FDA Publishes Draft Guidance on What is “Essentially” a Copy of a Commercially Available Drug Under FDCA Sections 503A and 503B: Section 503A Compounders

July 14, 2016

By Karla L. Palmer –   

On July 11, 2016, FDA published for comment two draft guidance documents addressing compounding of commercially available drug products by traditional pharmacies under FDCA Section 503A and outsourcing facilities under Section 503B (the Section 503A Draft Guidance is available here and the Section 503B Guidance is available here, blogged separately).  This non-binding, draft guidance documents reflect FDA’s latest attempt to significantly restrict what may be compounded by narrowly construing what is and is not essentially a copy of a commercially available drug product.  If finalized, the Section 530A guidance would affect, by FDA’s estimates, approximately 6,900 pharmacies.  The deadline for submitting comments on the draft guidance documents is October 11, 2016.

Section 503A Draft Guidance      

Under the plain language of Section of Section 503A, traditional compounders may compound essentially copies of commercially available drug products so long as not “regularly or in inordinate amounts.”  FDA’s draft guidance attempts to define the scope of “regularly or in inordinate amounts.”  FDA’s draft also defines “commercially available” and “essentially a copy of a commercially available” drug.  These terms have become increasingly important in the wake of FDA’s attempts to curtain how and what drugs may be compounded compounders may 

“Commercially Available” – FDA defines “commercially available” as a marketed drug product.  It will not consider a drug “commercially available” if it is discontinued and no longer marketed or it appears of FDA’s published shortage list.      

“Essentially a copy” – A compound is “essentially a copy” of a commercially available drug if: (1) it has the same active pharmaceutical ingredient (“API”); (2) the APIs have the same, similar or easily substitutable dosage strength; and (3) the commercially available drug can be used by the same route of administration as the compounded drug – UNLESS a prescriber determines there is a “change, made for an identified individual patient, which produces for that patient a significant difference.” 

FDA describes what may cause a compounded drug to be “essentially a copy” and thus violative of Section 503A:

“Same API” – FDA intends to consider drugs with the same API to be “essentially a copy” unless a prescriber determines there is a change between the compounded and manufactured drug product that will produce a significant difference for the patient for whom it is prescribed. 

“Same, similar or easily substitutable strength” – Two drugs will have similar dosage strength if the strength of the compound is within 10% of the commercial product.  FDA would consider dosages easily substitutable if a patient could take, for example two 25mg manufactured doses, instead of one 50 milligram compounded dose. 

“Same route of administration” (i.e., topical, intravenous, oral) – FDA states it does not intend to consider a product with the same API and similar/substitutable strengths to be essentially copies if they have different routes of administration.  FDA includes an important “however:” if the compound and manufactured drug have the same API and same/substitutable strengths, and the commercially available drug can be used “(regardless of how it is labeled)” by the route of administration prescribed for the compound, FDA considers the compound to be a copy of a commercially available drug.  FDA, Draft Guidance at 7, lines 250-59.  FDA uses as an example an injectable drug labeled for intra-muscular use, but can be drawn from the vial by a smaller needle for other administration.  If the doctor preferred a compound to be used in this situation, he or she must document the significant difference between the compound and the commercially available drug.  As another example, FDA states that if X and Y are two commercially available oral drugs, FDA intends to consider a compounded formulation of X and Y in strengths within 10% of the commercially available drugs to be essentially a copy, unless the prescriber determination of significant difference has been documented.  

“Statement of Significant Difference” – FDA proposes that any determination of a significant difference in the compounded preparation from the commercially available product should be documented on the prescription.  FDA states there would be no required format, but gives examples of acceptable statements. Just a patient name and formulation would not be sufficient, states FDA.  Importantly, FDA adds that the “significant benefit that the prescriber identifies must be produced by the change” the compounder makes to the commercially available product.  FDA specifically states that “lower prices” are not sufficient to establish something is not essentially a copy.  If the prescriber does not make clear the significant difference, then the compounder should contact the prescriber and make a specific notation of the difference, including date, on the prescription.

FDA’s Shortage List: Documentation Required – For compounding drugs on FDA’s shortage list, FDA states the compounder or prescriber should include a notation on the prescription that the drug is on the shortage list (including an indication of the date the list was checked). 

“Regularly or in Inordinate Amounts” – As required by the statute, FDA’s draft  defines the vague statutory phrase “regularly or in inordinate amounts.”  The statute permits compounders to compounding essentially copies of commercially available drugs so long as not “regularly or in inordinate amounts.”  FDA suggests “regularly” or “inordinate amounts” means if a drug “is compounded more frequently than needed to address unanticipated, emergency circumstances or in more than the small quantities needed to address unanticipated, emergency circumstances.”  As examples of other non-exhaustive factors FDA will consider:

  1. Compounding copies of more than a small number of prescriptions;
  2. The compounder routinely substitutes compounds that are essentially copies;
  3. The compounder offers pre-printed prescription pads that a prescriber may complete without making a “significant difference” determination;
  4. The drug is not compounded on an “as needed basis”, but on a routine or preset schedule. 

FDA states that, at this time, it does not plan to take action against a compounder that fills 4 or less prescriptions of essentially copies of the relevant drug product in a month.  If the prescription appropriately documents the significant difference, FDA would not count it in the four “permitted” prescriptions.


FDA’s draft states that a physician or pharmacist seeking to compound a drug under 503A should maintain records to demonstrate compliance with the statute.  This would include notation on prescriptions of “significant difference,” and records of the frequency of compounding “essentially copies” to that they can demonstrate such compounding is not “regularly or in inordinate amounts.” 

Given repeated emphasis of the importance of documentation, and maintaining the documentation, FDA plainly believes documentation is critical to establishing whether the compounded product is appropriate.  It will be interesting to see how compounders and drug manufacturers react to FDA’s draft guidance.