Proper Processes for Ensuring Contaminant-Free Equipment at cGMP API Facilities

Facilities that manufacture multiple products may share the same equipment.

Posted: December 8, 2015

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Tags: Blog | cGMP
API Manufacturing and Pharmaceutical Manufacturing

Since this significantly increases the potential for cross contamination, it is critical that extreme caution is taken to clean equipment in order to prevent cross contamination, which can be harmful to consumers.

In the production of pharmaceutical ingredients, the cleaning of manufacturing equipment not only makes good sense, but it’s also a strictly regulated aspect of chemical manufacturing, according to Good Manufacturing Practice (GMP) regulations.  This regulatory requirement mandates that cleaning procedures and the analytical methods used for analysis of their samples are demonstrated to be effective and repeatable, which is known as validation of cleaning procedures and analytical methods.

The primary goal of equipment cleaning is to reduce the levels of existing process residues in a particular piece of equipment to meet a predetermined specification.  This is established by assessing the toxicity and potency of the existing residues on potential human consumers of the next product to be manufactured in the same equipment. Cleaning procedures are designed based on the nature of process residues and equipment design and their effectiveness and repeatability must be demonstrated.

Cleaning procedures employ various techniques such as rinsing, soaking, or spraying equipment surfaces with a liquid-medium boiling of a solvent inside the enclosed space of a piece of equipment, manual scrubbing or wiping of equipment surfaces, and impingement of solid residues lodged on equipment surfaces manually or by a high-pressure liquid stream. While all cleaning techniques rely on basic principles such as chemical action, mechanical force, contact time, and temperature, different techniques are dependent on them to different degrees.

The appropriate cleaning techniques are determined based on equipment design. For example, the space where the reaction mixture is held in a large chemical reactor can be most efficiently cleaned by spraying with a liquid medium, boiling of a solvent, or impingement of solid residues manually or by a high-pressure liquid stream, whereas other components of the same reactor such as valves, gauges, gaskets, and various other pipe fittings that are geometrically restricted are best cleaned by manual scrubbing/wiping or rinsing with a liquid medium. Choice of cleaning techniques may also be limited by the nature of the residue. If a residue (e.g. certain polymers) is not soluble in any known solvent the choice of cleaning technique is limited to those that rely heavily on mechanical force such as manual scrubbing/wiping or impingement by a high-pressure liquid stream.

The effectiveness of a cleaning procedure is demonstrated by analyzing rinse and swab samples taken from equipment. In order to obtain a sample that is representative of the entire surface area of a piece of equipment, a rinse sample is taken from a set volume of solvent that has been routed throughout the equipment system and has come in to contact with almost all wet surfaces of the equipment system. Swab samples are taken by wiping predetermined locations of the equipment system (swab locations) with specialized swabs. Swab locations are usually those that are poorly or not covered by a rinse, such as geometrically restricted sites, and are deemed to be on the most difficult to clean pieces of equipment.

Appropriate cleaning of equipment in any chemical manufacturing plant is critical to the safety and success of a product, since contaminated equipment can be ultimately dangerous to consumers. 

In our next post, we will be discuss best practices in cleanroom operations.

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About the Author

Ed Price CEO of PCI Synthesis
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.