Jacobs Pills, Inc. MARCS-CMS 534441 — May 31, 2018

WARNING LETTER

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• Recipient: Philip E. Altman; Jacobs Pills, Inc.; 250 Clearbrook Road; Elmsford, NY 10523-1305; United States

• Issuing Office: New Jersey District Office; United States

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	Division of Pharmaceutical Quality Operations I 10 Waterview Blvd, 3rd FL Parsippany, NJ 07054 Telephone: (973) 331-4900 FAX: (973) 331-4969

Via UPS

WARNING LETTER
CMS # 534441

May 31, 2018

Philip E. Altman, Supervising Pharmacist
Jacobs Pills, Inc.
dba The Healthy Choice Apothecary
250 Clearbrook Road
Elmsford, NY 10523-1305

Dear Mr. Altman:

From February 22, 2017, to February 28, 2017, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Jacobs Pills, Inc. dba The Healthy Choice Apothecary, located at 250 Clearbrook Road, Elmsford, NY 10523-1305. 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. In addition, the investigator noted serious deficiencies in your practices for producing non-sterile drug products, which put patients at risk.

FDA issued a Form FDA 483 to your firm on February 28, 2017. FDA acknowledges receipt of your facility’s response, dated March 15, 2017. 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 practices (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 collected evidence that indicates:

1. Your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced.

2. Your firm compounded drug products using melatonin. Drug products compounded using melatonin are not eligible for the exemptions provided by section 503A(a), because melatonin is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved human drug, and does 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 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 manufacture of ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigator observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations included, for example:

1. Your firm failed to reject any lot of components that did not meet the appropriate written specifications for identity, strength, quality, and purity (21 CFR 211.84(e)).

2. Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).

3. Your firm failed to establish and follow adequate written procedures designed to assure batch uniformity and integrity of drug products that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch (21 CFR 211.110(a)).

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.

Unapproved New Drug Products

You do not have any FDA-approved applications on file for the ineligible drug products that you compounded.3 Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. § 331(d)], a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.

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.4 The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA. It is also 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.

D. Production of Domperidone

We note that between January and March 2016 you compounded and distributed domperidone products. Drug products compounded using domperidone are not eligible for the exemptions provided by section 503A of the FDCA. Our review of your records indicates that you have not compounded domperidone products since that time.

E. Corrective Actions

We have reviewed your firm’s response to the Form FDA 483.

As explained above, section 503A of the FD&C Act describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist in a State-licensed pharmacy or Federal facility, or by a licensed physician, to be exempt from the following three sections of the FD&C Act: section 505 (concerning the approval of drugs under new drug applications or abbreviated new drug applications); section 502(f)(1) (concerning the labeling of drugs with adequate directions for use); and section 501(a)(2)(B) (concerning current good manufacturing practice requirements). Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A. Additionally, for a compounded drug product to qualify for the exemptions in 503A, bulk drug substances used to compound it must: comply with an applicable USP or NF monograph, if a monograph exists; if such a monograph does not exist, be a component of an FDA-approved human drug, or; if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appear on the 503A bulks list. Your firm appears to have failed to meet these conditions 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.5

In addition to the issues discussed above, 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)].

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

F. 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 the violations. Please include an explanation of each step being taken to prevent the recurrence of the 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 (534441). Please address your reply to:

Ernest F. Bizjak
Compliance Officer,
FDA/OPQ Div 1
11919 Rockville Pike
Rockville, MD 20852

If you have questions regarding the contents of this letter, please contact Ernest Bizjak, Compliance Officer, by telephone at 301-796-4081, or by email at Ernest.Bizjak@fda.hhs.gov.

Sincerely,
/S/

Diana Amador Toro
Division Director/OPQ Division 1
New Jersey District Office 

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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. Melatonin was nominated for inclusion on the 503A bulks list. It has been identified as a substance that was not nominated with adequate support for FDA to evaluate the substance. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.

3 The specific products made by your firm are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) [21 U.S.C. 321(p)] of the FDCA because they are not generally recognized as safe and effective for their labeled uses.

4 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).

5 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.