AP401+Pharmacy+Regulation

= AP401 Pharmacy Regulation =

Resources
Sample Questions: 2008 [|2007] Sample Answers: 2008 2007
 * **Subject** || **Lecture Notes** || **mp3** ||
 * Bioequivalence and Generic Medicines || 2008 [|2007] || [|2008] ||
 * Medicines Scheduling in Australia || [|2008a] [|2008b] [|2007] || 2008 ||
 * Legislative Overview || [|2008] [|2007] || [|2008a] [|2008b] ||
 * Privacy Principles || [|2008] [|2007] || 2008 ||

Outline
Date: Monday, October 08 Handouts: [|Generic Substitution] Audio: Generic Substitution Note: The lecture audio for this presentation is posted in mp3 format and provided for the purpose of revision support only • Briefly discuss the basis for generic medicine registration • Discuss the limitations and practice implications of generic medicine substitution**
 * Generic Substitution: Allan Evans**
 * • Define the term ‘Generic Medicine’

Two products are bioequivalent when they give rise to the 'same' concentration-time profile (therefore, same efficacy) in plasma - however, no two formulations are identical, therefore they are different - we are willing to tolerate between 80-125% of AUC
 * Bioavailability**

//reasons not to substitute// - allergy - confusion over multiple boxes - doctors may prefer Australian brands etc.

Clinical trial versus market-image
 * When and why are bioequivalence studies conducted?**

Generic versus innovator - both companies are required to do this

New method of manufacture - change in formulations (compressed vs form-filled tablet) - includes changes during the development process to improve stability and shelf life (to prove that improved formulation is similar to previous)

New supplier of raw material - will need to conduct another study due to change in formulation - particle size and crystal form differences (changes dissolution rate)

Dose --//k dissolution-->// Drug in solution --//K absorption-->// Absorbed drug - if slow dissolution, changes in particle size would require a bioequivalence test
 * Measuring bioequivalence**

We are interested in Cmax and AUC (area under the curve), Tmax is highly variable and is not considered - not based on a single profile, need to know variance in order to be confident that the two formulations are the same

//Factors that need to be controlled -// inclusion/exclusion criteria - diet/medications/other - food and fluid intake (amount and time) - dosing method - posture - sample collection - sample storage - sample analysis The only variable should be the product
 * Design of a bioequivalency study**

//Balanced two-way cross-over study// Not every subject should take drug A in period 1 then drug B in period 2, the order that they are given should be randomised - this will reduce the effects of auto-induction of enzymes

If the mean AUC ratio (product A to product B) is 1.05, it means that on average, the AUC value for product A is 5% greater than that for product B - however, we need a 90% CI tell us how confident we are that the products are 'bioequivalent' - the mean AUC ratio should be within 10% (90-110%), and the 90% CI needs to be between 80-125% in order to prove 'bioequivalence'
 * 90% Confidence Interval**

If the mean AUC ratio is outside 10%, increasing the number of subjects will not improve the outcome (not bioequivalent - need to reformulate) - if the mean AUC ratio is within 10%, but the 90% CI is outside 80-125% (not bioequivalent), either increase the number of subjects or argue the position that Cmax is irrelevant etc.

//Solubility and permeability characteristics for a drug// Class I - high solubility and high permeability - dissolution and absorption are fast and difficult to interfere rate - rarely have bioequivalence issues - therefore, can ask to bypass a bioequivalency test
 * Bioavailability Classification System**

-** bioequivalence is measured between a generic and the market leader - however, if generic 1 is 10% lower and generic 2 is 10% higher than the market leader, might be worried about switching from one generic to another - although 20% difference should be ok
 * Bioequivalent to what?

- Patients vs Health subjects (elderly: difficulty swallowing/lying down - brands may not be bioequivalent in these patients) - Individuals vs population (individuals may respond differently - intra-individual vs drug's own variability) - The way people actually take medicines (take with a full glass of water - as was tested in the bioequivalency trial) - Confusion over brand names/generic names/multiple generics - Low therapeutic index drugs - Role of pharmacist to educate (warfarin: 15% variation can be clinically significant)
 * Issues**

Date: Monday, October 08 Handouts: [|Medicines Scheduling in Australia] Audio: Scheduling 1 & Scheduling 2 Note: The lecture audio for this presentation is posted in mp3 format and provided for the purpose of revision support only __Schedule 2 (S2) - Pharmacy Only__ - substantially safe in use but where advice or counselling is available if necessary - easy access (via pharmacy) to effective medicines if misused or pharmacist does not provide info, may be scheduled back to S3/S4 (less sales/profits) if no counselling is required, can be unscheduled
 * Medicines Scheduling in Australia: Adam Phillips**
 * • Define the drug schedules used in Australia**

__Schedule 3 (S3) - Pharmacist Only__ - substantially safe, but requires pharmacists advice, management or counselling - access (via pharmacist) to effective medicines that require professional advice - pharmacist must personally give oral directions, supplemented wherever possible with written directions, for safe and proper usage consumer behaviours can change, leading to rescheduling (pseudoephedrine)

__Schedule 4 (S4) - Prescription Only__ - for conditions that require specified diagnosis or management - safety and efficacy may require further evaluation (if a new therapeutic substance)

__Schedule 8 (S8) - Controlled Drug (Drugs of Dependence in SA)__ - medicines that are dependence producing and likely to be abused or misused - require restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence

- toxicity and safety: if high, keep out of supermarkets - risks and benefits: access vs risk - potential hazards: requires at least two years of local clinical use or local post-marketing experience before considering downscheduling - extent and patterns of use: prn or ongoing - dosage and formulation: different schedule in different sizes and formulations - need for access (compared with similar substances): access vs risk - potential for abuse: diversion (using drug to create illicit drug - pseudoephedrine) - purposes for use: severity of the indication - anything else necessary to protect public health labelling, packaging and presentation of a substance: adding more information on the packaging can help downschedule a medicine
 * • Discuss the work of the National Drugs and Poisons Schedule Committee in terms of considerations made when scheduling medicines into S2 and S3**

__Nurofen example__ - access: need in a timely manner - advice: may not occur, but little side-effect occurrence - demand: want Nurofen in supermarkets - risk:

Date: Monday, October 08 Handouts: [|Legislative Overview] & [|Privacy Principles] Audio: Pharmacy Legislation Note: The lecture audio for this presentation is posted in mp3 format and provided for the purpose of revision support only At the conclusion of this lecture series students should be able to:
 * Legislative Overview & Privacy Principles: Libby Hotham & Adam Phillips**
 * • Provide a basic description of the principles of the Pharmacy Act and Controlled Substances Act (and their relevant regulations) as they relate to pharmacy practice

• Discuss implications of the Controlled Substances Act (and Regulations) on the supply of DDA’s in pharmacy practice

• Understand the basic implications of the National Privacy Act in pharmacy practice**


 * Practice Questions:** [|Sample Questions (Pharmacy Regulation)]