Junkbond92 wrote: SPCEO1 wrote: Do you have any evidence that the FDA is planning to reinspect WuXi? You may be presuming something that is not even an issue.
Let's put 2 and 2 together to make 4. There were relatively "minor" manufacturing infractions. I stand by my statement that there are no such things as "minor" manufacturing infractions. The FDA found something they did not like at the plant when they inspected it and it was documented. Upon receiving the Form 483, the FDA realized they would need to get more documents as to assure themselves that some data submitted, likely related to the manufacturing process itself and the results that came out of it, was acceptable. This should immediately raise red flags to anyone familiar with the FDA, 483s, and approvals, be it for ANDAs or NDAs. If it was relatively minor, the PDUFA date would not have been pushed back. Minor infractions at a plant involve things like the following (taken from my 483 database): -
Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that in-process materials and drug products conform to appropriate standards of identity, strength, quality, and purity
The responsibilities and procedures applicable to the quality control unit are not fully followed
Buildings used in the manufacturing of API drug products are not maintained in good state of repair
Equipment used in the manufacturing of API in intermediate area not of appropriate design to facilitate operations for its cleaning and maintenance.
This 483 was given on 12/16/16 and cleared 3 months later on 3/15/17. Here's another minor one Procedures are not established or followed
Cleaning procedures or clean status is not established
Manually managed materials in the warehouse are not separated during storage
This one was given 9/15/17 and has yet to be cleared. My best estimate is it is completed by end of this month, early next month. A very serious 483 looks like this: Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards
Failure to prevent unauthorized access or changes to data, and to provide adequate controls to prevent omission of data
failure to record activities at the time they're performed
Failure to control the issuance, revision, superseding and withdrawl of all documents with maintenance revision history.
That happened 11/21/14 and still hasn't been cleared. It ended up in a Warning Letter that has yet to be fixed. The average time from 483 to EIR/Letter 145 in my database is ~155 days. The fastest was 85 days, the longest was 325. The fact that it was pushed out to April means that they didn't feel like they could fix the issues with the Form 483 between August and January 3nd which is 155 days. That, to me, raises alarm bells. If the CAPAs were able to be submitted in writing, the delay wouldn't be more than one or two months.
Why? Well, companies and the FDA start corresponding almost immediately after receiving the 483. They're required to.
This is when they submit the CAPAs, and the FDA judges them. If the FDA likes the CAPAs and the issues aren't too severe, they will trust the company and not require a reinspection.
If they like the CAPAs but the issues are severe, they'll accept the CAPAs but want to see them implemented in person during a reinspection.
If they don't like the CAPAs after repeated correspondence, they'll give out a warning letter. Lupin just got one of these a few days ago.
An issue in the 1st example likely wouldn't require a lot of extra documentation but the one in the 2nd would. I'm not saying that the 2nd example is what Wuxi is going to encounter, but it's certainly not the first. Just my $0.02