Pharmaceuticals process validation definition

In the present chapter, the pharmaceutical industry validation system has been reviewed. To have an appropriate validation system it is first required to define which equipment, facilities, and processes will be validated, when they will be validated, and by whom this must be performed. This definition is based on a risk assessment priority and is written in a specific document, the so-called MVP. In order to generate an adequate validation report, all the validation activities should be described in the validation protocols, SOPs, and specific procedures. 

Process development equals process validation plus process optimization. A well-developed process is, therefore, by definition a well-validated process. Once it is decided that a bulk pharmaceutical chemical (BPC) process should be validated, the question becomes How In the case of a new process, the answer is simple Do a good process development job and document it (4). 

It is important that after campaign 4 when chemistry and pharmaceutical development are ready to initiate their activities of process validations that the variables of drug substance and product are definitively fixed (point 4 in Fig. 40.4). Validation according to the definition means to provide documented evidence that the processes consistently works. It is logical for the validation processes that the analytical methods need to be validated first and all other activities subsequently. 

Process validation for biopharmaceuticals is somewhat different in application from traditional pharmaceuticals because the technology is different, but the theory and principles are similar [15], Biotechnology quality control is defined by the individual production process and the product itself [16] because quality cannot be tested into the product [4]. The manner in which the biopharmaceutical is produced is part of its description thus, biopharmaceuticals are characterized by chemical structure as well as by operational definition [17]. Few doubt the need for process validation, but there is disagreement and confusion about what needs to be validated and how to perform it [18], Operational definitions of process validation have been developed to suit the philosophies of individual companies [3], Thus, there is increased interest in developing industry guidelines for the design and performance of validation studies [19],... 

There are innumerable definitions of validation that have been written over the nearly 30 years since its appearance in the pharmaceutical industry. Rather than foster new definitions with the context of this chapter, the authors have chosen to draw upon some of the more widely quoted definitions. The FDA defines process validation as Process validation is establishing documented evidences, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics (4). This definition is referred to in FDA s subsequent guidance specific for BPCs (5). 

When this definition of fitness for purpose is applied to toe pharmaceutical industry, it can be seen to fit well with toe concepts of quality. Personnel have to be shown to be fit for purpose for toe job they are employed to do (training, education and experience). Equipment needs to be demonstrated as fit for purpose based on qualification/validation, maintenance and calibration. Manufacturing processes are deemed fit for purpose based on in-process testing, process validation, etc. Process materials are shown to be fit for purpose based on testing appropriate to their intended use in toe process. This use will vary depending on toe stage of processing and whether it is a primary (chemical) process or a secondary (formulation) process. 

This chapter defines the terms, responsibilities, requirements and recommended procedures involved in pre-installation, installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ), which are all part of a typical HPLC system validation process. As the FDA does not publish a definitive reference or cookbook for these procedures, the suggestions herein are only recommendations. These have been successfully incorporated into formal standard operating procedures (SOPs) that have been implemented at a number of larger pharmaceutical establishments. As long as proper SOPs... 

In this definition, the key words are documentation, specific process, product specifications, and quality. This automatically means that validation will play a vital role in guaranteeing the safety, identity, quality, and stability of all pharmaceutical, biological, and medical device products. We will now present an outline of the most important requirements for ensuring that packaging line equipment complies with the guidelines of the authorities. 

The preparation of any pharmaceutical product requires controls over the production operations to assure the end result is a product that meets the required quality attributes. The methods utilized for this control are supported by formalized validation studies in which proof of consistency is demonstrated by appropriately designed experiments. The definition of appropriate operating parameters is the primary objective of the development activities and is further confirmed during scale-up to commercial operations. The validation supports that the routine controls applied to the process are appropriate to assure product quality [36], This is typically accomplished in formalized validation activities in which expanded sampling/testing of the product materials is performed to substantiate their uniformity and suitability for use [30],... 

Data mining of chemical databases is still at its very early stage. Nevertheless, as a result of the data explosion in pharmaceutical industry, it is expected that data mining techniques will play an increasingly important role in the drug discovery process. Future studies may include, for example, the definition of chemical space, the validation of various algorithms (206), and the representation of extremely large virtual databases (207). 

Elucidation of how the general principles underlying the concept of validation should be expressed in practice is an evolving process, as exemplified by the ongoing evolution of validation requirements for bioanalytical assays in the pharmaceutical industry (Shah 1992, 2000 FDA 2001 Viswanathan 2007). The complementary principle of fitness for purpose (Section 9.2) applies not only to the assay method but also to the validation process itself. Procedures that are considered to be fit for purpose in validation of an analytical method to be used in drug development, for example, need not necessarily apply to, e.g., methods used to screen pesticide residues in foodstuffs. As noted in Section 9.2, this point of view appears to be consistent with the definition of validation applied to all measurements (ISO 1994) Validation Confirmation by examination and provision of objective evidence that the particular requirements for a specified intended use are fulfilled. Of course, some basic principles are common to all validation schemes. 

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