Preface It gives me immense pleasure to present a book entitled “Quality assurance techniques in pharmaceuticals”. Need to write this book is ever increasing the data on the subject matter of quality assurance. In the era of quality assurance, every firm need to be quality assured so that it can achieve its quality goal. Book is prepared to emphasis on the basic techniques, methods, plans, certification procedures for quality assurance, keeping in mind the syllabus of quality assurance techniques laid by various Indian universities. Goal of this book is to provide primary and update knowledge of various quality assurance data to master of pharmacy students in the professional programme of their study.

Accuracy The degree of closeness of the determined value to the nominal or known true value under prescribed conditions. This is sometimes termed trueness. Analyte A specific chemical moiety being measured, which can be intact drug, bio molecule or its derivative, metabolite, and/or degradation product in a biologic matrix. Analytical run (or batch) A complete set of analytical and study samples with appropriate number of standards and QCs for their validation. Several runs (or batches) may be completed in one day, or one run (or batch) may take several days to complete. Biological matrix A discrete material of biological origin that can be sampled and processed in a reproducible manner. Examples are blood, serum, plasma, urine, faces, saliva, sputum, and various discrete tissues.

TQM is an integrative philosophy of management for continuously improving the quality of products and processes. It is used around the world. TQM functions on the premise that the quality of products and processes is the responsibility of everyone who is involved with the creation or consumption of the products or services offered by an organization. In other words, TQM capitalizes on the involvement of management, workforce, suppliers, and even customers, in order to meet or exceed customer expectations. Considering the practices of TQM as discussed in six empirical studies, Cua, McKone, and Schroeder (2001) identified the nine common TQM practices as cross-functional product design, process management, supplier quality management, customer involvement, information and feedback, committed leadership, strategic planning, cross-functional training, and employee involvement. TQM and Six Sigma The Six Sigma management strategy originated in 1986 from Motorola’s drive towards reducing defects by minimizing variation in processes. The main difference between TQM and Six Sigma is the approach Six Sigma is a business management strategy originally developed by Motorola, USA in 1986. As of 2010, it is widely used in many sectors of industry, although its use is not without controversy.

It 9001:2000 Means customer satisfaction and continuous improvement ISO (International Organization for Standardization) is a worldwide federation of national Standards bodies from each country. The object of ISO is to promote the development of Standardization and related activities in the world with a view to facilitating international exchange of goods and services, and to developing cooperation in the spheres of intellectual, scientific, technological and economic activity. The results of ISO technical work are published as International Standards. Quality management Systems (QMS) certification as per ISO 9001 : 2000 is an important opportunity that can enable the companies acquire the label of an enterprise caring for the customer needs and improve their economic performance at the same time. QMS provides an organization a systematic structured documented and effective approach to consistently maintain the product quality meeting customer requirements.

Environmental management systems (EMSs) such as ISO 14000 are seen as mechanisms for achieving improvements in environmental performance and for supporting the trade prospects of “clean” firms. The potential advantages of EMSs are clear, but the adoption of ISO 14000 is very recent, and practical issues are emerging, among them the need for an emphasis on performance improvement and for simplification of certification; the potential for regulatory streamlining; and the trade consequences. This chapter outlines the key elements of an EMS and discusses these issues. The Benefits of an EMS An environmental management system (EMS) is a structured program of continuous environmental improvement that follows procedures drawn from established business management practices. The concept is straightforward, and the principles can be easily applied, given the necessary support. There has been increasing interest in the potential value of EMS approaches, ofwhich the recently released ISO 14000 series is the most widely known. The first steps in the control of industrial pollution have been the creation of the necessary regulatory framework and the specification and design of control equipment to reduce emissions. These efforts have been broadly successful in improving the performance of many polluters, but in other cases, investments in pollution equipment are wasted because the equipment is not operated properly. Attention, in the World Bank and elsewhere, is turning to support of regulatory and end-of-pipe approaches through incentives, production efficiencies, and management improvements a range of measures often grouped under the broad banner of cleaner production and eco-efficiency.

1. GMP Good manufacturing practices and requirements of premises, plant and equipment for pharmaceutical products To achieve the objectives listed below, each licensee shall evolve appropriate methodology, systems and procedures which shall be documented and maintained for inspection and reference; and the manufacturing premises shall be used exclusively for production of drugs and no other manufacturing activity shall be undertaken therein.

Introduction In the 1997 WHO guidance document: “WHO/VSQ/97.01: (A WHO guide to good manufacturing practice (GMP) requirements. Part 1: Standard operating procedures and master formulae)” some basic explanations and instructions were given for preparing various documents required by Good Manufacturing Practice guidelines from WHO and from several regulatory authorities. GMP guidelines include the requirements for documents (individual), documentation (the systems and formats for documents), and documenting (recording) of production and control activities. Most GMP guidelines provide the same or very similar information as the principles of Good Manufacturing Practice are now international in scope. In this guidance document, the requirement for master manufacturing instructions and the requirements as given in different GMP documents, different names for these documents and various forms that they can take will be described. This is to guide vaccine manufacturers who are applying for pre-qualification or re-qualification of their product(s) in the preparation or improvement of current documents for manufacturing operations.

Principle Good documentation constitutes an essential part of the quality assurance system. Clearly written documentation prevents errors from spoken communication and permits tracing of batch history. Specifications, Manufacturing Formulae and instructions, procedures, and records must be free from errors and available in writing. The legibility of documents is of paramount importance. General Specifications describe in detail the requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. Manufacturing Formulae, Processing and Packaging Instructions state all the starting materials used and lay down all processing and packaging operations. Procedures give directions for performing certain operations e.g. cleaning, clothing, environmental control, sampling, testing, and equipment operations. Records provide a history of each batch of product, including its distribution, and also of all other relevant circumstances pertinent for the quality of the final product.

Validation in the pharmaceutical and medical device industry is defined as the documented act ofdemonstrating that a procedure, process, and activity will consistently lead to the expected results. It often includes the qualification of systems and equipment. It is a requirement for Good Manufacturing Practices and other regulatory requirements. Since a wide variety ofprocedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:

This chapter focuses on the statistical methods used for method development. These are categories as follow : 1.SUPAC- Scale-Up and Post-Approval Changes 2.PAT -Process Analytical Technique 1. SUPAC - The acronym “ SUPAC “stands for “Scale-Up and Post- Approval Changes” . It refers to the FDA-recommended testing and filing actions to be taken by a pharmaceutical firm when it changes the manufacturing processes of a drug product that has been approved via a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), or an Abbreviated Antibiotic Drug Application (AADA). FDA has provided its recommendations to industry in the form of SUPAC Guidances or supac guidelines.

Analytical methods development and validation play important roles in the discovery, development, and manufacture of pharmaceuticals. Pharmaceutical products formulated with more than one drug, typically referred to as combination products, are intended to meet previously unmet patients need by combining the therapeutic effects of two or more drugs in one product. These combination products can present daunting challenges to the analytical chemist responsible for the development and validation of analytical methods. This presentation will discuss the development and validation of analytical method (Spectrophotometric, High performance liquid chromatography (HPLC), & High performance thin layer chromatography (HPTLC)) for drug products containing more than one active ingredient. The official test methods that result from these processes are used by quality control laboratories to ensure the identity, purity, potency, and performance of drug products.

1 Introduction The purpose of these Guidelines on Audit Quality is to assist Supreme Audit Institutions assure the high quality of their work and the resulting products. This Section describes the background of the document, provides key definitions applicable to these guidelines, discusses the types of SAIs and audits to which the guidelines apply, lays out the form in which the guidelines are presented and identifies some other sources of useful guidance for assuring quality. Section 2 then deals with quality control as the “hot review” ofthe audit process. Subsections 2.1 — 2.6 set forth some basic premises for establishing effective quality controls, discuss the nature of the controls required to assure quality in the areas of selection and timing of audits, planning specific audits, executing audits, reporting the results of audits, and following up on audits, respectively. Section 3 describes the procedures necessary to assure that needed quality controls are in place and operating effectively, that is it presents the characteristics of post-audit quality assurance. Finally, Section 4 focuses on institutional measures to enhance quality, especially management of human resources (recruitment, training, staff development and ethical standards), institutional risks and external relations. The Annexes provide other information that was considered potentially useful, including reference material, checklists and excerpts regarding quality controls from other guidance documents. The list of reference documents is contained in Annex A. Audit quality is obtained by a process of identifying and administering the activities needed to achieve the quality objectives of an SAI. All types of SAI need to understand the benefits that can be realised once audit quality is made a priority. Improving audit quality requires a systematic SAI- wide approach. Piecemeal efforts by individuals and individual audit teams are not enough and will not work. There are no quick fixes to be obtained where audit quality is concerned. SAIs needs to proceed methodically in an organised way to fix each quality issue and problem in turn. As new problems will always emerge, this should be a continuous process for the SAI. It is also evident that most audit quality related problems are mainly the result ofpoor management of the audit process or the SAI itself.

1. Pharmaceutical Quality System 1.1 Introduction This document establishes a new ICH tripartite guideline describing a model for an effective quality management system for the pharmaceutical industry, referredto as the Pharmaceutical Quality System. Throughout this guideline, the term “pharmaceutical quality system” refers to the ICH Q10 model. ICH Q10 describes one comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organisation (ISO) quality concepts, includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. Consequently, the content ofICH Q10 that is additional to current regional GMP requirements is optional. ICH Q10 demonstrates industry and regulatory authorities’ support of an effective pharmaceutical quality system to enhance the quality and availability of medicines around the world in the interest of public health. Implementation of ICH Q10 throughout the product lifecycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.