The United States Food and Drug Administration (USFDA) has banned over 30 generic medicines manufactured by Ranbaxy Laboratories after two of its manufacturing plants were found to have not followed the good manufacturing practices prescribed by the US authorities. The authority however clarified that there is no evidence to doubt the quality of the products that have been shipped by Ranbaxy.
The USFDA on September 16 issued two warning Letters and an import alert against Ranbaxy drugs produced from the company's Dewas and Paonta Sahib plants in India.
The warning letters identify the agency's concerns about deviations from US current Good Manufacturing Practice (cGMP) requirements at Ranbaxy's manufacturing facilities in Dewas and Paonta Sahib (including the Batamandi unit) and the import alert allows US officials to detain at the US border, any active pharmaceutical ingredients (API) (the primary therapeutic component of a finished drug product) and both sterile and non-sterile finished drug products manufactured at these Ranbaxy facilities and offered for import into the United States.
"The problems at these two Ranbaxy plants relate to deficiencies in the company's drug manufacturing process. These actions are proactive measures that the FDA is taking in order to assure that all drugs that reach the American public are manufactured according to cGMP requirements. While this action does not involve removing products from the market, FDA has no evidence to date that Ranbaxy has shipped defective products. We will continue to monitor the situation", a USFDA statement said.
In its response, Ranbaxy said that it “is very disappointed in the FDA action. The company has responded to each concern FDA has raised during the past two years and had thought that progress was being made. We are, however, pleased that FDA's testing and review led the agency to conclude that there is no reason to question the safety or effectiveness of Ranbaxy's drugs. The company has just received the warning letters that FDA has issued and has not had the opportunity to review those concerns that FDA has determined are unresolved. Once it has had an opportunity to review the issues, the company looks forward to continuing to cooperate with FDA to resolve the remaining issues.”
Today's announcement does not impact products from Ranbaxy's otherplants which are not affected by today's actions. FDA has inspected those facilities and, to date, they have met U.S. cGMP requirements for drug manufacturing.
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The FDA also informed Ranbaxy that until it resolves the deficiencies at each of these two facilities and the plants come into compliance with U.S. cGMP requirements, no new drug marketing applications from these facilities will be considered.
The FDA Import Alert covers more than 30 different generic drug products produced in multiple dosage forms and dosage amounts ( i.e., 25 mg, 50 mg, and 100 mg) at these two locations.
"With this action we are sending a clear signal that drug products intended for use by American consumers must meet our standards of safety and quality," said Janet Woodcock, M.D., director, FDA's Center for Drug Evaluation and Research (CDER). "The FDA has notified other agencies and health care professionals to make them aware of today's actions so that they can take appropriate action and advise patients as needed." The Warning Letters issued today document the results of FDA investigations at these two sites.
Following the two inspections, FDA provided Ranbaxy with a separate list of inspectional findings for each of the facilities. In mid-April and May, Ranbaxy responded in writing to these findings in lengthy submissions to FDA. The agency then evaluated its findings, Ranbaxy's responses, and the firm's overall inspectional history, an evaluation that required substantial time due to the complex scientific and technical nature of both the identified deficiencies, particularly at the Dewas site, and the firm's responses. Ultimately, FDA concluded that the firm's responses were not adequate and that the Warning Letters were the appropriate regulatory response.
"Today's actions are clearly warranted by the serious violations established by FDA's investigations at these two sites," said Deborah M. Autor, director, CDER's Office of Compliance, FDA. "Until the company addresses these deficiencies, APIs and finished drug products from these plants will remain on the Import Alert, and we will not approve any Abbreviated New Drug Applications or New Drug Applications that list either of the two facilities as the manufacturer of APIs or finished drug products."
This represents the second time in less than three years FDA has issued a Warning Letter to Ranbaxy. In 2006, FDA cited Ranbaxy for violations of U.S. cGMP at its Paonta Sahib facility.
Problems with Dewas facility
The facility's beta-lactam containment program (measures taken to control cross-contamination), which appeared inadequate to prevent the potential for cross-contamination of pharmaceuticals; Inadequate batch production and control records;
Inadequate failure investigations; (A failure investigation is done to address any manufacturing control or product rejection to determine the root cause and prevent recurrence); and, Inadequate aseptic (sterile) processing operations.
Problems with Paonta Sahib
The lack of assurance responsible individuals were present to determine the firm was taking necessary steps under cGMP;
Inaccurate written records of the cleaning and use of major equipment;
Incomplete batch production and control records; and, Inadequate procedures for the review and approval of production and control records for drug products.