- Morton Drug Company dba Morton LTC
December 16, 2016
Food and Drug Administration
Brian Garthwaite PhD
Minneapolis District Office
250 Marquette Ave, Suite 600
Minneapolis, MN 5540
Via E-Mail and USPS
Re: Morton Drug Company, Inc., d/b/a Morton LTC Warning Letter (MIN 17-01)
Dear Dr. Garthwaite:
We represent Morton Drug Company, Inc., d/b/a Morton LTC ("Morton"), and hereby submit to the Food and Drug Administration ("FDA") this letter in response to FDA's Warning Letter dated October 26, 2016 ("Warning Letter"). Please note that Morton received a written extension until December 16, 2016 to respond to the Warning Letter.
We want to emphasize at the outset that Morton takes the issues identified in the Warning Letter very seriously. As part of its continuing effort to meet the highest standards for compliance and patient safety, Morton continually reviews its overall operations to ensure that it remains in conformance with all applicable law, including Section 503A of the Food Drug Cosmetic Act ("FDCA“) and Wisconsin state law. Indeed, Morton implements policies which seek to ensure that the compounds it prepares for its patients comply with established standards of pharmacy practice. To this end, as set forth in Morton's multiple responses to FDA's December 2015 Form 483 ("Form 483"), Morton addressed all of the observations identified in the Form 483. FDA even acknowledges in the Warning Letter that Morton's corrective actions "appear to be adequate," and does not recommend that Morton take any further specific corrective action.
Nevertheless, FDA issued this Warning Letter. According to FDA's published policy on warning letters, "the agency position is that Warning Letters are issued only for violations of regulatory significance.”1 The issuance of this Warning Letter is therefore inappropriate for the following three reasons: (1) the Warning Letter applies cGMP standards to a pharmacy compliant with 503A; (2) the observations set forth in this Warning Letter, such as the use of non-sterile disinfectants and pharmacy technician garbing, do not seem to rise to the level of "regulatory significance” required under FDA's stated policy; and (3) even if the observations did rise to this level, Morton immediately addressed all FDA concerns and, as stated in the Warning Letter, FDA had found its corrective actions adequate. Consequently, Morton respectfully requests that FDA withdraw the Warning Letter.
A. FDA Should Not Apply cGMP Standards To Morton.
In the Warning Letter, FDA has continued to apply cGMP standards to Morton. For example, FDA continues to claim that Morton is required to use sterile disinfectants, although FDA acknowledges Moron's position that state regulations and USP <797> do not require their use. Although Morton bas determined that it will now use sterile disinfectants, as set forth below, Morton's past practice of using non-sterile disinfectants is not a violation of any law or regulation, but complies with state law and USP <797>. Using non-sterile disinfectants certainly is not a basis for issuing this Warning Letter, as it does not represent any violation, let alone one of regulatory significance.
The Warning Letter also appears to improperly hold Morton to standards outside applicable state and federal law to determine if its compounds are prepared under insanitary conditions and are therefore adulterated under Section 501(a)(2)(A) of the FDCA. For example, the Warning Letter cites the use of non-sterile disinfectants, monitoring pressure differential results, and pharmacy technician garbing as possible causes of insanitary conditions. However, it is unclear whether FDA is applying cGMP or some other standard for insanitary conditions to the observations cited in the Warning Letter. Morton is entitled to Section 503A's exemption from cGMP as a pharmacy acting within its requirements and therefore FDA should only hold Morton to state law standards when evaluating the conditions under which Morton's compounds are prepared. As such, to the extent it is doing so, FDA cannot use Section 501(a)(2)(A) to apply cGMP or some other standards outside of state law to evaluate Morton.
B. Morton Has Addressed All Issues Raised By FDA.
Notwithstanding Morton's objections, Morton undertook a comprehensive review and evaluation of its sterile compounding operations, and took the following actions to address the issues raised by FDA in the Warning Letter and the Form 483. Please note, Morton's cooperation with FDA should not be interpreted as a waiver of any of the above objections.
In response to both the laming Letter and Form 483, Morton addressed the following:
FDA Bullet Point ("BP") 1
1. Your firm used (b)(4) during aseptic production.
Morton acknowledges the importance of (b)(4) during aseptic production, but would like to provide insight into this observation before responding. The (b)(4) Isolator Hood ("Hood") used by Morton does not specify in its instruction manual that (b)(4) are required for aseptic production. Rather, the Hood's instruction manual only requires the use of (b)(4). A copy of the Hood's instruction manual is attached as Exhibit A. As such, Morton's use of (b)(4), which were sterilized when treated with (b)(4) prior to compounding, is in line with the directions in the Hood's instruction manual. Nonetheless, out of an abundance of caution, Morton implemented the use of (b)(4) on January 23, 2016.
FDA BP 2
2. Your firm did not monitor or document the pressure differential results between the ISO 5 (b)(4), what you refer to as the "clean room," and the ante room.
Morton understands the importance of monitoring pressure differential results between the ISO 5 (b)(4), and believes that its practices and procedures have met the requirements of USP <797> and Wisconsin state law at all relevant times. The Hood observed by FDA during its December 2015 inspection was in a non-ISO class segregated compounding area ("SCA"), which is supplied with HEPA-filtered air in accordance with USP <797>. Further, this Hood operates with an ISO 5 main compounding chamber and pass-thru chamber. The pressure differentials of the Hood’s ISO 5 main chamber to the pass-thru chambers and pass-thru chamber to the unclassified HEPA filtered cleanroom were monitored, but not documented. Out of an abundance of caution, Morton's pressure monitoring policy was updated to require employees to document the pressure differentials in the Hood on January 12, 2016. A copy of the updated policy is attached as Exhibit B. Finally, on February 27, 2016, Morton's cleanroom was certified as ISO 7 and the ante room ISO 8. A copy of the certifications are attached as Exhibit C. Pressure differential monitors were installed as part of the certification process and readings continue to be documented.
FDA BP 3
3. Your firm used (b)(4) non-sterile disinfectants to clean and sanitize the cleanroom area.
Morton objects to FDA BP 3 because it attempts to hold Morton to a cGMP standard that is inapplicable under Section 503A. Specifically, neither USP General Chapter <797> nor the Wisconsin state regulations require Morton's personnel to use sterile disinfectants to clean and sanitize cleanroom areas. Notwithstanding that Morton's use of non-sterile disinfectants complies with all applicable standards, Morton has gone above and beyond USP <797> requirements by replacing non-sterile disinfectant and sporicidal products with sterile alternatives on January 23, 2016.
FDA BP 4
4. Your firm's pharmacy technician had hair, arms, face, and neck exposed to (b)(4) while cleaning the ISO 5 hood.
Morton objects to FDA BP 4 because it attempts to hold Morton to cGMP, a standard that is inapplicable under Section 503A. Specifically, neither USP General Chapter <797> nor the Wisconsin regulations require Morton's pharmacy technician's hair, arms, face, and neck to be covered in the interior of the Hood. Further, the Hood can "maintain ISO Class 5 conditions within the work area when located in worse than an ISO Class 7 environment, as required by USP Chapter <797> (section: Environmental Quality and Control, sub-section: Placement of Primary Engineering Controls) and tested according to CETA CAG 002-2006. ISO Class 5 is maintained during the ingress and egress of materials, during simulated compounding activities, and when subjected to a 1imulated process-generated cross-contamination challenge.'" A copy of the (b)(4) "Maintenance of ISO 5 cleanliness conditions in (b)(4) Barrier Isolators (CAl & CACI) in background conditions as required by USP <797>" letter is attached as Exhibit D. Nevertheless, out of an abundance of caution, Morton updated its policies to require all sterile compounding personnel to wear shoe covers, gown, sterile gloves, mask, and bouffant cap while the Hood is open and being cleaned.
In closing, we would like to emphasize that Morton takes compliance with all applicable federal and state laws governing its pharmacy practice very seriously. Morton shares FDA's goal of ensuring that patients in need of custom compounded medications receive the highest quality preparations. To that end, we respectfully request that the Warning Letter be withdrawn and a closeout letter issued without delay.
Very Truly yours,
1 4-1-1- Warning Letter Procedures, FDA Regulatory Procedures Manual, http://www.fda.gov/ICECI/ComplianceManuals/RegulatoryProceduresManual/ucm176870.htm.