In 1997, Congress amended the Federal Food Drug and Cosmetic Act (FDCA) by adding section 353a (21 U.S.C. § 353a) to regulate compounding. Section 353a provided that a pharmacist could compound for an identified patient based on an unsolicited prescription order and that such compounds were exempt from certain provisions of the FDCA, including adequate directions for use, new drug application and Good Manufacturing Practice requirements. The "unsolicited" prescription requirement prohibited pharmacies from advertising their compounding capability.

Section 353a also provided that if a state had not entered into a Memorandum of Understanding (MOU) with the FDA, compounded prescriptions could not exceed five percent of the total prescription orders compounded by a pharmacy. In 1999, the FDA published a draft MOU for consideration by the states. Thereafter, lawsuits that challenged the constitutionality of Section 353a's restrictions on advertising were successful in certain federal courts, but they were also unsuccessful in others. As a result of the split among the federal courts, the FDA exercised enforcement discretion and left the regulation of compounding to the states.

Fast-forward to the New England Compounding Center (NECC) debacle of 2012. NECC was responsible for distributing contaminated epidural steroid injections that resulted in the deaths of at least 48 patients and the fungal infections in hundreds of patients. Congress reacted in 2013 by enacting Title I of the Act - Drug Compounding. Title I removed the "unsolicited" language from Section 353a that was previously found unconstitutional and added a Section 353b. As a result, the FDA now intends to enforce the compounding requirements of Federal law in Section 353a and Section 353b.

Under the now amended Section 353a, a pharmacy may compound for an individual patient based on the receipt of a valid prescription order if the compounding meets the requirements of the law and the compounding is done by a licensed pharmacist in a licensed pharmacy based on a prescription or is done by a licensed pharmacist in limited quantities in anticipation of a valid prescription based on previous history with a prescriber. The drug product must also be compounded in compliance with the U.S. Pharmacopeia Convention (USP) chapters on pharmacy compounding using bulk drug substances that comply with the standards of an applicable USP or National Formulary monograph, if one exists. If there is no monograph, the drug substance must be a component of an FDA-approved human drug product. If there is no monograph, and the drug substance is not a component of an FDA approved human drug product, the drug substance must appear on an FDA list of bulk drug substances that are approved for compounding by the FDA. The FDA list does not currently exist. The FDA will be developing the list through regulation. The FDA has issued guidance that, until the list is published, pharmacies should compound human drug product using only bulk drug substances that are components of FDA approved drugs or those that are the subject of USP of NF monographs. There are additional requirements for compounding drugs that are not included in this Regulatory Reference Manual.

A second component of Title I of the Act involves "outsourcing facilities." An outsourcing facility is a facility at one address that compounds sterile drugs; elects to register with the FDA as an outsourcing facility; and complies with the requirements imposed on outsourcing facilities. An outsourcing facility does not have to be a pharmacy and is not required to obtain individual patient prescriptions. Outsourcing facilities generally compound for office use and can ship across state lines without regard to the five percent rule. However, outsourcing facilities must meet Current Good Manufacturing Practice requirements, including, among other things, batch sterility testing.

• FDA Pharmacy Compounding Center, Including Warning letters
• FDA-Compliance Policy Guides

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ADDITIONAL RESOURCES

• United States Pharmacopeia
• International Academy of Compounding Pharmacists
• Pharmacy Compounding Accreditation Board
• American College of Apothecaries
• Compounding Today
• Professional Compounding Centers of America (PCCA)