It wasn’t so much a threat as a promise. FDA is going hard on foreign inspections.
In the last 2 months, we have become aware of a marked increase in both the frequency of foreign inspections and the severity of the findings from those inspections, with sites in India being hardest hit.
As consultants, we hear back-channel discussion of ongoing inspections and are often approached to help with the responses to FDA’s observations recorded on Form 483.
Folks, this is real, it’s ramping up right now and in our opinion, the current trend will only increase in strength.
What’s behind this increase in Inspection oversight, and why do we think it will continue?
On the 5th of May this year, the White House announced that President Trump had issued an executive order with the goal of tightening oversight of foreign pharmaceutical manufacturing plants. The order included the requirement that the names of chronically non-compliant foreign manufacturers would be made public.
The next day, 6th May, US FDA announced that it will “expand the use of unannounced inspections at foreign manufacturing facilities” to eliminate what FDA Commissioner Marty Makary called a “double standard” between domestic and foreign manufacturing sites.
Without getting into the political and policy-related aspects of these developments, it’s important to note that there is an inspection backlog of foreign manufacturing sites that dates back to the COVID era. In September last year, the AP reported that in India and China alone, there were more than 340 sites that had not been inspected since 2019.
It’s clear that FDA is now responding, and that FDA’s Investigators are starting to level the playing field on compliance standards. Manufacturers in India are being inspected without warning, perhaps for the first time for some of them.
What can you do to turn a risk into an Opportunity?
There are both short and longer term answers to this question.
In the short term, it’s important to learn how to present current capabilities in their best light. Due to differences in language, culture and plain lack of practices, many foreign manufacturers struggle with this. We’ve seen a great many unnecessary 483 observations arise from misunderstanding, poor presentation, poor inspection planning, or all of the above. Domestic manufacturers have learned how to be always inspection-ready and you should too.
In the mid-term, this means learning to respond to inspectional observations in a way that demonstrates objectivity, holistic thought and commitment to supporting fundamental improvement. All too often, responses to 483 lack one or more of the following elements:
- Recognition of the actual problem (as seen by the FDA investigator)
- Corrective response to the specific situation
- Assessment of where else the issue may have occurred, and proper response to this assessment
- Well-constructed response plan, with sensible timelines and resources
- Effective use of the Quality System to manage all of the above
We have seen many times that a well-written response, with effective implementation and follow-up communication, can turn a tough inspection into an increase in trust and communication with regulators. Conversely, inadequate responses often lead to enforcement actions that massively disrupt business.
Taking a longer-term view, it’s important to recognize that much has been written about the value of superior quality and the risk-avoidance aspects of compliance. Sometimes glib, sometimes inspiring, response to this message has been, ahem, variable. In our experience, too many foreign manufacturers have seen this situation as a drive to do just enough to get through the next (usually announced, sometimes softened by drug shortage consideration) inspection. Given current trends, we are certain that this position will not work in the future.
Business pressures give rise to positive response, with the early responders deriving competitive advantage.
Companies that manage quality proactively, efficiently and effectively, will always have lower costs when faced with high standards than companies that run on a minimum standards basis. Strong quality management confers compliance (let’s not forget, compliance is the minimum legal requirement for drug manufacturers) and also gives rise to improved operations:
- More material is produced right first time. Supply chains are smoother, safety stocks can be lower (less disruption) and there is less waste.
- Continuous improvement is fostered. There is a direct link between the ability of a manufacturer to manage deviations and CAPAs and the company’s ability to learn quickly from its mistakes
- Agility to respond quickly to changing conditions is greatly enhanced. The Quality System process of Change Control, when done well, provides for speedy and effective introduction of improvements and responses to changing technology and business conditions.
Getting to this improved state of affairs is not easy and takes time, but it’s well worth it, because when you’re inspected, your systems and processes will handle the challenge. Conversely, your competitor who thinks they can get by with yesterday’s status quo will be hit, hard.
There was never a better time to work on improving the capability of your organization to manage to a high standard of Quality. This means:
- Quality Systems and the associated procedures
- Human capital, organizational structure, training and development
- Culture, shared standards, goals and behaviors.
When you’re ready to prepare for your next inspection, be it next week, next month, or in a years’ time, you’ll benefit from getting expert help. We have a track record of working with foreign manufacturers and we would love to be your partners on this journey.
Mark Roache, QxP VP of Cell and Gene Therapies, has spent his 30-plus year career in GXP. Mark was the Chief Quality Officer for AveXis (now Novartis Gene Therapies) at the time of Zolgensma launch. He was previously Senior VP of Quality for KBI (a CDMO with cell-therapy capabilities) and has held other senior Quality roles at Novartis, Merck and Bayer.
