United States: FDA Gives Guidance On Compounding For Human Use

In July 2014, the U.S. Food and Drug Administration (FDA) released five documents containing policies and proposals that affect both traditional compounding pharmacies and outsourcing facilities that compound drugs for human use. These documents are:

  • Draft Interim Guidance setting forth FDA's current thinking as to its interim expectations for outsourcing facilities regarding compliance with Current Good Manufacturing Practices (CGMP) until regulations are developed;
  • A Proposed Rule adding 25 new drug products to the "do-not-compound" list, for both traditional compounders and outsourcing facilities;
  • Final Guidance for traditional compounders; and
  • Two separate requests, one for 503A and one for 503B, to nominate bulk drug substances for FDA lists of active bulk substances that traditional compounders and outsourcing facilities are permitted to use.

As detailed in an earlier Duane Morris Alert, Title I of the Drug Quality and Security Act (DQSA)—referred to as the Compounding Quality Act (CQA)—allows FDA to oversee drug compounding in human health. The DQSA amended and reinstated Section 503A, which sets out certain requirements for traditional compounding, and it created a new FDA-regulated entity called an "outsourcing facility" in Section 503B. These guidance documents and the proposed regulation flesh out FDA's current thinking and enforcement priorities for both traditional compounders and outsourcing facilities under the CQA.

Outsourcing Facilities—Draft Interim Guidance on CGMP Requirements

Unlike traditional compounding pharmacies, outsourcing facilities are required to comply with CGMP. Although FDA intends to develop specific CGMP regulations that apply to outsourcing facilities, until these regulations are promulgated, FDA issued draft interim guidance that sets out its CGMP expectations for outsourcing facilities during this interim period. In this Draft Interim Guidance, FDA expresses its intent to recognize the difference in its CGMP expectations between outsourcing facilities and conventional drug manufacturers.

FDA focuses on the CGMP requirements that relate to sterility assurance and safety of compounded drug products with respect to strength (sub and super potency), labeling and drug product mix-up. FDA sets out its CGMP expectations for the following areas:

  • Facility design, including air quality requirements for sterile drugs;
  • Control systems requiring separate or defined areas for facility operations to prevent contamination;
  • A system for environmental and personnel monitoring in aseptic processing areas;
  • Controls over equipment used to compound and containers and closures in which a compounded drug product is packaged;
  • Control over the source and quality of components;
  • Production and process controls (essential for sterile compounds);
  • Release testing (compounds tested for final product specification before distribution);
  • Laboratory controls for testing components and finished drug products;
  • A program for stability/expiration dating;
  • Packaging requirements for sterile drugs; and
  • A quality control unit to oversee various aspects of sterile production.

Comments to the Draft Guidance may be submitted by September 2, 2014. FDA is accepting comments electronically at http://www.regulations.gov or in writing to the FDA Division of Dockets Management. Further details on the procedure for submitting comments to the Draft Guidance are available on the FDA's notice in the Federal Register. In the Draft Interim Guidance, FDA specifically seeks public comment on alternative approaches on: (1) Reducing the need for laboratory testing of incoming components; and (2) minimizing the need for facilities to have an in-house laboratory.

Proposed Rule Adding 25 Drug Products to the Do-Not-Compound List

Both Sections 503A and 503B direct FDA to publish a list of drugs or drug components that cannot be compounded because they have been withdrawn or removed from the market as unsafe or not effective. The Proposed Rule is FDA's proposal to amend this list, found at 21 CFR Part 216, to add 25 additional drug products. As set forth in the Proposed Rule, FDA intends to prohibit all drug products for a certain molecule, possibly even if only one or a few dosage forms have been found either unsafe or not effective.

Comments to the Proposed Rule may be submitted by September 2, 2014. FDA is accepting comments electronically at http://www.regulations.gov or in writing to the FDA Division of Dockets Management. Further details on the procedure for submitting comments to the Draft Guidance are available on the FDA's notice in the Federal Register.

Final Guidance for Traditional Pharmacies Operating Under Section 503A

After soliciting public comment, FDA has published its Final Guidance, which reflects FDA's current thinking on the enforcement of Section 503A. It is important to note that, in the Final Guidance, FDA has changed its position on when it will begin to enforce the 5-percent limit on out-of-state distribution for pharmacies located in states that have not entered into the Memorandum of Understanding (MOU). As directed by Section 503A, FDA is currently working in collaboration with the National Association of Boards of Pharmacy on the MOU to address interstate distribution of compounded drugs. FDA now states that the Federal Register notice that announces the availability of the draft MOU will specify a time period during which the MOU will be made available for the states to sign. Only after this time period expires does FDA intend to enforce the 5-percent limit on interstate distribution of compounded drugs from traditional compounders in states that have not signed the MOU.

FDA Reopens Nominations for Bulk Drug Substances Lists Under Sections 503A and 503B

FDA issued two notices, one relating to the 503B bulk substances list and another relating to the 503A bulk substances list. FDA has indicated in both of these notices that the bulk substances required to appear on this list are for active ingredients only. Both of these notices reopened and restarted the nomination process for bulk substances drugs to appear on these respective lists. Both notices allow 90 days for bulk substances to be nominated for these respective lists.

Section 503B limits outsourcing facilities to using only bulk chemicals that appear on a positive list developed by FDA "identifying bulk drug substances for which there is a clinical need." 21 U.S.C. 353b(a)(2)(A)(i). In this notice, FDA takes the position that it needs the following information to evaluate this "clinical need": a statement describing the medical condition the product made from the substances would treat; if there is an FDA-approved drug to treat the condition; if so, why the compounded drug is necessary (why the approved drug is not suitable); an estimate of the size of the population that needs the compounded drug (due to an allergy or intolerance); bibliography of safety and efficacy data if available, including peer reviewed medical literature; and if an FDA-approved drug includes the bulk drug substance, an explanation of why the bulk drug substance needs to be used, and not the FDA-approved product. Information regarding the bulk drug substance's active ingredients, the dosage form, strengths and anticipated routes of administration is also required.

In contrast, under 503A, a bulk drug substance can be used if it has a United States Pharmacopeia (USP) or National Formulary (NF). Only if it has neither of these things is it required to appear on FDA's approved list. FDA is proposing to examine four criteria for a bulk substance to appear on the 503A list: (1) physical and chemical characterization of the substance; (2) safety issues raised by use of it in compounded drug products; (3) historical use of the substance in drug products, including information about medical conditions it has been used to treat and references in peer-reviewed medical literature; and (4) the available evidence of effectiveness or ineffectiveness of a drug product compounded with the substance, if any exists.

Nominations for the 503B or 503A bulk drug substances lists may be submitted by September 30, 2014. FDA is accepting nominations electronically at http://www.regulations.gov or in writing to the FDA Division of Dockets Management. Further details on the procedure for submitting nominations are available on the FDA's notices (503A list and 503B list) in the Federal Register.


These FDA guidance documents and proposed rule are the latest FDA action to implement its new authority under the CQA to regulate the compounding of drugs for human use. FDA's current thinking, its proposed regulation and Final Guidance are key guideposts for entities compounding for human use under either Section 503A, Section 503B, or both.

If you have any questions about this Alert or would like more information, please contact Rachael G. Pontikes, Brian L. Dougherty, Elinor L. Hart, any of the attorneys in our Pharmaceutical, Medical Device, Pharmacy & Food industry group or the attorney in the firm with whom you are regularly in contact.

Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.

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
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must 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