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Regulatory Focus™ > News Articles > Making Changes to an Already-Approved Drug? FDA's New Guidance Wants to Help

Making Changes to an Already-Approved Drug? FDA's New Guidance Wants to Help

Posted 02 December 2014 | By Alexander Gaffney, RAC

Making Changes to an Already-Approved Drug? FDA's New Guidance Wants to Help

The US Food and Drug Administration (FDA) has released a new final guidance document regarding how manufacturers of pharmaceutical products can make changes to their manufacturing equipment under FDA's scale-up and post-approval changes (SUPAC) requirements.


After a pharmaceutical product is approved, its sponsor and manufacturer must work to meet ever-changing manufacturing standards, as well as demand for the drug. Though the drug product itself is still approved, a manufacturer must show to FDA that each change it makes to its manufacturing process (e.g. new production lines, the use of new equipment or new processes) will have no effect on the safety, efficacy or quality of the approved medicine.

Depending on the magnitude of the proposed changes, FDA permits sponsors to make them in a variety of different ways. For minor changes, companies can either make note of those changes in their Annual Reports or notify FDA at the time a change is made using the Changes Being Effected (CBE) process.

For most manufacturing changes, however, sponsors must notify FDA of the change using the Prior Approval Supplement (PAS) (21 CFR 314.70) and await FDA's approval of the change before implementation.

Determining which change notification process to use—and knowing which documentation FDA needs to determine if a change is appropriate—can be difficult.

New Guidance

FDA's latest guidance, SUPAC: Manufacturing Equipment Addendum, is dedicated to creating a holistic set of recommendations about how to support proposed manufacturing changes using proper documentation.

The guidance is especially important in that it combines and replaces two earlier guidance documents on the same subject:

  • SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms, Manufacturing Equipment Addendum
  • SUPAC-SS: Nonsterile Semisolid Dosage Forms, Manufacturing Equipment Addendum.

As explained by FDA, the new SUPAC guidance is meant to define four things:

  • levels of chemistry, manufacturing and control change
  • recommended chemistry, manufacturing and controls tests for each level of change
  • recommended in vitro dissolution and release tests and/or in vivo bioequivalence tests for each level of change
  • recommended documentation that should support the change for new drug applications and abbreviated new drug applications

FDA said it will assess proposed changes "based on the types of equipment changes being considered."
While FDA's written approach is recommended, it is not mandatory, and sponsors can pursue alternate approaches provided they are "supported by a suitable risk-based assessment."

The guidance contains advice on how to support changes to:

  • particle size
  • blending, mixing, drying
  • granulation
  • unit dosing
  • soft gelatin capsules
  • coating, printing and drilling
  • emulsification
  • deaeration
  • transfer
  • packaging


SUPAC: Manufacturing Equipment Addendum (FR)

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