Under a recently introduced bill, the US Food and Drug Administration (FDA) would no longer provide advance notice of overseas drug inspections. Historically, the FDA has notified drugmakers outside of the United States weeks or months in advance of a scheduled surveillance inspection, whereas the FDA typically does not provide advance notice to domestic drugmakers. The Senate Finance Committee recently suggested that the delay between notification and inspection gives some foreign pharmaceutical facilities enough time to cover up non-compliance in their facilities.1
On January 13, 2022, Republican Senators Mike Braun of Indiana and Joni Ernst of Iowa introduced the Foreign Inspection Efficiency Creation Act, which proposes to eliminate the FDA’s practice of to announce surveillance inspections abroad in advance.2 According to Ernst, the current practice puts U.S.-based drugmakers at a significant disadvantage compared to their foreign counterparts who receive a “heads-up” notification before a facility inspection.3 Ernst thinks this bill will level the playing field for American companies.4 Ernst also hopes the bill will “help bring manufacturing back to the United States” and thereby lead to a stronger national drug supply chain for important pharmaceuticals.5
The Senate Finance Committee has previously expressed concern that providing advanced notice to foreign manufacturers has resulted in less stringent inspections and that foreign facilities are not meeting proper quality and safety standards.6 This is especially important because the majority of global active pharmaceutical ingredients (APIs) used in finished pharmaceutical products in the United States are manufactured in facilities outside of the United States.seven The FDA has maintained that the US drug supply chain is among the safest in the world (80% to 90% of drug manufacturing facilities supplying the US market are substantially compliant with Good Manufacturing Practices requirements, regardless of their location), as the agency follows a risk-based approach. approaches domestic and foreign inspections and uses a variety of tools to encourage compliance, such as untitled or warning letters, regulatory meetings, import alerts, injunctions and seizures.8
Foreign Inspection Efficiency Creation Act
FDA’s general practice is to notify all manufacturers of pre-approval and licensing inspections and to notify most foreign pharmaceutical facilities in advance of routine/surveillance inspections.9 These announcements, while not required under the Federal Food, Drug, and Cosmetic Act (FDCA), are intended to verify that the establishment to be inspected is a drug manufacturer under the jurisdiction of the FDA, to ensure that appropriate records and personnel will be available and to allow sufficient time for logistics such as travel, access to facilities and obtaining visas.ten In addition, since the FDA’s inspection authority under Section 704 (21 USC 374) does not apply to foreign facilities, the pre-announcement documents the foreign company’s agreement to allow FDA inspection.11
This bill proposes to amend Section 704 of the FDCA to allow the FDA to inspect foreign drug manufacturers without prior notification, unless notification is mandated by the host country or is necessary to protect public health. Notably, the bill’s requirements apply only to surveillance inspections and not to pre-approval, pre-authorization or reasoned inspections.
From 2014 to 2015, the FDA ran a pilot program in India that eliminated extended notice and instead relied on short notice or unannounced visits; The FDA selected sites for the program that it believed had significant problems.12 The program revealed widespread misconduct, such as falsified quality records and an infestation of birds at a sterile products manufacturing site.13 Under the pilot program, the results of “indicated official actions” increased by almost 60%.14
During a virtual enforcement conference on Dec. 9, 2021, Elizabeth Miller, Assistant Commissioner for Medical Products and Tobacco Operations in the FDA’s Office of Regulatory Affairs (ORA), indicated that the FDA plans restart this pilot program in India and extend it to China in early 2022.15 A House Appropriations Committee report accompanying the omnibus bill for fiscal year 2021 confirmed this pilot project and stated that “[t]The Committee is concerned that the FDA’s drug inspection program continues to lag behind the levels needed to match the growth of foreign drug manufacturing facilities” and reiterated “that the regular practice of the FDA’s pre-announcement of foreign drug inspections well in advance of an inspection raises serious questions about parity with domestic inspections, which are almost always unannounced.16
As it stands, the current version of the bill is solely sponsored by Republicans and is unlikely to pass the Democratic-controlled House and Senate this session of Congress. Nonetheless, Congress has focused on the large percentage of APIs and drug manufacturing outside of the United States, and depending on the November election outcome, this bill or the concept of unannounced foreign drug inspections could resurface. Any legislation that includes provisions similar to the draft bill would have a significant and immediate impact on foreign drug facilities. In theory, foreign facilities would not be able to schedule FDA surveillance inspections and, like domestic manufacturing facilities, would need to be “inspection ready” at all times. As India’s pilot program demonstrated, reducing or eliminating FDA inspection notices makes it harder for drug manufacturing facilities in foreign countries to conceal problematic practices from US regulators. Either way, there would always be opportunities for at least notice to foreign companies. For example, some countries may notify local drug manufacturers that FDA investigators have applied for a visa and/or entered the country. So, unannounced inspections would likely be more effective in countries like India and China, where the FDA already has field offices with on-site investigators.
1See Comm. of the US Senate. on finance, COVID-19 and Beyond: Oversight of the FDA’s Foreign Drug Manufacturing Inspection Process at 2 p.m. (June 2, 2020) (available on https://www.finance.senate.gov/imo/media/doc/456402.pdf) [herein referred to as Hearing].
2Efficiency Creation Act in the Foreign Facilities Inspections Act, S.3509, 117th Congress. (January 13, 2022) (available on https://www.congress.gov/bill/117th-congress/senate-bill/3509/text?q=%7B%22search%22%3A%5B%22Creating+Efficiency+in+Foreign+Inspections+Act%22 %2C%22Creation%22%2C%22Efficacy%22%2C%22in%22%2C%22Foreign%22%2C%22Inspections%22%2C%22Act%22%5D%7D&r=1&s=1).
3See Joni Ernst, No more “heads up” for foreign installations: Ernst wants to level the playing field for American producers (January 20, 2022) (available on https://www.ernst.senate.gov/public/index.cfm/2022/1/no-more-heads-up-for-foreign-facilities-ernst-wants-to-level-the-playing-field- for-american-producers).
6See Senator Charles E. Grassley, Lt. at HHS Sec. Azar and Acting FDA Comm. Dr Sharpless (August 6, 2019) (available on https://www.finance.senate.gov/imo/media/doc/2019-08-06%20CEG%20to%20HHS%20FDA%20(Importation%20Plan).pdf) [herein referred to as Grassley Letter]; see Hearing at pp. 14-15.
8See FDA Comm. Dr. Hahn, Lt. to Senator Charles E. Grassley (February 12, 2020) (available on https://www.finance.senate.gov/imo/media/doc/2019-3127%20RESPONSE.pdf); see Hearing at pp. 52-55.
9See FDA guidelines, Circumstances that Constitute the Delay, Refusal, Limitation, or Denial of a Medication Inspection at 3-4 (Oct. 2014); see Hearing at pp. 14, 52.
11See Hearing at 2 p.m.
12See Grassley’s letter; see Hearing at 15.
13See Grassley’s letter; see US House Comm. on energy and trade, Securing U.S. Drug Supply Chain: Oversight of the FDA’s Foreign Inspection Program (December 10, 2019) (available on https://www.govinfo.gov/content/pkg/CHRG-116hhrg44495/html/CHRG-116hhrg44495.htm); see Newsweek Magazine, Katherine Eban, Bottle X: Exposing impurities in the generic drug trade (July 2, 2019) (available at https://www.newsweek.com/2019/07/19/bottle-x-exposing-impurities-generic-drug-business-1446934.html).
15See RAPS, J. Elgovitch, Unannounced FDA inspections in India and China to begin soon (December 15, 2021) (available on https://www.raps.org/news-and-articles/news-articles/2021/12/us-fda-to-soon-start-unannounced-inspections-in-in).
16See HR Rep No. 116-445, at 86 (2020) (available at https://www.congress.gov/116/crpt/hrpt446/CRPT-116hrpt446.pdf).