- College Pharmacy Incorporated,
FIRM and AFFILIATE OFFFICES
RACHAEL G. PONTIKES
DIRECT DIAL:+ 1 312 499 6757
PERSONAL FAX: +1312 277 6903
190 SOUTH LASALLE STREET, SUITE 3700 CHICAGO, IL 60603-3433
September 7, 2016
VIA EMAIL- email@example.com
U.S. Food and Drug Administration
P.O. Box 25087
Denver, Colorado 80225-0087
Attn: Dr. Matthew R. Dionne
Re: Response to College Pharmacy's Warning Letter--Ref#: DEN-16-14-WL
Dear Dr. Dionne:
We represent College Pharmacy ("College') and hereby submit to FDA this letter in response to FDA's Warning Letter dated August 15, 2016 ("Warning Letter"). Please note, College received this Warning Letter on August 16, 2016.
We want to emphasize, at the outset, that College takes the issues identified in the Warning Letter very seriously. Indeed, College has made it a priority to address FDA's concerns as previously articulated in connection with the inspections to which FDA now returns. As part of its continuing, evolving efforts to meet the highest standards for compliance and patient safety, College has reviewed and continues to review its overall operations to ensure that it remains in conformance with all applicable law, including the Federal Food, Drug & Cosmetic Act ("FD&C Act"), FDA's implementing regulations, and the laws of Colorado and other relevant states.
Moreover, College is going above and beyond to ensure that the preparations it compounds and dispenses to patients not only meet their individual needs for therapeutic medication, but comply with established standards of pharmacy practice. As evidence of this effort, in deference to FDA, the pharmacy is now 100% patient specific in human health and has discontinued compounding biologics. For the reasons set forth below, although College believes that it was in compliance with all applicable state and federal laws during the time periods identified in the Warning Letter, College has altered its policies and procedures in response to FDA's observations and recommendations.
Nevertheless, a portion of FDA's Warning Letter requires clarification; Section 503A should not be applied to College prior to November 27, 2013. College was a party to Thompson v. Western States, in which the United States Supreme Court struck down Section 503A as unconstitutional. College filed the suit challenging Section 503A before it went into effect. In the appellate court, the Ninth Circuit found that the offending advertising provision was not severable from the remainder of Section 503A. Western States Med. Ctr. v. Shalala, 238 F.3d 1090 (9th Cir. 2001). When the United States Supreme Court found the advertising ban unconstitutional, it therefore invalidated all of Section 503A-meaning that Section 503A was rendered a nullity that could not apply and never has applied to College. Thompson v. Western States Medical Center, 535 U.S. 357 (2002). The Supreme Court's judgment in this matter is clear, and as such, FDA should not apply Section 503A to a March 2013 inspection of College. Otherwise, FDA would be suggesting that Section 503A has retroactive effect, which is not permitted. See Plaut v. Spendthrift Farm, Inc., 514 U.S. 211, 227 (1995) ("Having achieved finality, however, a judicial decision becomes the last word of the judicial department with regard to a particular case or controversy, and Congress may not declare by retroactive legislation that the law applicable to that very case was something other than what the courts said it was.")
Regarding the compounding of biologics referenced in the Warning Letter, we would like to note that historically there has not been clear guidance as to whether certain medications are classified as a drug or as a biologic. Before the passage of Drug Quality Security Act ("DQSA"), all pharmacy compounding was regulated by state law. After DQSA took effect, and compounding came under limited federal oversight, FDA had no policy regard compounding biologics or allergenic extracts. However, in February 2015, FDA issued its Mixing, Diluting, or Repackaging Biological Products Outside the Scope of An Approved Biologics License Application draft guidance ("Biologics Draft Guidance") which provided a draft of FDA's current thinking on this issue. In response to this FDA Biologics Draft Guidance, although the guidance is not yet final, College evaluated its practices and stopped compounding allergenic extracts. Please note, College ceased compounding allergenic extracts before receiving the Warning Letter.
As to preparing compounds for office use, please be advised that College is currently dispensing human health medications only based upon the receipt of a valid prescription for an individually-identified patient. We understand and appreciate as stated in the Warning Letter, that the agency is taking the position that all compounded drugs irrespective of interstate shipment must be dispensing pursuant to a patient specific prescription to comply with Section 503A. Please note, however, FDA only recently issued its Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act draft guidance ("Prescription Requirement Draft Guidance), which sets out FDA's expectation that Section 503A pharmacies dispense only pursuant to a patient specific prescription. In deference to the position FDA is taking in the Warning Letter and FDA's draft current thinking as set out in the Prescription Requirement Draft Guidance, although this guidance is not yet final, College is now dispensing human health medications only based on the receipt of a valid prescription for an individually identified patient.
As such, College is compliant with FDA's interpretation of the requirements of Section 503A and is therefore entitled to the exemptions set forth therein, including 503A's exemption from cGMP requirements. As a Section 503A pham1acy, College is exempt from cGMP standards as a matter of law, and therefore, any attempt to hold College to cGMP standards is invalid. See 21 U.S.C. § 353a(a)(1)-(2). Nonetheless, in response to this Warning Letter and the FDA May 2015 Form 483 ("Form 483''), College has undertaken a comprehensive review and evaluation of its compounding operations and has taken the following corrective actions to address the remaining issues FDA has raised. In response to both the Form 483 and the Warning Letter, the pharmacy has:
• Addressed its lyophilization process. College revised the air flow pattern around the pass through for both lyophilizers, purchased a new stainless steel bench that was placed below the pass through, and certified that the area passed ISO 5 testing requirements. Nevertheless College is discontinuing the use of lyophilizers.
• Performed smoke studies under dynamic conditions and certified that its facility passes all applicable standards. (Advanced Testing & Certification Report:, attached hereto as Exhibit A).
• Revised its gowning SOP and immediately implemented the revised procedures in response to the Form 483 . The revised gowning practices and procedures now require the use of goggles, sterile coveralls, and sterile hoods to minimize exposed skin. (SOP S1.010.1 "Gowns, Masks, Gloves, Shoe Covers-Sterile" is attached here to as Exhibit B).
• Revised its environmental monitoring SOP and immediately implemented these changes in response to the Form 483. (SOP S1.110.1 "Environmental Monitoring of the Clean Room Facility" is attached hereto as Exhibit C). The revised environmental monitoring procedures require that any level of growth found in the clean room to be sent to an independent lab for identification of the microorganism. Id.
• Reevaluated its use of sterile wipes. College acknowledges the importance of cleaning and disinfecting equipment to produce aseptic conditions. The use of sterile wipes, however, is a cGMP requirement which is inapplicable to College as pharmacy compliant with Section 503A. As sterile wipes are not required by USP General Chapter <797> or state law, College will continue to use non sterile wipes.
In closing, we would like to emphasize that College shares FDA's goal of ensuring that patients in need of custom compounded medications receive the highest quality preparations. College takes compliance with all applicable federal and state laws governing its pharmacy practice very seriously. To that end, we welcome a meeting with the District Office as part of our continuing constructive dialogue.
Very truly yours,
Rachael G. Pontikes