Definitions

DEFINITIONS

Several terms used in industrial and hospital production must be defined to enable the reader to follow this article. The inter-relationship between quality assurance (QA), GMP, quality control (QC) and in-process control is shown in Figure 23.1.

The UK Orange Guide (The Rules and Guidance for Pharmaceutical Manufacturers and Distributors, 2007) emphasizes the fundamental point:

Quality assurance is particularly important, and this type of manufacture must strictly follow carefully established and validated methods of preparation and procedure. Sole reliance for sterility or other quality aspects must not be placed on any terminal sterilization process or finished product test.

The difficulty in demonstrating quality is that the tests carried out are designed to show the absence of quality. For example, the test for sterility involves taking samples and testing for microorganisms. If 20 samples are tested, 3.4% of the batch needs to be contaminated to have a 50% chance of detecting that contamination. That level of contamination represents gross failure of GMP and problems would normally be detected by environmental monitoring. Indeed, it is not unknown for a batch to pass a sterility test but be rejected due to problems detected during environmental monitoring (section 5.2). Therefore it is important that a product be manufactured in a suitable environment by a procedure that minimizes the possibility of contamination occurring. At the end of this process the tests can be performed as an additional measure of quality.

A)  Quality

There are many definitions of quality (see Sharp, 2000). For the purpose of pharmaceutical products the term quality is usually taken to mean fitness for purpose. Not only must the product have the desired therapeutic properties, it must also be safe for administration by the route intended. Sharp (2000, 2001) discussed several meanings of quality but summarizes it as follows:

in a nutshell, it is fit to be given to a patient in the confidence that it will have the desired effects and not damage him or her, in any way, through faults in manufacture.

B)   Manufacture

Manufacture is the complete cycle of production of a medical product. This cycle includes the acquisition of all raw materials, their processing into a final product, and subsequent packaging and distribution.

C)   Quality Assurance (QA)

Quality assurance is a wide ranging concept covering all matters which individually or collectively influence the quality of a product. It is the total sum of the procedures needed to ensure the fitness of a pharmaceutical product for its intended use. QA incorporates GMP plus other factors.

D)   Good Manufacturing Practice (GMP)

GMP is that part of QA which is aimed at ensuring the product is consistently manufactured to a quality appropriate for its intended use and to meet the requirements of the regulatory authorities. GMP requires that: (1) the manufacturing process is fully defined before it begins; and (2) the necessary facilities are provided. In practice, this means that:

·                     Personnel must be adequately trained..

·                     Suitable premises and equipment must be employed.

·                     Correct materials must be used.

·                     Approved procedures must be adopted.

·                     Suitable storage and transport facilities must be available.

·                     Appropriate records must be made.

The reasons for GMP are (Sharp, 2001):

·        the poor chance of the patient detecting that anything is wrong

·        the weakness of product testing because:

·        we can only test samples

·        we cannot test for everything

·        the dangers to patients of even only a small number of defective or wrongly labelled items in a batch (and it is very difficult to detect a small number of defectives).

It is about getting things right all along the line.

E)   Quality Control (QC)

QC is that part of GMP concerned with sampling, specifications and testing, as well as the organization, documentation and release procedures which ensure that the necessary and relevant tests are carried out, and that materials are not released for use, nor products released for sale or supply, until their quality has been judged satisfactory. For sterile products QC includes testing for sterility and pyrogens. The Rules and Guidance for Pharmaceutical Manufacturers and Distributors (2007) states that QC is not confined to laboratory operations, but must be involved in all decisions which may affect the quality of the product. The independence of QC from production is considered fundamental to the satisfactory operation of QC.

F)   In-Process Control

This comprises any test on a product, the environment or the equipment that is used during the manufacturing process. An example of this is testing that an autoclave is functioning correctly (Gardner & Peel, 1998).

G)  Validation

A documented programme that provides a high degree of assurance that a specific process, method or system will consistently produce a result meeting predetermined acceptance criteria.