Understanding US Regulatory Guidance for Pharmaceuticals
Pharmacopeial monographs such as the US Pharmacopeia-National Formulary (USP/NF) provide standardized methods and specifications for generic pharmaceutical raw material and finished products. They are utilized as a basic requirement needed for most regulatory submissions in the United States.
USP <87> In-Vitro Biological Reactivity – Cytotoxicity Testing
Cytotoxicity tests are in-vitro assays used to assess the possibility of a test article to cause the death of cells in culture or to prevent their multiplication. The purpose of the study is to determine the potential biological reactivity of a mammalian cell culture (L929) in response to the test article extract.
Testing Categories and Specifications
| Test Name | Sample Needed | Turn-Around Time |
|---|---|---|
| L929 MEM Elution USP | 120 cm² ≤ 0.5 mm thick, 60 | 2-3 weeks |
| Agar Diffusion USP | 3 cm2 , 1 g, or 1mL (at least three units, if 1 unit cannot be subdivided into three 1 cm2 samples) | 2-3 weeks |
USP <88> In-Vivo Biological Reactivity – Class I–VI Testing
USP Class tests are assays designed to determine the biological response of animals to direct and/or indirect contact with a test article.
Testing Categories and Specifications
| Test Name | Sample Needed | Turn-Around Time |
|---|---|---|
| USP Class I | 120 cm2 < 0.5 mm thick, 60 cm2 ³ 0.5 mm thick, or 4 g | 4 weeks |
| USP Class II | 240 cm2 < 0.5 mm thick, 120 cm2 ³ 0.5 mm thick, or 8 g | 4 weeks |
| USP Class III | USP Class III 480 cm2 < 0.5 mm thick, 1200 cm2 ³ 0.5 mm thick, or 16 g | 4 weeks |
| USP Class IV | Extraction-360 cm2 < 0.5 mm thick, 180 cm2 ³ 0.5 mm thick, or 12 g Implant – 12 pieces at 1mm x 1mm x 10 mm | 4-5 weeks |
| USP Class V | 480 cm2 < 0.5 mm thick, 240 cm2 ³ 0.5 mm thick, or 16 g | 4 weeks |
| USP Class VI | Extraction- 480 cm2<0.5mm thick, 240 cm2 ³ 0.5 mm thick, or 16 g Implant – 12 pieces at 1 mm X 1mm X 10 mm | 4-5 weeks |
USP <381> Elastomeric Closures for Injections
The purpose of the study is to measure the physicochemical properties of impurities extracted from elastomeric closures. The extract solution is analyzed for non-volatile residue, turbidity, acidity/alkalinity, reducing substances, heavy metals, color, zinc, optical absorbance, ammonium, and volatile sulfides.
Testing Categories and Specifications
| Test Name | Sample Needed | Turn-Around Time |
|---|---|---|
| Physicochemical Test for Elastomeric Closures | 300 cm²/extract | 3-4 Weeks |
USP <661> Plastic Packaging Systems and Their Materials of Construction
The purpose of this study is to measure the physiochemical properties of impurities extracted from packaging for therapeutic products (pharmaceuticals, biologics, dietary supplements and devices). The plastics used in packaging systems are composed of homologous polymers with a range of molecular weights and contain additives such as antioxidants, stabilizers, lubricants, plasticizers, colorants, and others. The extracted solution undergoes tests for identification of the material, physiochemical properties, and extractable metals.
Available Tests
- USP 661.1
- USP 661.2
Plastic Materials of Construction
This monograph calls out several specific materials of construction specifying test and extraction mothods for each type of material
- Polyethylene (PE)
- Polypropylene (PP)
- Polyolefin
- Polyvinyl chloride (PVC)
- Polyethylene terephthalate (PET)
- Polyethylene terephthalate G (PETG)
Each material includes a series of tests to understand the material and extracts from it. These tests include:
- Identification (FTIR, DSC)
- Physicochemical Tests (Absorbance, Acidity/alkalinity, TOC)
- Extractable Metals (ICP/MS, ICP/OES)
- Plastic Additives, including phenolic and nonphenolic antioxidants (HPLC)
Testing Categories and Specifications
| Test Name | Sample Needed | Turn-Around Time |
|---|---|---|
| Plastic Materials of Construction | 300g | Approximate turnaround time is based upon study specific parameters. |
Plastic Packaging Systems for Pharmaceutical Use
This monograph focuses on the evaluation of your materials in the finished form. This evaluation includes:
- Physicochemical Tests (Absorbance, Acidity/Alkalinity, TOC)
- In Polyethylene terephthalate (PET) and Polyethylene terephthalate G (PETG) systems, evaluation of ethylene glycol and total terephthaloyl moieties is also performed
Physicochemical Techniques
- Differential Scanning Calorimetry (DSC)
- Fourier Transform Infrared (FTIR) Spectroscopy
- Total Organic Content (TOC)
- Inductively Coupled Plasma (ICP)
- High Performance Liquid Chromatography (HPLC)
Testing Categories and Specifications
| Test Name | Sample Needed | Turn-Around Time |
|---|---|---|
| Plastic Packaging Systems for Pharmaceutical Use, Physiochemical Testing | < 0.5 mm thick, 300 cm2 ≥ 0.5 mm thick, 600 cm2 | Approximate turnaround time is based upon study specific parameters. |
| Plastic Packaging Systems for Pharmaceutical Use, Ethylene Glycol & Total Terephthaloyl Moieties Testing | < 0.5 mm thick, 500 cm2 ≥ 0.5 mm thick, 1000 cm2 | Approximate turnaround time is based upon study specific parameters. |