Inspections, Compliance, Enforcement, and Criminal Investigations

Beacon Hill Medical Pharmacy, P.C. 9/24/14

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Detroit District
300 River Place
Suite 5900
Detroit, Ml 48207
Telephone: 313-393-8100
FAX: 313-393-8139 

 

WARNING LETTER

2014-DET-17

September 24, 2014

 
 
VIA UPS
DELIVERY SIGNATURE REQUESTED
 
 
Dr. Wisam (NMI) Alawieh, Pharm.D.
President and CEO
Beacon Hill Medical Pharmacy, P.C.
(dba) Rxtra Solutions Labs
18161 W. 13 Mile Road, Suite A1
Southfield, MI 48076-1113
 
Dear Dr. Alawieh:
 
From July 1, 2013, to July 19, 2013, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Beacon Hill Medical Pharmacy, P.C., located at 18161 W 13 Mile Rd., Suite A1, Southfield, Michigan, 48076. During the inspection, the investigators noted that you were not receiving valid prescriptions for individually-identified patients for a portion of the drug products you were producing. In addition, the investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk.  For example, our investigators observed that you clean the (b)(4) (an area used toperform aseptic operations) with soap, tap water, and non-sterile disinfectants. In addition, non-sterile gloves were used to manually stopper vials, and partially stoppered, aseptically filled vials were transferred unprotected to a table in an unclassified area. Furthermore, our investigators found that your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk. These observations and others were noted on a Form FDA 483, issued on July 19, 2013.
 
Based on this inspection, it appears that you have produced drugs that violate the Federal Food, Drug, and Cosmetic Act (FDCA).  
 
A. Compounded Drugs Under the FDCA
 
At the time FDA inspected your facility, there were conflicting judicial decisions regarding the applicability of section 503A of the FDCA [21 U.S.C. § 353a], which exempts compounded drugs from several key statutory requirements if certain conditions are met.[1] Nevertheless, receipt of valid prescriptions for individually-identified patients prior to distribution of compounded drugs was relevant for both section 503A of the FDCA and the agency’s Compliance Policy Guide 460.200 on Pharmacy Compounding (CPG) (2002), which was then in effect.[2] During the FDA inspection, investigators observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce. Based on this factor alone, those drugs were not entitled to the statutory exemptions for compounded drugs described in section 503A of the FDCA and did not qualify for the agency’s exercise of enforcement discretion set forth in the CPG.[3] 
 
Since FDA inspected your facility, Congress enacted and the President signed into law the Compounding Quality Act (CQA)[4], which amended FDCA section 503A by eliminating the advertising restrictions that had been the basis for conflicting judicial decisions.  The CQA otherwise left section 503A intact, and so clarified that the remainder of section 503A, including the requirement of valid prescriptions for individually-identified patients, is applicable in every federal judicial circuit.  Accordingly, the drugs you compound without valid prescriptions for individually identified patients are not entitled to the exemptions in section 503A.[5]
 
In addition, we remind you that there are a number of other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA.[6]
 
B. Violations of the FDCA
 
Because the drug products you manufacture and distribute without valid prescriptions for individually-identified patientsare not the subject of approved applications, they are unapproved new drugs and misbranded drugs in violation of sections 505(a) and 502(f)(1) [21 U.S.C. §§ 355(a) and 352(f)(1)] of the FDCA, respectively. In addition, your sterile drug products are prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health. As such, all sterile products you manufacture are adulterated within the meaning of section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)] of the FDCA. Furthermore, because you manufacture and distribute a portion of your drugs without valid prescriptions for individually-identified patients, the manufacture of those drugs is also subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211 (21 CFR 210 and 211). FDA investigators observed significant CGMP violations at your facility, causing such drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)]. 
 
Unapproved New Drug Products
 
You do not have any FDA-approved applications on file for the drug products for which you have not obtained valid prescriptions for individually-identified patients.[7]  Under sections 301(d) and 505(a) of the FDCA [21 U.S.C. §§ 331(d) and 355(a)], 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 [21 U.S.C. § 355] is in effect for the drug.  Your marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.
 
Misbranded Drug Products
 
Additionally, because the drug products for which you have not obtained valid prescriptions for individually-identified patients are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written for them 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, causing them to be misbranded under section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)], and they are not exempt from the requirements of section 502(f)(1) of the FDCA (see ,e.g., 21 CFR § 201.115).  The introduction or delivery for introduction into interstate commerce of these products therefore violates sections 301(a) of the FDCA [21 U.S.C. § 331(a)].   It is also 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 of the components used to make the drug and results in the drug being misbranded.
 
Adulteration Charges
 
Additionally, FDA investigators noted that your sterile drug products 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, our investigators observed that you clean the (b)(4) (an area used to perform aseptic operations) with soap, tap water, and non-sterile disinfectants. In addition, non-sterile gloves were used to manually stopper vials, and partially stoppered, aseptically filled vials were transferred unprotected to a table in an unclassified area. Furthermore, our investigators found that your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
FDA investigators also noted CGMP violations at your facility, causing the drug products for which you have not obtained valid prescriptions for individually-identified patients to be adulterated under 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 establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
 
3.    Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
 
4.    Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
 
5.    Your firm failed to establish an adequate air supply filtered through high-efficiency particulate air filters under positive pressure in the aseptic processing areas (21 CFR 211.42(c)(10)(iii)).
 
6.    Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a))
 
7.    Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).  
 
Under section 301(a) of the FDCA 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 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 of the components used to make the drug and results in the drug being adulterated.
 
C. Corrective Actions
 
We acknowledge your action on July 26, 2013, to recall certain sterile products. In your August 9, 2013, response to the Form FDA 483 you indicated that you suspended production of sterile injectable suspension products. In this response, you referenced the United States Pharmacopeia (USP)-National Formulary (NF) General Chapter <797> Pharmaceutical Compounding--Sterile Preparations as providing guidance to your Standard Operating Procedures (SOPs). As noted above, your firm manufactures and distributes drugs without valid prescriptions for individually-identified patients, and the manufacture of such drugs is subject to FDA’s drug CGMP regulations (21 CFR 210 and 211). 
 
During a teleconference on September 24, 2013, among other things, FDA notified you that your response to the Form FDA 483 received on August 9, 2013, was inadequate: specifically, it lacked sufficient detail for FDA to assess the firm’s compliance. 
 
On September 25, 2013, you provided a 714-page supplemental response to FDA’s request for additional documentation. Upon review, FDA found your supplemental submission insufficient in that it lacked critical details concerning your firm’s activities, and it still did not adequately address the deficiencies outlined in the Form FDA 483 issued on July 19, 2013.
 
During a teleconference on October 23, 2013, FDA asked you to voluntarily cease sterile production until further notice because FDA did not agree with your decision to resume sterile production on or around September 5, 2013. During that teleconference, you made it clear that you would not cease sterile operations at that time. A visit to your firm by FDA investigators on January 16, 2014, revealed that the firm ceased sterile compounding at the end of November 2013, and management stated that the firm would close within a few weeks. An e-mail from your attorney, Mr. Kim J. Sveska, dated January 21, 2014, asserted that your firm planned to cease all operations and formally close as of February 16, 2014. However, on June 6, 2014, you confirmed in an e-mail to Dr. Tina Pawlowski, FDA Compliance Officer, that although your firm is not producing sterile drug products, it is “attempting to utilize this time to salvage non-sterile business and is “in the process of winding down its business operations…to terminate the business incorporation in its entirety.”
 
FDA strongly recommends that if you decide in the future to resume production of sterile drugs, your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise could be useful in conducting this comprehensive evaluation. 
 
As noted above, your firm has manufactured and distributed drugs without valid prescriptions for individually-identified patients, and the manufacture of such drugs is subject to FDA’s drug CGMP regulations, 21 CFR Parts 210 and 211. Before resuming such operations, you should fully implement corrections that meet the minimum requirements of 21 CFR Part 211 in order to provide assurance that the drug product(s) produced by your firm conform to the basic quality standards that ensure safety, identity, strength, quality, and purity. 
 
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 FDCA, as amended by the Food and Drug Administration Safety and Innovation Act (Pub.L. 112-144, Title VII, section 711). We note that you have chosen to hire a contract testing laboratory to perform some of the required testing of your finished drug products. FDA inspected this laboratory in 2013 and observed deficiencies in its practices. 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 introduce into interstate commerce are neither adulterated nor misbranded. See 21 CFR 210.1(b), 21 CFR 200.10(b).
 
In addition, you should also correct the violations of FDCA sections 505, 502(f)(1), and 501(a)(2)(A) noted above.  
 
D. 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 and FDA regulations.
 
If you decide to resume sterile operations, 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. FDA may re-inspect to verify corrective actions have been completed.
 
Within fifteen working days of receipt of this letter, please notify this office in writing if you have taken any specific steps to correct violations, 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 the products discussed above are 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 prior to resuming production of any sterile drugs in the future. Your written notification should be addressed to: 
 
Tina M. Pawlowski, Ph.D.
Compliance Officer
U.S. Food and Drug Administration
300 River Place, Suite 5900
Detroit, MI 48207
 
If you have questions regarding the contents of this letter, please contact Dr. Tina Pawlowski, Compliance Officer, at (313) 393-8217.
 
Sincerely,
/S/ 
Art O. Czabaniuk
District Director
Detroit District Office 
 
 
[1] Compare Western States Med. Ctr. v. Shalala, 238 F.3d 1090 (9th Cir. 2001) with Medical Ctr. Pharm. v. Mukasey, 536 F.3d 383 (5th Cir. 2008).
[2] The CPG set forth a non-exhaustive list of factors that FDA considered in determining whether to take enforcement action when the scope and nature of a pharmacy's activities raised concerns. This CPG has been withdrawn in light of new legislation. See below.
[3] See 21 U.S.C. § 353a(a) (granting compounded drugs statutory exemptions if, among other things, “the drug product is compounded for an identified individual patient based on the . . . receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient . . . .”); CPG at 2 (“FDA recognizes that pharmacists traditionally have extemporaneously compounded and manipulated reasonable quantities of human drugs upon receipt of a valid prescription for an individually-identified patient from a licensed practitioner. This traditional activity is not the subject of this guidance.”).
[4] Drug Quality and Security Act, Public Law 113-54, 127 Stat. 587 (Nov. 27, 2013).
[5]The CQA contains a number of other provisions, including new exemptions and requirements for compounders seeking to operate as outsourcing facilities. A discussion of the CQA and the agency’s plans to implement the new law may be found at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.
[6] For example, section 503A also addresses anticipatory compounding, which includes compounding (not dispensing) before receipt of a valid prescription order for an individual patient. We are not addressing anticipatory compounding here.
[7] 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. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses. 

 

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