If you apply for marketing authorisation in the US, your manufacturing facility will be inspected by the US Food and Drug Administration (FDA).
While foreign sites will receive notice of inspection – unlike in the US – the process can still be extremely stressful, Robert Fish from the EAS Consulting Group said at the CPhI Pre-Connect Congress in Madrid yesterday, before giving tips on how to avoid a dreaded 483 with a list of observations of deviations from GMP.
“The reality is most companies will get an FDA-483 at some point but hopefully not with any major observations,” he said.
But to acquire a regulatory nod, Fish – who served as an FDA investigator for 33 years – told delegates it is essential to prepare, and knowing what to expect by reviewing the relevant compliance programmes can save major headaches later.
Similarly, knowing the details of the actual application will avoid embarrassments, while training employees and holding mock inspections could mean the difference between receiving an NAI (No Action Indicated) and receiving a Warning Letter.
Inspection Day
“It is essential for the first impressions to get off on the right foot,” Fish said, and thus if you are subject to an inspection make sure the site is orderly, all equipment is clean and you remain courteous: “If you push back and get argumentative, they will do the same.”
Furthermore, the FDA has free reign to speak to any staff member and so Fish advised firms to brief individuals to “answer questions honestly and directly, and if you don’t know the answer to a question then don’t guess.”
And, he continued, don’t offer up extra information. “As an FDA inspector, I was surprised by the amount of voluntary information I was told: ‘Oh Mr Fish, you should have been here last week, the stuff was flowing all over the floor!’”
Affidavits
The inspector can also demand any data, except for financial or personal, and so Fish said ensuring this is available on request was also important, as is not letting the inspector wonder around the plant alone (“except to the bathroom”).
It is also common practise for an inspector to prepare an affidavit on site. “Never sign anything - You don’t have to,” he said, as you may be admitting to GMP violations.
But what a drugmaker can do during an audit is make corrections. “It may still result in an observation on the 483 but typically an investigator will note that a correction was made.”
A drugmaker can also help itself post-inspection by responding appropriately and in a timely fashion:
“We recommend within 10 days you should respond to each observation, committing to corrections but making sure these are actually achievable.”