FDA’s Focus On Segregation

During a number of 2007 FDA inspections of cylinder fill plants, agency inspectors focused in on segregation practices. This concentration reflects current agency thinking that segregation and quarantine activities are a critical element in preventing medical gas mix-ups. Adequate segregation is also a clear regulatory requirement in 21 CFR, specifically § 211.42. This article will review FDA’s current expectations for segregation in our industry, and what many GAWDA members are doing to keep up with evolving FDA requirements.

In my opinion, one of the most challenging aspects to managing the operations of a high pressure cylinder fill plant is cylinder movement and storage, including segregation/quarantine. When the filling of medical cylinders and the attendant segregation and quarantine requirements are added to the equation, the challenges are even harder. We still see many fill plants operating without clearly defined and marked areas for storing/segregating different gases. Many facilities also do not have designated areas for segregating full from empty cylinders.

FDA regulations contained in 21 CFR are quite specific regarding segregation requirements for drug manufacturing, and these translate into some focused requirements for our industry. Today, FDA expects firms to segregate their full medical cylinders from the empty cylinders. Each individual gas also needs to be segregated. This means you can not store all full medical cylinders together unless they are all the same gas. Storing different size cylinders of the same gas together is acceptable. Industrial cylinders also must be segregated from medical cylinders of the same gas. This means, for example, that you can not store full medical and full industrial cylinders of the same gas together. A recent FDA enforcement trend is to require the segregation of empty medical cylinders from empty industrial cylinders. A second enforcement trend is to require the segregation of empty medical cylinders by each individual gas. While many firms view this last requirement as over the top, this appears to be where FDA is headed. Both of these issues have been included in recent 483s issued by FDA to medical gas firms. Simply creating groups of different cylinders in areas of the plant is not sufficient. FDA requires all segregation areas shall be “specifically defined areas of adequate size.” To meet the requirement, agency inspectors require medical gas manufacturers to have distinct segregation areas. A common method of meeting this requirement includes creating areas defined by painted lines on the floor, pipe railings or other methods, i.e., designated pallets, that clearly define the different segregation areas. Segregation areas must be adequately marked with signs or other markings that clearly define the expected contents of each segregation area. However, these types of permanently established areas are not the only approach to meet FDA requirements. Most firms that have had to re-engineer their segregation processes are now using a combination approach of permanently established areas, together with more flexible segregation practices so they can accommodate peak production times. Another item that facilitates managing segregation is the development of a facility map that shows the different segregation areas, and what products are expected to be in those different areas.

Once adequate segregation areas and procedures are established, they must be followed. One of the biggest errors a company can make is to establish a system for segregation and then fail to comply with its own requirements. Unfortunately, in today’s busy fill plants, this can be a difficult issue to manage. Plant managers need to clearly establish segregation expectation with fill plant employees, and assure they have been adequately trained in the company’s segregation management procedures. We also recommend that operations management periodically review the effectiveness of its segregation processes, especially as the volume of cylinders through the facility grows.

We strongly recommend that firms take into account their individual facility and business issues when designing their segregation areas and management practices. Assuring your segregation systems accommodate your unique business requirements and work flows is a key aspect in sustaining compliance related to FDA segregation requirements. Implementing a system that goes against the grain of how you run your business usually leads to more and bigger compliance problems down the road.

Gases and Welding Distributors Association
Meet the Author
GAWDA Medical Gases Consultant J. Robert Yeoman is president & CEO of B&R Compliance Associates LLC in Lehigh Valley, Pennsylvania. Members can reach him at (610) 868-7183 and at bob.yeoman@brcompliance.com.