Reference standards for liquid parenteral pharmaceuticals are produced by altering the container directly. For this purpose, pre-filled containers from our customers can be used or filling can be done by M.A.S… Reference standards can be prepared for the following container formats:

• • Vials
  • Prefilled syringes
  • Ampoules
  • Cylindrical ampoules
  • Infusion bags
  • BFS containers

For the preparation of particle samples, materials provided by the customer or particles from the extensive M.A.S… particle library can be used.

Particles of glass, metal or plastic can be prepared starting from a size of 50µm. Due to the thickness of fibers and hair we recommend their preparation from a fiber length of 100µm.

Each particle sample is provided with detailed documentation. All data are digitally calculated and stored using a stereomicroscope and the modified image program analySIS. The documentation consists of a certificate, detailed particle data (including size, circumference, form factor, diameter) and a microscopy image of each prepared particle.

Containers that are rejected during visual inspection due to defects may have the following deficiencies, among others:

• • Container defects:
    Scratches, cracks, contamination, chipping
    

     

  • Seal defects:
    Incorrect seal damaged stopper, incomplete crimping

     

  • Product characteristics:
    Discoloration, turbidity, incorrect filling volume

The various defects are simulated in the M.A.S… laboratory and documented in detail. Container defects such as cracks or chips are prepared according to customer specifications (e. g. in different size ranges, at different positions of the container) and then digitally measured. Deviating product characteristics such as turbidity or discoloration are manufactured according to customer’s specifications.

Freeze-dried pharmaceuticals are often not suitable for the preparation of reference standards due to the low stability of the lyo cake.

For the preparation of lyophilized reference standards, M.A.S… has therefore developed a lyo stabilizer formulation. Because of the high stability of the lyo cake, it is well suited for the quality control of freeze-dried products. At the customer’s request, the lyo cake can be adjusted in color if necessary. The stabilizer mixture is filled into the containers provided by the customer and the requested defects and particles are prepared. The samples are then lyophilized in our Christ freeze dryers.

Container Closure Integrity Testing (CCIT) is an important aspect of quality control in the pharmaceutical industry. For this purpose, M.A.S… offers the creation of laser-drilled holes (pinholes) in containers. Pinholes can be created from a size of 5-10µm in ampoules, pre-filled syringes, cartridges, and tubular glass vials. The pinholes can be used for various test methods such as immersion tests with a dye or high voltage leakage test.

A critical process in the production of parenteral pharmaceuticals is their sterile or aseptic filling. To validate the production line, so-called media fills must be conducted. For this purpose, a nutrient solution is filled in place of the product and, after a defined incubation period, subjected to a thorough microbiological and visual inspection.
For training purposes, M.A.S… creates the desired turbidity patterns based on the nutrient solution. Microbiological contamination can be simulated using a standard solution. The degree of turbidity of the media fill samples is adjusted according to customer requirements.