The draft guidance offers a number of different scenarios where a manufacturer’s actions to delay, deny, limit or refuse an inspection, as well as others times when such an action would cause their drugs to be considered misbranded by the FDA.
By far the biggest complaint among the manufacturers commenting on the guidance was a lack of clarity on circumstances when a manufacturer’s actions would be used against a company.
For instance, Merck says it would be “very helpful to have further guidance on what would be considered a ‘reasonable explanation’” for delaying an inspection.
Novartis echoes that sentiment, noting that “it is not clear exactly what the FDA would deem to be a ‘reasonable explanation’ or ‘adequate justification.’ These terms need to be better defined and FDA should provide detailed examples and explanations.”
The draft guidance therefore “leaves it too much to the opinion of any particular FDA investigator that the inspection process is being hindered,” Novartis adds.
Circumstances when an FDA investigator is left in a conference room without access to necessary documentation or responsible individuals for “an unreasonable period of time,” is also cited in the guidance as a cause for deeming a manufacturer’s products misbranded.
But Merck notes that the language used by the agency “seems to assume malicious intent to avoid providing records, and there is an underlying assumption that the record(s) requested actually exists.
“That reference could be open to a wide range of interpretations depending on the inspector(s) involved and their style of conducting inspections. What is an unreasonable period of time?” Merck asks.
The drugmaker also offers the example and questions what would happen if a company might fail to produce a deviation record that an inspector feels should exist, but “through an alternative assessment by the firm, does not, lead to an assessment of a GMP system issue (current state of affairs), or an immediate assessment that the product is adulterated under the new guidance.”
GSK, Celgene, BIO Comments
GSK also seeks to amend the guidance so that limits on photography and access to certain areas of a facility might be limited with adequate justification.
Celgene, meanwhile, seeks more consistency for foreign and domestic manufacturer inspections.
“When the FDA inspects facilities outside of the USA they usually provide approximately 1 months’ notice of the intent to perform an inspection,” Celgene says. “Foreign inspections are as effective as domestic so would FDA consider implementing a similar approach domestically, at least for routine inspections?”
In addition, biopharma industry group BIO took particular concerns with how manufacturers will be notified of inspections. The group says that it is “concerned that under the Draft Guidance an inspector would have the authority to characterize a delay or a limitation as sufficient to adulterate a drug without providing the Sponsor sufficient notice or due process.”
The comment period on the draft guidance closed on Sept. 13 and the FDA is now reviewing the comments.