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ASHP Comments in Response to Public Meeting on 503B Outsourcing Facilities Office Stock

Food and Drug Administration

June 21, 2019

U.S. Food and Drug Administration
Department of Health and Human Services
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Re: Docket No. FDA–2018–N–4087for “The Food and Drug Administration’s Proposed Current Good Manufacturing Practice Policies for Outsourcing Facilities: Considerations Regarding Access to Office Stock; Public Meeting; Request for Comments.”

ASHP is pleased to submit comments in response to FDA’s public meeting regarding the production of office stock by 503B outsourcing facilities. ASHP represents pharmacists who serve as patient care providers in acute and ambulatory settings. The organization’s nearly 50,000 members include pharmacists, student pharmacists, and pharmacy technicians. For more than 75 years, ASHP has been at the forefront of efforts to improve medication use and enhance patient safety.

ASHP appreciates FDA’s continued efforts to develop the 503B marketplace. In response to issues raised at the public meeting, ASHP would like to take this opportunity to reiterate a few areas of concern regarding 503B oversight.

1. Hospital/Health System Compounding Remains Essential to Patient Care.

As a foundational matter, ASHP believes that 503B outsourcing facilities play an essential role in the supply chain of quality compounded medications for hospitals and health systems. Many hospitals and health systems rely on 503B facilities for certain compounded products, but as ASHP and other stakeholders have noted in comments and during FDA listening sessions, 503Bs cannot or will not produce everything hospitals need. For example, 503Bs are disinclined to compound in small batches, they will not compound certain high-risk drugs, such as those required for cardiac procedures, and due to capacity limitations, new customers often cannot purchase everything a 503B produces because that supply has already been allocated. Further, current 503B capacity is not sufficient to meet all needs – without hospital compounding, there will be no safeguards or redundancies in place to protect against shortage situations. Thus, it is imperative that the FDA finalize a compounding framework that allows hospitals/health system to compound certain products.

2. Hospitals/Health Systems Need More Information on 503B Quality.

Discussions with our members indicate that hospitals and health systems continue to have questions about interpreting 503B inspection reports as well as concerns regarding recent recalls of 503B-produced products. ASHP fully supports publication of 483 inspection findings, but the reports offer little context or insight into the level of risk associated with various findings. Further, although the 483s are posted, information regarding 503B responses is not made public nor are the reports ever cleared or reconciled. Information related to a 503B’s response to a 483, particularly quality improvements undertaken by the 503B, could ease any hospital or health system concerns associated with purchasing product from a 503B outsourcing facility. We further recommend that the FDA consider implementing a quality ratings system to help inform hospital and health system purchasing decisions.

3. Definitions in 503B Guidance Documents Need Additional Clarification.

  • “Clinical Need” in the 503B Bulks Guidance: In the guidance, FDA notes that “supply issues, such as backorders” are not considered clinical need. As stated in previous comments to FDA, ASHP remains concerned that a narrow focus on the FDA Shortage List will not adequately address the potential impact of shortages on care. Thus, ASHP recommends a broader scope for the clinical need definition in the draft guidance as it relates to product availability. Specifically, in cases where patients cannot obtain a drug, and it does not appear on the FDA Shortage List, we encourage the agency to consider other sources of shortage information, including the ASHP Drug Shortages List. Because FDA’s shortage determinations are based on national drug production and utilization data, they do not always accurately reflect real-time, point-of-care shortage status. In particular, the FDA Shortage List may not reflect low allocation of shortage drugs by distributors to entities with limited buying power, contractual obligations prohibiting or strictly limiting off-contract purchasing or selling, limited distribution systems, and/or geographic areas with only one distributor or wholesaler. Thus, a comprehensive picture of shortages requires the use of multiple lists. If the FDA’s intent is that 503Bs should help address all shortages, the additional information offered by other sources such as the ASHP Drug Shortages List will be essential to mitigating shortages throughout the country.
  • Documentation of “Clinical Difference” in the 503B Copies Guidance: ASHP recommends that FDA reconsider the draft guidance’s requirements for documenting a “clinical difference” for an unidentified patient. As noted in Section I above, our understanding of the guidance’s bulk substances provision would mean that compounding done from both bulk substances and approved drugs would necessitate documentation of clinical difference unless the compounded drug is a copy or essentially a copy of a drug on FDA’s shortage list. Thus, under the guidance (and depending on how FDA interprets the definition of compounding), a 503B will need to “obtain a statement from the practitioner that specifies the change between the compounded drug and the comparable approved drug and indicates that the compounded drug will be administered or dispensed only to a patient for whom the change produces a clinical difference, as determined by the prescribing practitioner for that patient.” The guidance further suggests that a “hospital pharmacy manager” could make this representation.

    While we strongly support efforts to limit abusive copying, we question the necessity and effect of such a requirement. The responsibility for determining significant difference for individual unidentified patients rests with the prescriber. Assigning legal compliance with 503B requirements to vendors and dispensing pharmacists will achieve the letter, but not the intent, of DQSA. Aside from the potential liability associated with asking anyone other than the ultimate prescriber to make representations about how a drug will be used, there are also scope-of-practice ramifications. Physicians retain medical discretion and would not be bound by representations of the hospital pharmacy manager. Physicians could perceive such representations as an infringement upon their medical judgment. Further, FDA has repeatedly pointed to 503B outsourcing facilities as the preferred and, in some instances, sole provider of non-patient-specific compounded medications. By imposing additional documentation requirements on 503Bs, FDA may be undermining the incentive of hospitals and health systems to use 503Bs. As ASHP has previously emphasized, 503Bs are an essential link of the supply chain for many hospitals and health systems. We are concerned that imposing burdensome documentation requirements could threaten their ongoing operations, which would, in turn, threaten patient and facility access to medications. Thus, we encourage FDA to consider either removing this documentation requirement or, at a minimum, substantially revising it to address the concerns listed above.

ASHP thanks the FDA for the opportunity to comment on our concerns related to compounding by 503B outsourcing facilities. If you have any questions on ASHP’s comments or ASHP can be further assistance, please contact me at [email protected] or at (301) 664-8698.


Jillanne Schulte Wall, J.D.
Director, Federal Regulatory Affairs