Week 5 Flashcards
(15 cards)
Food Regulatory Framework
FSANZ
TGA Roles
Advisory Committee on Medicines (ACM)
Australian Register of Theraputic Good (ARTG)
Standard for uniform scheduling of medicines and poisons (SUSMP)
Steps from application to PBS
- TGA application
- ACM approval
- Drug put on ARTG
- PBS application
- Pharmaceutical benefits advisory committee (PBAC) review
- Pharmaceutical benefits pricing authority (PBPA) to determine PBS amount
- Drug on PBS
Aust L
“listed” evaluated for quality & safety ONLY (claims must be low level)
Aust R
“registered” must ALSO show efficacy (med. or high level claim)
OECD
Organisation for Economic Co-operation & Development International regulation
Non-Clinical Safety Program Design
Carcinogenicity studies
Genotoxicity studies
Toxicokinetics & pharmacokinetics
Toxicity testing
Reproductive toxicology
Biotechnological products
Pharmacology studies
Immunotoxicology studies
Joint safety/efficacy (multidisciplinary) topic
OECD Objectives
Protect Human and Environment
High Quality Instruments (GLP + Test guidelines)
Efficiency
Share the Burden
Avoid duplication
Avoid non-tariff barriers to trade
Discovery/Screening/Preclinical-Nonclinical stage objectives
is the compound biologically active?
Preclinical: Pharmacodynamics
(in vitro; in vivo)
is the compound safe?
Nonclinical: Safety Pharmacology & Toxicity (in vitro; in vivo)
what is the dose-response for the activity & safety?
Principles of In Vivo Toxicity Testing
- Test compound administered to ID doses causing:
* no adverse effect
* major toxicity - Use two routes of administration:
* Route intended for human use (e.g. oral)
* Intravenous administration - Animals are closely monitored following dosing for the effects of the compound
- Maximum possible PK & toxicological information is collected during the study
GLP Pros
Mandatory, Mutual recognition, increases assurance of integrity and quality, enhances credibility
What data is submitted by the sponsor?
Common Technical Document (CTD)
1. Regional administration info
2. CTD summaries
3. Quality (chemical and quality control)
4. Safety
5. Clinical study reports
Aspects Assessed in Pre/Nonclin. Reports
- Nature/rationale of testing program
- Primary & secondary pharmacodynamics
- Target organ damage – of form (histopath.) or function ?
- Relevance of animal model to humans – metabolism & pharmacological response
- Dose-response comparisons (I.D. the “NEL”)
- Toxicokinetics: relate exposure to dose; bioavailability; repeat dosing effects; safety margin
- Relate doses with effects (& NEL) to maximum recommended patient dose
- Compare PK parameters between human & test species: dose/AUC, exposure/Cmax
- Are stats signif. effects also biol. signif. ? (all stats done ?)
- Compare impurity profile for nonclin. tests vs. human use
- Any gender related effects ?
- Significance of any irreversible toxic effects
- Any potential stereoisomer problems ?
- Comparison of new drug with analogues (in same structural or therapeutic class)
- Comments on GLP status of studies & any important deviations from Aust. (EU) guidelines
- Do animal studies support claims of drug’s advantages?
- List any disadvantages or additional info needed
Primary pharmacodynamics
Pharmacodynamic (PD) effects relating to proposed indications (i.e. therapeutic basis of registration)
Secondary pharmacodynamics
- Actions of the drug that may be relevant to the expected use or adverse effects of the drug
- Other actions relevant to drug safety, but may not be relevant to proposed indications
