WARNING LETTER

Lohxa LLC MARCS-CMS 581785 — September 10, 2019

Delivery Method:: VIA UPS
Product:: Drugs

Recipient:: Recipient Name

Mr. Kreshnik Lohxa; Recipient Title

President; Lohxa LLC; 600 Main St. Ste 110
Worcester, MA 01608
United States

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

WARNING LETTER
CMS #581785

September 10, 2019

Dear Mr. Lohxa:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Lohxa, LLC, FEI 3014188920, at 600 Main Street, Suite 110, Worcester, Massachusetts, from March 12 to 22, 2019.

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 12, 2019 response in detail.

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

1. 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 stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

You assigned expiration dates to (b)(4) lots of repackaged unit dose drug products of 12 months from the date of repackaging without supporting stability data. For example, you repackaged atovaquone oral suspension lot (b)(4) and assigned an expiration date of January 30, 2020 to the unit dose containers.

In your response you state the (b)(4) lots were assigned a 12-month expiry period in error, and we acknowledge your recall of the four affected lots. You committed to ceasing the assignment of 12-month expiration dates to repackaged unit dose products and stated you have stability data supporting 6-month expiration dates, but you did not provide this data.

In response to this letter, provide the stability protocol(s) and summary data supporting the 6- month expiration dates for repackaged unit dose products.

2. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

You could not provide data to support that you had validated cleaning processes for your manufacturing equipment. While you provided cleaning validation protocols, upon request you could not provide the executed validation or data to support your cleaning processes. Your manufacturing equipment cleaning procedures were also not available for review. One of your repackaging machines is not dedicated. You use (b)(4) machines to manufacture drug products that are difficult to clean from product contact surfaces. For example, you use your (b)(4) Machine to repackage multiple drugs into unit dose containers, including various suspensions and products containing highly potent active substances such as atropine.

You stated that you executed cleaning validation protocols (b)(4) filling machines, but you failed to provide the executed protocols, summary reports, or supporting data. You committed to revalidating the cleaning processes for your repackaging machines but did not provide a date when this activity would be completed. You did not implement interim actions to ensure the continued use of the equipment does not contaminate finished drug products. You also did not commit to implementing cleaning procedures for production equipment.

In response to this letter, provide:

• A comprehensive plan to evaluate cleaning procedures and practices for each piece of manufacturing equipment.
• Cleaning validation protocols and summary reports. Your cleaning validation protocols should identify worst-case conditions and also include, but not be limited to:

o Evaluating drugs of the highest toxicity
o Assessing drugs of the lowest solubility in their cleaning solvents
o Evaluating drugs with characteristics that make them difficult to clean
o Swabbing equipment locations that are most difficult to clean

• A summary of updated SOPs that ensure an appropriate program is in place for cleaning manufacturing equipment, including verification and validation of cleaning procedures for all products, processes, and equipment.

3. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your investigations into complaints are not thorough, lack a description of the investigation, and do not include evidence supporting the conclusion(s). For example, your investigation into a complaint of leaking cups documented in CPAR 100018-01 did not include a review of batch records, an examination of retention samples, or an assessment of packaging operations. The investigation also failed to state how and when the complaint was received.

You committed to enhancing your documentation of complaint investigations to include retention sample examination, batch record review, and an indicator of how the complaint was received. You also committed to other, unspecified enhancements. You did not perform a comprehensive review of your complaint investigation process and you did not commit to revise the investigation procedure.

In response to this letter, provide a comprehensive assessment of your system(s) for investigating deviations, atypical events, complaints, out-of-specification results, and failures. Your corrective action and preventive action (CAPA) plan should include, but not be limited to, improvements in investigations, root cause analysis, written procedures, and quality unit oversight. Also include your process for evaluating CAPA plan effectiveness.

Quality Systems

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/media/71023/download.

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.

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.

Send your electronic reply to orapharm1_responses@fda.hhs.gov. Your written notification should refer to the Warning Letter Number above (CMS # 581785) and your FEI number 3014188920.

If you have any questions, contact Compliance Officer Lisa Orr at lisa.orr@fda.hhs.gov or 215-717-3062.

Sincerely,
/S/

Diana Amador-Toro
Program Division Director/District Director
U.S. Food and Drug Administration
OPQO Division I/New Jersey District