The Future Quality Laboratory

The International Society for Pharmaceutical Engineering (ISPE) issued a guidance document in September 2012 aimed at establishing a baseline for the design of quality laboratory facilities. The ISPE Good Practice Guide: Quality Laboratory Facilities provides step-by-step considerations for producing a quality pharmaceutical-product laboratory. Here, ISPE President Nancy Berg talks about the guide.

BioPharm: What were the primary goals in issuing a guide on this topic? In other words, what regulatory challenges and technology/engineering gaps were facing the bio/pharmaceutical industry that needed to be addressed?

Berg: One of ISPE's overall goals is to help the industry create common points of reference and common language, so that all levels and job functions can work together more easily to address and solve technical challenges. In the quality laboratory space, we identified that quality laboratory owners and engineers needed a tool to help define the requirements for renovating existing laboratories and/or developing new laboratory facilities. That was the primary goal of the ISPE Good Practice Guide: Quality Laboratory Facilities, which presents design guidelines focused on pharmaceutical quality laboratories within or part of a GxP regulated environment.

Using the guide will help eliminate the engineering gaps created by an engineering team moving ahead without a properly defined scope of work. The guide addresses concerns such as defining the requirements of the laboratory and finally performing the risk assessment with the entire team prior to detail design. By focusing on the client to define the requirements, this guide is useful to both the owner and the architect/engineer. Our aim is that firms will use this guide as a path forward for their clients to help define the deliverables and eliminate uncertainty.

BioPharm: The guide provides the industry with specific recommendations for meeting GMP requirements of global regulations such as 21 CFR 210–211, the International Conference on Harmonization Q7 guideline on GMP for APIs, the European Union GMP Guide, and other cGMPs. Performing a risk assessment is a key theme across these requirements, and the ISPE guide describes how to apply such an assessment to a quality laboratory facility.

BioPharm: Can you offer some key takeaways from the guide in this area in terms of what the industry must consider that perhaps they have not considered in the past with regard to risk?

Berg: The guide provides much needed guidance on how to apply a risk assessment to a quality laboratory facility and identifies issues to be considered when conducting the risk assessment. Basically, it tailors many of the same risk concepts described in ICH Q9 to this type of facility. For example, a risk assessment may reveal that a laboratory space is insufficient for the planned storage or staging of samples and reagents for testing. Of course, this type of deficiency may lead to several problems, including a mix-up of the samples or reagents.

The risk assessment allows the client to consider the requirements needed to meet regulations. All too often, the architect and engineering support team delivers a technically elaborate facility that is far beyond the need of the owner to support the testing. The owner is then strapped with ongoing calibration and validation that is not needed for the testing protocols. On the other hand, if the guide is used to its fullest, the laboratory owner can define those areas needed that are technically elaborate.

BioPharm: Specialty laboratories, such as those that test and release the drug substance or drug product that is biohazardous or produced in a sterile process, face unique challenges. The ISPE guide includes a section devoted to these complex laboratories. How do quality teams have to adjust their approach when working with these types of laboratories and facilities?

Berg: This is an interesting and very complex area. The guide does address several types of specialty laboratories, including aseptic and sterility test laboratories, biohazard laboratories, and potent-compound laboratories. Each of these laboratories has unique design challenges and regulatory considerations, and so it's difficult to make generalizations about this section.

Depending on the size of the sample, many of the special conditions can be accomplished in isolators or biohoods, especially if the sample is closed and only opened for testing in small quantities. Other areas of concern are the handling of solvents within the laboratory and their removal as waste products from the laboratory. Solvents play a large role in testing, and making sure that explosion hazards as well as fire hazards are mitigated is critical. The law allows fixed quantities of solvent within the laboratory, so the design aspect of this is critical to its ongoing operation. In general, however, I'd point those interested in this topic to the content of the guide, which contains much more detailed information than we can go into here.

BioPharm: The ISPE guide devotes a section to record management and recommends that each laboratory develop an operations manual to identify potential hazards, along with practices and procedures to be followed to minimize or eliminate those hazards. Do today's bio/pharmaceutical quality laboratory teams tend to have such manuals, and do you think they will be inclined to have them going forward?

Berg: While it's always difficult to predict the future, I think it's safe to say that the industry will have some form of risk-based documentation, particularly in light of ICH Q8, Q9, and Q10. Because the quality laboratory handles a variety of products, raw materials, and solvents, there is a definite need for standard operational procedures. There is also a need for documented proof that a training program is in place to make certain that the seasoned scientist and the support staff are fully aware of the hazards surrounding their operation and that the devices within the laboratory are used appropriately. The goal is to minimize the risk of these hazards, both to the scientist and to the sample. Besides training and operational procedure, the quality laboratory should be equipped with a validation system on maintaining records of the testing performed, which is the basis for the release of product to market.

BioPharm: The guide includes an appendix for key differences to consider in European-based bio/pharmaceutical laboratories. Were FDA or EMA officials involved in reviewing the guide before its publication, and do they support its recommendations?

Berg: Fortunately for ISPE, both agencies were involved in the review process of the guide, and their feedback was incorporated in the final draft. It's not typical for regulatory bodies, such as FDA and EMA, to endorse or tacitly support industry guidance– and it's not their role to do so. That being said, I think it's fair to say that having their input during the review process has helped the guide to be reflective of current regulatory thinking from both agencies on this subject.

BioPharm: In general, based on this new guide, what key differences do you and ISPE hope for in the bio/pharmaceutical quality laboratoryof the future?

Berg: Ultimately, ISPE hopes that this guide will provide quality laboratory facilities with the necessary risk-based tools to support the release of high-quality pharmaceutical products to patients.