USP〈1110〉 MICROBIAL CONTAMINATION CONTROL STRATEGY CONSIDERATIONS

GENERAL INTRODUCTION

Microbial contamination must be appropriately controlled for all drug product manufacturing per CFR §211.113 Control of microbiological contamination. This chapter was developed with the intent of converging with global standards and regulations. Some global regulatory agencies require a contamination control strategy (CCS), which encompasses all aspects of contamination control. This USP chapter will only focus on microbial considerations.

A CCS is a document supported by existing site and/or global microbial risk assessments that describes the approach to controlling contamination. It is intended to be a planned set of controls to minimize the risk of microbial contamination to assure product quality. Contamination control requirements for the manufacture of sterile drug products have been in place for many years. Historically these controls were developed individually. The newer, global CCS regulations advance the approach to contamination control making it holistic with individual elements being assessed and linked together for an overall effectiveness to a site’s contamination control program.

A CCS should be implemented for the manufacturing of sterile products and is recommended for low bioburden and/or nonsterile product manufacturing (see Bioburden Control of Nonsterile Drug Substances and Products 〈1115〉). The CCS should be holistic and include all elements of the entire manufacturing facility and process. Although the microbial contamination controls are usually assessed and monitored individually, the collective effectiveness of the controls should be evaluated as described in this chapter. The CCS should use quality risk management (QRM) principles, and appropriate risk assessments for contamination should be performed to support the effectiveness of the CCS.

The CCS should be documented as a compilation of the approaches adopted by an organization to ensure that the control of microbial contamination is applied to the products it manufactures. Multiproduct facilities may document their CCS in multiple documents such as a parent document for all shared elements and controls and then product- or process-specific CCS documents for the unique elements and controls. The facility CCS document(s) should be an overall summary document that briefly highlights the contamination controls per element and references all of the supporting technical documents (e.g., risk assessments, validations, qualifications, and technical documents).

An important piece of the CCS is ensuring that the proper technical and process knowledge is included in the development. The details of the product and manufacturing process should be fully understood to adequately assess hazards and ensure that controls in place are adequate to reduce the risk of contamination. The monitoring of the product and process must also be adequate to detect contamination. The CCS includes layers of controls that should be in place for the different elements. QRM is also a foundational piece of the CCS. Figure 1 represents CCS elements and microbial control that should be considered.

Source from USP:https://online.uspnf.com/uspnf/document/2_GUID-C75C160A-2C24-463D-84D3-918C2D6BE000_10101_en-US?

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