Introduction to Scale-Up and Post-Approval Changes (SUPAC)
Scale-up is an inevitable part of the product life cycle of every successful drug, and each time it is required, a meticulous process must be followed to ensure that the end result is identical to the product formulation as originally devised. American Association of Pharmaceutical Scientists (AAPS), the U.S. Food & Drug Administration (FDA) and the United States Pharmacopeia (UPS) to explore principles for making process and/or compositional changes in drug products post approval. These changes ultimately included formulation or compositional changes, process changes, process scale changes and process site or campus changes.
What does SUPAC means in drug industry?
SUPAC(Scale-Up and Post-Approval Changes) guidance provides recommendations to sponsors of new drug applications (NDA's), abbreviated new drug applications (ANDA's), and abbreviated antibiotic applications (AADA's) who intend, during the post approval period, to change: 1) the components or composition; 2) the site of manufacture; 3) the scale-up/scale-down of manufacture; and/or 4) the manufacturing (process and equipment) of an immediate release oral formulation.
This guidance combines and supersedes the following scale-up and post-approval changes (SUPAC) guidances for industry: (1) SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms, Manufacturing Equipment Addendum, and (2) SUPAC-SS Nonsterile Semisolid Dosage Forms, Manufacturing Equipment Addendum. It removes the lists of manufacturing equipment that were in both guidances and clarifies the types of processes being referenced.
What You Should Know about SUPAC?
Among the things you should know about SUPAC is that it is not regulation, but only guidance. It relates only to drug manufacturing and it’s only available for certain dosage forms: immediate release solid oral dosage forms including tablets, capsules, and soft gelatin capsules; modified release solid oral dosage forms including delayed release and extended release; and topical semi-solid dosage forms including creams, ointments, suspensions, emulsions and gels.
SUPAC: QUESTIONS AND ANSWERS
May one color be replaced with another by placing the batch on concurrent stability and reporting it in the annual report?
A change from one color to another should be submitted as a prior approval supplement.
Can color be changed under SUPAC-IR?
Yes. A change in color, either in amount or from one color to another, is a level 3 component and composition change which calls for a prior approval supplement. However, if the color is merely being removed, it is a level 1 change and can be reported in the next annual report.
What is the full definition of a change in ‘technical grade” of an excipient? Does this only mean a change in excipient specifications that may impact functionality or does it include a change in supplier even if all applicable specifications remain the same?
Technical grades of excipients differ in their specifications and intended use. Technical grades may differ in:
1) specifications and/or functionality;
2) impurities; and
3) impurity profiles.
If a supplier of an excipient changes but its technical grade AND specifications remain the same, the agency should be notified in an annual report.
How does one apply SUPAC-IR to multifunctional excipients, e.g., starch?
SUPAC-IR composition changes are based on being able to define the use or action of the particular excipient in the product. This rationale should be included by the applicants as part of their original applications. Not all multifunctional excipients are listed in the guidance. However, if an excipient was utilized to provide multiple functions such as pregelatinized starch as a filler, starch as a disintegrant, starch paste as a binder, then the most conservative recommended change should be followed (e.g., for an excipient that is a filler, disintegrant and binder, the recommended limit for a Level 2 change is ” 0.5 percent. An applicant may wish to add an explanation of how the change will affect other functions of the excipient in the product. If this information was not included in the original application, the review division should be consulted before filing such a SUPAC change, either through a CBE or annual report.
What is the reference source for defining the action of an inactive ingredient, for example, lubricant versus glidant? What if the action is defined differently in two sources?
An applicant should be able to justify the choice and the basis for the selection of a particular excipient, i.e., its expected function in the drug product. It may be useful to cite a source. The action may depend on the specific product.
Nonsterile Semisolid Dosage Forms:
This guidance provides recommendations to pharmaceutical sponsors of new drug applications (NDAs), abbreviated new drug applications (ANDAs), and abbreviated antibiotic drug applications (AADAs) who intend to change :
- The components or composition,
- The manufacturing (process and equipment),
- The scale-up/scale-down of manufacture, and/or
- The site of manufacture of a semisolid formulation during the post approval period.
This guidance addresses nonsterile semisolid preparations (e.g., creams, gels, lotions, and ointments) intended for topical routes of administration.
The guidance defines:
- The levels of change.
- Recommended chemistry, manufacturing, and controls (CMC) tests to support each level of change.
- Recommended in vitro release tests and/or in vivo bioequivalence tests to support each level of change.
- Documentation to support the change.