The draft guidance documents, which apply to pharmacies, physicians, federal facilities and outsourcing facilities, are focused on compounded drugs, which the agency says pose a higher risk to patients than FDA-approved drugs because the agency does not evaluate compounded drugs for safety, effectiveness and quality before they are used, despite some researchers saying they could be an alternative to pricey drugs. Some compounders are also not required to comply with current good manufacturing practice requirements, FDA says, and as history has shown, taking poor-quality compounded drugs has resulted in serious adverse events, including infections and deaths.
However, the Agency acknowledges that some compounded products may help patients with special needs. For example, someone who has an allergy to a certain dye and needs a medication to be made without that dye, an elderly patient who cannot swallow a pill and needs a medicine in a liquid form, or a child who cannot take an adult-strength pill and needs a drug in a strength that is lower than that of an approved drug, might all benefit from compounded drugs.
“However, taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality,” FDA says. “In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems.”
The two draft guidance documents deal with “Compounded Drug Products That Are Essentially Copies of Approved Drug Products” under Section 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
Section 503A, added to the FD&C Act by the Food and Drug Administration Modernization Act in 1997 and amended by the Drug Quality and Security Act (DQSA) in 2013, 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 current good manufacturing practice (CGMP) requirements, the labeling of drugs with adequate directions for use and the approval of drugs under new drug applications (NDAs) or abbreviated new drug applications (ANDAs). The DQSA also created a new section 503B of the FD&C Act, which describes a new category of compounders called outsourcing facilities, which are bound by conditions that must be satisfied for human drugs compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility to qualify for exemptions from those previously mentioned (though not the CGMP) requirements of the FD&C Act and others concerning drug supply chain security.
“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,” FDA says. “Sponsors might also be less likely to seek approval of an ANDA for a generic drug if compounders were permitted to compound drugs that are essentially copies of commercially available drugs without going through the ANDA process.”
In the 503A draft guidance, FDA says it intends to consider a compounded drug product to be “essentially a copy of a commercially available drug” if:
- the compounded drug has the same active pharmaceutical ingredient(s) (API) as the commercially available drug;
- the API(s) have the same, similar, or an easily substitutable dosage strength;
- the commercially available drug can be used by the same route of administration as prescribed for the compounded drug, unless a prescriber determines that there is a change, made for an identified individual patient, which produces for that patient a significant difference from the commercially available drug.
The release of the guidance comes as FDA in April 2016 put out three other guidance documents describing FDA’s interpretation of the prescription requirement in Section 503A, how the Agency intends to apply such a requirement to compounding for hospitals or health system pharmacies, and the definition of the term “facility,” in reference to section 503B.
REFERENCE: RAPS Regulatory Focus; 07 JUL 2016; Zachary Brennan