VALIDATION MASTER PLAN

In order to validate the Crystal^® Technology, Aseptic Technologies set up a Validation Master Plan (VMP), based on USP (United States Pharmacopeia), Ph. Eur. (European Pharmacopeia) and ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) recommended tests for each separated component of the vial, for the assembled vials as well as for the new technologies set up on the filling lines.

Validation studies focused on:

Container materials
- USP Class VI (USP <88> in-vivo toxicity and USP <87> cytotoxicity)
- USP <661> Biological and physicochemical tests
- Ph. Eur. 3.1.3. Polyolefin characterization
- USP <381> / Ph. Eur. 3.2.9 Elastomeric/rubber closure
Assembled vial
- Particle test
  - USP <788>
- Container Closure Integrity
  - Dye test
  - Microbiological challenge
- Cleanness
  - Endotoxins
  - Bioburden
- Permeability
  - Water loss
  - Water ingress
  - Oxygen ingress
- Low temperature storage (up to -80°C and in liquid nitrogen vapour)
- Extractable profile
- Ageing in ICH conditions (water vapour transmission rate, closure integrity, leachables)
- Gamma sterilization
  - Dose mapping
  - Ozone depletion speed
  - Sterility
Filling line
- E-beam sterilization
  - Dosimetry
  - Dose distribution
  - Penetration and energy
  - Biological effectiveness
  - Ozone generation
  - Temperature increase
- Filing
  - Accuracy of filling
- Laser re-sealing
  - Absorption coefficient
  - No change of stopper composition
  - Temperature increase
    - On stopper surfaces
    - Inside the vial
  - Resealing specifications

The VMP has been concluded by the performance of media fills in non-classifed environment (workshop area)
From that time more than 100,000 closed vials have been filled with media. No one has been identified as contaminated.
All the data are available free of charge to support product approval from our clients.

Contact-us to review our Validation Master Plan.