FDA Alleges Major Compliance Breaches by Manufacturer of Pain and ADHD Medications

The Food and Drug Administration (FDA) has issued a stern warning to the makers of products such as Tylenol with codeine, Adderall, and Klonopin, citing “significant violations” in their manufacturing practices.

Earlier this month, a formal warning letter was dispatched to Par Health USA, LLC & Endo USA, Inc. This action followed an inspection conducted in October at their Rochester, Michigan facility, which revealed several compliance issues.

In the letter, the FDA detailed breaches of Current Good Manufacturing Practice (CGMP) regulations related to finished pharmaceuticals. These breaches included improper handling and production of sterile drug products, raising concerns about the safety and efficacy of the medications.

Moreover, the FDA highlighted the company’s lapses in maintaining aseptic processes. Proper aseptic techniques are crucial to ensuring that both products and their environments remain free from harmful pathogens.

The agency’s findings pointed to “excessive and high-risk manual interventions” during the manufacturing process. Such practices were deemed to pose unacceptable risks to the sterility of the products, potentially compromising their safety for consumers.

Par Health makes dozens of popular products, including acetaminophen and codeine tablets, sold under the brand name Tylenol with codeine; alprazolam, previously sold under the name Niravam; clonazepam, sold as Klonopin; fluoxetine, sold as Prozac; Adderall, both regular and extended release (XR); and broad-spectrum antibiotics like doxycycline. 

Tens of millions of Americans take these drugs and if proper sanitation or manufacturing guidelines were not followed, the drugs could be contaminated with harmful impurities or be unsterile, posing a toxin or infection risk, especially for injectable products.

Par Health makes popular generic products sold under the brand names Tylenol with codeine, Klonopin, Prozac, Adderall and broad-spectrum antibiotics like doxycycline. (stock image)

The letter said: ‘Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. 

‘In addition to the lack of effective management oversight of your production operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. 

‘Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements 

An additional violation the FDA found was inadequate airflow and flaws in airflow-related design, which could have caused unsanitary contamination of the products.

The agency also said the company failed to establish and follow procedures to prevent microbiological contamination of sterile drugs.

Additionally, maintaining the aseptic cleanroom and equipment, along with the protection of sterile areas was ‘deficient,’ compromising the company’s ability to maintain sanitary conditions. 

Another violation the FDA said it witnessed was a failure to establish laboratory controls ‘that include scientifically sound and appropriate’ standards and testing to assure that products adhere to quality control measures. 

Business owners typically have 15 days to respond to FDA warning letters. Warning letters often are not issued until a company has been given months or years to correct problems. 

The FDA’s warning letter states the company responded to the agency’s initial notice in November, but it deemed the response ‘inadequate’ because it ‘does not overcome fundamental design flaws.’

In response to the FDA’s notice of violations, the agency said the company had implemented some changes, including temporarily suspending manufacture of aseptically filled products and ceasing work with a third-party glass supplier that had once had defects in its products. 

However, rather than make wholesome changes to the processes, the FDA’s letter said the company is ‘attempting to partially mitigate significant… hazards.’

It stated: ‘Overall, your response fails to address how you will ensure adequate aseptic processing operations and collect meaningful data to support your aseptic processes.’