Process qualification phase

The developer (the person who did the installation and model development) leaves too soon - voluntarily or otherwise. The developer generally needs to maintain involvement well into the long-term prove-out or qualification phase (Step 8). Plant personnel who inherit process analyzer systems before qualification is complete may experience extreme levels of frustration, especially if they have no previous NIR experience and were not involved in the earlier stages of the project. Another way to state this factor is The business fails to adequately staff the project. 

A validated manufacturing process is one which has been proved to do what it purports or is represented to do. The proof of validation is obtained through the collection and evaluation of data, preferably, beginning from the process development phase and continuing through the production phase. Validation necessarily includes process qualification (the qualification of materials, equipment, systems, buildings, personnel), but it also includes the control on the entire process for repeated batches or runs. 

The validation life cycle is typically split into eight main qualification phases as shown in Table 21.2 and are all execnted under the control of a Validation Plan. It must be clearly demonstrated that the Qnality Assnrance (QA) fnnction of the pharmaceutical manufacturer is endorsing the validation approach for the implemented LIMS as docnmented in the Validation Plan. In its simplest form this will reqnire the QA representative to anthorize the Validation Plan and the subsequent key documents prodnced to support validation (e.g., Qnalification documentation. Reports, etc.). Table 21.2 shows the linkage between project activities and the QuaUflcation process, which will be under the control of the Validation Plan. 

Validation is described as proof that the system performs as stated. As an engineering control, the LAF system must demonstrably support the intended aseptic or controlled process. Validation of the aseptic manufacturing process and the LAF systems that support terminal sterilization in pharmaceutical manufacturing applications should be carried out in accordance with industry standards. Such validation should be accomplished in three phases, consisting of installation qualification (IQ), operational qualification (OQ), and process qualification (PQ), with full and detailed documentation of all activities and... 

PROCESS QUALIFICATION (qualification de procede) The phase of validation dealing with the sampling and testing at various stages of the manufacturing process to ensure that product specifications are met... 

FIGURE 23.1 Flowchart of package manufacturing process qualification steps, phase 1. 

If a more advanced, research-oriented career is the goal, students should acquire a graduate degree (master s or doctorate). For these qualifications, coursework will include advanced physical and inorganic chemistry, calculus relevant to equihbrium processes and phase equilibria, fluid dynamics, and crystallography. 

Like design qualification, process qualification should be conducted at the prototype development phase. The intent is to ensure that the nominal manufacturing specifications and tolerances produce acceptable reliability in the hardware. Once qualified, the process needs requalification only when process parameters, materials, manufacturing specifications, or human factors change. 

The importance of the capabilities and qualifications of technical and operations staff at the toller site was emphasized in Chapter 2, The Toller Selection Process. It may have been a key factor in the selection of a toller. The expertise of the client personnel is equally important during this phase of the tolling effort. 

The certification activities include a series of process documentation and qualification studies that start with the initial installation of a sterilization system and continue as process engineering changes or new or revised product introductions are required. Qualification activities comprise installation, operational, change, and performance phases. 

Equipment qualification covers the entire life of a product. It starts when somebody has an idea about a product and ends when the equipment is retired. For computer systems validation, this ends when all records on the computer system have been migrated and validated for accuracy and completeness on a new system. Because of the length of time and complexity, the process has been broken down into shorter phases design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) [2]. The process is illustrated in Figure 17.1. 

Remark. We assumed that Y(t) is a Markov process. Usually, however, one is interested in materials in which a memory effect is present, because that provides more information about the microscopic magnetic moments and their interaction. In that case the above results are still formally correct, but the following qualification must be borne in mind. It is still true that p y0) is the distribution of Y at the time t0, at which the small field B is switched off. However, it is no longer true that this p(y0) uniquely specifies a subensemble and thereby the future of Y(t). It is now essential to know that the system has aged in the presence of B + AB, so that its density in phase space is canonical, not only with respect to Y, but also with respect to all other quantities that determine the future. Hence the formulas cannot be applied to time-dependent fields B(t) unless the variation is so slow that the system is able to maintain at all times the equilibrium distribution corresponding to the instantaneous B(t). 

Figure 1 depicts the most commonly used approach to the qualification process as used in the pharmaceutical industry. It shows a pyramid, which is the best way in which to plan a qualification/validation project. Investing more time in the first phases will save time and money in later and critical phases. If inadequate investment is made during the start-up of a project, the later phases of installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) will necessarily require an inordinate amount of time and money. The project will be a pyramid again, but now it is inverted. 

The results of any risk analysis should be well documented as they become the key input into the qualification and validation process. They are the basis for defining tests in the IQ, OQ, and PQ phases. It is often impossible to say prior to a risk analysis what steps of qualification need to be performed. It depends on the risks and measurements defined during the risk analysis. Equally important, this procedure increases the efficiency of the qualification process. In the past, the decision on which qualification tests to perform was outlined by writing qualification protocols. These usually prompted long and expensive discus-... 

The PQ is the phase in which either a technical system is tested over a long period of time (e.g., water system), or a complex technical system is tested overall (connected filling line). For many systems OQ is the last phase performed during qualification. If there are only a few performance tests needed, it might be more practical to include them during OQ or process validation. Combining OQ and PQ decreases the number of documents (less documentation work in the future) and cuts approval time and effort. Again, the procedure for PQ is the same as for IQ and OQ ([develop PQ protocols, approve PQ protocols (by the quality assurance, production, and technical departments), perform PQ, work out the PQ report, and approve the PQ report (by the quality assurance, production, and technical departments)]. The documentation and test description are identical to those in the OQ phase. 

Whenever this kind of activity becomes part of the manufacturing plan, the benefits of the setup-dominant process will be realized. This results because the quality standard, formed by the development function in the performance qualification, is carried over to the production setting. When production then incorporates this standard into its own operating procedures, the quality standard becomes a measurable criterion for performance. This example thus clearly shows how this phase of PV would be a QA tool for auditing. 

EOQC (1980) European Organization for Quality Control, 4th European Seminar (1980) Validation of Manufacturing Processes (Geneva) [5] Definitions, installation and operational qualification, development and manufacturing phase, responsibilities and organization, use of historical data, change control and revalidation... 

While it should be self-evident that a rational reactor design demands a knowledge of both the fluid dynamic environment and the detailed process kinetics, the latter are rarely available. In many instances this leads to the severe limitation of many important reactions by an inadequate fluid dynamic intensity. Some of these are known to be fast, e.g., liquid-phase nitrations, while others are (incorrectly) assumed to be slow, e.g., most polymerizations. In these circumstances the pragmatic approach is to use a high-intensity reactor for each system and then to assess the impact upon the space-time productivity. Obviously, an intrinsically slow system is resistant to further acceleration and this will rapidly become evident. One significant qualification of this contention involves the very... 

---