Compounding Essentially a Copy FAQs
Some of the most prevalent questions we get asked by compounding pharmacies and 503B outsourcing facilities have to do with the do’s and don’ts of compounding essential copies of drugs. To help compounders sift through the confusion and interpretation, we discuss the most frequently asked questions about compounding an essential copy of an approved drug and provide real life examples.
What is “Essentially a Copy” of a Drug?
An essential copy is a compound that is identical or nearly identical to an FDA approved commercially available drug (e.g., a compound that has the same or similar characteristics as an FDA approved drug that does NOT appear on the FDA Shortage List).
What is the Best Resource to Check if a Drug is FDA Approved and Commercially Available?
While pharmacies have historically relied upon national drug wholesalers to decipher if a drug is FDA approved and commercially available, the best resources for this research are:
It is recommended compounders check these lists on a continuous basis. New drugs are constantly being added and discontinued. Similarly, drugs come on and off shortage all of the time.
Which Characteristics Does a Drug Share with an Essential Copy Compound?
A compound is essentially a copy of a commercially available drug if the compound shares the:
Same API’s or active ingredients;
Same, similar or easily substitutable strength (e.g., within 10%); and
Same route of administration (e.g., intravenous) as a commercially available product.
For 503B’s, in addition to the above three similarities, the compound also shares the same excipients and same dosage form (e.g., injection solution) as the FDA-approved product.
What if My Compound Shares These Characteristics with an Approved Drug?
Compounders may not compound a copy of commercially available drug unless it is currently on the FDA Drug Shortage List. If your compound has all of the parameters in common with a commercially available drug then you cannot compound this preparation because you are infringing on the drug manufacturer’s domain and in that case you need to file an abbreviated new drug application and become a manufacturer.
What if My Compound Shares These Characteristics with an Approved Drug But has a Different Strength?
If the only difference between a compound and the commercial drug is the strength (e.g., 50 mg instead of 100 mg, etc.), then it may or may not be interpreted as an essential copy.
For example, if progesterone capsules are only commercially available in 100 mg and 200 mg strengths, and a patient requires 50 mg, a pharmacy may compound it to meet the clinical need because the capsule cannot be cut in half. If the patient requires 300 mg, they could potentially take one 100 mg capsule and one 200 mg capsule to meet their need. In that case, it may not be appropriate to compound because it may be considered an easily substitutable strength.
There could be other cases where a commercially available option might contain a vastly different strength or amount than what a patient needs (e.g., the drug is available as 1mg/mL 1mL vial and a patient requires a 30mg dose). Major differences in strength or amount available commercially against a patient’s dosage requirements could justify the case for compounding a different strength.
What if My Compound Shares These Characteristics with an Approved Drug But Contains a Different Volume and is Packaged Differently?
If the only difference between a compound that was prepared from scratch and a commercial drug is the volume and package (e.g., compounded 1mg/mL 3mL syringe vs. available 1mg/mL 5mL vial, etc.), then the compound may be interpreted as an essential copy. This is because the compound shares the same active ingredient, strength, and route of administration, which disqualifies it from being compounded by a pharmacy. Instead of compounding it, a 3mL single dose could be transferred from the FDA approved 1mg/mL 5mL vial to a syringe to be administered to a patient.
What if My Compound Shares These Characteristics with an Approved Drug But Has a Different Route of Administration?
If the only difference between a compound and the commercial drug is the route of administration (e.g., SQ instead of IV, etc.), then it may or may not be considered an essential copy. A drug that is suitable for intravenous administration, for example, may also be considered clinically suitable for subcutaneous administration even if the SQ route is not stated on the approved labeling.
What if My Compound Shares These Characteristics with an Approved Drug But is Packaged Differently?
If the only difference between a drug that has been compounded from scratch and a commercial drug is the primary packaging (e.g., syringe instead of vial, etc.), the compound is considered essentially a copy of the FDA approved product.
What is Repackaging?
Repackaging is the act of taking a finished drug product from the container in which it was distributed by the original manufacturer and placing it into a different container without further manipulation of the drug. Repackaging also includes the act of placing the contents of multiple containers (e.g., vials) of the same finished drug product into one container, as long as the container does not include other ingredients. If a drug is manipulated in any other way, including if the drug is reconstituted, diluted, mixed, or combined with another ingredient, that act is NOT considered repackaging. See the FDA Guidance on Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities for more information.
What is Administration?
If a commercial drug is used to draw a single dose, transferred to a different container, and administered to a single patient, this practice is not considered compounding or repackaging. Instead it is considered administration (as long as it is prepared in accordance with the directions in the manufacturer’s approved labeling).
A Drug is Not Listed on FDA Shortage but it is on Wholesaler Backorder and a Pharmacy Cannot Obtain it. Can a Pharmacy Compound it?
No. The drug must appear on the FDA Shortage List at the time of compounding, distribution and dispensing. In this case, pharmacists that choose to compound in this situation take a risk in regulatory backlash. The potential for loss of life may be a justification for the emergency compounding of a difficult-to-obtain drug if no other option exists. However, it is advised to obtain legal advice ahead of time to ensure compliance.
A Drug is Currently Listed on FDA Shortage, What are the Record Keeping Requirements for Compounding it?
Aside from typical compounding record-keeping (e.g., master formula, compounding record, etc.), the compounding facility must retain evidence that the drug was in fact on shortage during the time it was compounded and distributed/dispensed. The FDA Drug Shortage List is a dynamic list that changes at a fast pace. The FDA does not maintain a running public ledger of the dates a drug went on shortage and became once again available.
One way of proving compliance would be to capture a screen shot of the specific FDA drug shortage that also includes the date/time stamp. A conservative documentation approach would be to attach this evidence to each compounding record as proof the drug was on shortage at the time of each compounding activity.
What are Some Examples of Compounds that Produce a Clinical Difference?
Compounds are useful when there must be a change to a drug that produces a clinical difference for an individual patient as determined by the prescribing practitioner. The following may be justifications for compounds that produce a clinical difference from an available drug:
Compounding a ready-to-use premixed drug for surgery to prevent a delay in therapy
Substituting an inactive ingredient due to a patient allergy
Changing the dosage form from tablet to liquid for a hospice patient to ease swallowing the medication
Where Can I Learn More About Essentially a Copy Compounding?
The FDA released two guidance documents - one for 503A and one for 503B - to help compounders decipher what can and what cannot be legally prepared. Consultants at Restore Health Consulting can help your pharmacy or 503B outsourcing facility decipher if your compound is compliant with the regulatory framework.
The information provided on this website does not, and is not intended to, constitute legal advice; instead, all information, content, and materials available on this site are for general informational purposes only. Information on this website may not constitute the most up-to-date legal or other information. Readers of this website should contact their attorney to obtain advice with respect to any particular legal matter.