Scenario A
Paul Larocque
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Let's say you have a production facility in Trenton, San Francisco, or Boston—really anywhere in the United States. Your company's
drug-development efforts have been successful, and it's time for the US Food and Drug Administration to conduct a pre-approval
inspection. Your company has made careful preparations. One day, two FDA investigators arrive at the door of the facility.
Because the agency has not inspected your facility in recent years, the investigators announce that they plan to spend two
weeks on site. The investigators are fair and thorough. They ask to see:
- Your written procedures, which you quickly provide
- Your logs for deviations, out-of-specification results, rejected batches, change control, complaints, and stability failures.
They request trend reports for environmental monitoring and for the water system. Batch records and other product-specific
documents are also requested. You provide these logs and records promptly and, using risk-management principles, sort them
into piles from the most critical to the most minor.
- Finally, the investigators ask to see your records for all the critical lots, which you promptly provide.
The investigators scan the documents for any red flags. Every few minutes, they ask for clarification of various points; responses
are provided immediately so that the investigators can move on quickly.
During the exit interview, your company receives a Form 483 containing 12 observations, none of which are deemed critical
(i.e., related to fraud) but several will take significant time and resources to correct. (Once corrected, FDA will consider
granting approval for the product that was reviewed.) Your company makes the required adjustments and months later, the product
is approved and launched.
Scenario B
Instead, let's say your production facility is located in continental Europe, Asia, or Mexico—any non-English-speaking country.
Your company's drug-development efforts again have been successful. It's time for the FDA pre-approval inspection. The agency
contacts you weeks in advance to schedule the inspection with one investigator, who is scheduled to be on site for five days.
Your company makes careful preparations, including training the staff about the conduct of FDA inspections. On the agreed
day, the FDA investigator arrives at the door of the facility.
The investigator asks to see the same documents as noted in Scenario A, which you provide promptly. As required, the documents
are written in the local language. A handful of the most common standard operating procedures have been translated into English,
and these too are provided to the investigator. However, the logs, complaint records, trend reports, product-specific documents,
investigations, and change-control records are all written in the local language.
The investigator tries to scan each document for red flags but, not being proficient in the local language, frequently asks
for explanations about what is written. The FDA investigator would like to ask the analyst who generated the data (or the
operator who conducted the step) what happened, but neither person speaks English. The host, who is head of quality assurance,
speaks reasonable but halting English and acts as an interpreter.
Ultimately, the investigator ends up auditing far fewer documents than he would have in an English-speaking location. At the
exit interview, your company receives a Form 483 containing three observations, none of which are deemed critical. Within
about two weeks, the company addresses the observations, FDA approves the product, and the product launches.
