for potentially life saving drugs
- No alternative or significant improvement in benefit/ risk profile over existing products
- Enhanced post-market surveillance
- Sponsor agrees to verify the clinical benefit of the drug
- Increased monitoring and reporting to Health Canada
- Required to provide educational materials for px and practitioners
- Public and private drug plans may or may not cover b/c clinical benefit not yet confirmed
- Conditions removed once satisfactory evidence provided
Describe the special access programme (SAP)
- Program operated by Health Canada to give practitioners access to medicines that aren’t approved or otherwise available in Canada
- Administered by TPD
- Ability to prescribe drugs w/o NOC to specified px
- Legitimate need and qualified physician involved
What is a patent?
- Legal means of preventing anyone from producing or copying an invention w/o permission of the owner
- The Act permits the patent holder to prevent third parties from manufacturing or selling any product which uses the invention which is the subject of the patent
How long is a patent good for?
- Between 8 and 15 years (average 12 years)
- Market exclusivity depends on length of clinical trial period
What are the rules regarding brand name and generic patents and regulatory approval?
- Generic drug firm can’t apply for regulatory approval until brand drug has been on market for at least 6 years
- Can’t receive regulatory approval until brand drug has been on the market for at least 8 years
- Applies to “innovative drugs” where the medicinal ingredient hasn’t been previously approved
Describe the ANDS (abbreviated new drug submission)
- No clinical trials
- Bioequivalence studies
- Only in healthy volunteers in order to reduce the variability not related to differences between products
Describe biologic medicines
- Drugs derived through the metabolic processes of living organisms (ex: recombinant DNA, controlled gene expression, antibody method)
- Important innovations for the tx of many chronic diseases
- Tend to be more variable and structurally complex than chemically synthesized drugs
- Costly $$$
How are biologics different from conventional pharmaceutics?
- Small molecule vs. big molecule
- Complex mixtures that aren’t easily identified or characterized
- Heat-sensitive and susceptible to microbial contamination (requires sterile processes to be applied throughout manufacturing and distribution process)
Key differences w/ biological drug reviews
- On-site evaluations -> assessment of production process and facility for a specific product which ensures manufacturing process conforms to info described in the submission
- Additional GMP (good manufacturing practices) -> special considerations and issues pertinent to manufacturing and control of biological drugs, blood and blood components
Describe the PMPRB (patented medicine price review board)
- Independent federal agency that reports to Minister of Health
- Regulatory mandate = ensure prices charged by patentees for patented medicines sold in Canada aren’t excessive (doesn’t considered “cost-effectiveness” in determining whether prices are excessive)
- Regulatory process based on scientific review and pricing review
- Reporting mandate = report on pharmaceutical trends of all medicines and on R & D spending by pharmaceutical patentees
Describe CADTH (Canadian agency for drugs and technology in health)
- Reviews new drugs, new combination products, and drugs w/ new indications and provides formulary listing recommendations to all publicly-funded drug benefit plans in Canada (except Quebec)
- Aims to reduce duplication and maximize use of resources
Generally describe the drug formulary review process
- Health Canada = market authorization
- Manufacturer = submission of clinical and economic evidence to CADTH
- CADTH = reviews and recommendations to drug plans
- Drug plan = listing decision
