Inspections, Compliance, Enforcement, and Criminal Investigations

OPS International Incorporated D/B/A Olympia Pharmacy 2/4/16

  

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

Public Health Service
Food and Drug Administration
 
Florida District
555 Winderley Place, Suite 200
Maitland, Florida 32751
Telephone: 407-475-4700
Fax: 407-475-4770

 

VIA UPS NEXT DAY AIR
w/ DELIVERY CONFIRMATION
 
WARNING LETTER
FLA-16-09
February 4, 2016
 
Marco Loleit, Chief Executive Officer
OPS International Inc., dba Olympia Pharmacy
6700 Conroy Road, Suite 155
Orlando, FL 32835
 
 
Dear Mr. Loleit:
 
You registered with the U.S. Food and Drug Administration (FDA or the Agency) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b][1] on March 10, 2014, and again on January 27, 2015. From November 17, 2014, to November 21, 2014, an FDA investigator inspected your facility, OPS International Inc., dba Olympia Pharmacy, 6700 Conroy Road, Suite 155, Orlando, FL 32835. During the inspection, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, the investigator observed poor aseptic practices that would not provide adequate protection of sterile drug products in the ISO 5 area, including processing sterile drug products in a laminar flow hood that was not turned on, using a (b)(4) that was not sterilized, and passing materials over open vials which may disturb unidirectional airflow, and contaminate the drugs in the open vials.  Furthermore, (b)(4) in your facility allowed direct access between an unclassified area and ISO 5 room, and a built-in refrigerator opened directly inside the ISO 5 room. Therefore, your products may be produced in an environment that poses a significant contamination risk. In addition, the investigator observed that you failed to meet the conditions under section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain requirements under the FDCA. FDA issued a Form FDA 483 to your facility on December 4, 2014. FDA acknowledges receipt of your facility’s response, dated December 23, 2014, as well as the updates to that response submitted on March 31, 2015, and June 26, 2015. 
 
Based on this inspection, it appears your facility is producing drugs that violate the FDCA. 
 
In addition, FDA notes that Olympia Pharmacy has a history of poor sterile practices. In March 2013, prior to your firm’s registration as an outsourcing facility under 503B of the FDCA, the Agency inspected your firm (then operating as Lowlite Investments, Inc., dba Olympia Pharmacy) at its previous location at 6700 Conroy Road, Suite 140, Orlando, FL 32835. During this inspection, FDA observed serious deficiencies in your practices for producing sterile drug products that resulted in a recall of all sterile products produced before March 27, 2013 and the issuance of a warning letter to your firm at that location. In addition, our 2014 inspection at your current location found that only limited improvements had been made to your firm’s practices for producing sterile drug products. 
 
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 intends to re-inspect your facility to verify corrective actions have been completed.
                                                  
A.  Compounded Drugs under the FDCA
 
The Drug Quality and Security Act (DQSA) was enacted on November 27, 2013. Title I of the DQSA, the Compounding Quality Act (CQA), added a new section 503B to the FDCA. Under section 503B(b), 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 can 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.
 
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 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.
 
B.  Violations of the FDCA
 
The FDA investigator noted that drug products that were intended or expected to be sterile were prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth or rendered injurious to health, causing them to be adulterated within the meaning of section 501(a)(2)(A) of the FDCA. Furthermore, the FDA investigator observed significant CGMP violations at your facility, causing your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA.
 
In addition, the FDA investigator observed that your facility failed to meet the conditions of section 503B. For example, during the inspection, the FDA investigator noted that:
 
1.    Your facility failed to submit a report to FDA upon registering as an outsourcing facility in March 2014, 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)]]. 
 
2.    Not all bulk drug substances used by your facility to compound drug products are manufactured by an establishment that is registered under section 510 of the FDCA [21 U.S.C. § 360] [section 503B(a)(2)(C) of the FDCA].
 
3.    Some of your facility’s drug products do not include the following on the label: the established name of the drug, the statement of volume, the statements, “This is a compounded drug” and “Not for resale,” and for drugs dispensed or distributed other than pursuant to a prescription for an individual identified patient, the statement “Office Use Only” [section 503B(a)(10)(A) of the FDCA [21 U.S.C. §353b(a)(10)(A)]].
 
Because your compounded drug products have not met all of the conditions in section 503B, they are not eligible for the exemption under section 503B from the FDA approval requirements in 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.[2] 
 
Specific violations are described below.
 
Adulterated Drug Products
 
The FDA investigator noted that drug products compounded in your facility that were 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 investigator observed poor aseptic practices that would not provide adequate protection of sterile drug products in the ISO 5 area, including processing sterile drug products in a laminar flow hood that was not turned on, using a (b)(4) that was not sterilized, and passing materials over open vials which may disturb unidirectional airflow and contaminate the drugs in the open vials.  Furthermore, (b)(4) in your facility allowed direct access between an unclassified area and ISO 5 room, and a built-in refrigerator opened directly inside the ISO 5 room. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
The FDA investigator also noted CGMP violations at your facility, causing 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 ensure adequate systems for maintaining any equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).
 
2.    Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile (21 CFR 211.113(b)). This violation was observed during the 2013 inspection.
 
3.    Your firm failed to adequately design the facility with adequate separation or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(b)).
 
4.    Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)). This violation was observed during the 2013 inspection.
 
5.    Your firm did not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
 
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 draft guidance, Current Good Manufacturing Practice — Interim 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.  
 
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 your drug products.[3] Under sections 301(d) and 505(a) of the FDCA [21 U.S.C. §§ 331(d) ], a new drug may not be introduced 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. 
 
Misbranded Drug Products
 
You compound drug products that are intended for conditions that are 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, causing them to be misbranded under section 502(f)(1) of the FDCA, 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 section 301(a) of the FDCA.  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 upon initial registration as an outsourcing facility in March 2014, 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)].
 
C.  Corrective Actions
 
FDA acknowledges your responses to the Form FDA 483 dated December 23, 2014, March 31, 2015, and June 26, 2015. In your December 23, 2014, submission you indicated that you are “continuing to make improvements to ensure compliance with all applicable law and regulations” including, but not limited to, “compliance with Title 21 CFR Parts 210 and 211.” In addition, your responses described certain corrective actions you have taken or plan to take in response to the Form FDA 483 observations. Although several of your proposed corrective actions appear adequate, others are deficient.  For example, you did not provide rationale for sanitizing, rather than sterilizing, the (b)(4) prior to use in the ISO 5 area. In addition, your corrective action to address the observation regarding testing and release of lyophilized drug products indicates you will institute (b)(4). However, it is unclear whether reconstitution time studies will be performed for lyophilized drug products as a part of this corrective action.
 
FDA strongly recommends that 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. You should fully implement necessary corrections in order to ensure that the drug products produced by your firm conform to the basic quality standards that ensure safety, identity, strength, quality, and purity.
  
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, 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. FDA intends to re-inspect your facility to verify corrective actions have been completed.
 
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps 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 the corrective actions cannot be completed within fifteen working days, state the reason for the delay and the time frame within which the corrections will be completed.  Your written notification should refer to the Warning Letter Number above (FLA-16-09). Please address your reply to Andrea Norwood, at the address above.
 
If you have questions regarding the contents of this letter, please contact Andrea Norwood at 407-475-4700.
 
Sincerely,
/S/ 
Susan M. Turcovski
Director, Florida District
 
__________________________________

[1] See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).
[2] See, e.g., section 503B(a)(11) of the FDCA [21 U.S.C. § 353b(a)(11)].
[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) 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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