FDA warns US sterile injectable maker on contamination controls, another US maker warned for poor building conditions

Regulatory NewsRegulatory News | 28 October 2022 |  By 

Two domestic drug manufacturers were lambasted in recent warning letters sent by the US Food and Drug Administration (FDA) for good manufacturing practice (GMP) violations; one was told to adopt better contamination controls and to keep outsourced drugs separate from those made at the facility, while another was reprimanded for keeping the facility in a poor state of repair.
FDA also targeted two firms for failing to file accurate product information in its electronic Drug Registration and Listing System (eDRSL).
Nephron warned not to mix up drug products
The first warning letter, to Nephron, a drug manufacturing facility in West Columbia SC, said the firm failed to prevent the mix up and contamination of products made at their facility with those that are outsourced, and for having other issues related to microbial contamination.
“Your firm’s testing found cross contamination of drugs in at least three lots of drug products. You failed to adequately identify the root cause or scope of potentially impacted lots in a timely manner,” according to the warning letter.
The firm launched an investigation and detected the presence of the drug bupivacaine produced from their outsourcing facility in a lot of drug product pending approval. They attributed the root cause of the problem “to a combination of the nature of terminal sterilization cycles and the permeability of the container closure system (CCS) used to produce your drug products.”
In response, FDA said “it is essential that your firm does not introduce risks through overlap of your outsourcing and conventional production operations by sharing equipment, facilities, processes, or personnel, as the applicable standards significantly differ in certain respects. The attempt to mix these operations and follow two different standards increases complexity and product hazards.”
The firm also had inadequate microbial contamination controls as shown by two media fill failures, in which Pseudomonas aeruginosa (gram-negative rods) were detected in cooling water, according to the letter.
FDA said that “it is highly atypical to have gram-negative microbes in the aseptic production cleanroom environment or identified in a media fill.”
After being contacted by FDA, the firm recalled its lot of ketorolac tromethamine injection product as well as products made by four outsourcing facilities.
The firm was given 15 days to respond to the warning letter. Failure to address violations may prompt FDA to withhold export certificates or withhold approval of new applications or supplements.
Filthy conditions observed at Advanced Cosmetic
Substandard building conditions were addressed by investigators in a warning letter to Advanced Cosmetic Research Laboratories in Chatsworth, CA.
Investigators noted that rusty pipes covered with debris were directly above open mixing tanks, and foreign particles were floating in a mixing tank directly below one of the pipes.
Also, numerous aluminum sheet panels on the ceiling were partially over open mixing tanks and were either torn, falling, or had gaps, exposing the products in the tanks to dirt and debris. Multiple bug zappers were also near failing and packaging lines, according to the letter.
FDA noted that the firm also had inadequate quality control unit (QCU) controls. For example, a product analysis report used to release batches for a sunscreen product was signed and approved on 23 March 2022, even though the batch was still being filled.
Further, complaints and out-of-specification results were not adequately evaluated or investigated.
FDA told the firm that “without adequate quality procedures and oversight, you cannot ensure the consistency of your manufacturing process and the purported identify, strength, quality, and purity of drug products released to the market.”
The firm was also cited for making lidocaine cream for an unapproved use.
Failure to address these violations “may result in regulatory or legal action including a seizure or injunction” and prompt the agency to withhold export certificates, FDA said.
The company has 15 days to respond to the letter.
Two firms cited for listing violations
Two warning letters also targeted RiteAid Corporation and Unit Dose Services for failing to submit correct product information in its eDRLs system.
The letter to Rite Aid noted a discrepancy in the listed active ingredient between the submitted labeling and the electronic listing file. The electronic listing includes an extra active ingredient, phenylephrine HCL, that the label does not have.
Unit Dose Services’ eDRLs for lisinopril had an incorrect carton label image for the listed product.
The warning letters to both companies’ states that “complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance.

Nephron warning letter
Advanced Cosmetic Research Lab warning letter
Rite Aid warning letter
Unit Dose warning letter


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Tags: FDA, GMPs, letter, warning

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