United States: Recent Traction In FDA's Development Of The 503A And 503B Bulks Lists

Just as the U.S. Food & Drug Administration ("FDA") promised in its 2019 compounding priorities statement, FDA published a notice and proposed rule in the Federal Register in the past week related to bulk drug substances that can be compounded subject to the conditions of Section 503A and Section 503B of the Federal Food, Drug, & Cosmetic Act ("FDCA"):

(1) On September 5, 2019, FDA published a proposed rule regarding its intent to amend its regulations to add five bulk drug substances that can be used in compounding under Section 503A (the "503A Bulks List") and proposed excluding another 26 bulk drug substances from the 503A Bulks List. Specifically, FDA proposes to amend the 503A Bulks List to include glutaraldehyde, glycolic acid, L-citrulline, pyruvic acid, and trichloroacetic acid (TCA), and proposes not to include 7-keto dehydroepiandrosterone (DHEA), acetyl-L-carnitine (ALC), alanyl-L-glutamine, Aloe vera 200:1 freeze dried, artemisinin, astragalus extract 10:1, boswellia serrata extract (BWSE), cesium chloride, chondroitin sulfate, chrysin, curcumin, D-ribose, deoxy-D-glucose, diindolylmethane, domperidone, epigallocatechin gallate (EGCG), germanium sesquioxide, glycyrrhizin, kojic acid, nettle, nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide disodium reduced (NADH), rubidium chloride, sodium dichloroacetate, vanadyl sulfate, and vasoactive intestinal peptide (VIP).

(2) On September 3, 2019, FDA published notice of its intent to exclude nine more bulk drug substances from its 503B clinical need list (the "503B Bulks List"). These substances are: dipyridamole, ephedrine sulfate, famotidine, hydralazine hydrochloride, methacholine chloride, sodium bicarbonate, sodium tetradecyl sulfate, trypan blue, and vecuronium bromide.

If the bulk drug substances above are ultimately not included in the 503A Bulks List, compounding pharmacies will not be able to compound with the substance unless the substance appears on an applicable United States Pharmacopeia or National Formulary monograph or if the substance is part of a commercially available drug product. Additionally, if the bulk drug substance does not appear on the 503B Bulks List (which is based on FDA's interpretation of whether there is a "clinical need" for the substance), FDA-registered outsourcing facilities will not be able to compound with that substance unless it appears on the FDA drug shortage list. The Agency's revisions to these Bulks Lists could significantly impact the compounding practices of these facilities nationwide and their ability to get patients access to the unique and critical compounded medications they need.

FDA's Role And Progress In Developing The Bulks Lists

FDA has been consistently evaluating bulk drug substances that were nominated for inclusion on the abovementioned Bulks Lists. During this interim period while the Bulks Lists are being formally developed, FDA operates according to its 2017 interim policies, which set out conditions under which the Agency does not intend to take action against compounding facilities that compound drug products from bulk drug substances that cannot otherwise be used in compounding under Sections 503A and 503B.

FDA issued a proposed regulation in 2016, in which it proposed to place six of the nominated bulk drug substances on the 503A Bulks List and proposed to exclude four substances, and the FDA identified the criteria it will continue to use to evaluate bulk drug substances for inclusion on the 503A Bulks List. The six substances proposed for inclusion were: Brilliant Blue G, also known as Coomassie Brilliant Blue G-250; cantharidin (for topical use only); diphenylcyclopropenone (for topical use only); N-acetyl-D-glucosamine (for topical use only); squaric acid dibutyl ester (for topical use only); and thymol iodide (for topical use only). The four substances the FDA proposed not to include were: Oxitriptan, piracetam, silver protein mild, and tranilast. After considering public comments to this proposed regulation, the Agency will issue a final regulation as to these substances.

At this time, FDA has not placed any bulk drug substances on the 503B Bulks List but it has decided not to include two substances: Nicardipine Hydrochloride and Vasopressin.

Could More Litigation Be In FDA's Future?

Depending on where these bulk drug substances are ultimately placed (that is, whether they are approved for inclusion on the Bulks Lists or formally excluded from the same), there may be litigation—as there already has been.

Most recently, earlier this year in March 2019, FDA determined that there was no clinical need to compound bulk drug substance Vasopressin, and thus Vasopressin would not be placed on the 503B Bulks List. In response, New York-based outsourcing facility Athenex, Inc. ("Athenex"), who submitted the original nomination to FDA for Vasopressin to be included on the 503B Bulks List, sued the Agency based on allegations that the Agency's interpretation of key provisions of Section 503B ran afoul of Congress' desire that FDA not interfere with the practice of medicine.

The drug manufacturer of the only commercially available vasopressin product on the market intervened in the Athenex suit as defendants on behalf of FDA, supporting the notion that FDA's determination on Vasopressin was well within the bounds of FDA's discretion. In August 2019, the U.S. District Court for the District of Columbia ruled in FDA's favor, finding that: (1) the Agency's method of determining whether there is a "clinical need" for a bulk drug substance gives effect to the intent of Congress; and (2) the exclusion of Vasopressin from the 503B Bulks List was not arbitrary and capricious. Athenex has indicated it plans to appeal the ruling but has ceased compounding with Vasopressin for now.

In light of the above, we encourage stakeholders to remain apprised of FDA's ongoing evaluation and placement of bulk drug substances on the Bulks Lists. Stakeholders interested in submitting comments to FDA's proposed rule on the 503A Bulks List have until December 4, 2019, to comment, and those interested in submitting comments to FDA's notice on the 503B Bulks List have until November 4, 2019, to comment. FDA's recent proposed rule and notice in the Federal Register are further indications that the Agency is actively engaged in the implementation of the Drug Quality and Security Act, the federal law that regulates human health compounding practices.

This article is presented for informational purposes only and is not intended to constitute legal advice.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Mondaq Free Registration
Gain access to Mondaq global archive of over 375,000 articles covering 200 countries with a personalised News Alert and automatic login on this device.
Mondaq News Alert (some suggested topics and region)
Select Topics
Registration (please scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions