Article review: Long-term stability of bevacizumab repacked in 1 mL polypropylene syringes for intravitreal administration
M. Paul*, V. Vieillard, E. Roumi, A. Cauvin, M.C. Despiau, A. Astier. Long-term stability of bevacizumab repacked in 1 mL polypropylene syringes for intravitreal administration Annales Pharmaceutiques Françaises 70 (2012), pp 139-154
The following table sets out how this paper either does or does not comply with the NHS (UK) guidance on the assessment of stability for biological products. The table uses the NHS guidance section headings and numbering to assist the reader.
Study Design
| NHS Guidance | Property to Evaluate | Criteria for Evaluation | Compliant (Yes/No) | Comment |
|---|---|---|---|---|
| 5.2 | Containers | Non-PVC | Yes | |
| 5.3 | Storage | Refrigerated in absence of light | Yes | |
| Room temperature (25±2˚C) | No | |||
| 5.4 | Concentration | Low & high clinically significant | Not applicable | Single dose syringe |
| 5.5 | Storage period | 48 hours to 3 months | Yes | |
| 5.6 | Sampling strategy | At least 4 sampling points in addition to the baseline (T=0) data. | No | 3 sampling points in addition to T=0. Data only presented at 2 points. |
| For studies ≥6 months, monthly sampling up to 3 months, then 3 monthly until study end. | Not applicable | |||
| 5.7 | Sampling number | Three independent batches | Yes | |
| Three replicates per batch | Yes | 20 syringes per batch | ||
| 6 | Testing protocol | Minimum protocol to include: | ||
| a) color, clarity, particulate | No | Not performed | ||
| b) pH | No | Not performed | ||
| c) chemical stability | Yes | |||
| d) physical stability | Yes | |||
| e) sub-visible particles | Yes | |||
| f) biological activity | No | Not performed | ||
| g) Assessment of degradation | Yes | Results from a previous study used. |
Storage at room temperature (5.3) was not assessed. Insufficient sampling points are taken (5.6). A number of analyses in the testing protocol (6a,b,f) are not included in the study.
Study Methods
| NHS Guidance | Property to Evaluate | Criteria for Evaluation | Compliant (Yes/No) | Comment |
|---|---|---|---|---|
| 7.1 | Forced degradation | A combination of some of: | Previous study used | |
| a) change in pH | No | |||
| b) realistic elevated temperature | Yes | |||
| c) exposure to UV light | Yes | |||
| d) agitation | No | |||
| 7.2 | Visual characteristics | Color, clarity and particulates | No | Not performed |
| 7.3 | pH | Changes to pH | No | Not performed |
| 7.4 | Sub-visible particulates | Evaluate particle levels over necessary range (1–100 μm) | Yes | |
| 7.5 | Physio-chemical analysis | Range of techniques to assess conformational, physio-chemical and aggregates (below size in 7.4). Should comprise a combination of: | ||
| a) SEC | Yes | |||
| b) DLS | Yes | |||
| c) CEX | Yes | |||
| d) capillary or SDS electrophoresis | No | |||
| e) circular dichroism | No | |||
| f) FT IR | Yes | |||
| 7.6 | Chemical | a) HPLC | Yes | |
| b) UV | Yes | |||
| c) mass spectrometry | No | |||
| 7.7 | Biological activity | Relevant to specific biological activity that enables product to achieve specific pharmaceutical action. Can comprise any of: | No | No assessment of biological activity performed |
| a) biochemical (ELISA) | ||||
| b) cell based | ||||
| c) animal |
Visual characteristics (7.2) and changes in pH (7.3) were not assessed. Although electrophoresis (7.5d) and circular dichroism (7.5e) were not performed, the combination of other techniques employed is sufficient for a comprehensive assessment of physical stability. The combination of only HPLC (7.6a) and UV (7.6b) would not provide a comprehensive chemical characterisation. Assessment of biological activity (7.7) is a key component of NHS guidance criteria to demonstrate the product achieves its specific pharmaceutical effect. No evaluation of biological activity has been performed.
© Maria Connolly, Andy Watts & mAbstalk.com. Copies of this material can be made for the sole purpose of aiding in the assessment of the stability of the product presented in the study. Any copies must be made in full and retain this notice and reference to A Standard Protocol for Deriving and Assessment of Stability Part 2 — Aseptic Preparations (Biopharmaceuticals).