If you wonder whether you need to conduct SUPAC-SS Testing on you semi-solid product, or you have learned that you do have to perform IVRT testing as per SUPAC-SS Guidance, you have come to the right place.

About In Vitro Release Testing (IVRT)

In vitro release testing (IVRT), an analytical method employed by the pharmaceutical and cosmeceutical industries for assessing performance of a topical product. It allows formulators to develop a topical product with Quality by Design principles. IVRT measures the rate of release of a drug across a non-interactive membrane (synthetic membrane or skin) into an appropriate receiving medium.

IVRT is a useful test during product development, allowing appropriate selection of a clinical candidate with Quality by Design principles (QbD), and can serve as a cost effective means to monitor the consistency in manufacturing of semi-solid dosage forms during clinical trials. IVRT is often conducted using vertical diffusion cells (also called Franz diffusion cells) and can be used to develop performance tests for a variety of semisolid dosage forms including: Creams, Ointments, Lotions, Liquids, Suspensions, Gels, Hydrogels, Pastes, Pump Sprays, Topical Aerosols, Foams, Microencapsulation, Liposomes/Ethosomes, Suppositories, and Nail Lacquers.

SUPAC-SS Explained

Certain levels changes in approved products such as site transfer, changes in excipient supplier or grade, and some other such changes, SUPAC-SS guidance requires an IVRT to be performed to compare equivalency between pre and post change batches. SUPAC-SS stands for FDA’s Guidance for Industry on Nonsterile Semisolid Dosage Forms for Scale-Up and Post approval Changes and was issued in May of 1997.

The FDA has stated in the SUPAC-SS Guidance document that “in vitro release testing has shown promise as a means to comprehensively assure consistent delivery of the active component(s) from semisolid products.”

The SUPAC-SS Guidance is applicable to the following regulatory submission types:
  • new drug applications (NDAs)
  • abbreviated new drug applications (ANDAs)
  • abbreviated antibiotic drug applications (AADAs)
The following list is a subset of the SUPAC-SS Guidance, but these are some of the changes we see more commonly where IVRT is either required or suggested:

Excipients:

  • Level 2 change: changes that are likely to have a significant impact on formulation quality and performance. Examples are:
    • changes in >5% but <10% of an approved excipient
    • changes in supplier or technical grade of a structure forming excipient
    • changes in particle size of API when it is suspension
  • Level 3 change: changes that are likely to have a significant impact on formulation quality and performance. Examples are:
    • changes in excipient beyond the ranges in level 2
    • changes in crystalline form of API—IVRT not required but highly encouraged

Manufacturing:

  • Level 2 change
    • change in equipment to a different design or different operating principles
    • IVRT required

Process:

  • Level 2 change
    • process change such as rate of mixing
    • mixing times, rate of cooling
    • operating speeds
    • holding times outside approved application ranges (IVRT required)

Batch size:

  • Level 2 change
    • Changes in batch size beyond a factor of ten times the pivotal/clinical batch (IVRT required)

Manufacturing site:

  • Level 3 change
    • Different campus (IVRT required)

SUPAC-SS Reference

For the full SUPAC-SS guidance please refer to:
GuidanceComplianceRegulatoryInformation