PLANT DESIGN

Plant design and manufacturing principles in (bio) pharmaceutical production



Plant Design and Manufacturing Principles in (bio) Pharmaceutical Production

Introduction

A detailed design and layout of the facility for the manufacturing of DNA vaccines was developed. The factors foremost in the design and layout of the DNA vaccines facility were compliance to current good manufacturing practices (cGMP), regulatory guidelines, health, safety and environment, effective production, optimum material and personnel flow, effective cleanliness, minimisation of contamination and enhance maintenance. The total site area is 108m X 91m (9828m2) and plant/production area is 32m X 20m (640m2) with space for future expansion. To reduce the impact of airborne particles, relative humidity, pressure and temperature on the purity, efficacy, and safety DNA vaccines product, a containment/cleanrooms of class 100 was design with controlled-air environment with access via airlock, HVAC and high efficiency particulate air (HEPA) filters. In order to conform and comply to current good manufacturing practices (cGMP) and regulations, the following key component of cGMP were incorporated into the design, validation master plan (VMP), standard operating procedures (SOPs), appropriate quality control (QC), cleaning-in-place (CIP), sterilisation-in-place (SIP), trained personnel, documentation, health, safety and environment, utilities required and waste treatment process. The entire project timeline was estimated with the aid of Gantt chart project management technique to be a year and 4.5 months with reference to literatures on similar projects.

The issue of location for the manufacturing facility is crucial to its profitability as it is influenced by raw material supply, transportation, utilities, environmental impact, waste disposal, local community considerations, personnel, climate, plant size and availability of land (Kim 2010 139-57). Moreover, before the design and installation of a new facility for pharmaceutical and biopharmaceutical product manufacture, an environmental impact assessment (EIA) is perform and approved (Dunn 1996 77-8). Hitherto, the design of any manufacturing facility must integrate the design of a treatment process and safe disposal of the waste generated to specified legal standards by regulatory authorities and eliminate/minimise harm to health and safety of personnel, environment and product contamination.

Aims and objectives

The defined goal of this project is to develop a detailed design and layout of a manufacturing facility for the production of DNA vaccines for commercial scale, applying current Good Manufacturing Practices (cGMP) and in compliance to regulatory guideline (FDA, FDA, MHRA, WHO, etc.).

Provide detail methods for qualification and validation of the design and layout, performance, quality control and enumerate the personnel/staff involved in the project.

3. Estimate the timeline of the project.

Process overview

DNA vaccines production mainly starts on a bench scale through pilot scale to large scale production (Carlson 2008 22-3). The design of a large scale facility for the manufacturing of DNA vaccines involves the selection of suitable plasmid DNA constructs/vectors (ColE1-type vectors, pUC vectors, pBR322 plasmid vector, etc.) that will replicate at high copy numbers, the production microorganism cell bank (Escherichia Coli), subsequently followed by fermentation process in the bioreactor under optimum conditions and control media (temperature, pH, pressure, etc.) to maximise cell growth, cell lysis to break the cells to release ...