Regulatory inspections of sterile facilities – the focal points Part 1: Visual inspection of particulate matter

Sterile manufacturing is a continuum that stretches from development to manufacturing, to finished product; and to marketing and distribution, as well as the utilisation of drugs and biologics in hospitals and in patients’ homes. Although the terms ‘sterile manufacture’ or ‘aseptic manufacturing’ are widespread, there is no generic approach to the manufacturing of sterile products. Each plant or process will differ in relation to the technologies, products and process steps.

The preparation and operation of regulatory inspections represent an important part of the biannual or annual cycle for pharmaceutical organisations. With sterile products, the main hazards are viable microorganisms, particulate matter (particles which may or may not be microbial in origin), and microbial by-products, especially pyrogens.

As Section III of the USA Food and Drug Administration (FDA) guidance on sterile products notes: “Nearly all drugs recalled due to non-sterility or lack of sterility assurance in the period spanning 1980–2000 were produced via aseptic processing.” 

Such trends are also reflected in outcomes reported by other regulatory agencies, such as the UK Medicines and Healthcare Products Regulatory Agency (MHRA). This is the first in a series of articles that attempts to present an overview of the general topics relating to the manufacture of sterile products and to outline some of the more important aspects which the manufacturer should review and prepare for prior to a regulatory inspection by a body like the FDA, a European inspector (as required by the European Medicines Agency) or by the World Health Organization. These selected topics are what we consider to be the ‘focal points’, and they reflect the deficiencies most commonly cited by regulators. 

This is an extract from an article by Madhu Raju Saghee, Tim Sandle and Palash Das from GMP review Vol. 17 No. 2, to read more subscribe now.