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WARNING LETTER
WL # 612459

August 26, 2021

FEI 3008231170

Dear Ms. Ferrari:

You registered your facility 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 January 24, 2014, and most recently on December 19, 2018. Your facility’s registration as an outsourcing facility was withdrawn on July 5, 2019.

From May 6, 2019, to June 25, 2019, FDA investigators inspected your facility, Infusion Options, Inc. located at 5924 13th Avenue, Brooklyn, NY 11219. Additionally, from May 30, 2019, to June 25, 2019, FDA investigators inspected the warehouse belonging to your facility, located at 745 64th Street, Brooklyn, NY 11219. During the inspections, the investigators 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 investigators noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.

At the conclusion of the inspections, FDA issued a Form FDA 483 to your facility and to your facility’s warehouse on June 25, 2019. An amended Form FDA 483 was issued to your facility on July 8, 2019.

FDA acknowledges receipt of your firm’s responses, dated July 16, 2019, July 29, 2019, August 29, 2019, and September 27, 2019, as well as additional correspondence regarding corrective actions taken dated August 22, 2019, August 23, 2019, August 26, 2019, August 28, 2019, September 27, 2019, October 29, 2019, and November 26, 2019. We also acknowledge that on June 12, 2019, your firm initiated a voluntary recall of all sterile products within expiry due to lack of sterility assurance. In addition, we acknowledge your statement that “your facility permanently discontinued 503B compounding on June 11, 2019,” and that you de-registered as an outsourcing facility on July 5, 2019. Furthermore, we have noted your correspondence (submitted by your counsel) on October 30, 2020 acknowledging, among other things, that Infusion Options terminated its lease at 745 64th Street, Brooklyn, NY 11219, and does not intend to resume operations of any kind at this location, and additionally, that while Infusion Options continues to own or lease space at 5924 13th Avenue, Brooklyn, NY 11219, you intend to discontinue any and all pharmacy-related activities at this location.

Based on these inspections, it appears that, during the time your facility was registered as an outsourcing facility, you produced drugs that violate the FDCA.

A. Compounded Drug Products under the FDCA

Under section 503B(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

An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that —(i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.

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)]). For example, for a compounded drug product to qualify for the exemptions, the label of the drug must include: the statement “This is a compounded drug.” (§ 503B(a)(10)(A)(i)), and, with respect to the drug, the lot or batch number, the date that the drug was compounded, and the statement “Not for resale” (§ 503B(a)(10)(A)(iii)(I), (V), (IX)). Furthermore, for a compounded drug product to qualify for the exemptions, the container from which the individual units of the drug are removed for dispensing or administration must include the following information to facilitate adverse event reporting: www.fda.gov/medwatch and 1-800-FDA-1088 (§ 503B(a)(10)(B)(ii)).

Further, 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) including 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)]).]

B. Failure to Meet the Conditions of Section 503B

During the inspection, FDA investigators noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigators noted:

1. Some of your facility’s drug products did not include the following statements on the label: “This is a compounded drug,” “not for resale,” the date of compounding, and the lot or batch number. Some of your facility’s drug products did not include the following information on the container: information to facilitate adverse event reporting, http://www.fda.gov/medwatch and 1-800-FDA-1088.

2. Your facility failed to submit reports to FDA in June 2014, December 2016, December 2017, June 2018, December 2018, and June 2019, identifying the drug products that you compounded during the previous 6-month period.

Because your compounded drug products did not meet all of the conditions of section 503B, they were not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.

Specific violations are described below.

C. Violations of the FDCA

Adulterated Drug Products

FDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigators observed:

• poor aseptic techniques and cleanroom behavior,
• drugs requiring temperature-controlled conditions stored on the floor of a bathroom that appeared to be actively used as such,
• drug products stored on the floor of your warehouse under filthy and uncontrolled temperature/humidity conditions,
• HEPA filters in International Organization for Standardization (ISO) 5 laminar flow hoods with stains, and
• additional residue and staining inside an ISO 5 laminar flow hood.

FDA investigators also noted CGMP violations at your facility, that caused your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:

1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
2. Your firm failed to follow written procedures regarding storage and warehousing of drug products (21 CFR 211.142).
3. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).
4. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
5. Your firm failed to follow written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(b)).
6. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
7. Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.42(c)(10)).
8. Your firm failed to ensure that only personnel authorized by supervisory personnel enter those areas of the buildings and facilities designated as limited-access areas (21 CFR 211.28(c)).
9. Your firm failed to ensure that aseptic processing areas include floors, walls, and ceilings of smooth, hard surfaces that are easily cleanable (21 CFR 211.42(c)(10)(i)).
10. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
11. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance, Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.

It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.

Misbranded Drug Products

You compounded drug products intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling failed to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FDCA.³ It is a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.

Failure to Report Drugs

As noted above, your facility failed to submit a report to FDA in June 2014, December 2016, December 2017, June 2018, December 2018, and June 2019, identifying the drug products that you compounded during the previous 6-month period (section 503B(b)(2) of the FDCA). 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)].

D. Corrective Actions

We have reviewed your facility’s responses to the Form FDA 483s. We acknowledge your statement that “your facility permanently discontinued 503B compounding on June 11, 2019,” and that you deregistered as an outsourcing facility on July 5, 2019. We also have noted your correspondence (submitted by your counsel) on October 30, 2020, acknowledging that Infusion Options terminated its lease at 745 64th Street, Brooklyn, NY 11219, and does not intend to resume operations of any kind at this location, and additionally, that while Infusion Options continues to own or lease space at 5924 13th Avenue, Brooklyn, NY 11219, you intend to discontinue any and all pharmacy-related activities at this location.

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).]

FDA strongly recommends that if you decide to resume production, holding, or distribution of sterile drug products, your management first undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.

We have addressed certain corrective actions and other statements in your responses to the FDA Form 483 in the event you resume compounding drug products under section 503A or section 503B.

Regarding observations related to the conditions of section 503B of the FDCA, we acknowledge your statement that reporting requirements in section 503B(b) “pertain only to products that are compounded as 503B drugs, and therefore, …these reporting requirements will not apply” in the event you resume compounding drug products under section 503A. We also acknowledge your statement that labeling conditions in section 503B(a)(10) “pertain only to products that are compounded as 503B drugs, and therefore, …these labeling requirements will not apply” in the event you resume compounding drug products under section 503A.

Further, if you wish to resume compounding, please note that section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].⁴ Receipt of valid prescriptions for individually identified patients is one of the conditions for the exemptions under section 503A. Another condition is that the licensed pharmacist or licensed physician preparing the compounded drug product does not compound a drug product that appears on the withdrawn or removed list (section 503A(b)(1)(C)).

If the drug products you compound do not meet the conditions of section 503A, the compounding and distribution of such drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the drug CGMP regulations.

Should you re-register your facility as an outsourcing facility in the future and resume compounding and distribution of drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.

Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A or 503B of the FDCA.

E. Conclusion

The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

If you decide to resume production, holding, or distribution of drug products, you should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.

Within fifteen (15) working days of receipt of this letter, please acknowledge receipt of this letter and confirm in writing your continuing intention to not resume production, holding, or distribution of drug products. If you intend to resume such activities in the future, please include a current and updated 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 the products discussed above were in violation of the FDCA, include your reasoning and any supporting information for our consideration. In addition to taking appropriate corrective actions, you should notify this office fifteen (15) working days prior to resuming production, holding, or distribution of drug products in the future.

Send your electronic response to [email protected]. Please identify your response with FEI # 3008231170 and refer to Warning Letter #612459.

If you have any questions, contact Compliance Officer Juan Jimenez at [email protected] or call 1-518-453-2314 X-1014.

/S/
Diana Amador-Toro
Program Division Director/District Director
U.S. Food and Drug Administration
OPQO Division I / New Jersey District

_____________________________

1 See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).

2 We remind you that there are conditions, other than those discussed in this letter, that must be satisfied to qualify for the exemptions in section 503B of the FDCA.

3 Your compounded drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).

4 We remind you that there are conditions other than those discussed in this letter that must be satisfied to qualify for the exemptions in section 503A of the FDCA.