Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Comments of National Center for Health Research
on the draft guidance documents
“Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act”
[Docket No. FDA-2016-D-1309]
and
“Compounded Drug Products That Are Essentially Copies of Approved Drug Product Under Section 503B of the Federal Food, Drug, and Cosmetic Act”
[Docket No. FDA-2016-D-1267]
The National Center for Health Research, National Physicians Alliance, and Jacobs Institute of Women’s Health support the above draft guidance documents (Docket No. FDA-2016-D-1309 and Docket No. 2016-D-1267), which would place tighter restrictions on the compounding of drugs.
The 503A draft guidance places restrictions on pharmacy compounding by licensed pharmacists and physicians for drug products that are essentially copies of commercially available drugs. The 503B draft guidance places restrictions on pharmacy compounding by outsourcing facilities for drug products that are essentially copies of FDA approved drugs.
The 503A draft guidance states that if the compounded drug has the same active pharmaceutical ingredients (API), the same or similar dosage strength, the same route of administration, and the same characteristics of two or more commercially available drugs, then it is essentially a copy of a commercially available drug—and it cannot be compounded.[1] This is a necessary safety precaution because commercial drugs are subject to FDA approval, labeling, and Current Good Manufacturing Practices (CGMP) requirements, which compounded drugs are not. Therefore, compounded drugs should not replace essentially identical FDA-approved drugs.
The 503B draft guidance states that a compounded drug cannot be a copy of one or more approved FDA-approved drugs, or a drug that has not been withdrawn from the market because the drug (or its components) has been found to be unsafe or not effective. Also, it states that if the compounded drug has bulk components of one or more approved drugs, it is essentially a copy of an approved drug.[2]
The draft guidance documents address compounded drug safety issues that were brought to light during the 2012 fungal meningitis tragedies caused by contaminated compounded drugs that led to more than 60 deaths and hundreds of infections.
The 503A draft guidance describes the conditions that licensed pharmacists and physicians must meet for a compounded drug to qualify for the exemptions under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C). It states that the pharmacist and physician compounders cannot compound “regularly or in inordinate amounts any drug products that are essentially copies of a commercially available drug product.”
We strongly agree with the FDA that section “503A is not intended to provide a means for compounders to produce compounded drugs exempt from the Act’s requirements that are essentially copies of commercially available drug products.”[1] We strongly agree with the 503B draft guidance that compounded drugs from outsourcing facilities should only be distributed to health care facilities or dispensed to patients to fulfill specific patient needs that cannot be met by an FDA-approved drug.
Compounded drugs are an important option for patients who have special needs such as patients with allergies to a pill’s dye, or a senior who cannot swallow a pill, or a child who needs a lower dosage drug than those commercially available. However, compounded drugs are not FDA-approved, which means they have not been subject to FDA’s “premarket review for safety, effectiveness, and quality.”[1] That is why we strongly agree with the FDA that “compounded drugs pose a higher risk to patients than FDA-approved drugs,” and that compounded drugs should be subject to severe restrictions for patients who cannot safely use FDA-approved drugs.
Restrictions are needed to:
• Protect patients from less safe and less effective medications. Pharmacists and physicians should not compound drugs for patients who could use commercially available drugs, and outsourcing compounders should not be allowed to sell copies of FDA approved drugs.
• Protect the “integrity and effectiveness” of the FDA approval processes for new and generic drugs. Drug makers would be less likely to invest in new drugs, if a compounder could make substitutes that would not have to demonstrate safety and effectiveness and other FDA requirements.
• Protect FDA’s drug monograph process for over-the-counter (OTC) medications. Restrictions in the 503A draft guidance prevent licensed pharmacist and physician compounders from making drugs without having to comply with monograph standards or Current Good Manufacturing Practices (CGMP) requirements.
Exemptions
The 503A draft guidance spells out when a compounded drug is exempt from being a copy of a commercially available product. It notes that when a drug has been discontinued and is no longer marketed then it should not be considered a “commercially available drug product” and so can be compounded.
Drugs compounded for “an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner” are exempt from being a copy of a commercial drug.1 And, a compounded drug made to address a shortage need would also be exempt from the copy provision.
The 503B draft guidance lists several exemptions when compounded drugs are not “essentially a copy of an approved drug.” The list includes when a prescriber makes a determination of clinical difference; when an outsourcing facility compounds a drug that differs on its active ingredients, route of administration, dosage strength and form, and excipients; and when the drug appears on FDA’s drug shortage list at the time of compounding, distribution, and dispensing.[2]
Clear definitions
We are pleased that the 503A draft guidance defines “regularly or inordinate amounts.” We had criticized a 2014 compounding draft guidance for not specifically defining “inordinate amounts.”[3] We strongly support FDA’s proposed safe harbor definition of “regularly or inordinate amounts” as meaning when a compounder fills four or fewer prescriptions for the compounded drug in a month.
Conclusions
We strongly support the draft guidance documents because they place tight restrictions on pharmacy compounding under sections 503A and 503B of the FD&C Act to prevent compounding drug products that are essentially copies of commercially available drug products and for those that are copies of approved drugs. Although compounded drugs are needed in certain circumstances (patients with allergies, seniors who need a liquid form of a pill, or children who need a lower dosage amount), these drugs are not FDA approved and are not subject to FDA safety standards (such as performing clinical trials), or labeling requirements. That is why compounded drugs need to be tightly restricted.
National Center for Health Research
National Physicians Alliance
Jacobs Institute of Women’s Health
- Food and Drug Administration (2016). Draft Guidance: Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act [Docket No. FDA -2016-D-1309]
- Food and Drug Administration (2016). Draft Guidance Compounding Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act [Docket NoFDA-2016-D-1267]
- Patient, Consumer, and Public Health Coalition (February 6, 2014). Comments on the Food and Drug Administration’s Draft Guidance “Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act” Docket No. FDA-2013-D-1444 https://center4research.org/public-policy/letters-to-government-officials/comments-on-the-food-and-drug-administrations-draft-guidance-pharmacy-compounding-of-human-drug-products-under-section-503a-of-the-federal-food-drug-and-cosmetic-act/