Compounding/Regulatory Sciences

Question 1

Compounding

Answer 1

• “preparation”
• Prepared in limited quantities as a result of a prescription order
• Regulated by state boards of pharmacy (NOT FDA)

Question 2

Manufacturing

Answer 2

• “product”
• Mass produced from natural or synthetic bulk chemicals and legally marketed for resale by pharmacies
• Regulated by the US FDA

Question 3

Drug Quality and Security Act

Answer 3

Federal legislation passed in 2013 to clearly distinguish between compounding and manufacturing

Question 4

Compounding pharmacies are exempt from:

Answer 4

• cGMP requirements
• labeling of drugs with adequate directions for use
• approval of drugs under NDA or ANDAs

Question 5

Fillers (Diluents)

Answer 5

• Added to increase bulk of preparation suitable for administration
• Must be compatible with drug (ex. Don’t use calcium salts w tetracycline or lactose w/ amine drugs)
• Use water soluble diluents with drugs that have low water solubility to avoid precipitation
• Ex. Lactose, Microcrystalline cellulose, Sodium chloride, Mannitol, Starch

Question 6

Binders

Answer 6

• Increase cohesive qualities of powdered materials
• Ensure that the tablet will remain intact after compression
• Improve free-flowing quality of powder mix
• too much or too strong of a binder will delay tablet disintegration
• more effective if used in solution rather than dispersed in dry form
• Ex. Cellulose derivatives, PVP, PEGs, starch paste, Gelatin

Question 7

Lubricants

Answer 7

• Reduce friction at the interface of tablet and dye wall during compression and ejection
• Ex. PEG 4000, Sodium Benzoate, magnesium lauryl sulfate

Question 8

Gildants

Answer 8

• Improve flow characteristics of granulate

- Ex. Corn starch, Amorphous silica

Question 9

Anti-adherents

Answer 9

• Prevent sticking to the punch and to a lesser extent, to the dye wall
• Ex. Talc, Magnesium stearate

Question 10

Desintegrants

Answer 10

• Facilitates tablet breakup after administration

- Ex. Ac-Di-Sol, Polyplasdone XL, Explotab

Question 11

Colorants

Answer 11

• Esthetic appeal
• identification
• many are photosensitive
• water soluble dyes or color lakes

Question 12

Keep in mind that compounded preparations:

Answer 12

• Are not FDA approved
• Are not clinically tested for safety, efficacy, or bioequivalence
• Are not subjected to extensive quality testing
• Are exempt from cGMP requirements
• Do not comply with extensive labeling requirements
• Are exempt from adverse event reporting

Question 13

Beyond Use Date (BUD)

Answer 13

• Date after which a compounded preparation shall not be used
• should be assigned conservatively
• determined from the date when preparation is compounded
• compounders shall consult and apply drug-specific and general stability documentation and literature

Question 14

BUD for non-aqueous preparations:

Answer 14

earliest expiration date of any API or 6 months, whichever is earlier

Question 15

BUD for water-containing oral preparations:

Answer 15

not later than 14 days when stored at controlled cold temperatures

Question 16

BUD for water-containing topical/dermal and mucosal liquid and semi-solids:

Answer 16

not later than 30 days

Question 17

Content Uniformity

Answer 17

• can be applied to all dosage forms
• AV = M-X +ks
• Requirement is met if AV is greater than or equal to L1%

Question 18

L1

Answer 18

max allowed acceptance value (15 unless otherwise specified)

Question 19

Weight Variation

Answer 19

• limited to selected dosage forms presented in dosage units (hard capsules, uncoated or film-coated tablets containing greater than or equal to 25mg of dosage unit)
• Xi = (wi x A)/W

Question 20

“A” rated

Answer 20

considered therapeutically equivalent to other pharmaceutically equivalent products

Question 21

“B” rated

Answer 21

are not, at the time of publication, considered to be therapeutically equivalent to other pharmaceutically equivalent products

Question 22

Therapeutic Equivalence

Answer 22

• approved as safe and effective
• “pharmaceutical equivalents”
• expected to have the same clinical efficacy and safety profile when administered to patients under conditions specified in the labeling
• Bioequivalent
• Adequately labeled
• Manufactured in compliance of cGMP

Question 23

Pharmaceutical Equivalents

Answer 23

• contain identical amounts of the same active drug ingredient in the same dosage form
• meet compendial or other applicable standards of strength, quality, purity, and identity

Question 24

Pharmaceutically equivalent drug products may differ in:

Answer 24

• excipients
• release mechanism
• shape/scoring
• packaging
• expiration date and within certain limits, labeling

Question 25

Pharmaceutical Alternative

Answer 25

Contain the same therapeutic moiety but are chemically different and produced as different dosage forms or strengths

Question 26

Bioequivalence

Answer 26

The absence of difference in the rate and extent to which the active ingredient becomes available at the site of drug action when administered

Question 27

Waxman-Hatch Amendments 1984

Answer 27

- abbreviated review process - developed 180 day exclusivity for first generic that hits the market - increased availability of generics - created the generic drug industry by speeding up approval of generic drugs - allowed generic firms to rely on findings of safety and efficacy of innovator drug after expiration of patent and exclusivities

Question 28

Requirements for a generic drug

Answer 28

- same active ingredients - same route of administration - same dosage form - same strength - same condition of use - compared to RLD - may differ in excipient, PK data, and how supplied (i.e. packaging)