GDUFA III Raises Hopes for Surprise PSG Issuance/Revision Explained at AAM’s GRx-Biosims Conference

The product specific guidance (PSG) has been a big help to industry in outlining the requirements for establishing bioequivalence requirements for generic drug products.  OGD has issued over 2000 PSGs since the practice began.  While this has been a big boon to industry, there are times when the issuance or revision of a PSG may cause a big headache for industry.

Prior to GDUFA III, we have blogged about impact that revisions in a PSG can have on the industry (see here, here, here, and here. The biggest impact comes when the FDA issues a new PSG or makes a major revision in an existing PSG where the sponsor has already conducted a bioequivalence study. This can happen either pre- or post-submission of the ANDA or even after an ANDA is approved.

GDUFA III outlined in its commitment letter additional actions firms would have available to them under the new enhancement for this 5-year cycle to address the pre-and post-ANDA submission with the issuance or changes to a PSG.  These were explained in more detail in by Lei Zhang, Ph.D., Deputy Director, Office of Research and Standards, Office of Generic Drugs CDER, FDA by addressing new touch points and meetings with FDA in the development and review process of an ANDA. These come in the form of PGS telcons, PSG pre-submission meetings, and PSG post-submission meetings as outlined in following slides taken from Dr. Zhang’s presentation:

PSG T-con Pre-Submission PSG Meeting Post-Submission PSG Meeting
• New in GDUFA III
• Purpose:For applicant to obtain Agency feedback on the potential impact of the new or revised PSG on its development programIf the applicant seeks further feedback
from FDA after a PSG T-con, the applicant may utilize the Controlled Correspondence process or request an additional meeting		 • New in GDUFA III
• Purpose:For applicant to have further scientific discussion following the PSG T-conTo provide a forum in which industry can discuss the scientific rationale for an approach other than the approach recommended in the PSG to ensure that the approach complies with the relevant statutes and regulationsRequest if ANDA has not been submitted yetCan request regardless of whether prospective applicant have had a PDEV Meeting		 • New in GDUFA III
• Purpose:For applicant to have further scientific discussion following the PSG T-conTo provide a forum in which industry can discuss the scientific rationale for an approach other than the approach recommended in the PSG to ensure that the
approach complies with the relevant statutes and regulationsRequest if ANDA has been submittedCan request regardless of whether applicant have had a PDEV Meeting or a Post-CRL Scientific Meeting

 

PSG T-con (Pre- or Post-Submission) Pre-submission PSG Meeting Post-submission PSG Meeting
New in GDUFA Ill? Yes Yes Yes
Eligible Products Both complex and non-complex if PSG (new or revision) impacts in vivo BE study Both complex and non-complex if PSG (new or revision) impacts in vivo BE study; follow up from prior PSG T-con
When to Request a
Meeting		 When applicants has already commenced an in vivo BE study that is different from FDA newly published PSGs (new or revision) Following PSG T-con, this meeting can be requested for further scientific discussion
Format of the Meeting T-con or WR1 FTF, videoconference, T-con or WR2
Grant/Deny Decision Timeline (14 days) 14 days*
Days to Conduct the
Meeting		 30 days from meeting request receipt 120 days from meeting request receipt 90 days from meeting request receipt
When to Send a
Controlled Correspondence in Lieu
of a Meeting Request		 Seek further feedback from the FDA after a PSG T-con; Clarification questions or questions outside of the scope of the meeting Clarification questions or questions outside of the scope of the meeting. Applicants can send CC after meetings if they
are seeking further clarification or have new questions.
www.fda.gov      *In the Commitment Letter         1 If applicant requests a WR instead of T-con, it may be granted as WR           2 FDA can provide a T-oon or WR, if requested by the applicant or if FDA grants the meeting above and beyond the commitment letter

 

 

 

 

 

 

 

 

 

 

 

 

I  was fortunate to be able to ask Robert (Bob) Lionberger, Ph.D., Director, Office of Research and Standards, Office of Generic Drugs at FDA about the issue of how a major change in a PSG post-ANDA approval can impact marketed generic products and when does such a change move the Agency to request that new studies be conducted for approved products?  He noted that typically, when a revision is made to a PSG, OGD does not require applicant of an already approved product to redo studies to conform to the new change unless the Agency determines that the safety or efficacy of the marketed product could be impacted.  He also noted that there have only been two instances when OGD required new studies for an approved marketed ANDA product after a major change was made to a PSG.  The two instances were in the case of bupropion extended-release and methylphenidate extended-release products. Thus, approved products as not nearly as likely to require new studies as pre-submission ANDAs or post-ANDA submissions.

Now under GDUFA III there are new options open for discussion with OGD in dealing with the a.ppearance of a new PSG or a major revision to a PSG prior or post-ANDA submission. The additional detail presented by Dr. Zhang and the offline response from Dr. Lionberger takes much of the angst out of PSG revisions to or issuance of a new PSG in certain circumstances. The new options allow for applicants to make their case with OGD to determine if, based on what the applicant has already done, whether new studies will be needed.