By Karla L. Palmer –
On Friday, June 14, 2013, Congressman Morgan Griffith (R-VA) released a draft bill addressing compounding of human drugs. The draft primarily was influenced by the revised draft guidance document the Food and Drug Administration (“FDA”) was prepared to release in the fall of 2012, prior to the New England Compounding Center (“NECC”) incident. This bill does not define a “compounding pharmacy” or create a “compounding manufacturer” category, unlike the pending Senate Health, Education, Labor and Pensions Committee (“HELP”) legislation (S. 959). Congressman Griffith’s draft proposal retains two categories – pharmacies and manufacturers – and clarifies how FDA would distinguish compounding pharmacies from drug manufacturers. The issue of linking compounding to identified patients is a key feature of the bill.
The draft also requires that all compounding pharmacies comply with both USP <795> (non-sterile compounding) and USP <797> (sterile compounding). The draft proposal emphasizes sharing of information between FDA and states, and provides a framework to ensure FDA receives timely notifications from states concerning whether a compounding pharmacy may be acting as a drug manufacturer. When a state provides notice to FDA that a compounder is or may be violating the law, for example, FDA would be required to provide notification to other states and make a determination whether there is enough evidence to inspect the pharmacy in question. The draft proposal gives FDA full inspection authority of a compounding pharmacy, but only if there is prior evidence that a compounding pharmacy is acting as a manufacturer in violation of the FDCA. Under current practice, FDA often conducts a comprehensive inspection of a pharmacy to determine whether that pharmacy was entitled to the more limited inspections authorized for pharmacies.
The draft does not include in its definition of “essentially copies of a commercially available drugs” (i.e., drugs which cannot be compounded) those products that appear on FDA’s drug shortage list. Lastly, the draft proposal makes falsifying a prescription for a drug compounded under section 503A a violation of the FDCA subject to criminal penalties. Comments on the proposed draft are due by close of business on Thursday June 20, 2013. Below is a more detailed summary of the proposed bill.
Summary of Proposed Amendments to FDCA Section 503A
The draft proposal amends Section 503A of the FDCA (21 U.S.C. § 353a). Sections 501(a)(2)(B) (cGMPs), 502(f)(1) (adequate directions for use labeling), and 505 (new drugs) of the FDCA will not apply to a compounded drug product if each of the following conditions is met:
• Individual patient prescription requirement: The product is for an identified individual patient based on a prescription demonstrating the compounded product is necessary for that patient; and
o The product is compounded by a state-licensed pharmacist/physician/other licensed practitioner.
• Anticipatory compounding: A drug can be compounded in limited quantities prior to the receipt of an individual prescription when:
o The pharmacist/ physician has historically received prescriptions for the compounding of the product; and
o The orders have been generated solely within an established physician/pharmacist relationship with the patient or the physician who will write the order.
• Office use compounding: A pharmacist/physician may compound a non-patient-specific purchase order from a health care provider, after receiving assurances that:
o The drug will be administered within a doctor’s office, hospital or health care setting;
o One or more patient-specific orders or notations will be submitted to the compounder within 7 days of drug administration that will account for the full amount of drug product compounded; and
o The drug may not be compounded for office use or in anticipation of a prescription if prohibited under state law.
• Bulk substances: If a drug is compounded using bulk substances, it must comply with a USP or NF monograph if such exist, and USP chapters on compounding (including sterile preparations). If a USP/NF monograph does not exist, then the drug must be compounded using components of approved drug products. If a monograph does not exist and the drug is not compounded using components of approved products, then it must appear on a substance list published in FDA regulations. Bulk substances used in compounding also must be manufactured at a FDA-registered establishment, and accompanied by a valid certificate of analysis.
o If, however, a drug is compounded using ingredients other than bulk substances, then those ingredients must comply with USP/NF monograph, if applicable, and USP chapters on compounding (including sterile preparations).
• Do not compound list: The compounded drug must not appear on a list published by FDA (per regulations) concerning drugs or drug components withdrawn for reasons of safety or effectiveness. For drugs that are demonstrably difficult to compound, FDA will publish a “do not compound list” of those drugs that reasonably demonstrate an adverse effect on the safety or effectiveness of that product.
• Essentially copies of available drugs/FDA drug shortage list: The compounded drug may not be a copy or essentially a copy of a commercially available drug. “Essentially a copy of a commercially available drug product” would not include: (1) a drug product for which there is a change for an identified individual patient which produces for that patient a significant difference, as determined by the prescribing or practitioner, between the compounded drug and the commercially available drug; or (2) a drug product that appears on the drug shortage list in effect under FDCA section 506E.
• Federal/State notification system: FDA is required to develop, in consultation with NABP, a notification system for receiving and reviewing submissions from state boards of pharmacy on actions taken against compounding pharmacies. Submissions from state boards warranting FDA notification would include: (1) warning letters, sanctions or penalties for violations of state regulations; (2) suspension/revocation of a state issued pharmacy license; and (3) recall(s) of compounded drug products due to quality or purity concerns. FDA must implement the notification system within one year after implementation of the act.
o The proposal requires FDA to review state submissions and other necessary information including information collected through an inspection or maintained in the Adverse Event Reporting System database; FDA would make a determination whether the pharmacy is in violation of section 503A.
• Inspections: Within 60 days after receipt of a state submission, FDA must assess whether there is evidence suggesting that the pharmacy is in violation of the section, and, if so, must conduct an inspection in coordination with the state board.
• Section 704 inspection authority: FDA also would have inspection authority under FDCA section 704 (inspections) to determine whether a compounding pharmacy is not eligible for the inspection exemption under 704(a)(2) (pharmacies) only if the FDA receives the above-described submission from a state described above.
o If, after receiving a state submission, FDA determines that a pharmacy is in violation of section 503A, then FDA would be required to notify other state boards of pharmacy.
• Advisory committee: Before issuing regulations, FDA would be required to convene an advisory committee (including representatives from NABP, USP, physician and consumer groups, and experts) on compounding unless FDA claims that issuance of such regulations more promptly is necessary to protect the public health.
• Definitions/Criminal penalties: “Compounding” is defined as not including mixing, reconstitution, or following other directions provided by the manufacturer. The proposal would permit criminal penalties for intentionally falsifying a prescription order for a compounded drug product.