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Scott Sutton discusses the current state of USP â€¹1117â€º and USP's plans for future revisions.
US Pharmacopeia's General Information Chapter ‹1117› "Microbiological Best Laboratory Practices" is currently under revision after being in effect since 2006. It currently stands as the only guidance document that covers the basics of running a microbiological laboratory in the pharmaceutical industry. Scott Sutton is on USP's Committee of Experts, Microbiology and Sterility Assurance, and spoke to Pharmaceutical Technology regarding the recent developments in this chapter.
PharmTech: Can you provide a brief background into the state of the industry that led USP into thinking a chapter on microbiology laboratories was necessary?
Sutton: We had been talking about a chapter on microbiology laboratory practices since the 1990s. USP would get regular requests from laboratories for clarification on how you should be performing certain activities, some of these activities very basic to the laboratory functions. There was also a lot of interest in how to perform investigations and what is the best way to do a variety of standard operations. It was pretty clear that the people that were functioning as managers and supervisors and were heading-up the laboratory were asking very basic questions about how to perform microbiological testing. There were just not enough, and still aren't, microbiologists to go around.
PharmTech: Which types of companies were asking these questions?
Sutton: Smaller companies in particular were asking for a lot more clarification in terms of a USP informational chapter. On the other hand, however, the larger companies were less enthusiastic about additional USP guidance on this topic. For them, fewer regulations were better, which was an entirely understandable position. But that still left most laboratories searching for answers and unsure of their practices during regulatory audits. Also, as a historical perspective, at the same time these discussions were going on, there was a big push to harmonize sterility test and the antimicrobial efficacy test. It was obvious that it was going to be a wasted effort if once these tests went out, laboratories employed questionable procedures.
PharmTech: Once the decision was made to get started on the chapter, what was the approach?
Sutton: We talked about the chapter for years as an interesting idea before actually trying to publish it, and circulated several versions of a potential chapter among the committee before publication. Within the committee there was significant concern about the issue of being too proscriptive while at the same time being relevant and "informational." The result was what is admittedly a vague description of guiding principles for how you should run a quality control microbiology lab. We published this as the first draft of the proposed new informational chapter (see Pharmaceutical Forum (PF) 29 (3), 842 ). It originally was released under the title of "good laboratory practices for microbiology." But because of input from the agency, we amended the title to the current one and incorporated several comments from the field (see PF 30 (5), 1713 ).
For example, some of the comments said media was not important, and that we should consider dropping the media section of the chapter. But that is wrong. Media is critical in a microbiology laboratory but this point was apparently not coming across in the original and so the text was amended to try to clarify this. Other comments pointed out potential improvements in the chapter and were incorporated. The point of the chapter was to focus people's attention on those aspects important to running a well-controlled microbiology lab in a controlled manner, including media, culture, training, cleanliness, hygiene, and equipment. And for that purpose, it has been an extremely successful chapter.
PharmTech: What has been the response to this chapter?
Sutton: The official chapter first appeared in USP's Supplement 2, in 2006. The response has been generally very positive, although it has been interesting to see how people are applying it. For example, the PMFList (pharmaceutical microbiology forum) is an active online discussion group devoted to QC microbiology. Different aspects of this chapter are regularly debated in this forum, and in fact some of these discussions directly influenced changes in the chapter to be proposed in the upcoming proposed revisions to the chapter (due out in the March-April 2009 PF).
PharmTech: Who should be aware of the principles stated in USP ‹1117›?
Sutton: The principles stated in USP ‹1117› are important for the integrity of the data coming from the QC microbiology lab. All personnel working in that laboratory should be familiar with these principles, as should the QA unit responsible for reviewing the data and auditing the lab. It should also be noted that internationally regulatory agencies are certainly familiar with this chapter, and so all those responsible for product submissions, regulatory inspections and relationships with those agencies should be aware of current expectations.
PharmTech: Why is training, particularly of supervisors, such a concern in this chapter?
Sutton: You would like the situation to be that everybody in the microbiology laboratories work for people who are well-trained and academically trained microbiologists. Unfortunately the common situation in a lot of laboratories is that the person who heads up the microbiology laboratory may have not have any training in microbiology at all. And that is reflected in how the laboratory operates. You can't run a lab the way you run a chemistry lab. Microbiology labs should be headed by someone who really knows the scientific discipline, not only for the confidence you have in the results but also the fundamental biosafety requirements. The biosafety manual published by the Centers for Disease Control requires all Level 2 laboratories to be led by a microbiologist who is able to set safety rules and guidelines. But in the industry today, this is not true for many microbiology laboratories. So this provides a minimal set of requirements.
PharmTech: What other situations in the industry has created a need for this chapter?
Sutton: I would refer you to a recent publication by Luis Jimenez (J. Jimenez, "Microbial Diversity in Pharmaceutical Product Recalls and Environments," PDA J Pharm Sci Tech. 61 (5), 383-398 ). He published an interesting retrospective on recalls over the past years looking at both sterile and nonsterile product recalls. There are a large number of those recalls from the smaller pharmaceutical companies. It should be noted that some companies do not have a microbiology department at all and send all microbiology testing out-of-house for testing. The danger in this approach is that the company fails to develop the in-house expertise in microbiology, and may run risks that other companies might avoid. The quality of safeguarding the finished product has a large, and a critical microbiology component.
PharmTech: What are the revisions that need to be made?
Sutton: There have been a couple of gaps that have been identified in the chapter that should be corrected. One deals with sample handling and transport, which is especially useful for samples going out to contract laboratories. There is nothing in the chapter right now that discusses how to collect samples for shipping and transport, how much time is permissible between sample collection and sample testing. These issues should be addressed. Additional information needs to be included on equipment (especially lab autoclaves) and on laboratory resources. In addition, the section on supervision of the laboratory may also be strengthened, depending on the comments we receive after the publication in the Pharmacopeial Forum. So we are hoping those in industry will be active in this ongoing revision process.