Peter Smith agrees that paying attention to guidances, even if they're not technically enforceable, is crucial to passing
an inspection. "Any good investigator can make a tie from a failure to follow a certain guidance to a true GMP deficiency,"
"It's unprecedented right now what's happening globally from a risk-management perspective," says Medina. "We've had over
10 risk-management guidances or global initiatives in the past three years—that's huge. Risk management is on everyone's minds."
In preparation, many companies expect to address risk management according to quality guidelines issued by International Conference
on Harmonization (ICH) in addition to those issued by FDA.
Seeking conformance to international regulations is critical when preparing for inspections from other countries' regulatory
agencies such as the European Medicines Agency. "Europe, Japan, Brazil, and others are all using similar ICH guidelines, even
World Health Organization or PIC/S guidelines, so it's important to pay attention to them," adds P. Smith.
ICH Quality Guidelines (i.e., Q7, Q8, Q9, and Q10) are receiving increased attention. Addressing product development, quality
risk management, and quality systems, respectively, these guidelines help to put frameworks around some of the issues important
to FDA and to other international regulatory agencies.
"We are hoping companies will read and study these documents and find out how to use the concepts within them as they operate
their program of drug discovery, development, assessment, and manufacturing controls," says Nicholas Buhay, deputy director
of the Division of Manufacturing and Product Quality in FDA's Division of Manufacturing & Product Quality in the Office of
Compliance. "We hope through harmonization to make our operations more efficient for industry while still providing valuable
approaches to manufacturing, manufacturing control, and development that will make a more certain and reliable product."
Pay attention to overseas operations
Preparing for an overseas inspection may require more time and, in many instances, extra resources than preparing for a local
inspection. In addition to reviewing FDA's international inspection guide, there are several unique points to keep in mind.
For example, for inspections in non-English speaking countries, have an interpreter on site. "Sometimes there are misunderstandings
caused because a proper English word is not used or because the question is not clearly understood. Use an interpreter to
make sure things are clarified," says P. Smith.
"It's also a good idea to have an English translation of critical documents and standard operating procedures (SOPs)," adds
P. Smith. "They don't have to be official, but good translations on items such as change control, deviation investigations,
and validation reports are important."
FDA has more stringent standards when it comes to imported goods. "The law doesn't provide us the authority to go to another
sovereign jurisdiction and do what we want there," explains Buhay. To remedy this, investigators can use an "appearance standard"
rather than "a full conformance standard," he says. "We can refuse a product's entrance if it appears to violate the law."
Overseas inspections are announced and are usually for a shorter, predetermined length of time. "One of the flexibilities
you don't have in the foreign arena is to extend the inspection. These trips often involve multiple firms and commitments
to inspect other sites the following week," explains Rogers. "We also need to have the data and management available before
International inspections are often shorter also due to the additional resource burden, adds Buhay. "We can't go out as frequently
as we would like to. On the other hand, we prioritize pretty effectively. We are getting to places that matter according to
the conditions that apply, like risk and the impact of drugs on the US market."