WARNING LETTER
United Exchange Corporation
MARCS-CMS 561814 —
March 06, 2019
Product:
Drugs
Recipient:
Recipient Name
Ms. Carol Choi
Recipient Title
President and Owner
United Exchange Corporation
5836 Corporate Ave, Suite 200
Cypress
,
CA
90630
United States
Issuing Office:
Division of Pharmaceutical Quality Operations IV
19701 Fairchild
Irvine
,
CA
92612
United States
949-608-2900
WARNING LETTER
VIA SIGNATURE CONFIRMED DELIVERY
March 6, 2019
Ms. Carol Choi
President and Owner
United Exchange Corporation
5836 Corporate Ave, Suite 200
Cypress, CA 90630
Dear Ms. Choi:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facilities, United Exchange Corporation (FEI 3006266338) at 5836 Corporate Ave, Suite 200, Cypress, CA 90630 from April 2 to 6, 2018 and United Exchange Corporation (FEI 3013978005) at 1552 Alder Ave, Rialto, CA 92377 from April 4 to 6, 2018.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
We reviewed your April 25, 2018, response in detail.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. Your firm failed to establish a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products, including drug products manufactured, processed, packed or held under contract by another company. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit. (21 CFR 211.22(a) and (d)).
Your firm uses contract manufacturing organizations (CMOs) to perform manufacturing, processing, and packaging activities on your behalf. You receive drug products from these contract manufacturers and conduct final release for distribution in the U.S. market. You have responsibility for CGMP activities you perform. In your response, you also maintain that you have CGMP responsibilities including, but not limited to, release or reject of finished drug products for distribution, complaint and deviation investigations, and supplier and CMO oversight. In addition, you have quality agreements with your customers. For example, your quality agreement with
(b)(4)
also states that you “shall develop, design, manufacture, and commercialize the Products [sic] in compliance with applicable FDA Good Manufacturing Practices (“GMPs”)…”
A.) Inadequate quality unit (QU) oversight of your contract manufacturers
Your QU failed to institute adequate oversight and controls for your contract manufacturers, which led to your use of multiple sub-standard contract manufacturers. Since 2016, FDA has taken the following actions in response to CGMP violations found at your contract manufacturers.
1.
(b)(4)
.
2.
(b)(4)
.
3.
(b)(4)
.
4.
(b)(4)
.
5.
(b)(4)
.
6.
(b)(4)
.
During the inspection, you provided a memo stating that you discontinued your business relationships with
(b)(4)
. However, this does not address the fact that your firm lacks a robust quality system and enabled the introduction of adulterated drug products into the U.S. market.
In your response, you acknowledged that audits and qualifications of your contractors had not been performed or adequately documented. You also acknowledged that the responsibilities of the QU had not been formally established in writing and that you would draft a new standard operating procedure for the QU, including “Supplier and CMO Oversight.” You stated that you intend to establish a more formalized qualification program and procedure and verify the reliability of Certificate of Analysis test results from your contractors with the use of a third-party testing laboratory. However, your response is inadequate. You failed to provide any details about your newly established qualification process nor have you provided specifics about the type of testing to be performed.
In response to this letter, provide:
• Provisions for requalifying all suppliers you plan to use in the future
• A risk assessment to determine whether all your drug products currently on the market within expiry conform to their specifications
• Scientific justification of how you can be confident of the accuracy of your assessment
B.) Inadequate batch review or release
As the drug product owner, you have final batch release responsibilities including determining whether drug products meet specifications for safety, identity, strength, quality, or purity. Our investigator found that your firm was not performing final reviews of each batch to determine its disposition. Determining the suitability of each batch for release is an essential component of your QU responsibility.
In response to this inspection, you stated that it is your “responsibility to release or reject finished drug products against formal specifications.” You also stated that you would develop new procedures for the release or rejection of finished drug products for distribution and establish internal specifications for all finished drug products. You committed to qualify a contract testing laboratory to test the next
(b)(4)
batches or shipments of finished drug products.
Your response is inadequate because you failed to provide details about your new procedures nor did you provide an update on your progress for implementing the proposed corrective actions. Additionally, your response did not address a retrospective review of drug products still on the market within expiry.
In response to this letter, provide:
• Your new procedures for your batch review and release process
• Drug product specifications
• An assessment of any risks to the quality of drug products released before implementing your new procedures and your mitigation plans
• A summary of the test results you committed to in your response along with the underlying data (e.g., test reports)
• A plan for addressing the quality of your products currently on the market and within expiry.
C.) Inadequate QU procedures
Your “Product Complaints” procedure outlines investigation attributes as a part of receiving product complaints, but you did not establish adequate procedures for handling investigations, deviations, and specification failures from your contractors pertaining to your drug products.
In addition, your QU failed to establish adequate procedures for the receipt, examination, and storage of incoming drug products. For example, our investigator found quarantined drug products stored in the same space as released drug products.
Your firm lacks suitable quarantine controls to distinguish quarantined drug products from released finished drug products.
In your response, you stated that you will develop a new procedure for deviations and investigation handling. Your response is inadequate because you did not provide details about your new deviation and investigation procedure or how it would be implemented.
In your response, you also stated you installed proper signage and would build a separate area for rejected products. However, your response is inadequate. You failed to provide details on your process for the receipt of incoming drug products.
In response to this letter, provide:
• Your new procedure for deviation and investigation handling including specifics on the handling of all investigations
• Your new procedures for the receipt, examination, and storage of incoming drug products including the status of your facility addition
Owner’s Responsibilities when using Contract Manufacturer or Laboratory
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.
You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at
https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf
.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
Quality Systems Guidance
Significant findings in this letter indicate that your QU is not fully exercising its authority and/or responsibilities. Your firm must provide the QU with the appropriate authority, sufficient resources and staff to carry out its responsibilities and consistently ensure drug quality. Provide evidence that you are following through on your commitment to staff at more appropriate levels (e.g., personnel qualifications, updated organizational chart).
Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at
https://www.fda.gov/downloads/Drugs/Guidances/UCM070337.pdf
.
Conclusion
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations in all your facilities.
Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Your written notification should refer to the Warning Letter Number above (561814). Send your electronic reply to
ORAPHARM4_Responses@fda.hhs.gov
or mail your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food & Drug Administration
19701 Fairchild
Irvine, California 92612-2506
If you have questions regarding the contents of this letter, please contact William V. Millar, Compliance Officer via email at
William.Millar@fda.hhs.gov
or by telephone at 510-337-6896.
Sincerely,
/S/
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
Content current as of:
03/19/2019
Regulated Product(s)
Drugs