Guidance on process analytical

Regulatory guidance on process analytics The specifics of regulatory guidance in the pharmaceutical industry are defined in a number of publications, such as ... 

Multivariate analysis (MVA) is the statistical analysis of many variables at once. Many problems in the pharmaceutical industry are multivariate in nature. The importance of MVA has been recognized by the US FDA in the recent guidance on process analytical technology [3]. MVA has been made much easier with the development of inexpensive, fast computers, and powerful analytical software. Chemometrics is the statistical analysis of chemical data. Spectral data from modern instruments is fundamentally multivariate in character. Furthermore, the powerful statistical methods of chemometrics are essential for the analysis and application of spectral data including NIR and Raman. In this section, we will briefly review the subject of chemometrics and MVA. 

There is one additional general requirement included in Directive 75/318/EEC as amended, which affects all parts of the pharmaceutical section of the dossier. This is a blanket requirement that all analytical methods are to have been adequately validated and the validation data included in the submission. This applies to all analytical methods including those used in connection with preclinical and clinical parts of the dossier. Additional guidance on how to meet these requirements is included in the two notes for guidance developed on the topic of analytical validation through the ICH process, available at the EMEA web site or at the Commission s web site, mentioned earlier. 

With that said process analytical chemistry (PAC) has been commonplace in several industries, even the pharmaceutical industry, prior to 2004. Riebe and Eustace differentiate PAC from analytical chemistry with one word location. PAC is typically spectroscopy, separations or chemometrics, as apphed either at-, in- or on-line to manufacturing. Several comprehensive application reviews of process analytical chemistry have been published in Analytical Chemistry since 1987. " In one of these reviews Workman et al. comment that PAT has continued to evolve as a more appropriate term than PAC while noting PAC has existed since 1911 but is just now finding common usage. The scope of PAT is much broader than that of PAC as the FDA guidance outlines the following desired state for manufacturing ... 

Process analytical technology is consistent with the quality systems approach in that it is based on science and engineering principles for assessing and mitigating risks related to poor product and process quality. In the PAT guidance, the FDA indicates that the desired state for pharmaceutical manufacturing may be characterized as follows ... 

It is beyond the scope of this chapter to discuss and explain how the requirements can be implemented in analytical laboratories. This has been described in a six-article series published in Biopharm [16-21]. We elaborate here on the validation aspect of the rule. Part 11 requires that computer systems used to acquire, evaluate, transmit, and store electronic records should be validated. This is not new, as processes and steps to validate such systems were described earlier in the chapter. FDA s expectations for validation have been described in the Part 11 draft guidance on validation [4]. This guidance makes it very clear that functions as required by Part 11 should be validated in addition to functions that are required to perform an application such as chromatographic instrument control, data acquisition, and evaluation. Specific functions as required by Part 11 are as follows ... 

In recent years, the International Conference on Harmonization (ICH) has published two documents that serve as expert guidance on analytical and related validation [53,54], As part of the outsourcing process, the client and provider should review these and related regulatory guidances (e.g cleaning validation) to ensure that there is a mutual understanding and agreement on the scientific basis of methods validation. 

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