On Thursday, July 7th, the FDA issued two draft guidance documents regarding the compounding of drugs that are essentially copies of commercially available or approved drugs. In these documents, which apply to pharmacies, physicians, federal facilities, and compounding facilities, the FDA describes how the Agency would implement statutory restrictions concerning the compounding of these products. The draft guidance documents include products compounded under both sections 503A and 503B of the Federal Food Drug and Cosmetic (FD&C) Act.
Draft Guidance #1
According to the FDA, in order to qualify for exemptions under section 503A of the FD&C Act, “a drug product must be compounded by a licensed pharmacist or physician who does not compound regularly or in inordinate amounts any drug products that are essentially copies of a commercially available drug product, among other conditions.” In its recent draft guidance, entitled “Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act,” the Agency outlines its policies regarding this provision of section 503A.
Section 503A of the FD&C Ac
Section 503A was added to the FD&C Act in 1997 with the addition of the Food and Drug Administration Modernization, and was amended in 2013 by the Drug Quality and Security Act. The section “describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist in a State – licensed pharmacy or Federal facility, or by a licensed physician, to qualify for exemptions from the following three sections of the FD&C Act:
- Section 501(a)(2)(B) (concerning current good manufacturing practice (CGMP) requirements)
- Section 502(f)(1) (concerning the labeling of drugs with adequate directions for use)
- Section 505 (concerning the approval of drugs under new drug applications (NDAs) or abbreviated new drug applications (ANDAs)).”
Furthermore, the draft guidance states that, in order for a product to qualify for exemptions under section 503A, it must be compounded by a licensed pharmacist or physician who “does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product.”
Compounded Drug Products & Associated Risks
Compounded drugs serve a critical role for certain patients “whose clinical needs cannot be met by an FDA-approved drug product, such as a patient who has an allergy and needs a medication to be made without a certain dye, an elderly patient who cannot swallow a pill and needs a medicine in a liquid form that is not otherwise available, or a child who needs a drug in a strength that is lower than that of the commercially available product.” Under section 503A, licensed pharmacists and physicians can compound drug products for individual identified patients in state-licensed pharmacies and Federal facilities. However, section 503A restricts pharmacists from “compounding drug products that are essentially a copy of a commercially available drug product.”
Although they fill important, unmet needs for many patients, drugs that are compounded pose much a higher risk than those products that have gone through (and successfully completed) the FDA’s approval process. Because they are not approved by the Agency, compounded drugs are not subject to FDA’s premarket review for safety, effectiveness, and quality; furthermore, according to section 503A, the individuals who compound these drugs are not required to comply with FDA’s typical cGMP requirements. There are many other factors that increase the risk associated with the use of compounded drug products. For additional details, view the FDA’s full draft guidance.
Compounded Drugs That Are Essentially Copies of Commercially Available Drug Products
Section 503A of the FD&C Act provides compounded drug products with a number of exemptions compared to the Agency’s typical regulations and requirements, however the section explicitly restricts the compounding of drugs that are essentially copies of a commercially available drug product. This restriction is in place to ensure that pharmacists and physicians “do not compound drug products under the exemptions for patients who could use a commercially available drug product.” In its draft guidance, FDA explains that this would introduce significant public health risks, as it would expose patients to products that have not been shown to be safe or effective. Also, the possibility that these products may have been manufactured in conditions that are considered to be unsatisfactory is greatly increased.
In addition to the above mentioned public health risks, section 503A restricts the compounding of these products in order to protect the integrity and effectiveness of the new drug and abbreviated new drug (NDA & ANDA) approval processes that has been out in place to protect patients from unsafe, ineffective, or poor quality drugs.
In its draft guidance, FDA notes that “sponsors may be less likely to invest in and seek approval of innovative, life-saving medications if a compounder could, after a drug is approved, compound ‘substitutes’ that have not had to demonstrate safety and effectiveness and are not produced in accordance with CGMP requirements or labeled with adequate directions for use.” Furthermore, the Agency states that the copies restriction also protects the FDA’s drug monograph process that is in place for over-the-counter (OTC) products.
According to the draft guidance, “a compounded drug product is not eligible for the exemptions in section 503A if it is both:
- Essentially a copy of a commercially available drug product, and it is
- Compounded regularly or in inordinate amounts.”
When determining whether a drug product meets the conditions of section 503A. FDA will first determine whether the product is essentially a copy of a commercially available drug product. If the answer to that is yes, FDA will determine second whether the product was compounded regularly or in inordinate amounts.
In its draft guidance, FDA outlines a number of policies regarding the following terms:
- Commercially Available Drug Product
- Essentially a Copy of a Commercially Available Drug Product
- Regularly or in Inordinate Amounts
These policies are outlined as follows:
Commercially Available Drug Product
The FDA considers a drug product to be “commercially available” if it is available on the market. Generally, these products are subject to the requirements of the FD&C Act with regards to approval, labeling, and cGMP requirements. The copies restriction under section 503A applies to all of these products.
Furthermore, the Agency states that a product is not considered to be “commercially available” if:
- “The drug product has been discontinued and is no longer marketed”
- “The drug product appears on the FDA drug shortage list in effect under section 506E of the FD&C Act. A drug “appears on the drug shortage list in effect under section 506E” if the drug is in “currently in shortage” status (and not in “resolved” status) in FDA’s drug shortage database.”
Essentially a Copy of a Commercially Available Drug Product
In defining and outlining this term, the FDA provides details various different topics, including:
- What is Essentially a Copy?
- Statement of Significant Difference
- Documentation of Shortage
For additional details on FDA’s recommendations and policies, view the full draft guidance.
Regularly or in Inordinate Amounts
If a drug product that is essentially a copy of a commercially available drug is regularly compounded by a pharmacist or physician, or if it is compounded in inordinate amounts, it is not eligible for the exemptions in section 503A. “FDA interprets this to mean that to be compounded in accordance with section 503A, a drug product that is essentially a copy of a commercially available drug product cannot be compounded regularly – i.e., it cannot be compounded at regular times or intervals, usually, or very often. Nor can the amounts compounded be inordinate, in light of the purpose of section 503A.”
Draft Guidance #2
Details on FDA’s second draft guidance, regarding compounding drugs that are essentially copies of a commercially available drug product under section 503B of the FD&C Act is available in our FDA News article, entitled “FDA Outlines Policies for Compounding Drug Products That Are Essentially Copies of Approved Drugs Under Section 503B of the FD&C Act.”