By Phil Crooker, VP - Technical, Regulatory & Access, Parexel International
There have been two recent activities from the U.S. Food and Drug Administration (FDA) that provide industry more insight into how the agency is approaching product and manufacturing quality during the COVID-19 pandemic and how some of those trends could stick around. Here are the items:
- On June 2, 2020 three FDA officials testified before the United States Senate Committee on Finance on the oversight of the agency’s foreign drug manufacturing inspection process. You can find a copy of the testimony here - https://www.fda.gov/news-events/congressional-testimony/covid-19-and-beyond-oversight-fdas-foreign-drug-manufacturing-inspection-process-06022020.
- On June 23, 2020 the FDA Commissioner released a statement that the FDA has maintained the same pace of meeting its goals on review of applications for medical products during the pandemic that it has maintained in recent years.
The Office of Pharmaceutical Quality (OPQ) also published its Annual Report for FY 2019 and it contains some information that helps put some of the agency’s remarks in June into context.
Let’s have a look at some of the points raised by FDA and then I’ll add some thoughts about steps industry can take to be prepared for these policy and operational shifts at FDA.
FDA Congressional Testimony
- FDA is postponing foreign and domestic routine surveillance inspections on an interim basis during the pandemic. The postponement of inspections will continue indefinitely as the public health conditions warrant.
- Only certain mission critical inspections – such as preapproval (PAI) and for-cause inspections – are being considered on a case-by- case basis.
- FDA is evaluating additional ways to perform inspections – this includes (but is not limited to):
o Requesting and evaluating records in advance of or in-lieu of an on-site inspection.
o Reviewing a firm’s previous compliance history.
o Using information sharing from foreign governments as part of mutual recognition and confidentiality agreements.
o And using risk scores from the PREDICT database to screen for specific high-risk products.
To get a sense of how frequently FDA had been relying in reports from foreign governments as part of the Mutual Recognition Agreement (MRA) before the outbreak of the pandemic, the OPQ Annual Report indicates that the agency reviewed and classified 109 drug quality inspections performed by European Union investigators during FY 2019.
FDA Commissioner’s Statement
- FDA staff has been very innovative and strategic in completing facility assessments.
- FDA has assessed records of recent inspections to review the facility’s compliance history.
- Used information shared by foreign regulatory partners through mutual recognition and confidentiality agreements.
- Conducted reviews of documents typically evaluated on site to assess the processes implemented at the manufacturing facility.
- The agency will be prioritizing future inspections based on the expected health benefit of the products under review and the overall importance in advancing medical care, taking into account user fee commitments.
- FDA will use other tools to help prioritize future inspections.
These last two points are new bits of policy insight and were not raised by FDA in its Congressional testimony.
What Steps Can Industry Take Now?
- FDA has consistently noted its use of requesting and reviewing records in advance or or-in lieu of an inspection. Be knowledgeable about the FDA policy for this type of request – you can find the FDA Staff Manual Guide (SMG) for these requests here - https://www.fda.gov/media/124338/download.
- Be fully prepared to respond to a request for records or for some type of remote or hybrid inspection alternative. These fall into the “additional ways” to perform inspections. Parexel has a comprehensive suite of tools to help firms prepare for and facilitate these types of on-site inspection alternatives. For more information about this new service please see our website here - https://regulatory-access.parexel.com/access-portal-assets/remote-desktop-cgmp-audits-factsheet. More information about health authority desktop audits is also found in a recent blog by my colleague Mark Birse that can be found here - https://regulatory-access.parexel.com/parexel-blog/desk-based-health-authority-inspections-a-risk-based-approach-to-compliance.
- Reports of inspections conducted by foreign regulators can be just as important as FDA inspections. If your firm has been inspected by a foreign regulator that has a cooperative agreement and confidentiality commitment in place with FDA, then presume that information is being more readily shared now than perhaps 6 months ago. FDA may or may not act on that information. But treat every CGMP inspection as if the results will be shared with FDA. Having a facility consistently assessed as acceptable by foreign agencies is preferable to gaps in compliance that can detract from the facility’s profile.
- If you have an application under review at FDA – whether that is a marketing application or supplement – keep in mind that FDA can use correspondence with the applicant holder for additional information to make decisions about a facility’s assessment. These can include requests for firms to rely on certain facilities listed in the application if there are others that cannot be fully assessed at the time of the goal date for the application.
- What is not explicitly mentioned in either the agency’s Congressional testimony or the statement from the Commissioner is the use of discretion by the agency. An executive agency is normally given a wide berth in determining how to allocate its resources and expertise, and the pandemic has arguably stretched that to its outer limits. It’s wise to keep in mind that the use of this discretion can both enable FDA to waive an inspection just as much as it can result in a decision that an inspection or alternative is necessary even if it can’t be reasonably conducted. Industry should not rely on predicting if or how FDA would use its discretion.
- Take steps to assess the risk in your supply chain. This is likely to become a larger focus for FDA in the future, beginning with the risk assessments for critical drugs that was in Sec. 3112 of the CARES Act (see https://www.congress.gov/116/bills/hr748/BILLS-116hr748enr.pdf).
- Don’t wait for FDA to act or not – since these are extenuating circumstances, consider using all appropriate channels to communicate with FDA about facility inspections and assessments, including timing. FDA has signaled that it will begin prioritizing inspections and some facilities may experience delays. This is more readily done for applications that are under review or for facilities that are expecting re-inspections than for routine surveillance inspections. There will be a limit to what FDA can discuss and when it can have those discussions. Be prepared to step into FDA’s shoes and engage in productive discussions about risk assessment and inspection alternatives that protect public health while balancing operational concerns from both sides