WARNING LETTER

Green Wave Analytical, LLC MARCS-CMS 630965 — August 19, 2022

Delivery Method:: Electronic Mail
Product:: Drugs

Recipient:: Recipient Name

Mr. James P. Polansky; Recipient Title

Co-owner/Scientist; Green Wave Analytical, LLC; 10366 Roselle St., Suite C
San Diego, CA 92121-1543
United States; jpolansky@ecalab.com

Issuing Office:: Division of Pharmaceutical Quality Operations IV; United States

WARNING LETTER

August 19, 2022

Dear Mr. Polansky:

The U.S. Food and Drug Administration inspected your contract testing laboratory, Green Wave Analytical, LLC, FEI 3016367069, at 10366 Roselle Street, Suite B/C, San Diego, California, from February 15 to March 7, 2022. Our inspection determined that you are a contract testing laboratory for drugs including, but not limited to, finished sterile injectable drugs and components.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, the drugs you tested 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).

Furthermore, during the first three days of our inspection, you denied access to the registered suite for Green Wave Analytical (Suite B) and falsely represented that your firm did not perform CGMP testing of finished drug products or components under contract. Due to your delay of the inspection, the drugs you tested are also deemed adulterated within the meaning of section 501(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(j).

We have not received a response from your firm with corrective actions to the observations identified during the inspection and provided to you on the Form FDA 483.

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. Your firm failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).

Your firm is a contract testing laboratory that performs chemistry and microbiological analysis of drug components (ingredients), injectable drugs, and ophthalmic drugs. Your firm failed to perform method validation (or verification, as appropriate) of test methods to ensure that they were suitable for their intended use. For example, you did not determine the suitability of your assay test for the active ingredient phenobarbital sodium, as you deviated from compendial methods without validation of the method and without performing system suitability to ensure equipment was functioning properly at the time of use. You also tested various drug products for sterility, endotoxin, and other microbial attributes using compendial test methods without verifying the suitability of the methods for each drug product under the actual conditions of use.

Method validation and verification is necessary to support reliable determinations of identity, strength, quality, purity, and potency of drugs. Without evaluating the validity of methods, you lack the basic assurance that the data provided to customers was an accurate reflection of pharmaceutical product quality.

2. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).

Your laboratory records did not include complete data to support the analysis performed. For example, laboratory records for the chemical and microbiological testing of drugs lacked the identification of the method used, documentation of a method’s execution, identity of standards, reagents, and test kits used, identification of the sample’s lot number for traceability, or equipment used (including, but not limited to, microbiological media, micro-pipette, and high performance liquid chromatography (HPLC) instrument).

Reliability of data is compromised when there is a failure to maintain complete records of the conditions and data associated with all tests. Furthermore, the lack of complete data compromises the quality unit’s (QU) ability to exercise its function of ensuring compliance to applicable standards.

3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

Your firm lacked sufficient controls over your HPLC data acquisition systems used in the testing of drugs for release. For example, your (b)(4) Series HPLC instrument did not have sufficient controls to prevent deletion and alteration of raw data files. During the inspection, our investigators observed laboratory personnel performing drug testing and analyses. Personnel had administrative privileges to the (b)(4) operating software for the HPLC equipment. These privileges included, but were not limited to, the ability to delete data sequences and change method parameters.

In addition, the HPLC instrument was found to be operating in the absence of an activated audit trail to record information about each analytical test, such as:

• Type of injection
• Date and time
• Identity of analyst
• Nature of action taken and reason

You also stated that data from the HPLC was not securely backed up and you did not review the HPLC audit trail data. In addition, you failed to validate electronic signatures used to approve analytical testing records for release testing of drugs performed from at least January 2020, to September 2021.

Your customers rely on the integrity of your laboratory data to make decisions regarding drug quality. It is important to maintain strict control over electronic data to ensure that all laboratory data is retained and that any additions or modifications of information in your electronic records are authorized and appropriately documented.

4. Your firm failed to establish a system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv).

Your firm performed sterility testing for over (b)(4) lots of finished drug products purported as sterile but failed to effectively establish a system for monitoring environmental conditions to ensure ISO 5 air quality within the testing equipment and in adjacent areas. You also did not establish a system for monitoring of personnel who performed drug sterility testing.

Your testing laboratory was also deficient in that it did not employ adequate facilities and controls to assure robust conditions for sterility testing.

Poor or deficient sterility test facilities or controls can result in inaccurate data used by customers in determining final drug product batch disposition.

The validity of results obtained under deficient testing conditions should be thoroughly evaluated.

5. Your firm failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed (21 CFR 211.22(a) and (d)).

Your QU did not adequately exercise its authority and responsibilities, including but not limited to, effective procedures and oversight. For example, your written procedures did not address QU oversight and responsibilities including the authority to review laboratory records for errors and to ensure your firm maintains adequate laboratory facilities. In addition, many of your written procedures (e.g., Documentation of Work Performed, Recording of Analytical Data, and Evaluation of Out of Specification Results) were not implemented or followed by your personnel.

Furthermore, your QU did not ensure proper controls over electronic laboratory data and documentation practices to ensure the accuracy of your approved and released records.

Your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. 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 the CGMP regulations (21 CFR, parts 210 and 211) at https://www.fda.gov/media/71023/download.

Moreover, you failed to establish and implement roles and responsibilities that are appropriate to meet minimum CGMP standards for a pharmaceutical contract laboratory.

Responsibilities of a Contract Testing Lab

FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any out-of-specification results or significant problems encountered during the testing of these drugs. For additional information refer to FDA Guidance for Industry Contract Manufacturing Arrangements for Drugs: Quality Agreements (https://www.fda.gov/media/86193/download).

Data Integrity Remediation

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you test. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

Delaying, Denying, Limiting, or Refusing a Drug Inspection

We provided your firm with prior notice of an FDA inspection on February 10, 2022. During the first three days of our inspection, you denied having access to the registered suite for Green Wave Analytical (Suite B) or that you performed drug CGMP operations in that suite. You also falsely stated to our investigators that your firm did not perform CGMP testing of finished drug products or components under contract. On day four of the inspection, and contrary to your prior assertions, you provided a written statement confirming that Green Wave Analytical performed CGMP drug testing from at least January 2020 to September 2021 on behalf of a sole customer, (b)(4). You provided records including laboratory notebooks that included testing of finished drug products including, but not limited to, sterile injectable drugs. You only then provided FDA investigators with access to Suite B on day five of our inspection.

When an owner, operator, or agent delays, denies, limits, or refuses an inspection, the drugs manufactured, processed, packed, or held in the facility may be deemed adulterated under section 501(j) of the FD&C Act. See FDA’s guidance document, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, at https://www.fda.gov/media/86328/download.

CGMP Laboratory Operations Ceased

We acknowledge your commitment during the inspection to de-register and cease the CGMP testing of drugs at this facility. During our inspection you stated that you do not intend to resume testing for any drugs at this facility in the future.

If you plan to resume any activities regulated under the FD&C Act, including the testing of drugs for the U.S. market, at this location or any other location, notify this office prior to resuming your operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure, and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a contract testing laboratory until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Please identify your response with unique identifier CMS 630965 and send electronically to orapharm4_responses@fda.hhs.gov or by mail to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612-2506

If you have questions regarding this letter, please contact William V. Millar, Compliance Officer via email at william.millar@fda.hhs.gov or by phone at (503) 671-9711 Ext. 30.

Sincerely,
/S/

Lance M. De Souza
Acting Director, Division of Pharmaceutical Quality Operations IV