With the US FDA stepping up the inspections across the world and sending out a spate of warning letters, Ahmedabad-based leading API player Synbiotics Ltd has also come under the scanner for deviations from the Current Good Manufacturing Practices.
In a letter sent last month to the chairman of Synbiotics Ltd, the FDA has listed out the specific deviations in detail. The warning letter has been sent after the inspection on API facility located at Plot Nos. 570, 571, 576A, Maitry Marg, Village-Luna, Tal Padra, Vadodara in August and based on the explanatory letter from the company. The investigator was not given access to the facility and the information provided by the company was limited, it said, adding that significant deviations were found.
“These deviations cause your API(s) to be adulterated within the meaning of section 501(a) (2) (B) of the Federal Food, Drug, and Cosmetic Act (the Act),’’ the letter said. The FDA said it had reviewed the response of September 1, 2010 from the company but found that the note lacked sufficient corrective actions. This has prompted the US agency to send a warning letter citing specific deviations observed during the inspection.
“Failure to prepare, review, and approve documents related to the manufacture of APIs: For example, you shipped lot (b) (4) of (b) (4), to the United States in January 2010 from this site. At the time of shipment, no procedures were in place for change control, out-of-specification investigations, process deviation investigations, laboratory incidents, consumer complaint handling, or annual product reviews. Without these and other basic CGMP procedures in place, there is minimal assurance of appropriate systems to assure product quality. Your response acknowledges that your quality system “was inadequate” and that “critical Quality Assurance functions were missing.” Your response also includes SOPs, covering topics such as change control, out of specification results, deviation control, market complaints and product quality reviews, which were specifically requested during the August 2010 inspection attempt. It is your responsibility to ensure these and other critical procedures and essential quality assurance functions are in place prior to manufacturing. Your quality system will be thoroughly reviewed during the next FDA inspection,’’ the letter said.
The letter also pointed out the failure of the quality system to provide confidence that the API manufacturing processes would consistently yield a product meeting its intended specifications. Citing an example, the letter said the validation of manufacturing process was not done at the time of shipment of the above-referenced lot. “Without an adequate validation plan or written procedures to execute pre-defined qualification protocols, your manufacturing process can not be confirmed as being capable of reliable commercial manufacturing that consistently delivers a product that meets its pre-defined quality attributes,’’ it said.
“The deviations detailed in this letter are not intended to be an all-inclusive statement of deviations that exist at your facility. You are responsible for investigating and determining the causes of the deviations identified above and for preventing their recurrence and the occurrence of other deviations. If you wish to continue to ship APIs to the United States, it is the responsibility of your firm to ensure compliance with all US standards for CGMP and all applicable US laws and regulations. Until all corrections have been completed and FDA has confirmed corrections of the deviations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as an API manufacturer. In addition, failure to correct these deviations may result in FDA refusing admission of articles manufactured at Synbiotics Limited, Plot Nos. 570, 571, 576A, Maitry Marg, Village-Luna, Tal Padra (Dt), Vadodara, India into the United States,’’ the FDA has warned.