United States: FDA Addresses Compounding Of Animal Drugs From Bulk Drug Substances

The U.S. Food and Drug Administration (FDA) has released a Notice of Draft Guidance and Withdrawal of Compliance Policy Guidance (Guidance Notice), along with a Draft Guidance for Industry (Draft Guidance) addressing compounding of animal drugs from bulk drug substances. A separate Notice announced that FDA is soliciting nominations for the Bulk Drug Substance List (Bulk List Notice) for use in the compounding of animal drug products. In the wake of FDA's publication of a number of guidance documents relating to the implementation of Section 503A and 503B of the Drug Quality and Security Act (DQSA), which is only applicable to the compounding of human drugs, there remained outstanding questions as to the status of compounded animal drugs. Through this Draft Guidance, FDA is trying to provide some clarity on the remaining animal compounding issues. Comments and nominations are due by August 17, 2015.

Guidance Notice

The Guidance Notice indicates that the Draft Guidance provides information on the application of the Federal Food, Drug, and Cosmetic Act (FFDCA) to compounded animal drug products. Specifically, the Guidance Notice clarifies that sections 503A and 503B of the FFDCA do not apply to animal drugs and that, while there are exemptions for compounding from FDA approved products, FDA makes no distinction between the compounding of animal drug products from bulk substances and the manufacturing or processing of other animal drug products. Thus, the same requirements that apply to manufactured animal drugs also apply to compounded animal drugs, with the limited statutory exception provided in FFDCA sections 512(a)(4) and (a)(5) which allows for extra-label use of a compounded animal drug made from already-approved animal or human drugs. The extra-label use is exempt from FDA approval requirements and adequate directions for use if the product complies with 21 C.F.R. Part 530, which addresses extra-label use in animals of approved animal and human drugs. The Guidance Notice specifies that the Draft Guidance does not address extra-label use or repackaging of approved animal drugs. However, FDA is soliciting responses to specific questions posed in the Guidance Notice, including, but not limited to:

  • Is additional guidance needed to address the repackaging of drugs for animal use?
  • Is additional guidance needed to address the compounding of animal drugs from approved animal or human drugs under sections 512(a)(4) or (a)(5) of the FFDCA and 21 CFR Part 530?
  • Is additional guidance needed to address the compounding of animal drugs from bulk drug substances for food-producing animals?
  • Do United States Pharmacopeia and National Formulary (USP–NF) chapters <795> and <797> provide suitable standards for animal drugs compounded by veterinarians, and if not, what standards of safety, purity, and quality should apply to animal drugs compounded by veterinarians?
  • Should licensed veterinarians be able to sell or transfer an animal drug compounded from bulk drug substances by a state-licensed pharmacy or an outsourcing facility to owners or caretakers of animals under the veterinarian's care?
  • Should the final guidance include a condition on the amount or percentage of compounded animal drugs that a state-licensed pharmacy or outsourcing facility can ship in interstate commerce? If so, what would a reasonable amount be?

The Guidance Notice also announces the withdrawal of FDA Compliance Policy Guide (CPG) Section 608.400 which was issued in 2003. FDA is withdrawing this CPG because it "is no longer consistent with FDA's current thinking on the issue it addresses" because "it does not focus on the three main concerns FDA has about animal drug compounding." (Guidance Notice at 28624, 28625). These concerns include: (1) using bulk drug substances to compound copies of approved animal or human drugs, (2) compounding from bulk drug substances for food producing animals, and (3) compounding office stock from bulk drug substances. Because the issuance of the Draft Guidance and the withdrawal of the CPG may lead to enforcement confusion among stakeholders, FDA has indicated that until the Draft Guidance is finalized, it will "look at the totality of the circumstances when determining whether to take enforcement action for unlawful animal drug compounding activities." (Id.).

Draft Guidance

The Draft Guidance addresses compounding of animal drugs from bulk drug substances that do not fall within the limited extra-label use exception, as FDA is concerned that the "unrestricted compounding of animal drugs from bulk drug substances has the potential to compromise food safety, place animals or humans at undue risk from unsafe or ineffective treatment, and undermine the incentives to develop and submit new animal drug applications." (Draft Guidance at 3). FDA does not plan to take enforcement action if a state-licensed pharmacy, licensed veterinarian, or outsourcing facility uses bulk drug substances to compound animal drugs in accordance with the conditions set out in the Draft Guidance.

For example, if an animal drug is compounded by an outsourcing facility, to satisfy the requirements spelled out in the Draft Guidance the compounded drug must:

  1. Be compounded only from bulk drug substances appearing on Appendix A of the Draft Guidance, for which FDA is currently soliciting nominations;
  2. Be compounded by or under the direct supervision of a licensed pharmacist;
  3. Not be intended for use in food-producing animals;
  4. Be compounded in accordance with current good manufacturing practices requirements;
  5. Be compounded with bulk drug substances manufactured by an establishment that is registered under section 510 of the FFDCA (21 U.S.C. § 360) and is accompanied by a valid certificate of analysis;
  6. Not be sold or transferred by an entity other than the outsourcing facility that compounded such drug;
  7. Comply with the adverse event reporting requirements, i.e., within 15 days of becoming aware of any product defect or serious adverse event associated with animal drugs it compounded from bulk drug substances, the outsourcing facility reports it to FDA, on Form FDA1932a;
  8. Be included, along with all other drugs compounded for animals by an outsourcing facility, on the report required by section 503B of the FFDCA to be submitted to FDA each June and December identifying the drugs made by the outsourcing facility during the previous six-month period;
  9. Be accompanied by a prescription or order that states the drug is intended to treat the species and condition(s) for which the substance is listed in Appendix A; and
  10. Be labeled in accordance with the Draft Guidance.

Bulk List Notice

The Bulk List Notice explains the nomination process for bulk drug substances to be included in the Draft Guidance Appendix A and is applicable only to animal drug compounding conducted by outsourcing facilities using bulk drug substances. FDA intends to review nominations for the initial version of the list based on the responses submitted to the Bulk List Notice, but will then review nominations on a rolling basis and periodically update Appendix A.

A bulk drug substance will be included in Appendix A only when the following criteria are met:

  1. There is no marketed approved, conditionally approved, or index-listed animal drug that can be used as labeled to treat the condition;
  2. There is no marketed approved animal or human drug that could be used under sections 512(a)(4) or (a)(5) of the FFDCA and 21 CFR Part 530 to treat the condition;
  3. The drug cannot be compounded from an approved animal or human drug;
  4. Immediate treatment with the compounded drug is necessary to avoid animal suffering or death; and
  5. FDA has not identified a significant safety concern specific to the use of the bulk drug substance to compound animal drugs (under the listed conditions and limitations).

FDA notes that inactive ingredients are not required to appear in Appendix A to be used in compounding animal drug products.

Comments on the Draft Guidance and nominations for the Bulk Drug Substance List are due by August 17, 2015, and can be submitted electronically to http://www.regulations.gov.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

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.

Authors
 
In association with
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
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
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
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.

Disclaimer

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.

Registration

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.

Cookies

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.

Links

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.

Mail-A-Friend

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.

Emails

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 .

Security

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.