Compounding/Regulatory Sciences Flashcards
Compounding
- “preparation”
- Prepared in limited quantities as a result of a prescription order
- Regulated by state boards of pharmacy (NOT FDA)
Manufacturing
- “product”
- Mass produced from natural or synthetic bulk chemicals and legally marketed for resale by pharmacies
- Regulated by the US FDA
Drug Quality and Security Act
Federal legislation passed in 2013 to clearly distinguish between compounding and manufacturing
Compounding pharmacies are exempt from:
- cGMP requirements
- labeling of drugs with adequate directions for use
- approval of drugs under NDA or ANDAs
Fillers (Diluents)
- 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
Binders
- 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
Lubricants
- Reduce friction at the interface of tablet and dye wall during compression and ejection
- Ex. PEG 4000, Sodium Benzoate, magnesium lauryl sulfate
Gildants
- Improve flow characteristics of granulate
- Ex. Corn starch, Amorphous silica
Anti-adherents
- Prevent sticking to the punch and to a lesser extent, to the dye wall
- Ex. Talc, Magnesium stearate
Desintegrants
- Facilitates tablet breakup after administration
- Ex. Ac-Di-Sol, Polyplasdone XL, Explotab
Colorants
- Esthetic appeal
- identification
- many are photosensitive
- water soluble dyes or color lakes
Keep in mind that compounded preparations:
- 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
Beyond Use Date (BUD)
- 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
BUD for non-aqueous preparations:
earliest expiration date of any API or 6 months, whichever is earlier
BUD for water-containing oral preparations:
not later than 14 days when stored at controlled cold temperatures
BUD for water-containing topical/dermal and mucosal liquid and semi-solids:
not later than 30 days
Content Uniformity
- can be applied to all dosage forms
- AV = M-X +ks
- Requirement is met if AV is greater than or equal to L1%
L1
max allowed acceptance value (15 unless otherwise specified)
Weight Variation
- 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
“A” rated
considered therapeutically equivalent to other pharmaceutically equivalent products
“B” rated
are not, at the time of publication, considered to be therapeutically equivalent to other pharmaceutically equivalent products
Therapeutic Equivalence
- 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
Pharmaceutical Equivalents
- 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
Pharmaceutically equivalent drug products may differ in:
- excipients
- release mechanism
- shape/scoring
- packaging
- expiration date and within certain limits, labeling
Pharmaceutical Alternative
Contain the same therapeutic moiety but are chemically different and produced as different dosage forms or strengths
Bioequivalence
The absence of difference in the rate and extent to which the active ingredient becomes available at the site of drug action when administered
Waxman-Hatch Amendments 1984
- 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
Requirements for a generic drug
- 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)
