Regulatory Focus™ > News Articles > New FDA Staff Policy Manual Defines 'Major Amendments' to Generic Drug Submissions

New FDA Staff Policy Manual Defines 'Major Amendments' to Generic Drug Submissions

Posted 04 October 2012 | By Alexander Gaffney, RAC 

The US Food and Drug Administration's (FDA) Office of Generic Drugs (OGD) has released a new guideline for its internal review staff on how to handle amendments to generic drug applications.

The Manual of Policies and Procedures (MAPP), Reviewer Determination of Major/Minor Amendments to Abbreviated New Drug Applications, is specifically intended for OGD's chemistry review staff. After submitting an original or supplemental Abbreviated New Drug Application (ANDA), which are used to support approval for generic drugs, companies may file amendments to the application to reflect new information or desired changes.

These changes fall into two general categories, explained FDA: major or minor amendments. The difference between the two, aside from severity, largely comes down to a matter of review time. Major amendments take approximately 180 days to review, while minor amendments take between 30 and 60 days.

Major amendments involve changes to a drug's composition or formulation, changes to the source of a drug substance, a major change to the drug's manufacturing process or manufacturing site, the need for a new bioequivalence or in vitro study, a stronger product concentration, failed stability data, the use of unapproved excipients, or a change to the container or closure system for non-solid oral dosage drugs.

Several other instances constitute major amendments, added FDA. These include amendments to analytical methods and validation data, which may be considered major if data does not indicate the stability of a compound, the rate of degradation or the presence of genotoxic impurities.

FDA noted, however, that method verification by itself could be construed as a minor amendment.

Poor quality ANDA submissions will be characterized as requiring major amendments, particularly if they require the overhaul of major application sections. FDA also said that submissions that fail to show conformity to existing standards, such as those maintained by the US Pharmacopoeia or the International Conference on Hamonisation (ICH) will require major amendments to their applications.

Other amendments will be taken by FDA review staff to be minor amendments, but are not enumerated in the MAPP.


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