BLOG: Build the Ideal Contamination Control Strategy

BLOG: Build the Ideal Contamination Control Strategy

In this blog series on the latest developments in regulation concerning the pharmaceutical industry, we take a look at the newest tool for product quality–the contamination control strategy (CCS). The CCS is designed to ensure quality risk management is present in every pharmaceutical process from the ground up, and every quality decision made has a foundation in scientific reasoning. Build the ideal contamination control strategy with our experts in the field!

Why do we need a Contamination Control Strategy?

Mass-produced pharmaceuticals have come far since the industrial manufacturing of synthetic drugs at the end of the 19th century[1] with rapid advancement in technology, process control, and sterility requirements. Yet even as improvements to Pharma develop and stick, recalls still occur with regularity[2] and their significant impact on both the manufacturer and consumer are why worldwide regulation of the industry is so enforced. Environmental monitoring (EM) is one facet of the greater picture of current good manufacturing practices (cGMPs) that has been standardized for the safety of human health.

In a typical cleanroom, EM takes the form of monitoring non-viable and viable particles to maintain a reliable state of control in production. Limits per an area’s classification or “grade” are defined by both the FDA’s Sterile Drug Products Produced by Aseptic Processing, and the European Commission’s EU GMP Annex 1 2020 Draft.

Viable particles are living organisms such as bacteria, molds, and yeasts. EU GMP limits found in Table 7, Maximum action limits for viable particle contamination [3]. FDA cGMP limits found in Table 1, Air classifications [4].

Nonviable particles do not contain a living organism, but act as transportation for viable particles. EU GMP limits found in, Table 6, Limits for airborne particulate concentration for the monitoring of non-viable contamination [3]. FDA cGMP limits found in Table 1, Air classifications [4].

Past focus was placed on sampling methods for the measurement of potential contamination: particle counters, active air samplers, Petri dishes, and swabs for surface monitoring. Bioburden of bulk product and filter integrity were also tested to increase the detection of microbiological contamination along the production process. This approach has been remodeled to prevent and control potential contamination from reaching the point of no return: the product. Once contamination occurs, there is no cost-effective removal scheme to continue production, making the determination of sources all the more important. This is achieved by:

  1. Implementing Quality by Design into the manufacturing area.
  2. Using quality risk management to identify the critical control points (CCPs).
  3. With the CCPs, identifying the process phases where it is necessary to establish mitigation actions to control the identified risks.

The collective execution of controls is called the contamination control strategy (CCS).

Defining the Strategy

So, what do regulatory bodies dictate should be included in a CCS? In the document, EU GMP Annex 1: Manufacture of Sterile Medicinal Products, you will find the following background:

“Contamination Control Strategy (CCS) – A planned set of controls for microorganisms, pyrogens and particulates, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to active substance, excipient and drug product materials and components, facility and equipment operating conditions, in process controls, finished product specifications, and the associated methods and frequency of monitoring and control… A Contamination Control Strategy (CCS) should be implemented across the facility in order to define all critical control points and assess the effectiveness of all the controls (design, procedural, technical and organizational) and monitoring measures employed to manage risks associated with contamination. The CCS should be actively updated and should drive continuous improvement of the manufacturing and control methods.” [3]

Note that “critical control points” do not have any associated measurements and are not an In Process Control (IPC). They are instead process phases in which a risk to be mitigated has been identified.

Learn more… Get the full paper here


[1] Daemmrich A, Bowden ME. The top pharmaceuticals that changed the world. A Rising Drug Industry. Chemical & Engineering News. June, 20 2005. 83(25).
[3] European Commission. EU GMP Annex 1: Manufacture of sterile medicinal products. Annex 1 Draft. Published December 2020.
[4] Food and Drug Administration. Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice. Published September 2004.

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