eChapters

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.

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:

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.

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.

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.

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.

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.

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.

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.

ABSTRACT

Medicinal plants are known to contain innumerable bioactive compounds that play an important role in conventional as well as western medicine. These bioactive molecules occur in plants as secondary metabolites, which have pharmacological relevance and aid in defense mechanism. In India, herbal medicines have been the basis of treatment and cure for various diseases. Conventionally, natural products have been tested as crude extracts containing complex mixtures of compounds, which if showing a desired activity, require a process of purification and identification of the active components, which can be lengthy and efficient.

In order to understand the function of these active compounds, X-ray crystallographic studies are carried out.

The present study involves the three dimensional structure analysis of purified compounds from the plants Phyllanthus amarus, Sphaeranthus indicus, Scoparia dulcis and Mangifera indica and Leonotis nepetaefolia.

ABSTRACT

Nature provides a wealth of information on natural products with novel architectur and very high medical potential. Given the enormous medical and economic impac of natural product pharmaceuticals we have obvious reasons to improve the activitie of the existing compounds and to discover new metabolites. Although natural product are a proven source of drug candidates they exert powerful physiological effects in one form or other. Only a small proportion of these compounds satisfy the rigorou criteria set by the pharmaceutical company. Also the amount of active compound isolated from the natural products is so small that it is difficult to exploit it in an industrial level. So there arises a need to synthesise synthetic compounds which ma be tested for bioactivity from the easily available starting materials by a simpl methodology. The quest for finding new drugs against various diseases such as AIDS cancer etc. act as a motivating factor in designing synthesis of new materials. In thi way most of the compounds synthesized can be tested for bioactivity to be effectivel used to fi ht a ainst certain dreadful diseases.

We have synthesised some polycyclic heterocycles through cycloaddition methodology and explored the bioactivity of the products. These molecules have basic skeleton of the natural products and possess the biological properties of the natural products. Thus they may be termed as pseudo natural products. These compounds are screened for antifungal and antibacterial activities and are found to possess bioactivity.

Keywords : Heterocyclic compounds, antifungal activity, DMSO, pathogens, inhibition zone.