Stability Assays For The Top Five Types Of Sterile Products
What is the importance of sterility assurance and stability testing for sterile medical devices, cosmetics, and medical products?
Sterile products must prove that the product is stable over time and that the product can remain sterile over time. A sterility test is performed at set time periods for stability testing of sterile products (such as any prefilled injectable product). These set periods are typically the beginning of the stability testing period, at one month, two months, three months, six months, and annually to ensure the container-closure system protects products from contamination until expiry. Sterile products must also be tested for bacterial endotoxins at the beginning and the end of the stability period. Sterile solid or ampoule products only need initial sterility and endotoxin data.
Stability Data Requirements By FDA Development Phase
Phase 1
A brief description of initial stability studies and test methods used to monitor stability during Phase 1 clinical studies is required. Stability data are considered preliminary, and detailed stability data are not needed. However, there must be stability data that shows the drug will remain stable during the course of the Phase 1 trial.
Phase 2
The Phase 1 and Phase 2 stability data must be robust enough to provide information on the final formulation and container and closure system. New stability studies may need to be started to support the product’s shelf life throughout Phase 2 studies.
Phase 3
Final formulations in their proposed market packaging and manufacturing site will be tested. A final stability protocol must be well defined before the initiation of Phase 3 studies.
Stability Assays For The Top Five Sterile Product Types
The FDA requires various product characteristics to be monitored during stability testing depending on the sterile product type. Five of these product types and their monitoring requirements are detailed below.
#1: Solution Formulations (Injectable Solution Products)
Stability data to acquire for solution-based injectables include evaluation of:
- Active ingredient(s)
- Antimicrobial preservatives (if applicable)
- Appearance (especially any changes in color and clarity)
- Degradation products
- Particulate matter
- pH
- Sterility
- Pyrogenicity
#2: Sterile Dry Products That Will Be Reconstituted into Solutions
Stability data must be obtained both from the solid-state and from the solution state after reconstitution.
Stability data to acquire immediately after reconstitution include:
- Residual moisture right before reconstitution
- Active ingredient(s)
- Appearance (clarity, color)
- Particulate matter
- Reconstitution time
- pH
- Sterility (annual determination)
- Pyrogenecity
Stability data to acquire at various times after reconstitution include:
- Active ingredient(s)
- Appearance (clarity and color)
- pH
- Particulate matter
#3: Dispersed System Products (Injectable Suspension or Emulsion Products)
Most of the same assays for solution formulations apply to suspensions and emulsions.
Stability data to acquire for suspensions include:
- Particle-size distribution
- Re-dispersibility
- Rheological properties
Stability data to acquire for emulsions include:
- Mean globule size and distribution
- Phase separation
- Viscosity
#4: Products Contained in Prefilled Syringes
Syringe products are evaluated for functionality and integrity tests described below, along with tests for their specific formulation (solution, emulsion, or suspension).
Stability data to acquire for prefilled syringes include:
- Applied extrusion force (pressure required to move the rubber plunger)
- Glide force (movement of the product through the barrel of the syringe)
- Syringeability (ease of withdrawal, clogging and foaming tendencies, and accuracy of dose measurements)
- Leakage
#5: Combination Products
For combination products, stability data must be obtained with both the lowest and highest concentrations of the active ingredients in each diluent. Additionally, three different lots of the final drug product formulation must be tested.
Combination products require compatibility testing for additives and active ingredient combinations. Compatibility testing is to be performed in containers that are in upright, inverted, and sideways orientations.
Stability data to acquire for combination products include:
- Overall appearance
- Color
- Clarity
- Active ingredient potency
- Degradation products
- pH
- Particulate matter
- Interaction or compatibility data in the container-closure system
- Sterility
Summary
All in all, sterility assurance and stability testing are critical regulatory criteria for sterile medical devices, cosmetics, and medical products. For all sterile products, the Food and Drug Administration (FDA) will need proof of container-closure integrity over time in addition to general evidence of stability. Additional stability assessments for sterile products that are solutions, dry products to be reconstituted, dispersed system products, prefilled syringes, and combination products are detailed above. If you are looking to outsource your stability testing, ensure that you choose a contract testing organization that can support you with all your stability testing needs for your medical devices and products.
MycoScience is a contract manufacturing organization that specializes in filling sterile syringes and vials for parenteral products. MycoScience also offers Stability Testing, Bacterial Endotoxin Testing, Preservative Efficacy Testing, Sterilization Validations, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, Cytotoxicity Testing, EO Residual Testing, Package Integrity Testing & Environmental Monitoring services for medical device companies, and allied industries. MycoScience is an ISO 13485 certified facility.
References
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
