Insulin Glargine Processing Plant
One of the world’s leading pharmaceutical companies, having a wide product portfolio containing medicines for several therapeutic areas as cardiovascular, thrombotic or metabolic disorders, awarded to SACOME the calculation, design and manufacture of all the tubular heat exchangers for one of their Insulin Plant in Frankfurt am Main (Germany).
The scope of supply for this project was composed of 17 heat exchangers to heat and cool different products as protein suspensions, 30%-n-Propanol, or 10%-n-Propanol. This bioengineering production facility has an approximate production capacity of 1.700 kg of insulin glargine per year.
Product specifications and process
Different products were processed in the tubular heat exchangers, as listed below:
- Product solutions.
- Protein suspensions.
- 30% N-propanol.
- Regeneration solutions.
- Inputs chromatographies.
- 10% N-propanol.
- Bio-waste water.
Our engineers took into consideration this product portfolio and, in close collaboration with the client, they set the different thermal properties (density, specific heat, thermal conductivity and viscosity) for each case. The main objetive is to do an accurate thermal design of the different sections, that were operating as point-of-use coolers/heaters as well as within batch processes.
Furthermore, our technnicians chose tube geometries and configurations having suitable Reynolds number and process velocities of the products, contributing thus to avoid liquid stagnation.
Design of tubular heat exchangers
Getting the highest levels of security, efficiency, and asepsis in any process of the pharmaceutical industry is the main point to be considered to choose the equipment to be installed. In the case of heat exchanger, the fact to comply with FDA and GMP recommendations regarding to velocities, self-drainability, inner roughness, no dead points, etc. involves the no recommendation to use some types of exchangers, which are not able to comply with some of such as requirements, as in the case of plate heat exchangers.
The SACOME range of heat exchangers for the pharma industry are specially designed to avoid dead zones, where colonies of bacteria may accumulate, avoiding then the growth of these microorganisms. To this end, the fittings to the pipelines were sterile flanges.
One of the client’s requirements was that the product channel (inner tubes, tubesheets, eccentrical reduction cones and bends) should be fully electro polished. We spell this out more clearly in the following section.
Concerning the inner tubes, our engineers decided to use inner tubes in DIN 1.4435 (316L) with certified inner roughness Ra ≤ 0.8 µm (bright finish version) and in accordance to ASME BPE standard.
Double tubesheet design
Every heat exchanger was manufactured in double tube sheet version, as leakage detector, which makes impossible the cross contamination (i.e. service fluid leaking into the product side) in the case of a cracked weld. The industry offers other solutions to this end, as double wall pipes configurations, but this is not a very efficient configuration from the thermal point of view, due to the thermal resistance provided by the intermediate chamber.
Fatigue stress analysis
Our technical department analyzed the production, cleaning and sterilization programs of the different items, and recommended to fit expansion joint on the heat exchangers. As a worldwide benchmark company designing and manufacturing metal expansion joints and compensators since 1978, we checked the stress analysis of this component taking care of the thermal expansions and cycles.
Keeping in mind the design conditions (particularly design pressures up to 40 bar) and the necessity to fit gaskets compliant with GMP and FDA regulations, our engineers, in close collaboration with our gaskets suppliers, decided to choose metallic ring DIN 1.4541 gaskets, with two graphite layers enveloped in PTFE (Teflon).
As shown in the picture, in the also known as anodic or electrolytic polishing, the equipment is immersed in a temperature-controlled batch of electrolyte. It’s connected to the positive terminal of a DC power supply, whilst the cathode is attached to the negative terminal, in such a way that the heat exchanger acts as the anode of the circuit.
When the electrical circuit gets closed, an electrical current circulates from the anode (heat exchanger) to the cathode, taking place an oxidation process in the surface of the work-piece, so that the metal on the surface is dissolved in the electrolyte and later is deposited on the cathode surface.
As a result of this treatment, the metal is removed from the surface of the tube, getting to smooth the microscopic surface of the product side and level the micro-peaks, thus contributing to enhance the passivation, make the surface easier to clean and sterilise, and to get better corrosion protection.
In this project, once the heat exchangers were manufactured, tested and certified in our workshop, they were sent to the electropolishing facilities in Germany to be electro polished, where SACOME personnel attended to check in site the correct carrying out of the process.
Once the anodic polishing was over, the heat exchangers were returned to our facilities, where all the tests, particularly the pneumatic and hydraulic test, were carried out again, in order to check the perfect condition and absence of leakages of the equipment previously to the delivery up to the client’s facilities in Frankfurt where our tubular heat exchangers would be installed inside the Insulin Plant.
3. Work-piece to polish (Anode)
4. Particle moving from the work-piece to the cathode
5. Surface before polishing
6. Surface after polishing
Inspections and certifications
One of the key issues of this project were the stringent program inspections point and the demanding documentary and certification requirements.
The Quality Plan carried out for this project included inspections previous, during and after manufacturing, as listed below:
- Visual inspection.
- Dimensional control.
- Hydraulic and pneumatic test.
- Welding procedures acc./ EN287-288, with TÜV approved norms.
- Non-destructive tests (dye penetrants) 100%.
- X-ray longitudinal butt welds.
- Chemical composition analysis.
- Intergranular corrosion test acc./ DIN50914.
- Delta ferrite in straight seam welds.
- Roughness analysis.
In this regard, the engineering company of the project, by mean of its inspectors, attended at the different levels of inspection, as reception and acceptance of raw material, manufacturing process or validating every test, before electropolishing as well as after it, certifying the correct finishing of our equipments.
Production of the insulin glargine plant (Kg/year)
Scope of supply (tubular heat exchangers)
Units thermal power
Number of sections