Closing the functionality gap with off-the-shelf pharmaceutical LIMS

Introduction
The new buzzword in the pharmaceutical industry, COTS, refers to commercial-off-the-shelf and it is being used frequently in reference to laboratory software. COTS software is a hot topic because many companies are hoping to significantly reduce the risk of laboratory information management system (LIMS) implementations, and subsequent validation processes. Companies also look to COTS for reduced maintenance and training costs, simplified upgrades, and much greater user acceptance. There is confusion, however, about what a COTS solution really is, and what the true validation requirements of such a solution would be.

A LIMS Primer
Historically, LIMS vendors have designed their systems as generically as possible in order to appeal to as wide a market as possible across multiple industries. These systems offered basic sample- and test-management capabilities, but to meet industry- or application-specific requirements, customizations were necessary. Vendors provided tools that allowed the customer, the vendor, or third-party consultants to extend the system and the database.

In some industries, this approach was less problematic, as the basic functionality was close enough to industry requirements that customization was not overly significant. For the pharmaceutical industry, as well as biotechnology and contract research organizations, however, life was not quite that simple. Pharmaceutical researchers are working in labs ranging from early stage drug discovery to bioanalytical testing of drug candidates to manufacturing development and quality control. Applying one LIMS to those varying labs requires extensive customization. Customization is also required due to the batch- versus sample-oriented production processes, complex specifications and test methods, and tight regulatory requirements. Like a snowball, each additional requirement would generate an avalanche of additional work: specifications, design, development, testing and validation, documentation, and more. Customers also ran the risk of breaking their customizations when upgrading to new releases.

The scenario increased the risk of failed or significantly delayed deployments. Pharmaceutical customers often found they needed to build via customization as much as 60% to 70% of their desired functionality. Today, COTS solutions are designed to deliver as much as 85% of required functionality right out of the box, leaving a fraction of functionality to be achieved via configuration or customization. From a timeframe perspective, past experience with generic solutions has seen LIMS implementations taking as long as 36 months and, in some cases, dragging on for so long that the projects were cancelled. It is little wonder, then, that COTS have generated great interest in the pharmaceutical industry.

What is a COTS Solution?
There are several interpretations for whether a software system is COTS or not. The war of words often revolves around “customization” versus “configuration.” Given the challenges of our industry, and the extensive impact associated with software customization, we define customization as ANY manually written code that modifies the system behavior. Whether the LIMS embeds a scripting language or requires custom functionality to be written in an external tool or environment, any written instructions to create functionality represents customization – at additional cost in time, money and resources to the customer. This would include manually creating XML or HTML for web-based user interfaces, or stored procedures to automate workflow processes.

Configuration, on the other hand, offers control over the software without requiring any additional code.

Take the example of automatically printing sample labels at the time of registration. In a configurable scenario, a COTS LIMS may include a checkbox in the setup options that activates label printing at the time of sample registration. In the customization scenario, systems that do not offer such an option would require the system administrator to write code that triggers sample label printing at registration time. In the first scenario, the customer relies on vendor testing as evidence that the label printing capabilities are functioning as designed; in the second, there is no such vendor testing. The functionality has been implemented at the customer site in a specific instance, and requires complete lifecycle management and validation at additional expense to the customer.

That is a small and simplistic demonstration of the differences between configuration and customization. A more complex example can be found in dissolution testing for oral dosage forms. LIMS administrators reading this may be cringing already, since dissolution testing represents a complex, multi-stage test that is typically not supported by generic LIMS. The majority of LIMS systems available require extensive customization to handle the stage-to-stage evaluation of results, as well as the cumulative results review that is necessary to assess whether or not the dissolution testing meets specifications. Customization to build this functionality, as noted in the previous example, requires extensive testing, validation, documentation, training and maintenance. Many LIMS administrators have actually had to build dissolution testing functionality from scratch more than once, as their companies have moved from one LIMS platform to another.

Can a Pharmaceutical LIMS Really Be a COTS?
For years, pharmaceutical customers have been asking in frustration why they must rebuild what they consider should be standard functionality in their LIMS. Dissolution testing procedures, for example, are clearly defined in the USP and other pharmacopoeia, and have been for many years.

Yet vendors have resisted incorporating industry-specific functionality. The commonly cited reason is that they cannot incorporate industry-specific features into a product that is designed to be generic enough to be sold across industries.

Currently, however, some vendors are recognizing that solutions which satisfy the pharmaceutical industry’s unique needs can be mutually beneficial. After all, the pharmaceutical industry is the LIMS industry’s predominant market.

New COTS solutions, rather than trying to append stopgap solutions to aging architectures, are meeting specific business needs from scratch. While formal data is not available, anecdotal evidence indicates that the majority of pharmaceutical customers would pay a higher license fee for software with more application- or industry-specific functionality. This may seem improbable, but the advantages are numerous. Every feature that eliminates the need for custom development work provides significant savings during implementation and production use. Equally important, the reduced customization allows a pharmaceutical company to have a better grasp on actual deployment costs and timelines, since there are far fewer opportunities for delay when customization is minimized.

To reduce risk and customization further, Thermo provides four distinct COTS LIMS solutions for the pharmaceutical industry. Each LIMS is “purpose-built” to support a specific application, such as early stage R&D, particularly in biotechnology (Nautilus LIMS™), in vitro ADME/Tox research (Galileo LIMS™), bioanalysis (Watson LIMS™), and manufacturing R&D and quality control (Darwin LIMS™).

This may raise a seeming contradiction between the trend towards more granular out-of-the-box functionality and the global trend toward standardization. However, this is not a contradiction at all when viewed at the right level of standardization in an organization. The fact is, one should standardize only where it is advantageous to do so. If a company has 25 manufacturing facilities worldwide, with a QC lab in each, standardization can have great benefit in harmonizing processes, and in reducing deployment and validation costs across those 25 sites. It would not make sense, however, to try and apply a tool designed for QC testing to a protocol-driven clinical bioanalysis laboratory, nor would it make sense to use an MRP/ERP system to manage complex testing and sample management. That is not “standardization,” and for the end users, it’s more like abuse!

Given the current situation – pharmaceutical companies are competing for sales in the same markets, they must satisfy the same regulatory agencies, and they face regulatory trends towards standardization as evidenced by the success of the ICH -- COTS solutions do offer multifaceted benefits. Not only do they greatly reduce customization, COTS solutions place the burden of following and implementing new regulatory and industry developments and trends on the shoulders of COTS providers. Domain expertise on the part of the vendor is therefore critical.

100% is not possible
There are several challenges that make a 100% COTS solution impossible to attain, or expect, or even desire. The sheer volume of tests and results that need to be supported, the extensive calculations, and the wide variety of reporting requirements are all areas of high variability that seemingly do not mesh will with the COTS philosophy.

The objective is not to find a panacea that will meet 100% of a company’s needs. The real objective is to minimize customization to the maximum extent possible. The wide variation in requirements and workflow between companies working on small molecules or in biotech, different routes of administration, differences between research and development and the production world make it virtually impossible to design a one-size-fits-all solution. Customers should be wary of any vendor who suggests they can provide the perfect solution with no customization whatsoever. LIMS buyers who are promised a solution that requires “no customization” should ask their vendor to confirm that no additional code will need to be written.

When examining a LIMS to assess the extent to which they may meet your requirements, do not expect to find a 100% fit. A realistic assessment will always identify some areas which represent gaps between user requirements and out-of-the-box functionality available from the system. The important thing, after reducing the gap as much as possible by selecting a COTS solution, is to have a complete understanding of the vendor’s strategy for closing the remaining functional gaps. Tools to extend the software must be available; the vendor should be able to provide experienced analysts to assist in the deployment; and the technology platform should use modern architecture and open standards to facilitate the required extensions. In addition, a COTS solution does not eliminate the burden of responsibility on the part of the user. While the validation effort may be greatly reduced, there will still be some effort required to provide reassurance that the system, as configured, is functioning according to expectations.

It is also important to assess the levels of compliance and flexibility inherent in the COTS solution. Historically, despite extensively customizing generic systems, pharma companies have been unable to implement one solution to concurrently meet the needs of the less regulated users, such as in analytical R&D labs, and those working in tightly monitored production laboratories. The configuration of the system should include the definition of compliance rules based on the type of data being manipulated.

Conclusions
The COTS philosophy has great appeal and provides tangible benefits in the pharmaceutical world. While pharmaceutical LIMS buyers should not seek out a 100% off-the-shelf solution, a system that can provide as much as 85% of industry- or application-specific functionality out-of-the-box will be a great boon to LIMS administrators, users, and their pharmaceutical companies. The significant reduction in deployment time and costs, as well as the reduced risk associated with clearly defined pre-existing functionality can change the nature of a LIMS from an overhead expense implemented to provide regulatory compliance to a truly effective business solution with measurable gains in efficiency and timeliness. The LIMS may not be a 100% COTS solution, but the drive towards COTS is already bearing fruit, and will continue to do so as more companies take advantage of solutions that address the majority of their business needs, rather than requiring customizations to do so.