Quality Systems in a Production Facility Chapter 7

Issues relating to resources Facilities and Equipment Process must flow in an orderly fashion Storage of approved and unapproved raws Storage of sterile and nonsterile items Control of environmental factors Humidity Temperature Dust Accommodate equipment and personnel

Facilities, continued Good housekeeping Clean Pest and rodent control Environmental monitoring and control Suitable equipment that is maintained and where needed calibrated Thermometers Scales

Raw materials Raw materials are considered to be resources Flow in, transformed to product, flow out Receive  quarantined  tested  approved  used for production Disapproved  returned to supplier

Raw material handling Must be labeled upon arrival to avoid confusion Raws must be tested and found to conform to specifications before they are used by production Storage conditions must avoid material hazards and address perishabiltiy issues Traceability of materials must be assured

Specifications Descriptions that define and characterize properties that a product must possess based on its intended use Specifications for the same property may vary depending on use Specifications are associated with analytical methods Specs are written as ranges due to variations from product to product

Establishing specifications Is a key element for any quality program Establish specs by: Defining characteristics of product Document those specifications Ensure that specifications are met FDA scrutinizes specs for regulated products

Processes Products are made by processes Processes are a set of interrelated resources and activities which transform inputs into outputs Process must include monitoring Critical points or points of control In process testing . pH control of oxidation Use of oxygen rather than nitrogen

Validation of Processes and Equipment Goal of Validation is to ensure that product quality is built into a product as it is produced Process validation is defined “as establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specs and quality attributes” (FDA)

Steps for designing a process Table 7.3 Define purpose of process Define the endpoint of the process Select a method to define/measure desired endpoint Establish specs for raw materials Determine steps for the process Scale up process from lab to plant scale P-116

Continued Analyze potential problems Determine operation at critical points Develop methods to monitor the process Develop methods to control the process Develop effective record keeping of process Write and approve all SOPs required for the process

Items to be validated Table 7.4 Processes (Unit operation) Cleaning and sterilization Fermentation Purification, packaging labeling of product Analytical methods Mixing and blending Major equipment Heating, venting, and air conditioning Water purification P-119

Continued Tests and assays Autoclaves and steam generators Computers that control manufacturing Freeze dryers Tests and assays Microbiological assays Contaminant tests Raw materials analyses Final product tests

Validation of process Occurs when process is in place Requires a validation protocol Validation protocol is a document which details how the validation tests will be conducted Equipment must be validated Installation qualification Operational qualification

Components of a validation protocol, Table 7.5 Description of process Explanation of features of process to evaluate Description of equipment, raws, and intermediate products that are evaluated Explanation of sampling Procedures for tests and assays P-120

Continued Explanation of how results of the assays are to be analyzed including statistical methods A statement of how many times a test is repeated SOPs describing how to run the process Give students a description of a process (cookie baking) and have them validate