The letter takes issue with poor quality assurance testing of teething products and levels of belladonna that exceed the levels claimed on labels. In response to the letter, the drugmaker has said it has recalled the products and has since ceased manufacturing them.
The FDA sent Raritan Pharmaceuticals a warning letter after an inspection of its facility in East Brunswick, New Jersey, revealed several significant violations of Current Good Manufacturing Practice (CGMP) regulations and adulteration of the company’s teething product. Inspectors also uncovered misbranded product that contained excessive levels of belladonna, exposing infants using the products to potentially serious harm.
Inspectors observed several deviations from CGMP for finished pharmaceuticals, including Raritan’s failure to test components of its homeopathic teething product for conformity with written specifications for purity, strength and quality. In one instance, Raritan failed to test product received from a supplier for any quality data, including identity, before using it in production. FDA inspectors found some components for which conformity testing wasn’t done were received without a certificate of analysis. A sample of the lot revealed the material exhibited high variability, making it of unacceptable quality for the manufacture of drug product. Inspectors determined that the variability exposed infants given the product to safety hazards from belladonna levels beyond the labeled content.
The drugmaker was chided for failing to establish sufficient procedures for production and process controls to ensure drug products have the identity, strength, quality or purity they are represented as having. Inspectors found the procedures used when making teething tablets and cold tablets are not supported by sufficient process validation. They noted that an analytical standard used for identity testing is not a properly qualified standard, and process validation studies failed to show the process is able to reliably produce finished drugs that consistently meet label claims. In samples of teething tables, inspectors observed belladonna that exceeded the alleged content levels on the product label. The FDA is asking the drugmaker to implement a scientifically sound program that appropriately identifies and controls sources of variability so that finished product consistently meets quality attributes and label claims.
The warning letter cites Raritan’s failure to carefully investigate unexplained discrepancy or failure of a batch or component to meet specifications, regardless of whether it had been distributed. In one case, Raritan’s investigation into a complaint about a seizure due to teething tablets included sending samples to QC for analysis, but Raritan didn’t document whether additional analysis was conducted. In another instance, expired components were used to make a finished product, but Raritan didn’t investigate whether the use of the expired components had any impact on the finished product.
The letter also takes issue with a homeopathic teething product that contained alkaloid content that varied widely from the content stated on the product labeling, making the product misbranded. Inspectors found the quantity of belladonna alkaloids listed on the label failed to accurately reflect the quantity found in the product. The FDA notes that while the product is labeled as a homeopathic drug, it is subject to the same regulatory requirements as other drugs. While Raritan initiated a recall upon the FDA’s analysis demonstrating excessive belladonna levels and stopped making the product, the FDA is asking for confirmation that Raritan has permanently stopped production.