Say Cheese! FDA Issues Warning Letter Based Solely on Company’s “Refusal”

By Anne K. Walsh & Robert A. Dormer –

As we predicted it might, FDA effectively shut down a drug facility based solely on its conduct during an FDA inspection, without any observed GMP or safety concern related to the company’s products or procedures.  In a September 15, 2016 Warning Letter issued to Nippon Fine Chemical Co., Ltd., FDA cited the provision deeming drugs adulterated based on an owner or operator limiting or refusing inspection, 21 U.S.C. § 351(j), and tersely identified three ways in which the company violated this provision:

1. Barring access to areas – the quality control manager allegedly directed employees to “stand shoulder-to-shoulder” to bar access to portions of the laboratory and equipment.
2. Refusal to provide copies of documents – although the FDA investigator appears to have reviewed complaint records, the firm allegedly refused to provide take-home copies of these records for the investigator.
3. Limiting photography – the quality assurance manager allegedly prevented the investigator from taking photographs of a piece of equipment used to manufacture drugs; it is not clear from the Warning Letter how exactly the manager prevented pictures from being taken.

FDA has used this adulteration provision only a handful of times since it was added to the Federal Food, Drug, and Cosmetic Act (FDC Act) in 2012. In earlier Warning Letters, the refusal was an add-on violation to other GMP violations.  Here, FDA bases the entire Warning Letter solely on the firm’s refusals, without alleging any other issues.  Notably, the company’s refusal to allow photographs is identified as evidence of refusal.  As discussed in earlier posts (here and here), FDA’s authority to take pictures has never been tested by the courts, yet FDA asserts it has this power in its guidance and in Warning Letters as if it that authority is accepted in FDC Act jurisprudence.

Also, because the recipient of the instant Warning Letter is a foreign firm, the company’s refusal during the inspection results in a ban of that company’s products into the United States. As referenced in the Warning Letter, FDA placed the company on Import Alert 99-32 for the same reasons underlying the Warning Letter.  The Import Alert means that FDA can detain, without physical examination, products imported to the United States, and can continue to detain these products until it completes an inspection.  The Import Alert further states that inspection reports from third parties may help FDA prioritize inspection requests, but it is clear FDA will not permit product to enter the United States without conducting its own inspection.  Given the limited availability of foreign investigators, timing for relief of a firm placed on this list is unknown.  

One observation about Import Alert 99-32: although it includes companies from seven different countries (Canada, China, Hong Kong, Hungary, India, Italy, and Japan), the breakdown of countries placed on the list due to import refusals skews heavily to Chinese and Indian firms. We can only speculate as to why these countries have more targets, and note that companies in these highly scrutinized countries should be made aware of this provision and its dire implications.

Lastly, this is not an issue limited to foreign inspections. A domestic firm also received a Warning Letter in 2014 for, among other things, refusing to allow photographs of its medicated feed storage conditions.   That Warning Letter was closed out after eight months, which is lightning speed for any close-out letter.  This timing would be near impossible for a foreign firm, which would require a scheduled reinspection to be prioritized above the queue of other foreign establishment inspections.