Inspections, Compliance, Enforcement, and Criminal Investigations
Lincare, Inc. FDA Response Letter
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
|297 Plus Park Blvd.
Nashville, TN 37217-1003
August 9, 2006
Ms. Lisa Wegrzyn, General Counsel
Reliant Pharmacy Service (Reliant)
19387 US 19 North
Clearwater, Florida 33764
Re: Your Response to FDA Warning Letter No. 2005-NOL-06
Dear Ms. Wegrzyn:
This letter responds to your December 30, 2004, letter. We apologize for the delay, which was occasioned in part by FDA's recent inspection of Reliant's facility in Clear-water, Florida. That inspection reaffirmed the concern expressed in our warning letter of December 9, 2004, pertaining to Reliant's operations at its Southaven, Mississippi, facility. As specifically noted in that letter, we believe that Reliant is not engaged in the traditional practice of pharmacy, but rather, its "operation is akin to that of a drug manufacturer."
Drug Manufacturing vs. Practice of Pharmacy
In our December 9, 2004, letter, we warned that Reliant produces [redacted] of what are essentially copies of commercially available drugs . This practice goes well beyond the scope of traditional pharmacy compounding and instead more closely resembles a drug manufacturing operation." The observations during the Florida inspection reinforce our view that Reliant is a drug manufacturer and is subject to the requirements of the Federal Food, Drug, and Cosmetic Act (the Act) and its implementing regulations applicable to drug manufacturers. The arguments in your December 30, 2004, letter do not convince us to exercise enforcement discretion in this case.
In determining whether to initiate enforcement action against a pharmacy engaged in compounding, FDA examines the facts of each case and considers whether the pharmacy engages in any of the acts enumerated in FDA's Compliance Policy Guide (CPG) on human drug compounding. The factors in the CPG are not intended to be exhaustive, and other factors may be appropriate for consideration in particular cases. FDA makes its enforcement decisions regarding compounding activities after thorough evaluation of a firm's operations, and it may consider other indicia of deviance from traditional pharmacy practice.
From what we learned from the limited inspections that it allowed, Reliant receives patient information from [redacted], which sells products including nebulizers and other equipment. Reliant then markets its drugs to [redacted] nebulizer customers. Reliant does not work closely with physicians to tailor individualized products for specific patients with medical needs that commercially available products cannot meet. Rather it provides [redacted] of doses each year of standard compounded products to patients throughout the country. This operation makes Reliant's activities akin to a drug manufacturer.
Our inspections provided other evidence that Reliant is a manufacturer, not a pharmacy engaged in traditional compounding . For example, as noted in our letter and as discussed below, Reliant produces what are essentially copies of commercially-available drugs. In addition, although it avoids the use of "[redacted]" the firm achieves the same result -- production of [redacted] of drugs -- by using a [redacted] much larger than the numbers [redacted] by traditional compounding pharmacies.
From a safety perspective, Reliant's manufacturing approach creates a range of serious concerns. First is the burden to train and equip Reliant's [redacted] work force to properly produce drugs. The potential for introducing bacteria or other contaminants into Reliant's drugs, and the potential for manufacturing error, is increased because of the [redacted] of employees handling these products. Our limited inspections disclosed individual and general practices suggesting a poorly trained workforce and a lack of adequate quality and safety procedures. Indeed, laboratory analysis of compounded budesonide samples collected during the inspection at your Clearwater, Florida, facility shows product strength averaging only 77.6% of declared potency. This reinforces our concerns about the adequacy of Reliant's quality control process. Because Reliant produces a [redacted] volume of drugs for a vulnerable population, the potential for harm to consumers because of ineffective or dangerous dosage levels, or by introducing significant sources of infection, is real.
Your December 30, 2004, letter attempts to rationalize the volume of Reliant's compounding by pointing to the fact that Reliant "centralized [its] national operations" (we note that you did not disclose Reliant's operations in Florida and California that manufacture similarly [redacted] volumes of drugs). You compare Reliant's volume of compounded products to what might be produced by of [redacted] chain pharmacy operations. This argument does not withstand scrutiny.
Traditional compounding involves a physician asking a pharmacist to provide a unique product tailored to the individual needs of a patient, when commercially available products do not meet that patient's needs. For example, a physician might request a compounded product because of a patient's sensitivity to an ingredient in a commercially-available product. Compounding of this type, even if performed by multiple pharmacies within a chain operation, likely would fall within FDA's compounding CPG. By contrast, our inspections showed that Reliant [redacted] of doses of inhalation products annually. There is no evidence of patient-specific need for these doses and there is a genuine question as to whether physicians understand that their patients are being switched to compounded products.
Based on these observations, we view Reliant as engaged in a commercial manufacturing operation rather than the traditional practice of pharmacy. Because of the scope of the problems identified, and the very real safety consequences, we are unwilling to exercise enforcement discretion to allow these practices to continue.
Compounding of Commercially Available Products
Your letter also focuses on two of Reliant's approximately [redacted] compounded drug products, acetylcysteine (10% and 20% in unit-dose vials) and budesonide solution (0.25 mg. and 0.5 mg in unit-dose vials).
You dispute our findings that Reliant compounds a copy of a commercially-available product. You claim that Reliant's unit-dose packaging benefits clients who may be able to make better use of the firm's single-dose product. However, you offer to notify "those physicians who prescribe acetylcysteine filled by the Southaven pharmacy that there is a commercially available multi-dose form . . . [and] offer each such physician the choice" of the commercially-available product. You do not indicate whether you will take such corrective measures for other Reliant operations or products.
While certainly appropriate, these steps do not change our view that Reliant's acetylcysteine product is essentially a copy of a commercially-available drug. Nor does the possible convenience of a single-dose vial make Reliant's product meaningfully different from the FDA-approved, commercial products with which it competes. This is especially the case given the absence of documented patient-specific need for Reliant's dosage form.
You contest our findings that Reliant's budesonide solution is essentially the same as commercially-available suspensions. You argue that Reliant's budesonide solutions are more easily mixed with other medications and that this, in turn, saves patients' time. You further argue that the product can be used in ultrasonic nebulizers, which "are becoming more popular with patients ." However, once again, there is no indication that you attempt to relate the difference between your solution and the commercially-available suspensions to the needs of individual patients, or that you supply the commercially available product to patients who do not use ultrasonic nebulizers or mix medication. There is no indication on the prescriptions we sampled that physicians requested dosages for ultrasonic nebulizers, nor any documentation that physicians approved the substitution of the compounded product for the prescribed commercial product.
You have indicated that Reliant will "cease compounding unit dose vials of budesonide solution (0.25 and 0.5 mg), except in instances where the commercial product is unavailable from the manufacturer." You do not state whether this policy applies solely to the Southaven operation or to all Reliant operations. Nor do you state whether Reliant will similarly stop compounding other drugs for which there are commercially-available alternatives.
For the reasons set forth above, your letter does not dispel our concern that Reliant's activities bear little relationship to the traditional practice of pharmacy. Based on all available evidence, we must conclude that Reliant is a manufacturer and that it is subject to the provisions of the Act and its implementing regulations that apply to drug manufacturers. Your arguments do not convince us that we should exercise enforcement discretion in this case.
This letter also serves as notice for your Florida site, and we remind you that if similar practices are performed at any of your other sites, these sites may also be in violation. Should you continue to violate these provisions, we may take immediate enforcement action, including seizure and injunction, against your firm, its products, and its principals.
If you have any questions concerning this letter, please contact Kari L. Batey, Compliance Officer, 297 Plus Park Blvd., Nashville, TN 37217-1003 or telephone her at 615-781-5380 extension 112.
Carol S . Sanchez
Acting District Director
New Orleans District