"CSPE process cuts delivery times and accelerates the commissioning of pharmaceutical systems"

Comprehensive Scientific Process Engineering

CSPE Process cuts Delivery Times and Accelerates the Commissioning of Pharmaceutical Systems

Comprehensive Scientific Process Engineering

As short a time as possible between placement of the order and the start of production: a priority for both the manufacturers and operators of pharmaceutical systems. As a supplier of overall systems, with CSPE, Optima Pharma has created a comprehensive, systematic concept that supports this goal and leaves nothing to chance in the entire process.

The aim is to deliver new products to the market as quickly as possible. This does not only apply to pharmaceuticals. But for pharmaceutical manufacturers, it is particularly important to keep the time between completion of the approval phase and putting a product on the market to a minimum: on one hand because of the lengthy development times and high development costs, on the other as international competition is increasingly keen. The long delivery times that arise in many areas of plant engineering when capacities are stretched to their limits are a serious problem in the pharmaceutical industry.

At the same time, increased requirements are placed on the flexibility of the system. It needs to be able to handle smaller batch sizes, and various containers, for example syringes, vials and cartridges, need to be filled on one system. This makes systems increasingly complex – and normally, it would make the entire process, from design and engineering to the actual construction of the plant right through to validation, even lengthier.

CSPE - Comprehensive Scientific Process Engineering
Pharmaceutical filling systems are becoming increasingly complex. With CSPE, Optima Pharma is introducing an engineering process that reduces delivery times and thus time-to-market. CSPE encompasses the entire process from project risk analysis before the start of the design phase through to service call-outs after SAT and the start of production.

To Media Fill in Record Time

A fast and safe production start

Optima Pharma has the solution for this problem: Comprehensive process engineering following a scientific approach allows the realization of short delivery and commissioning times together with quick qualification of the system and a facilitated official audit. The pharmaceutical system manufacturer calls this approach “Comprehensive Scientific Process Engineering,” or CSPE for short. It combines tried and tested, accelerated concepts and procedures such as digital engineering, simulation, virtual reality and integrated FATs. This minimizes so-called “time thieves.” In this way, the “media fill,” proof that sterile products can be produced on the finished filling system, is successfully carried out in record time.

iFAT
“We have been using all these methods for quite some time,” explains Gerhard Breu, who, as Chairman of the Optima Pharma Division, is responsible for the locations Optima Pharma Schwäbisch Hall and Mornhausen as well as Metall+Plastic in Radolfzell, adding that the company set up its own Digital Engineering department to provide support for pharmaceutical plant construction six years ago. Its repertoire includes all standard simulation methods, for example strength calculation, determination of the resonance value of individual components etc. And for some time now, both Optima engineers and customers have been able to experience and contribute their input on 3D models of the planned systems at the VR Center in the Schwäbisch Hall technology center at an early stage in the engineering process.
Time-to-Market
Time-to-Market
  • Reduced time between odrder placement and production start
     
  • Faster qualification with the iFAT
     
  • Faster requalification on-site
     
  • Accelerated start-up at the customer's site
Recucing Risks
Risk Reduction
High Security
Highest Safety Level
  • Complete test of the machine during the iFAT
     
  • Scientific based qualification support
     
  • Support during FDA or other authority audits with verifiable simulation processes

Spot-on “first shot” thanks to advance Virtual Mock-Up

Consistently exploiting the potential of digital engineering

The “high art” of digital engineering ultimately leads to the virtual mock-up, which Optima Pharma sees as an “advance virtual mock-up.” Design engineers and future operators of a system can get an idea of the circumstances and accessibility in the VR Center – giving them a much more realistic picture than the 3D image on a computer screen. Breu does not see the virtual mock-up study completely replacing the usual wooden mock-up until it becomes possible to simulate weights, tactility and haptics, too. “With the real-life mock-up, you can test the handling of a heavy intermediate container or a sensitive component such as a filling needle using the isolator glove,” he states. However, he points out that the “first shot” in a real mock-up is significantly more accurate where bottlenecks were eliminated in advance with the help of the virtual mock-up. In addition, he says, the virtual system can be used for training purposes.
Virtual Reality
Strength calculations, flow simulations or determination of the resonance values of individual components support the developers during the design phase. CSPE can act as an enabler throughout the entire life cycle of a system – for example as an aid during service call-outs as part of the “Optima Total Care” portfolio. There are many examples. Breu remembers one specific case where a folding table on the freeze-dryer of a loading system had become warped. The cause: the customer had begun cold loading. As a result, the mounting plate on the freeze-dryer was cooled, which led to the folding table no longer being able to dock on correctly. Instead of simply sending out a service technician “blind” and hoping that he would be able to solve the problem on-site by trial and error, Optima first simulated the deformation caused by freezing and immediately produced a suitable component to compensate for the warping. The service technician then only needed to fit this part. 
Flow Visualisation
So what’s new about CSPE? Gerhard Breu points out the systematic approach and the consistent application of the possibilities offered by digital engineering, which, as a result of the integrated approach, becomes a necessity rather than an option. “Previously, the configuration of systems was primarily a question of experience. And in-depth experience is still a prerequisite today. But with CSPE, we also exploit the full potential offered by digital engineering.” The process begins even before the design stage: with a project risk analysis that involves all specialist departments and draws parallels with similar projects. As a result, the engineers can take possible obstacles during the new project into account from the word go – and overcome them at an early stage with the help of digital engineering and simulation. “This means the minimization of risk – that is, the ability to deliver quickly and problem-free commissioning,” says Breu.
Gerhard Breu, Chairman Optima Pharma Division
„In the course of CSPE, we are using the full potential
that digital engineering offers.“
Gerhard Breu, Chairman Optima Pharma Division
He adds that as in the past, Optima Pharma still uses real experimental setups in its technical center, as this is a must with certain assemblies. “However, our engineers aim to resolve as many issues as possible in advance via digital engineering,” the Chairman explains. For example, the distribution of VHP (Vaporized Hydrogen Peroxide) in the isolator can be simulated. Worst-case positions scarcely reached by the VHP gas are identified, and the positioning of the injection nozzles in the isolator is adjusted accordingly. Simulation of the sterilization process brings advantages not only for the design engineers. With it, Optima supports cycle development. The simulation shows where biological indicators would be most effective. During Performance Qualification, this allows the user to verify for the authorities that his system can be reliably decontaminated with hydrogen peroxide vapor.
 
As a further example of an application where simulation has already been successfully used, Breu mentions the process of freezing vials on a freeze-dryer shelf. Following modification of the shelf design compared with a previous system, the customer wanted proof that a newly designed side guide had no negative effect. Breu recalls: “We were able to prove that a firmly installed guide rail actually had a positive effect on the freezing process.” In this way, the customer received a welcome design modification without the need for time-consuming test constructions.
Simulation
What effect does the modified shelf design on the freeze-dryer have on the freezing process? Simulations as part of CSPE replace time-consuming experimental setups in the technical center.

Reliably qualified with integrated FAT

Comparing your results with reality is essential if you are aiming for continual improvement

Complete test of the entire machinery during iFAT
Fast start-up at user's site
Safe production
The integrated FAT (iFAT) is a further CSPE-related feature offered by Optima Pharma. All components of a system are brought together in Schwäbisch Hall, for example the isolator from affiliated company Metall+Plastic in Radolfzell as well as the freeze-dryer feed and loading system. These are then tested together with the filling system manufactured in Schwäbisch Hall under conditions that are as realistic as possible. This allows reliable performance of qualification work – very similar to the later SAT of the overall system at its destination. “The only deviations which might arise later result from special features of the cleanroom environment on the customer’s premises,” says Breu. Optima is already able to carry out a first cycle development. To ensure that conditions at Optima are as realistic as possible, the company is currently building a new final-assembly hall optimally equipped for the installation and commissioning of complete lines. Construction is scheduled to be completed in the second quarter of 2019.
 
And with realistic system qualification as part of the iFAT, the process comes full circle. The engineering department receives direct feedback on the accuracy of the previous simulations and thus input for further optimization of the simulation models.

Turnkey plus CSPE = faster time-to-market

The operators of systems will see the positive effects of CSPE in many areas

Shorter commissioning times and on-site deployment times for Optima specialists. In-depth preparatory work by the system manufacturer accelerates qualification on the customer’s premises; validation via digital engineering and iFAT means that in some cases, it is more a re-qualification. This means production can get underway much faster than was previously possible. According to Breu, the amount of overall project time saved varies greatly from project to project: “It can be up to six months.” These effects are also heightened by the turnkey approach. Freeze-dryer, isolator and filling units supplied by one manufacturer are optimally coordinated as an overall system, including the qualification concept for all system components. This reduces the time-to-market yet again.
The Key Advantages
  • Advance virtual mock-ups and training via digital engineering
  • Qualification via iFAT, quick re-qualification at the point of use
  • Faster, low-risk commissioning on the user’s premises
  • Scientific approach provides support during official audits
  • Cuts time between placement of the order and start of production
  • Minimization of risks before the start of the design phase

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