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.

In association with
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
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement

Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of www.mondaq.com

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). 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 & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd 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 or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

*** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at enquiries@mondaq.com.

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.