Pharmaceutical products, validation

C. C. Chan and E. Jensen, Overview of pharmaceutical product development and its associated quality system, in Analytical Method Validation and Instrument Performance Verification (eds. C. C. Chan, H. Lam, Y. C. Lee and X.-U. Zhang), Wiley-Interscience, Hoboken, NJ, 2004, pp. 1-10. 

Hokanson, G. C., A Life Cycle Approach to the Validation of Analytical Methods During Pharmaceutical Product Development, Part II Changes and the Need for Additional Validation, Pfjarm. Tech., 18(16) 92-100, 1994. 

Over the past 40 years, capillary electrophoresis (CE) has advanced significantly as a technique for biomolecular characterization. It has not only passed the transition from a laboratory curiosity to a mature instrumental-based method for micro-scale separation, but also emerged as an indispensable tool in the biotech and pharmaceutical industries. CE has become a method of choice in research and development (R D) for molecular characterization, and in quality control (QC) for the release of the therapeutic biomolecules.In the biopharmaceutical industry, more and more CE methods have been validated to meet International Conference on Harmonization (ICH) requirements. In this chapter, we present real industrial examples to demonstrate the role of CE in R D of pharmaceutical products. The focus in this chapter is on method development analytical control for manufacturing and release of therapeutic proteins and antibodies. 

Lilian M Azzopardi studied pharmacy at the University of Malta, Faculty of Medicine and Surgery. In 1994 she took up a position at the Department of Pharmacy, University of Malta as a teaching and research assistant. Professor Azzopardi completed an MPhil on the development of formulary systems for community pharmacy in 1995, and in 1999 she gained a PhD. Her thesis led to the publication of the book Validation Instruments for Community Pharmacy pharmaceutical care for the third millennium published in 2000 by Pharmaceutical Products Press, USA. She worked together with Professor Anthony Serracino Inglott who was a pioneer in the introduction of clinical pharmacy in the late sixties. Professor Azzopardi is the author of Further MCQs In Pharmacy Practice (2006) and MCQs in Clinical Pharmacy (2007) by Pharmaceutical Press. 

Azzopardi LM (2000). Validation Instruments for Community Pharmacy Pharmaceutical Care for the Third Millennium. Binghamton, New York Pharmaceutical Products Press. 

The critics of government-imposed price controls on pharmaceutical products do have a valid point. As long as the price ceilings are set above the incremental cost of producing these products, manufacturers will be tempted to sell at whatever those controlled prices are, because they earn at least a positive margin toward the recovery of fixed costs. The problem is that the price ceilings may be set at levels far below fully allocated fixed costs per unit. If every payer followed that strategy, pharmaceutical companies would soon become insolvent. 

To gain FDA approval or license for marketing, a pharmaceutical product must be shown to be safe and effective for its proposed or intended use. The drug company or sponsor must also provide evidence to show that the processes and control procedures used for synthesis, manufacture, and packaging are independently validated to ensure that the pharmaceutical product meets established standards of quality. The overall effort from the inception of a new molecular entity and the establishment of analytical, scale-up, and quality control procedures, to the collection of safety and efficacy data for consideration by the FDA as part of an NDA or BLA, is called the drug development process. 

In the case of recombinant proteins intended for use in sterile pharmaceutical products, additional process controls on microbiologic aspects of analysis must be established and validated to ensure aseptic conditions throughout the manufacturing process. 

Since the mid-1970s validation has become an increasingly dominant influence in the manufacture and quality assurance of pharmaceutical products. In 1976 the FDA proposed a whole set of current GMP regulations which were revised several times. 

Pharmaceutical products quality must be consistent and meet the health and regulatory requirements. The pharmaceutical industry has the obligation to validate GMP to their process to be in compliance with GMP requirements. 

Validation of aseptic pharmaceutical processes is specihcally assembled in the second edition as a reference for use by managers, supervisors, and scientists in the pharmaceutical industry. The primary intent of this work is to guide design engineers, manufacturing personnel, research and development scientists, and quality control professionals in validating those processes needed for nonaseptic and aseptic pharmaceutical production. 

The purpose of the second edition is to meet the need for a ready-to-use text on the validation of aseptic pharmaceutical production and to provide general information and guidelines. It is a compilation of various theories, sterilization variables, and engineering and microbial studies that can be used independently or in combination to validate equipment and processes. The concepts and methods presented in this edition are not intended to serve as a final rule. Reciprocal methods for achieving this purpose exist and should also be reviewed and consulted, if applicable. 

The CISs are rapidly becoming more popular and reliable as their field of application broadens. This is mainly due to the production of surface images by multipoint scanning and mapping. Hyperspectral imaging has proven its potential for qualitative analysis of pharmaceutical products and can be used when spatial information becomes relevant for an analytical application. Even if online applications and regulatory method validation require further development, the power of CIS in quality control and PAT needs no further demonstration, whatever the wavelength domain or method of spectra collection. 

The aim of validation of an analytical procedure is to demonstrate that the method employed in any product testing, such as the identification, control of impurities, assay, dissolution, particle size, water content, or residual solvents, is validated in the most important characteristics. Identification tests, quantitative tests for impurities content, limit tests for control of impurities, and quantitative tests of the active moiety in samples of pharmaceutical product are the most common types of analytical procedures that validation addresses [1]. 

The pilot-production phase may be carried out either as a shared responsibility between the development laboratories and its appropriate manufacturing counterpart or as a process demonstration by a separate, designated pilot-plant or process-development function. The two organization piloting options are presented separately in Figure 1. The creation of a separate pilot-plant or process-development unit has been favored in recent years because it is ideally suited to carry out process scale-up and/or validation assignments in a timely manner. On the other hand, the joint pilot-operation option provides direct communication between the development laboratory and pharmaceutical production. 

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