Suppliers of API & formulations likely to face heightened US FDA scrutiny

Supplier companies should make every effort to ensure their written responses do not fail to adequately address FDA’s concerns, alerts an industry report.

Active pharma ingredient (API) and formulation suppliers from countries like India may have to face tougher regulatory scrutiny from US Food and Drug Administration in coming years, as the federal drug regulator heightens its sensitivity to drug safety.

The US Food and Drug Administration (FDA) has issued more than 25 warning letters to manufacturers of finished pharmaceuticals and active pharmaceutical ingredients (APIs) for violations of the current good manufacturing practice (GMP) regulations, in the past twelve months.

FDA’s warning letters show that the agency is taking a more systemic and risk-based approach to assessing GMP compliance and paying particularly close attention to such areas as the quality control unit, manufacturing process validation, and laboratory out of specification (OOS) test results and investigations, according to a new industry report by analysts Hogan & Hartson (H&H).

The FDA appears to have become more aggressive in its use of GMP warning letters to notify drug companies about violative conduct in other areas of their business. In some cases, the FDA has alerted companies that some of their products lack the necessary FDA approvals. In others, the agency has raised concerns about a company’s promotional activities. In still other cases, the FDA has notified companies that they are violating FDA’s pharmacy compounding rules.

An H&H review found that virtually all GMP warning letters address the inadequacies of the company’s reaction to inspectional observations, which serves as an important reminder of the necessity for a company to submit a high quality response to the FDA that demonstrates the company’s commitment to implementing aggressive corrective action in response to the inspectional observations.

By enhance their quality systems and improving their manufacturing processes, the API suppliers can more effectively manage future FDA establishment inspections, the report pointed out.

Notwithstanding the fact that in the past year majority -nearly 80% -FDA’s GMP warning letters were directed at U.S.-based manufacturers, the trend will start changing in the near future and that the agency will dedicate a larger portion of its resources to international inspections.

The FDA has already announced that it will establish offices overseas in countries like China, where the agency believes that closer working relationships with its counterpart regulators will be beneficial, as part of its “Beyond Our Borders” initiative.

FDA has already started an office in New Delhi, India and is planning to start another one in Mumbai too soon.

However, recognizing that the FDA will have limited resources to devote to international inspections even with inspectors based overseas, the FDA will more carefully scrutinize how domestic manufacturers qualify their international suppliers.

More recently, the FDA warned a Chinese API manufacturer Qingdao Jiulong Biopharmaceuticals and its subcontractor Shanghai No 1  about the inadequate systems they had in place to ensure the safety of raw materials used in their manufacturing of heparin sodium. As a result of these GMP deficiencies, and broad concerns with the reliability of information generated at each facility, the FDA placed materials imported from each facility on import alert, thereby refusing those materials admission into the United States.

Most of the FDA’s GMP warning letters from the past year address the inadequacies of the company’s inspection response. Often, it has been observed that warning letter responses that fail to adequately address FDA’s concerns even though there are a variety of acceptable ways to respond to an inspection.

So, the supplier companies should make every effort to ensure that their written responses demonstrate a commitment to manufacturing high quality drug products and to implementing aggressive corrective action as part of a robust pharmaceutical quality system, H&H report suggests.

Recently,FDA has issued warning letters to several Indian drug makers exporting drugs to US including Ranbaxy, Cipla, Sun Pharma and Lupin. FDA even went to the extend of banning the drugs manufactured in Ranbaxy’s Paonta Sahib facility, severely impacting its revenues.