FDA’s Publishes (Yet Another) Interim Policy on Compounding with Bulk Substances for Both Section 503A and Section 503B Compounders

On Friday, January 13, 2017, FDA issued two revised interim policies on compounding with bulk substances for Section 503A compounders and Section 503B outsourcing facilities.  As you likely recall, FDA’s guidance on use of bulk substances in compounding has had a slow start, in part because of “over nominations” in early 2014 and general confusion in the nomination process (see our previous posts here and here).  And, once FDA created its original “bulks” lists of substances that may be used in compounding, those lists caused significant additional consternation because they included substances that plainly should not have been included. .

FDA’s latest iterations of its two sets of bulks lists include updates based on public comment and meetings of the Agency’s Pharmacy Compounding Advisory Committee, which has held several (quarterly) meetings to review whether bulk substances should be placed on one of FDA’s three bulks lists for Sections 503A and 503B (however, PCAC input is not statutorily required for Section 503B’s bulks lists). The lists are divided into the same three categories as previous lists (i.e., Category 1 (may be used in compounding based on sufficient support in a nomination, and no apparent safety risk); Category 2 (may not be used in compounding based on significant safety risk); and, Category 3 (substances nominated without adequate support, thus may not be used in compounding)). As an aside, FDA continues to assert in these guidances that USP/NF substances referenced in 503A and 503B only include substances that are the subject of a USP/NF “drug” monograph, and not a dietary substance monograph. Presumably, to the extent a compounder seeks to compound with a dietary substance as the active bulk ingredient in a compounded formulation (that is not a component of an approved drug product or otherwise on FDA’s list 1); it would need to nominate that substance per FDA’s interim policy.

Ultimately, FDA must promulgate final lists through notice and comment rulemaking pursuant to the applicable statutes. Because so many substances are at issue, FDA has adopted its interim policy approach, where it reviews and then nominates for comment the proposed substances at a pace of about ten at a time. On December 16, 2016, FDA published its first notice proposing six substances to the Section 503A bulks list, four to not be included on the bulks list, and setting forth criteria for evaluation of substances. [Here, comments due by March 16, 2017]

New Policy Concerning Re-Nominations, Mistaken Nominations, Withdrawal of Nominations

FDA’s latest iterations make one significant change – benefiting those who failed to nominate a particular substance, or who mistakenly nominated a substance which was inadvertently included on, for example, List 3 (substances nominated with insufficient support; thus may not be used in compounding).

Specifically, FDA had repeated several times that once FDA received nominations for the bulks lists (for the nomination period that ended back in 2014), interested parties could nominate additional substances (in a docket opened in October of 2015); but FDA would review those substances only after completion of the review process for the original nominated substances. Thus, any substances inadvertently omitted, or new substances necessary in compounding would, in effect, go to the bottom of the nominations stack. Given the number of already nominated substances, and pace of FDA’s review, any chance of review of new or overlooked substances at any point in the next several years seemed dim at best.

FDA now states that after a substance is nominated to the nominations docket for bulk substances (now deemed the “October docket”), FDA will determine whether the nomination is supported with sufficient information to allow FDA to evaluate it. After FDA makes that determination, the nominated substance will be placed in one of the three bulks categories and published on FDA’s website. FDA states it “generally expects to categorize bulk drug substances nominated to the October docket and to publish updated categories on its website on the first business day of each month.” FDA notes that until substances nominated for the “October docket” have been categorized, FDA’s interim policy does not apply to those substances.

In addition, FDA has created a solution for those substances that may not appear on an appropriate list. Those comments may be submitted to docket number FDA-2015-N-3534.  Further, if a commenter has new information on a previously nominated substance that was placed in Category 3, the substance can be re-nominated with the additional information.  A nominator may request withdrawal of any of its nominations. If the party nominating the substance was the sole nominator, FDA will update the categories described in this guidance to reflect the withdrawn nomination, and will provide notice to the public before removing any nominated substances from Category 1 or Category 2. However, FDA may continue to evaluate a substance at its discretion even if the nominator submits a comment requesting withdrawal of the nomination.

Shortage Medications: Section 503B

As a final note, for medications in shortage, FDA states that does not intend to take action against an outsourcing facility for compounding a drug product using a bulk drug substance that is not on the 503B bulks list if the drug compounded from the bulk drug substance: (i) appeared on FDA’s drug shortage list within 60 days of distribution and dispensing, and (ii) was to fill an order that the outsourcing facility received for the drug while it was on FDA’s drug shortage list. FDA’s Section 503A interim policy does to contain a similar provision for Section n503A facilities that may compound shortage medications.