Eliminate misconceptions involving this often complex processMike Garry, Product Manager Spectroscopy Software and Compliance Products, Thermo Fisher Scientificgulatory compliance for molecular spectroscopy systems (FT-IR, FT-NIR, Raman and UV-Visible) is essential for any instrument but the complex processes involved can often lead to misconceptions about specific compliance requirements. Recent research has shown that with the involvement of the instrument vendor, companies can substantially reduce the overall cost of regulatory compliance and compress the entire process by as much as 75%.
This article will explore the various aspects of regulatory compliance as well as cost considerations and options associated with selecting a compliance program.
The standards set for spectrometers are often developed by third-party organizations such as ASTM, NIST and the US, European and Japanese Pharmacopeia. However, where guidelines do not already exist for a specific type of instrument or technology, the instrument vendor may establish its own. In addition to the specific standards relating to spectrometers, the instruments must also comply with the overall guidelines concerning the environment in which they are used, including the FDA's cGMP and GLP regulations and in particular 21 CFR Part 11. These regulations require drug makers, medical device manufacturers, biotechnology companies and other FDA-regulated industries to implement control processes including regular audits, validation programs and full documentation of products and systems.
In order to comply with this wide range of regulatory requirements, it is essential that companies using spectroscopy systems implement a carefully planned compliance program.
The term 'compliance' refers to the overall process of meeting a set of regulations or guidance, whether these are government-mandated or self-imposed. Compliance comprises a number of processes, including verification, qualification and validation, representing differing levels within the compliance process. These procedures can be carried out in-house or by an external company such as the instrument vendor.
Verification - Verification is an ongoing process that occurs in most spectrometer compliance programs and is important in order to demonstrate that the instrument is working correctly at any time. This process involves taking a set of preset measurements on a regular basis to monitor for any changes. If the measurements exceed the specified acceptance limits, corrections must be made as soon as possible in order to prevent results that are out of specification from entering the process.
Verification can help to minimize instrument downtime by detecting potential problems at an early stage. The process can be adapted to suit moderately to highly regulated environments, where selected qualification tests can be re-run, or quality control samples can be measured on a regular basis to ensure optimum instrument performance.
Qualification - The aim of the qualification process is to provide users with full confidence that the spectroscopy system will work for its intended purpose and to document this for the necessary regulating agencies. Qualification involves a strict and well-documented evaluation process initially at the time of purchase, often called design qualification (DQ), and again when commissioning the instrument. It comprises a more extensive set of procedures than with verification alone. Verification generally involves checking the system when it is operational, while with qualification the instrument performance is checked and documented at all stages of use.
Where qualification is required, the procedures used are typically based on the operational qualification, installation qualification (OQ), (IQ) and performance qualification (PQ) models. These procedures involve documenting that the instrument is properly installed and is performing to factory specifications, and can correctly perform the analyses for the intended application. IQ, OQ and PQ tests are in general more controlled than those used in verification-only environments, making them more appropriate for moderately to highly regulated situations.
Validation - Validation is the process of proving and documenting that a spectrometer is appropriate for the intended task and that it is fit for purpose. It includes completing the qualification process. During validation, the installation and operation of the complete spectroscopy system are inspected, including the software, accessories and potential applications. Full system validation is an essential part of any compliance program in highly regulated environments, due to the complete examination of both the system and the intended application. The process is also an essential stage of achieving compliance with FDA 21 CFR Part 11 as well as FDA CFR Parts 58, 210, 211 and 820 and specific EuraLex regulations governing medicinal products in the European Union.
The costs involved in qualification and validation can vary depending on the type of compliance program taken. The overall cost is determined by the degree of regulation (i.e. moderate, high or self-imposed) or the criticality of the instrumental measurements being made; the availability and cost-effectiveness of using the company's human resources to perform the compliance-related tasks; and the degree of compliance expertise of those developing, documenting and performing the necessary activities. Any compliance program can be broken down into two stages of commissioning and maintenance. Each of these stages involves a separate set of costs. (see table below)
Implementing a compliance program can often contain 'hidden' costs such as the impact on human and instrument resources when compared to the life of the system. These hidden costs can have a significant impact on profitability for smaller companies, while for larger organizations coordinating compliance programs involving multiple instruments can lead to increased costs, particularly if instrument procurement and commissioning is not properly managed.
Streamlining Instrument Commissioning
• Complete documentation for instrument design qualification.
• Fully documented procedure with signoffs for installation qualification and operational qualification for the entire system.?• Software and traceable reference materials to complete the qualification and for ongoing performance qualification.
• Certified service engineers trained on the technical service and qualification procedures for the specific instrument and software purchased.
• Factory certification of instrument performance results when system is installed and qualified by company service representatives These elements are necessary to ensure that the qualification will withstand any regulatory and audit challenges, and that the instrument qualification process can be completed in the minimum amount of time. If this information is readily available from the vendor, a typical spectrometer can be fully qualified and ready for first measurements on the same day that it is installed. Without these processes, the purchaser can be left with significant additional work and in some cases the qualification may not stand up to audit. Second, when full installation is required, an instrument vendor with the knowledge of the regulations and the technical knowledge of the spectrometer system can streamline the commissioning process. However, time and cost savings can only be realized if the vendor has the ability to work with the customer in a consultative relationship to tailor the implantation to the customer's exact needs.
A large biopharmaceutical company had an aggressive time-to-market goal on a newly approved drug of 180 days following approval. In order to accomplish this goal while still achieving compliance with cGMP and 21 CFR Part 11 regulations, the company needed to streamline its system validation and instrument qualification processes. Although the company had the in-house resources to deal with a compliance program, they chose to invest in instrument qualification and validation services from their instrument supplier, Thermo Fisher Scientific, in order to avoid over-allocating internal resources and compromising the time-to-market goal. The company also streamlined the internal paperwork and approval processes by including the equipment, factory qualification and system validation on a single purchase order.
By using Thermo Fisher Scientific to implement these processes, the company was able to save approximately $90,000 as well as cutting the instrument commission time by six months. This enabled the company to achieve regulatory compliance while also attaining its self-imposed time-to-market goal. These time and cost savings are expected to continue as the company expands and adds new instruments, as new purchases will fall into the same validation plan.