Degassing Recombinant Protein Vials to Prevent Ring Formation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Recombinant proteins packaged in vials often form rings at the air-liquid-glass interface due to bubble accumulation, leading to cosmetic defects that can cause vials to be rejected despite being medically acceptable.

Innovation Solution

A method involving degassing the recombinant protein composition using a vacuum to prevent bubble formation and ring deposition, where a bubble indicator value of at least 5.9 is calculated using the formula BI = ha*t*1000/hl*PV, ensuring the composition is suitable for administration with minimal DNA concentration and without adding benzonase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the composition is packaged in vials without degassing, then the packaging process is simple and fast, but bubbles accumulate at the air-liquid-glass interface forming rings that cause cosmetic defects

Engineering Contradiction:
Improvepackaging speedVSAvoidappearance quality
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The composition is degassed before filling into vials, removing dissolved gases in advance to prevent bubble formation during packaging. This preliminary degassing action eliminates the cause of ring formation while maintaining efficient packaging operations.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies vacuum pressure (reducing pressure parameter) to the composition to degas it before filling. By changing the pressure parameter during degassing, dissolved gases are removed from the composition, preventing bubble accumulation and ring formation in the final product.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If a vacuum is applied to degas the composition, then bubble accumulation and ring formation are prevented, but the degassing process time increases

Engineering Contradiction:
Improveappearance qualityVSAvoiddegassing process time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent optimizes degassing parameters including vacuum pressure level and degassing duration to achieve effective bubble removal in minimal time. By carefully controlling these parameters, the process removes enough gas to prevent ring formation without unnecessarily extending processing time.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The degassing process is applied to a sufficient extent to remove the critical amount of dissolved gas needed to prevent ring formation, rather than attempting complete degassing. This partial action approach achieves the cosmetic quality goal without the time cost of exhaustive degassing.

Inventive Principle:
Principle #16Partial or excessive action

3Stability of the object's composition

If the composition is stored under positive pressure, then storage stability is improved, but bubble accumulation occurs leading to ring formation

Engineering Contradiction:
Improvestorage stabilityVSAvoidappearance quality
Core Design Contradiction:
Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The composition is degassed before storage under positive pressure, removing dissolved gases in advance. This preliminary action prevents bubbles from forming during subsequent pressurized storage, allowing the composition to maintain both stability and appearance quality.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

By degassing the composition before storage, the patent applies a preliminary anti-action that counteracts the tendency of gases to come out of solution during pressurized storage. This prevents the harmful effect of bubble formation and ring deposition.

Inventive Principle:
Principle #9Preliminary anti-action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The degassing process effectively prevents ring formation on vials, reduces bubble accumulation in fill lines, and maintains the protein's native conformation, ensuring the recombinant protein is suitable for human administration with low DNA concentration.

Implementation Method 1

applying a vacuum to the container; allowing the vacuum to degas the composition

Methodology Applied
Scientific EffectVacuum: Vacuum

Data Source

PatentEP3212510B1Manufacturing method of a degassed composition
Publication Date: 2020.12.09 MEDIMMUNE LLC
  • EP3212510B1 patent drawingFigure 1A~1B
  • EP3212510B1 patent drawingFigure 2A~2B
  • EP3212510B1 patent drawingFigure 3A~3B

AI summary

This application is directed to a method of producing vials containing a composition comprising a recombinant protein. In some embodiments, the method comprises: (a) providing a container containing a composition comprising a recombinant protein optionally where the container has been stored under positive pressure; (b) applying a vacuum to the container containing a composition comprising a recombinant protein; (c) allowing the vacuum to degas the composition; and (d) filling vials with the degassed composition comprising a recombinant protein.