Source: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/bella-pharmaceuticals-inc-572550-02112019
Timestamp: 2020-07-08 11:16:12
Document Index: 586863559

Matched Legal Cases: ['§ 353', '§ 353', '§ 355', '§ 352', '§ 360', '§ 356', '§ 353', '§353', '§353', '§353', '§ 353', '§ 331']

Bella Pharmaceuticals, Inc. - 572550 - 02/11/2019 | FDA
Bella Pharmaceuticals, Inc. - 572550 - 02/11/2019
Bella Pharmaceuticals, Inc. MARCS-CMS 572550 — February 11, 2019
Michael B. Younan
4301 Regency Dr.
Case# 572550
Dear Mr. Younan:
You registered with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b][1] on February 23, 2017. Although, as of the date of this letter, your facility is no longer registered as an outsourcing facility, this letter discusses violations identified during the time you were registered as an outsourcing facility.
From June 10, 2017 to July 18, 2017, an FDA investigator inspected your facility, Bella Pharmaceuticals, Inc., 3101 W. Devon Avenue, Chicago, IL 60659-1407. During the inspection, the investigator noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigator noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your facility on July 18, 2017. FDA acknowledges receipt of your facility’s response, dated August 4, 2017. On August 15, 2017, you voluntarily recalled all sterile drug products distributed between April 17, 2017 and August 10, 2017 that were within expiry, and ceased sterile drug production until adequate corrective actions were implemented to correct lack of sterility assurance. Based on this inspection, it appears you produced drugs that violate the FDCA.
Under section 503B(b) [21 U.S.C. § 353b(b)] of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.[2]
In addition, for a compounded drug product to qualify for the exemptions under section 503B, bulk drug substances used to compound it must appear on a list established by the Secretary identifying bulk drug substances for which there is a clinical need (“503B bulks list”), or that appear on the drug shortage list in effect under section 506E [21 U.S.C. § 356e] of the FDCA at the time of compounding, distribution, and dispensing (section 503B(a)(2)(A)(i) of the FDCA [21 U.S.C. § 353b(a)(2)(A)(i)]).
Furthermore, for a compounded drug product to qualify for the exemptions under section 503B, the labeling of the drug must include certain information (section 503B(a)(10) of the FDCA [21 U.S.C. §353b(a)(10)]).
Lastly, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b) [21 U.S.C. §353b(b)]. This includes the requirement to submit a report to FDA upon initially registering as an outsourcing facility, once in June of each year, and once in December of each year identifying the drug products compounded during the previous 6-month period (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]).
1. Your facility compounded a drug product using Fluorescein Sodium. Drug products compounded using Fluorescein Sodium are not eligible for the exemptions provided by section 503B because Fluorescein Sodium does not appear on the 503B bulks list, and is not used to compound a drug that appears on the drug shortage list. [3]
2. Some of your facility’s drug products did not include the following statements on the label: “This is a compounded drug”, “Not for Resale”, “Office use only”, your facility phone number, dosage form, the date of compounding, specific storage and handling instructions, and a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingredient. Some of your facility’s drug products did not include the following information on the container: Information to facilitate adverse event reporting and route of administration.
3. Your facility failed to submit reports to FDA in February 23, 2017 upon initial registration as an outsourcing facility, and in June 2017 identifying the drug products that you compounded during the previous 6-month period.
During the prefilling of syringes of sterile drug product, your firm’s Chief Pharmacist did not sanitize the exterior of any of the components before introducing them into the ISO 5 classified area or prior to putting them in the (b)(4).
Your firm used non-pharmaceutical grade sterilizing (b)(4).
Your firm used a broad-spectrum hard surface disinfectant that was not labeled as sporicidal or sterile as the sole sanitizing agent for sanitizing the ISO 5 classified area.
Your firm used disposable towels that were not non-shedding when cleaning and sanitizing the ISO 5 classified aseptic processing area.
Your firm did not use any media fill simulations to validate aseptic filling operations. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.
Your firm’s (b)(4), which is (b)(4) just outside the (b)(4) of the ISO 5 classified (b)(4) Room, was observed to be dusty. Also, our investigators observed that stained transparent packing tape was used to cover the (b)(4) the (b)(4) and the (b)(4) Room.
The floor in the IV Room, which is considered an IS0 5 classified area, is a laminate floating floor that shows chipping.
Your firm’s employee was observed with exposed skin around the eyebrow, eyes, neck, and/or wrist during aseptic processing.
1. Procedures designed to prevent objectionable microorganisms in drug products required to be sterile are not established, written, or followed. [21 CFR 211.113(b)]
2. Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions. [21 CFR 211.42(c)(10)(v)]
3. Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. [21 CFR 211.42(c)(10)(iv)
4. The finished product testing for product release does not include an appropriate laboratory determination of satisfactory conformance to final specification for the drug product, including identity and strength. [21 CFR 211.165(a)
5. Clothing of personnel engaged in the compounding, processing, packing, and holding of drug products purporting to be sterile is not appropriate for the duties they perform. [21 CFR 211.28(a)
As noted above, your facility failed to submit a report to FDA upon initial registration as an outsourcing facility in February, 2017, and again in June, 2017, identifying the drug products that you compounded during the previous 6-month period (section 503B(b)(2) of the FDCA [21 U.S.C. § 353b(b)(2)]). The failure to report drugs by an entity that is registered with FDA in accordance with section 503B(b) is a prohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].
We have reviewed your facility’s responses to the Form FDA 483. We acknowledge your voluntary recall of all sterile drug products distributed by your firm, from April 17, 2017, to August 10, 2017, remaining within expiry. We also acknowledge that you ceased sterile drug production until adequate corrective actions could be implemented.
We are unable to fully evaluate the adequacy of the following corrective actions due to lack of supporting documentation:
1. You state that you now have a log book next to each (b)(4) to record all sterilizing cycles, dates, and materials, but you did not provide any updated standard operation procedures (SOPs), training records or copy of the log book. In addition, your response did not include an updated procedure with the current validated (b)(4) cycles, calibration frequencies, maintenance, and general use of the (b)(4).
2. You state that you now have a log book to document all dates and times of sanitizing rooms, but you did not provide any updated cleaning SOPs. In addition, your response did not include a list of the newly purchased sporicidal disinfectants and efficacy studies to support established contact time.
3. You state that your firm has obtained a (b)(4) for your clean room to (b)(4) prior to making any sterile preparations; however, you did not provide a revised SOP or training records for the use of the equipment.
4. You state that your firm will be conducting potency, endotoxin, suitability, and sterility testing on all lots, but you did not provide current testing results, lot sample numbers, validation protocols or updated testing SOPs.
5. You state that sterile gowns and proper protective gear have been procured, but you did not provide any updated gowning SOPs or gowning training records.
6. You state that your product labeling has been corrected to include all of the information required under section 503B, but you did not provide any samples of the labeling.
In addition to the issues discussed above, should you decide to re-register as an outsourcing facility, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b)]
Within fifteen (15) working days of receipt of this letter, please notify this office in writing if you have taken any specific steps to correct the violations cited in this letter, or you may inform us that you do not intend to resume production of sterile drugs. If you intend to resume production of sterile drugs in the future, please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that products discussed above violated the FDCA, include your reasoning and any supporting information for our consideration. In addition to taking appropriate corrective actions, you should notify this office 15 days prior to resuming production of any sterile drugs in the future.
Please address your reply via email to: ORAPHARM3_RESPONSES@fda.hhs.gov
Division of Pharmaceutical Quality Operations Division III
Your written notification should refer to the Warning Letter Number above (Case# 572550). If you have questions regarding the contents of this letter, please contact Russell Riley at (630) 323-2763 ext. 101.
[3] On June 9, 2016, FDA issued a final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s interim regulatory policy for outsourcing facilities registered under section 503B of the FDCA while the 503B bulks list is being developed. Specifically, the guidance sets out conditions under which FDA does not intend to take action against an outsourcing facility for compounding a drug product using a bulk drug substance that is not included on the 503B list and does not appear on the drug shortage list in effect under section 506E at the time of compounding, distribution, and dispensing until the substance is identified in a final rule as included or not included on the 503B bulks list. These conditions include that the substance may be eligible for inclusion on the 503B bulks list, was nominated with adequate support for FDA to evaluate it, and has not been identified by FDA as a substance that appears to present significant safety risks pending further evaluation. Fluorescein Sodium was not nominated. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469122.pdf