Bioequivalence Slides (Fang) Flashcards
Bioequivalency studies originated in what era (due to growing recognition that different products with the same amount of active ingredient demonstrated different responses)?
Mid 1950s
The very first BAC studies were conducted in the 1940s using what scientific instrument?
Spectrophotometer
What drug vehicle was used by many pharmacists in Sulfanilamide Elixirs in the 1930s, leading to the deaths of many young children (& subsequent formation of the FDA)?
Diethylene Glycol (Washer Fluid component)
Name of the scientist who discovered that Thalidomide was inducing many birth defects in infants?
Frances Kelsey (Canadian)
Important amendment to the Federal FDC Act in 1962?
Generics now had to meet safety, efficacy & bioequivalency criteria (prior to ‘62 just had to meet safety requirements & you could patent a generic drug).
In 1984, the Hatch-Waxman Act came into play… What did it describe?
ANDA (Abbreviated New Drug Application)… Generics assumed safe & effective, so only criteria that needed to be met was bioequivalence.
I’m developing a generic form of an existing drug, and I’m worried about getting sued if new, previously undetected side effects come about. Under what conditions do I not have to worry about getting sued (if new side effects come about from my generic drug)?
Utilize the exact warnings on the brand name equivalent (& you cannot get sued)!
The Canadian Pharmaceutical Drugs Directorate (PDD) defines “bioavailability” as what?
Rate & extent of drug absorption into systemic circulation.
Provide examples of physiochemical drug properties that may cause differences in bioavailability.
-Particle Size
-Crystalline Structure
-Polymorphic Form
-Hydration Extent
-Salt / Ester Forms
Provide examples of formulation / manufacturing variables that may influence a drug’s bioavailability.
-Amount of Disintegrant / Lubricant
-Coatings
-Nature of Diluent
-Compression Force
Compare Absolute Bioavailability to Relative Bioavailability.
Absolute: Comparison of [Plasma] vs. Time curves of IV Bolus & Oral dosage forms… Within same patient!
Relative: Comparing rate & extent of drug bioavailability between two oral dosage forms (generic versus brand products).
Calculate the Relative Bioavailability (Frel) and Absolute Bioavailabilty (F) of the following data set:
Innovator (Oral Bolus): AUC = 75mg / L x h ; F = ?
Innovator (IV Bolus): AUC = 225mg / L x h ; F = 1
Generic (Oral Bolus): AUC = 60mg / L x h ; Frel = ?
AB = (75mg / L x h) / (225mg / L x h) = 0.333
RB = (60mg / L x h) / (75mg / L x h) = 0.80
When are bioequivalency studies required to be conducted?
-New generic product
-Innovator showing BE
-Introducing new dosage forms or strengths of existing drug
What BCS drug class is eligible for a bioequivalency waiver?
Class I
Which of the following drugs would not be eligible for a bioequivalency waiver?
a) Oral Naloxone (F = 0 ; intended for opioid constipation relief)
b) Regular Strength Topical Diclofenac (intended for local use)
c) Fluticasone (delivered via oral inhaler device containing HFA propellant)
d) Compounded Clonazepam Suspension (containing OraBlend with Sucrose derivative)
-Clonazepam Suspension (no good as OraBlend contains Sucrose [Sugar Alc] that can influence F)…
-Naloxone is not orally absorbed (good), Diclo is for localized use topically (good), and the Fluticasone inhaler contains a propellant that does not influence bioavailability (good).
