The Center for Devices and Radiological Health (CDRH) has spent years developing a standardized set of compounds to help analytical laboratories detect a broad spectrum of chemicals. The Chemicals List for Analytical Performance (CLAP) database provides a benchmark for assessing analytical methods’ adequacy and, in doing so, aims to enhance medical devices’ safety and efficacy.
The database comprises more than 100 readily available chemicals that were specifically chosen to represent broad physicochemical properties. It also includes detailed information on each chemical’s trivial name, full name, CAS number, empirical formula, molecular weight, boiling point, pKa, logP, and relative response factors (RRFs) for gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS).
At the request of CDRH’s Office of Science and Engineering Laboratories, WuXi AppTec provided information to be included in the CLAP database and helped validate the wide range of relevant compounds it contains. Here, we explore the database’s benefits, limitations, and practical applications to understand its usefulness and provide recommendations for device manufacturers.
CLAP Database: Benefits & Practical Applications
The primary benefit of the CLAP database is its utility as a starting point for new labs and a validation tool for established laboratories. For new labs, the database provides a foundational set of chemicals that can guide the development of their analytical capabilities. For established labs, it offers a benchmark to validate existing methods and demonstrate the robustness of their chemical detection processes.
The database also facilitates a means to determine detection coverage of various chemical species for the purposes of establishing a robust toxicological risk assessment. With the CLAP database, labs have access to a wide array of experimental data that could serve as a benchmark for the ability to successfully detect and identify chemical compounds relevant to medical devices.
The CLAP database also provides an additional level of transparency into regulatory expectations. Labs using the CLAP database as a reference may better understand the types of evidence and validation the FDA seeks in submissions. This understanding helps sponsors prepare comprehensive and targeted study designs. This approach can reduce the time and resources spent on revisions and additional information requests.
CLAP Database: Potential Limitations
Despite its benefits, the CLAP database is not without limitations. RRFs, a critical component of the database, are used to measure how different chemicals respond compared to a standard compound. However, depending heavily on RRFs can deliver variable results in specific protocols, even when analyzing the same chemical under similar conditions.
The CLAP tool emphasizes that RRFs depend highly on the protocols used for GC-MS or LC-MS analyses. Therefore, when using the CLAP database, it is important for labs to consider how the specified protocols may differ from their own established processes. The primary consequence of this is that a direct numerical comparison of RRF values to the CLAP database may not be possible.
CLAP Database: For Manufacturers’ Consideration
While the CLAP database could become an invaluable resource for chemical characterization, it’s not there yet. The tool should be viewed as a foundational starting point rather than a comprehensive solution for manufacturers’ analytical needs.
Given the limited number of chemicals in the database, it is unlikely to include all the compounds relevant to a particular manufacturer’s products. For this reason, the database could be valuable in early-stage chemical characterization, but manufacturers will likely require additional testing and validation of their products. At this stage, the CLAP database should be considered a mere framework upon which testing laboratories can build comprehensive chemical libraries tailored to myriad products.
Collaborating with experienced laboratories can help fill the gaps for manufacturers while these chemical libraries slowly develop. Three distinct advantages for working with a trusted lab partner include:
- Experienced labs bring a wealth of knowledge in chemical characterization, having developed and validated numerous analytical methods over years of practice. These labs understand the intricacies of different analytical techniques and the potential pitfalls associated with varying protocols and standards.
- Trusted lab partners can offer comprehensive analytical services beyond the CLAP database’s capabilities. These services include customized method development, multi-point calibration, and extensive validation to cover a wider range of chemicals and their interactions.
- Navigating regulatory submissions can be challenging. Experienced labs are well-versed in the latest regulatory guidelines and standards, including those outlined in the CLAP database. They can provide invaluable support in preparing and submitting robust documentation, addressing potential queries from regulatory bodies, and ensuring that chemical characterization submissions are timely and compliant.
A Final Word
The CLAP database is indeed a starting point in chemical characterization, but its true value lies in its potential. As it grows and becomes more robust, using the database could potentially streamline submissions, reduce regulatory confusion, preserve precious resources, and lead to safer devices. For now, however, leveraging the CLAP database in addition to input from expert laboratories is the best way to ensure robust and reliable results.
