1 pharmaceutical registration process

Question 1

what is the outline of this lecture?

Answer 1

drugs development process
-preclinical phase
-clinical phase
-post-marketing surveillance

regulatory considerations
-health canada
-review process of drug submissions

international pharmaceutical regulations and registration

Question 2

what is the drug development process?

Answer 2

Question 3

what is drug discovery?

Answer 3

1. target validation and identification
2. new insights into a disease process: to inhibit or reverse the effects of the disease
3. exploring different compounds for potential therapeutic benefits across diverse diseases
4. computational approaches: high-throughout screening techniques

Question 4

what are the goals of drug discovery?

Answer 4

-start with a “hit”
-does it have an effect?
-optimize effect: lead optimization techniques (inspecting functional groups, replace or remove or add to optimize function)
-transform hits into leads (compound that is ready to test in animal models)

Question 5

what is the preclinical phase components?

Answer 5

-pharmacokinetics

Question 6

what is the pharmacokinetics and pharmacodynamics testing for in the preclinical phase?

Answer 6

Question 7

what is the required testing in the preclinical phase?

Answer 7

-single-dose toxicity (acute toxicity) (LD50)
-repeated dose toxicity (subchronic and chronic)
-reproductive and developmental toxicity
-mutagenic potential (change DNA)
-carcinogenicity

Question 8

what are the special studies in the preclinical phase?

Answer 8

most aren’t mandatory (depend on the purpose of the drug)
-dermal irritation/corrosion (single or repeated dose)
-ocular irritation/corrosion
-dermal sensitization
-phototoxicity
-inhalation toxicity (single or repeated dose)
-immunotoxicity
-neurobehavioral toxicity

Question 9

what are the phases of the clinical phase?

Answer 9

-phase I (<50 patients): is it safe? healthy volunteers (dont actually have the disease. want to establish baseline and side effects)
-phase II (100 patients): is it efficient? (some have the disease)
-phase III (>1,000 patients): is the efficacy better?(likelihood of side effects are more likely)

most fail at phase 2 and 3

Question 10

what is out regulatory agency in canada?

Answer 10

health products and food branch (HPFB) -health canada
-mandate: to manage the health-relayed risks and benefits of health products and food

Question 11

what does HPHB do?

Answer 11

evaluating and monitoring the safety, quality and efficacy of:
-health products (including pharmaceutical, biological and radiopharmaceutical drugs, medical devices, and natural health products)
-foods
-veterinary drugs

Question 12

what are the directorates and offices of HPFB?

Answer 12

-biologic and radiopharmaceutical drugs directorate
-food directorate
-marketed health products directorate
-medical devices directorate
-natural and non-prescription health products directorate (deal with non-prescription drugs)
-office of nutrition policy and promotion
-pharmaceutical drugs directorate (deals specifically with prescription drugs)
-policy, planning and international affairs directorate
-resource management and operations directorate
-veterinary drugs directorate

Question 13

what is the PDD?

Answer 13

pharmaceutical drugs directorate
-formerly the therapeutic products directorate (TPD)
-reviews scientific information to assess the safety, efficacy and the quality of a prescription drugs as required by food and drug regulations
-assesses the potential benefits and risks of a prescription drug (no such thing as a safe drug on the market, all have a certain level of risk, so it’s risk vs. benefits ratio)
-reviews clinical trial applications(CTAs) for prescription drugs to ensure that the studies are well-designed and that participants will not be exposed to undue risk
-monitors the evolving safety of drugs in development through the review of adverse reaction reports that are submitted as a requirement of the food and drug regulations (watch results of all clinical trials, can stop at any phase)
-provides guidance documents (says dose, contains warnings, labelling standards)

Question 14

how does the review process happen?

Answer 14

pass all the clinical trials

Question 15

what is the first step of the review process?

Answer 15

drug manufacturer files a “new drug submissions” with health products and food branch (HPFB)-health canada
-information and data about the drug’s safety, effectiveness and quality
-results from preclinical and clinical studies
-therapeutic claims (what disease you are making the drugs for) and side effects
-details regarding production, packaging and labelling details (need to provide healthcare provider with information, like pamphlets)

Question 16

what is the second and third step of the review process?

Answer 16

2. HPFB performs a thorough review of the submitted information, sometimes using external consultants and advisory committees
3. HPFB evaluates the safety, efficacy and quality data to assess the potential benefits and risks of the drug

Question 17

what is the fourth step of the review process?

Answer 17

-HPFB reviews the information that the drug manufacturer proposes to provide to health care practitioners and consumers about the drug (e.g. the label, product brochure)

Question 18

what is fifth step of the review process?

Answer 18

if, at the completion of the review, the conclusion is that the benefits outweigh the risks and that the risks can be mitigated, the drug is issued a Notice of Compliance (NOC), as well as a Drug identification number (DIN) which permits the drug manufacturer to market the drug in canada and indicates the drug’s official approval in canada

Question 19

what is the sixth step of the review process?

Answer 19

in addition, health canada laboratories may test certain biological products before and after authorization to sell in canada has been issued. This is done through its Lot Release Process, in order to monitor safety, efficacy and quality
-if drug is not approved: drug manufacturer can ask for reconsideration, or submit the additional information and re-submit at a later date

Question 20

what is the priority review of drug submissions?

Answer 20

-health canada aims a regular review target of 300 days (lying)
-other accelerated review pathways are availably for life-threatening or severely debilitating conditions (e.g. cancer, AIDS, parkinson’s disease) with review target of 180 days
-same quality, safety, and efficacy requirements as non-priority submissions
-orphan drugs are also eligible for the priority review pathway (treat rare diseases, not interested in)

Question 21

how expensive is the drug development process? (downsides)

Answer 21

-expensive: 314 million to 2.8 billion
-lengthy process (around 15 years)
-health canada review and approval (1-2 years)

Question 22

what happens if canada wants to use a drug created made in another country?

Answer 22

international pharmaceutical regulations and registration

Question 23

what is the ICH?

Answer 23

international council for harmonization (ICH) of technical requirements for pharmaceuticals for human use

Question 24

what does ICH do?

Answer 24

to make the drug regulatory process more efficient in the member countries
-prevent unnecessary duplication of clinical trials and post-market surveillance
-reduction of unnecessary animal testing without compromising safety and effectiveness

issues technical guidelines for the manufacturing, development and testing of new pharmaceuticals

Question 25

how was the ICH reformed?

Answer 25

-1990 brings together the regulatory authorities and pharmaceutical industry
-2015 reformed as a non-profit legal entity globally
-health canada is an official member of ICH

Question 26

what are the steps in ICH guideline development and implementation

Answer 26