Lec 21- compounding

Define compounding according to the FDA and apply it to a pharmacy scenario

• Combining, admixing, mixing, diluting, pooling, reconstituting, or otherwise altering a drug or bulk substance to create a drug.”

  • Does not include mixing and reconstituting performed in accordance with the manufacturer’s directions when performed on receipt of a prescription order for a patient 

Identify when a compounded drug violates FDCA 503A (1-3)

Failure to meet any of the following:

1) Compounded drug must be for an individual patient pursuant to a valid prescription order and compounded by a licensed pharmacist or physician.
2) If the compounded drug is prepared in anticipation of receiving a prescription, a limited quantity is prepared:	Amount anticipated must be legitimately based on the established practice history. Limited quantity is no more than a 30-day supply, based on previous history of valid prescriptions received during a 30-day period within the previous year. Dispensing should not occur until the patient-specific order is receive
3) The compounded drug cannot essentially be a copy of a commercially available product, unless compounded occasionally and not in inordinate amounts	NOT A COPY: A change has been made from the commercial product for an individual patient that produces a significant difference for that patient. Guidance provides additional detail: A commercial drug is any marketed drug product, except those discontinued, no longer marketed, or on the FDA drug shortage list. A copy consists of the same active pharmaceutical ingredient, with a same/similar/easily substitutable dosage strength (within 10% of the commercial product) and used by the same route of administration.

Identify when a compounded drug violates FDCA 503A (4-9)

4) It is compounded in compliance with USP chapters on compounding [USP <795> and <797>] and using bulk substances that comply with monograph standards, if one exists.	If no monograph exists, the drug must be a component of an FDA-approved human drug product. If neither of those are true, it must appear on a list of bulk drug substances developed by FDA regulation. FDA will not take action against entities that do not meet this as long as: The entity is using Category 1 drugs for 503A. The manufacturer is registered, and the bulk drug has a certificate of analysis. Note: USP <795> and <797> have the force of federal law for compounding under the federal definition!
5) The bulk drugs used for compounding are manufactured by an entity registered with the FDA.	6) It is compounded with ingredients (other than bulk substances) that comply with USP standards.
7) It does not include drugs from an FDA list of items withdrawn from the market due to safety or efficacy concerns.	8) It does not include drug products identified by the FDA as presenting difficulties for compounding due to safety or efficacy risks
9) The compounder does not distribute more than 5% of total prescriptions dispensed or distributed by the pharmacy unless an MOU exists between the pharmacy and the FDA.

Describe the “safe harbors” for hospitals and health systems to compound without meeting 503A requirements

The FDA does not intend to take action when a hospital or health system compounds a drug product regularly or in inordinate amounts that is essentially a copy of a commercially available drug product when:

• The compounded product is administered only to patients in the hospital or health system.

• The pharmacy obtains from the prescriber a statement that:

  • Specifies a change between the compounded and commercially available drug product.

  • Indicates that the compounded drug will be given only to patients for whom the change produces a significant difference.

  • Describes the intended patient population for the compounded drug.

• A statement is on file for each prescriber covering each drug product that is compounded.

• The statement is maintained in the hospital or health system pharmacy to address routine orders for patients needing the change.

Describe how a 503B outsourcing facility is different from a 503A pharmacy

•  503B outsourcing facilities can compound sterile products in unlimited quantities without individual prescriptions, which 503A pharmacies cannot. 

• 503B outsourcing facilities do not have to be licensed pharmacies, but compounding must be done by or under direct supervision of a pharmacist. 

• 503B outsourcing facilities have less flexibility to compound drugs that are “essentially a copy” compared to 503A.

  • Identical copies cannot be compounded just for a clinical difference.

  • Non-identical copies with a meaningful change for the patient are allowed.

Identical or nearly identical means all of the following are the same:

• Active ingredients

• Route of administration

• Dosage form

• Dosage strength

• Excipients

Explain what “compendially applicable” means and list the USP compounding chapters that are compendially applicable

•  “compendially applicable = force of federal law

• USP <795> and <797> are compendially applicable

  • Only cross-referenced parts of <800> are enforceable; the rest is just information.

• All of <825> is compendially applicable

Recognize the alignment of current Wisconsin compounding rules with USP compounding chapters

• Wisconsin’s current compounding regulations are generally well-aligned with USP <795> and <797>.