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  5. La Vita Compounding Pharmacy, LLC - 575286 - 02/28/2019
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WARNING LETTER

La Vita Compounding Pharmacy, LLC MARCS-CMS 575286 — 28/02/2019

La Vita Compounding Pharmacy, LLC - 575286 - 02/28/2019

Product:
Drugs

Recipient:
Recipient Name
Christine Givant
Recipient Title
Pharmacist-In-Charge
La Vita Compounding Pharmacy, LLC

3978 Sorrento Valley Boulevard, Suite 300
San Diego, CA 92121-1436
United States

Issuing Office:
Division of Pharmaceutical Quality Operations IV

19701 Fairchild
Irvine, CA 92612-2506
United States

(949) 608-2900

WARNING LETTER

 

VIA SIGNATURE CONFIRMED DELIVERY

 

February 28, 2019

 

Christine Givant

Pharmacist-In-Charge

La Vita Compounding Pharmacy, LLC

3978 Sorrento Valley Boulevard, Suite 300

San Diego, CA 92121-1436

 

Dear Ms. Givant:

From June 4, 2018, to June 8, 2018, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, La Vita Compounding Pharmacy, LLC, located at 3978 Sorrento Valley Blvd, Suite 300, San Diego, CA 92121. During the inspection, the investigator noted that drug products you produced failed to meet the conditions of section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a] for exemption from certain provisions of the FDCA.  Additionally, 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 firm on June 8, 2018. FDA acknowledges receipt of your facility’s response, dated June 28, 2018, and your subsequent correspondence. Additionally, FDA acknowledges that on June 22, 2018, your firm voluntarily ceased sterile production and on June 25, 2018, voluntarily recalled all drug products intended to be sterile within expiry.

Based on this inspection, it appears that you produced drug products that violate the FDCA.

 A.   Compounded Drug Products Under the FDCA

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)].[1] Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A. 

In addition, for a compounded drug product to qualify for the exemptions under section 503A, bulk drug substances used to compound it must: (I) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (II) if such a monograph does not exist, be components of drugs approved by the Secretary; or (III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appear on a list developed by the Secretary through regulation (“503A bulks list”) (section 503A(b)(1)(A)(i) of the FDCA).

B.   Failure to Meet the Conditions of Section 503A

During the inspection, the FDA investigator noted that drug products produced by your firm failed to meet the conditions of section 503A. Specifically, the investigator noted that your firm compounded drug products using grape seed oil, green tea extract, hyaluronic acid and dimethylaminoethanol bitartrate. Drug products compounded using grape seed oil, green tea extract, hyaluronic acid and dimethylaminoethanol bitartrate are not eligible for the exemptions provided by section 503A(a), because these bulk dug substances are not the subject of an applicable USP or NF monograph, are not components of FDA-approved human drugs and do not appear on the 503A bulks list.[2]

Therefore, you compounded drug products that do not meet the conditions of section 503A and are not eligible for the exemptions in that section from the FDA approval requirement of section 505 of the FDCA, the requirement under section 502(f)(1) of the FDCA that labeling bear adequate directions for use, and the requirement of compliance with CGMP under section 501(a)(2)(B) of the FDCA. In the remainder of this letter, we refer to your drug products that do not qualify for exemptions under section 503A as the “ineligible drug products.”

Specific violations are described below. 

C.   Violations of the FDCA

 Adulterated Drug Products

The FDA investigator 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, 

  1. Your firm produced drug products while construction was underway without adequate controls to prevent contamination of the production environment and products.
  1. Animals were observed in areas adjacent to the production areas. Specifically, multiple dogs were on site in the office of the pharmacist in charge that is in the same suite of the production areas.
  1. The ISO classified aseptic processing areas had difficult to clean, particle generating, and visibly dirty equipment.  Specifically, the investigator observed the following in the ISO classified areas: unsealed ceiling tiles and gaps between the tiles; broken plastic cover of a light fixture; a rust-colored discoloration on the HEPA grate; visible dust and dirt on top of the ISO 5 hood and on the frame and door of the (b)(4); and, visible dust and dirt on the door and (b)(4) of the (b)(4). In addition, the (b)(4) located between the ISO 8 anteroom and ISO 7 cleanroom appears to be made of particle board which is particle-generating, not easily cleanable, and may harbor contamination.
  1. Non-medical grade containers were used to store (b)(4) and (b)(4),” which were used in the production of non-sterile drug products.
  1. Within the non-sterile production area, our investigator observed powder residue on work surfaces, utensils, and equipment, which were inadequately cleaned to prevent cross-contamination.

Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, 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

The ineligible drug products you compounded are 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 fails to bear adequate directions for their intended uses.[3] Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA. 

D.   Corrective Actions

We have reviewed your firm’s responses to the Form FDA 483. We also acknowledge your September 5, 2018, letter indicating that you would resume sterile production on September 10, 2018. 

Regarding the insanitary condition observations noted during the inspection, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation: 

  1. You provided a one-page summary report to demonstrate that “La Vita’s sterile pharmacy met all acceptance criteria and is in compliance with USP <797>.” However, you did not provide adequate documentation, such as the full detailed report.
  1. In response to the broken light cover and unsealed ceiling tile observed in the cleanroom, you stated that the whole ceiling in both ISO 7 and ISO 8 rooms was resealed and that “the light cover was replaced.” However, you did not provide supporting documentation such as the type of ceiling sealant utilized.
  1. In response to the visible dust and dirt in the ISO 7 cleanroom, you stated that you cleaned these areas and updated your cleaning procedures to include these areas in the future and are in the process of training employees on the SOP. However, you did not provide adequate supporting documentation such as the updated cleaning SOP(s), revised cleaning logs, and did not provide a timeframe for the completion of training.
  1. In response to the non-medical grade containers that were used to store (b)(4) and (b)(4) observation, you stated that you were in the process of purchasing glass containers for storing (b)(4) and will “change our procedures to reflect the use of only glass bottles.” However, you did not provide your interim corrective actions before the new containers are purchased. In addition, you did not provide supporting documentation to demonstrate that these glass containers are suitable for drug storage, and you did not provide the updated procedures, training materials, and training records.

The following corrective action appears inadequate to address the insanitary conditions noted:

The cleaning agents used on “glassware and washable equipment/devices” for non-sterile drug production do not appear to be adequate. For example, your procedure (SOP No. 3.30.2.1, “Cleaning of Non-Sterile (b)(4)”) indicates that only (b)(4) and (b)(4) are used to clean equipment. These cleaning agents do not deactivate hazardous and potent drugs. You do not have dedicated “glassware and washable equipment/devices” for hazardous drugs, therefore, we remain concerned that your practice may cause cross-contamination if these items are not adequately cleaned.

For more information on compounding, please see FDA’s website, at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.  

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, including the condition on compounding drug products using a bulk drug substance that complies with an applicable USP or NF monograph, is a component of an FDA-approved human drug or appears on the 503A bulks list.

As explained above, the compounding of drug products using a bulk drug substance that complies with an applicable USP or NF monograph, is a component of an FDA-approved human drug or appears on the 503A bulks list are conditions of section 503A, which your firm failed to meet for a portion of the drug products you produced.

Should you continue to compound and distribute drug products that 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. Before doing so, you must comply with the requirements of section 505 and 502(f)(1) and fully implement corrections that meet the minimum requirements of the CGMP regulations. 

FDA strongly recommends that your management first undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems.  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.

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 the violations identified above 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.

You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these 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 notify this office in writing of the specific steps that you have taken to correct violations. 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 the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.

Your written notification should refer to the Warning Letter Number above (575286). Please address your written response to:

CDR Steven E. Porter, Jr.

Director, Division of Pharmaceutical Quality Operations IV

U.S. Food & Drug Administration

19701 Fairchild Road

Irvine, California 92612-2506

If you have questions regarding the contents of this letter, please contact Mariza Jafary, Compliance Officer via email at Mariza.Jafary@fda.hhs.gov or by telephone at 949-608-2977 and reference unique identifier 575286.

 

Sincerely,

/S/

CDR Steven E. Porter, Jr.

Director, Division of Pharmaceutical Quality Operations IV

 

[1] 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.

[2] On June 9, 2016, FDA issued a final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s interim regulatory policy for State-licensed pharmacies, Federal facilities, and licensed physicians that compound human drug products using bulk drug substances that do not otherwise meet the conditions of section 503A(b)(1)(A)(i) while the 503A bulks list is being developed. Specifically, the guidance sets out the conditions under which FDA does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, until the substance is identified in a final rule as included or not included on the 503A bulks list. These conditions include that the substance may be eligible for inclusion on the 503A 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. Grape seed oil, hyaluronic acid, and dimethylaminoethanol were nominated for inclusion on the 503A bulks list without adequate support to evaluate the substances. Green tea extract was not nominated for inclusion on the 503A bulks list. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf

[3] Your ineligible 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).