Inspections, Compliance, Enforcement, and Criminal Investigations
University Pharmacy Response
CUSTOM COMPOUNDING SPECIALISTS
TOLL FREE: (888) 768-7414
Phone: (801) 582-7624/Fax: (801) 582-7633
1320 East 2nd South,
Salt Lake City, UT 84102
January 5, 2007
By Facsimile/Confirmation Copy by Overnight Delivery
Food and Drug Administration
Denver District Office
P.O. Box 25087
Denver, Colorado 80225-0087
Re: Warning Letter to University Pharmacy DEN No 07-02
Dear Ms. Barrell:
University Pharmacy appreciates the opportunity to respond to the issues raised in FDA's December 4, 2006 Warning Letter, and to clarify the nature of our retail pharmacy operations. We also thank you for agreeing to extend our response due date to January 5, 2007.
University Pharmacy is committed to complying with applicable laws and regulations, and to ensuring high quality care for its patients. This letter responds to FDA's concerns and, where appropriate, identifies areas where we intend to make voluntary changes to address these concerns.
FDA states in the Warning Letter that it believes our compounded drugs are "new drugs" under Section 201(p) of the Food, Drug, and Cosmetic Act (FDC Act). Although the Warning Letter cites several court cases, it fails to mention this position was recently rejected by the only federal court to have directly addressed the issue. In Medical Center Pharmacy v Gonzales, the federal District Court for the District of Western Texas granted the plaintiff pharmacies' summary judgment on their "claim that compounded drugs do not fall under the [FDC Act's] new drug definitions."1. The court based this conclusion on "relevant case and statutory law, as well as legislative intent."2. Thus, the Warning Letter omits the single most relevant decision.
The Warning Letter also refers to the Supreme Court's pharmacy compounding decision in Thompson v Western States Medical Center, 3 but neglects to mention that the Medical Center Pharmacy court's opinion stated that "the language of Western States demonstrates that compounding is a process that has been approved by the Supreme Court."4
University Pharmacy does not introduce unapproved new drugs into interstate commerce, does not manufacture drugs, and does not need approved NDAs before dispensing its compounded medications. Our compounded medications are not misbranded. We are lawfully engaged in the practice of pharmacy in compliance with the Utah Board of Pharmacy's laws and rules. The Medical Center Pharmacy court determined that the kinds of activities we engage in do not result in the introduction of new drugs into interstate commerce.
Compounded Topical Analgesic Medications
Contrary to the Warning Letter's assertions, University Pharmacy has not developed a standardized topical anesthetic product. We compound a variety of topically analgesic formulations in accordance with the requests of prescribing physicians. While we have averaged over [redacted] unique formulas per month during the last; year, physicians do ask University Pharmacy to compound some formulations more frequently than others. The formula is determined solely by the physician. We compound to fill the prescription or order as it is presented. That does not mean that we compound only a limited number of formulations, or that we have developed standardized formulas.
We have assigned a name for the medication referred to in the Warning Letter primarily for purposes of internal, electronic record keeping and as a convenience to physicians. We also note that naming formulas is a common practice in pharmacy, and does not mean that a compounding pharmacy is a manufacturer. Nonetheless, to address FDA's concerns, we will no longer name the medication referred to in the Warning Letter and instead will require physicians to specify the desired chemical formulation in each prescription.
The Warning Letter also refers to potentially serious health risks associated with the misuse of topical analgesics. Misuse is a risk with virtually all drugs. The possibility that a compounded drug may be misused provides no basis for FDA to assert jurisdiction. The Warning Letter also notes that a topical analgesic compounded by University Pharmacy has been associated with a death. We believe that this event stemmed exclusively from misuse of the product, and not from any issues relating to the safety of the product as compounded.
We are also puzzled by FDA's reference to this event in its December 4 Warning Letter. According to the Warning Letter, the death occurred in November of 2004, FDA inspected our pharmacy on March 21, 2005, and the Warning Letter was issued on December 4, 2006, two years after the death and nineteen months after FDA's inspection. We assume that if FDA had determined that there was significant potential risk to the public health, FDA would not have waited two years to issue the letter.
The timing of the Warning Letter is also curious because it does not comply with FDA's internal procedures. Warning Letters are to be issued in a timely fashion, because they are " the agency's principal means of notifying regulated industry of violations and achieving prompt voluntary corrections."5. The five most recent Warning Letters issued by FDA's Denver District Office to non-pharmacy drug and device manufacturers were sent, on average, 192 days after the recipients' facilities had been inspected. The Warning Letter we received, by contrast, arrived 623 days after FDA's inspection of our pharmacy. While we take the welfare of our patients very seriously, we believe this significant delay is inconsistent with FDA's rhetoric regarding the risks of our compounded products.
The Warning Letter also refers to a drug information sheet for one of our compounded medications, characterizes it as promotional, and takes issue with the contents of the document. As a legal matter, we believe that FDA lacks the authority to prescribe the wording of informational sheets for compounded drugs. The requirement for adequate directions of use do not apply to compounded drugs for the same reason reasons that the NDA provisions are inapplicable. Moreover, the Supreme Court in Western States Medical Center established that a pharmacy can lawfully inform physicians and patients about the types of medications it can compound. Nonetheless, University Pharmacy understands FDA's concerns and will voluntary review the drug information sheet referred to in the Warning Letter and make any appropriate revisions.
University Pharmacy compounds progesterone [redacted] capsules because medical practitioners have issued prescriptions for compounded versions. Contrary to the Warning Letter's assertion, the absence of [redacted] in our compounded progesterone capsules, as requested by prescribing physicians, is a meaningful difference between compounded progesterone capsules and the commercially available version of the drug. Allergic reactions to [redacted] are common, can be severe, and can develop swiftly. Patients who are prescribed progesterone require access to a product that poses no risk of suffering potentially deadly allergic reactions. FDA's own approved labeling for Prometrium, an FDA-approved progesterone drug, contraindicates the product for patients with [redacted] allergies.6 This contradicts the Warning Letter's assertion that there is no meaningful difference between the formulation for progesterone capsules we are frequently asked by physicians to compound and the commercially available product. We believe that the decision to prescribe a compounded product that lists [redacted] falls within the practice of medicine by physicians. These decisions reside with physicians responsible for treating patients, not with pharmacists.
University Pharmacy will not dispense prescriptions for [redacted] progesterone vaginal. cream unless the FDA approved version is no longer commercially available.
We trust that we have adequately addressed each of the concerns FDA raised in the Warning Letter. FDA's policy states that responses to Warning Letters will be posted on the FDA website at the Warning Letter recipients' request. We therefore request that this letter be posted on FDA's website. We have enclosed with the copy of the letter delivered to you via overnight delivery, a computer diskette containing an electronic version of this response in PDF format for the purposes of redaction and website posting.
Thank you again for this opportunity to clarify the nature of our compounding pharmacy operations.
Richard E. Rasmuson
1 Med. Ctr. Pharmacy v. Gonzales, 451 F. Supp. 2d 854, 865 (W.D. Tex. 2006), appeal docketed, No. 06-51583 (5th Cir. Dec. 11, 2006).
2 Id. at 858
3 535 U.S. 357 (2002).
4 451 F. Supp. 2d at 864.
5 FDA, Regulatory Procedures Manual 4-10 (March 2006).
6 The first contraindication listed in the FDA-approved labeling reads [redacted] Similarly, the first page of the patient insert reads, [redacted]
(Emphasis in original).
Similarly, the Food Allergen Labeling and Consumer Protection Act of 2004 requires that.the labeling for all foods containing [redacted] include a declaration alerting consumers to the presence of [redacted] in the food product.