Lecture 8 Flashcards
Objectives
Identify the key aspects of USP <795>, USP <797>, and USP <800>
Differentiate between expiration dates and beyond use dates, when they are to be utilized, and how to determine appropriate dating
Define repackaging and the aspects of the Food, Drug and Cosmetic Act the FDA does not intend to enforce related to repackaging
Establish the minimum requirements needed for two products to be considered generically equivalent, and the resources utilized to ensure equivalency
Review pertinent aspects of federal law related to FDA inspections, DEA inspections, and Board of Pharmacy inspections
USP <795>
Nonsterile Compounding
Focuses on ensuring the quality and safety of nonsterile compounding
Requires beyond-use dates (BUDs) to be assigned to nonsterile products
USP <797>
Sterile Compounding
Covers numerous sterile compounding requirements, including personnel, training, facilities, environmental monitoring, and storage and testing of finished products.
USP <800>
- Hazardous Substances
Discusses the handling of hazardous drugs in healthcare settings.
Hazardous means one of the following:
Carcinogenic
Teratogenic or Developmental Toxicity
Reproductive Toxicity
Organ Toxicity at low doses
Genotoxicity
New Drugs that mimic existing hazardous drugs
Expiration Date Requirements
All manufacturers must assign an expiration date to their product and include this information on the product label.
The expiration date is the last date the product will meet the requirements of the USP monograph for strength or stability
Expiration dates can come in two ways:
Exact dating (January 21st, 2029)
Month and year (January 2029) - assume it expires on the last day of the month
Beyond Use Dates (BUDs)
Beyond use dates (BUDs) are required for some medications when dispensed to patients or within institutions.
A BUD is a date after which a product should not be used. It cannot be later than an expiration date and is often sooner.
BUDs are based on many different factors, including when a product is opened, storage, reconstitution, and stability or sterility data, to name a few.
A BUD shall not be later than the expiration date on the manufacturer’s container, or
1 year from the date the drug is dispensed, whichever is earlier
Repackaging
When a drug is repackaged it must have expiration date and BUD (only exception is if its a stock bottle of pills going into a prescription bottle)
EXAMPLES:
Moving tablets from a large container into unit-dose packaging
Taking creams from large containers into smaller containers
Must meet all provisions of the FDCA
Repackaging Guidance
The FDA knows many companies do not follow all rules of FDCA and they have a list of time where they would not take legal actions in the case of not following rules
-A prescription drug product on the drug shortage list
-A drug product repackaged under direct supervision of a licensed pharmacist
-If repackaged by a pharmacy, only distributed upon receipt of a valid prescription for an individual patient
-Repackaged product is assigned a BUD as described in the repackaging guidance
Guidance in determining BUDs
Non-aqueous formulation – no more than six months or the expiration date, whichever is sooner
Water-containing oral formulations – no more than 14 days or the expiration date, whichever is sooner
Water containing topical, mucosal, and semisolid formulations – no more than 30 days or the product expiration date, whichever is sooner
Repackaging Guidance BUDs
FDA-approved sterile product with specified in-use time: BUD established with in-use time or the expiration date on the product repackaged, whichever is sooner
FDA-approved sterile product without a specified in-use time or unapproved product: BUD established by USP <797> or the expiration date of the product repackaged, whichever is sooner
FDA Inspections
Pharmacies are exempted from FDA inspection per the FDCA, unless the pharmacy manufacturers, prepares or compounds drugs or devices. 503b compounding
Despite this, the FDA may inspect a pharmacy to determine if they manufacture drugs and to verify compounding is done appropriately
FDA inspectors may request entry to a pharmacy by showing a notice of inspection (FDA form 482) and their credentials
FDA Inspections of pharmacies are rare, the FDA primarily focuses on the pharmaceutical industry and outsourcing facilities.
DEA Inspections
The DEA may inspect any place where controlled substances are kept.
They may examine records and reports related to controlled substances, inspect the premises, and inventory controlled substances without a warrant.
When requesting inspection, a DEA inspector must:
- State the purpose of their inspection,
- Show their credentials, and Provide written notice of inspection to the pharmacy owner or pharmacist in charge
you have the ability to deny a inspection but they will come back with a warrant and angry
DEA Notice of Inspection (NOI)
You have the right to require the DEA to get an administrative inspection warrant (AIW)
You have the right to refuse an inspection (at which point they will get an AIW)
Anything incriminating found can be seized and used against you in prosecution
You will get a copy of the NOI
You may withdrawal your consent to inspection at any time
Only the owner, operator, or agent in charge may sign an NOI.
Administrative Inspection Warrants (AIWs
provided for anything considered a valid public interest. Low bar to clear
only served during business hours
Search Warrants
provided if an officer can “convince a judge that a reasonable person would believe that a crime has been or will be committed on the premises to be searched or that evidence relevant to a crime exists at the premises.” Higher bar to clear
can be served during any time of the day
Board of Pharmacy (BoP) Inspections
In almost every state, you cannot say no to these inspections (including Indiana)
BoP inspectors can inspect without a warrant
Pharmaceutical
Equivalence
Active ingredient
Dosage form
Strength
Route
Labeling
The Orange Book Information
Market Status
Active Ingredient
Proprietary Name
Application Number
Dosage Form
Route
Strength
Therapeutic Equivalence (TE) Code
Reference Listed Drug (RLD)*
Reference Standard (RS)*
Applicant Holder
Bio-
Equivalence
In Vivo (human) results
In Vitro (lab) results (kinetics, dynamics, clinical effects)
What is Therapeutic Equivalence?
To be therapeutically equivalent, the product must be both pharmaceutically equivalent AND bioequivalent
Therapeutic Equivalence (TE) Code A_
The first letter, A, represents Therapeutic Equivalence.
The second letter can be one of many options (B, O, T, N, P, etc), and is related to the dosage form
Therapeutic Equivalence (TE) Code B_
The first letter, B, denotes that the product is not therapeutically equivalent
The second letter can be one of many options (B, O, T, N, P, etc), and is related to the dosage form
Three-character TE Codes
Nifedipine has two brand names (Adalat CC and Procardia XL)
These brands are not bioequivalents because they have different release mechanisms, therefore they are not therapeutic equivalents
