Laboratory Equipment Validation and the Importance of a Manufacturer

Many types of equipment in both manufacturing and laboratory areas are critical to a properly functioning pharmaceutical process. The validation of laboratory equipment is not as clearly defined as the validation of equipment used directly in the production of pharmaceutical products, which requires thorough validation in almost all situations.

Should My Laboratory Equipment Be Validated? The evaluation should begin by determining the requirements of the end user, which are often defined in the User Requirements Specifications (URS). Additionally, it is critical to consider the laboratory applications as well as the associated equipment. Next, a risk analysis should be performed. Some types of equipment may seem less critical, but upon more thorough analysis, their real importance is revealed.

Responsibility for complying with the appropriate industry standards ultimately falls on individual companies, divisions, or departments. Failure to comply with current good manufacturing practices (cGMPs) or good laboratory practices (GLPs) can have serious consequences, including regulatory restrictions — such as the inability to sell the product.

Validation reduces the risks of non-compliance with regulatory agencies. It also can reduce compulsory in-process controls and testing. Validation is a means of improving procedures and final product quality. Rather than adding constraints imposed by regulatory bodies, validation is a process for improving efficiency and quality that ultimately can lead to cost savings.

Pharmaceutical companies are responsible for the qualification and validation of their equipment. As a result, they must be able to justify choices concerning these procedures to a regulatory agency auditor. The documented evidence supporting these choices is one of the fundamental requirements of validation. After all, validation is verifying and documenting with a high degree of assurance that specific equipment will perform consistently according to predetermined specifications. The documented evidence presented also must comply with cGMPs, incorporate preventive maintenance, and include a requalification schedule.

It is important that the pharmaceutical company works in conjunction with equipment suppliers to determine the appropriate validation protocols as well as the frequency of requalification. A manufacturer's validation capabilities can be an indicator of the quality of the equipment being supplied.

Water Purification Systems To further discuss validation principles, a single system with downstream effects on manufacturing and testing processes will be examined. The data in a laboratory is impacted by a variety of instruments, including water purification systems. If the water system does not consistently produce purified water, the validity of the data from these instruments can be compromised.

Manufacturers' Capabilities When acquiring equipment, particular attention must be paid to the equipment suppliers' ability to provide either direct or indirect help with equipment validation and qualification — even if the qualification will be performed by internal qualification services. When choosing a water purification system that will be validated, it is important to consider more than just the specifications of the water produced. Other equally important factors should be considered, such as the level of service provided and the manufacturers' validation experience. In order to meet user requirement specifications and regulatory guidelines, an equipment manufacturer that has implemented a comprehensive program must be chosen to ensure that their products can be qualified. Evaluation should include consideration of the manufacturer's design, manufacturing process, quality controls, traceability, documented evidence, training for users and service personnel, support for periodic maintenance, qualification, requalification, and other factors (see Table 1).

Water purification systems are essential pieces of equipment in most pharmaceutical laboratories for drug production, drug testing, and quality control applications. The quality of purified water used in these processes ultimately can affect the quality of the final product. This is why organizations such as the United States Pharmacopeia (USP) and the European Pharmacopoeia (EP) frequently state that water purification systems must be validated.

As with any other equipment, it is important to work with the water purification system manufacturer to determine the appropriate qualification protocols, how to carry them out, and an appropriate requalification schedule. The manufacturer's knowledge can be crucial, especially if they have developed specific documentation to assist with validation procedures. In addition to meeting cGMP requirements, this documentation also should be applied to each qualification stage and offer users comprehensive help in conducting system qualification.

The engineers who deploy system qualification protocols should be trained in validation procedures and familiar with production processes and regulatory requirements in the pharmaceutical industry. Furthermore, preventive maintenance helps ensure that the water purification system is kept in optimal condition and prevents down-time.

Validation Parameters Since the system qualification begins at the design stage, it is important to have a qualification team involved in the development of all new systems. This enables the manufacturer to incorporate the pharmaceutical requirements for system design and specifications.

An important parameter to be considered for the qualification of water purification systems is the calibration of measuring instrumentation. The product water should be monitored continuously for conductivity and, if required, total organic carbon (TOC) levels using calibrated instrumentation. Water purification systems should be designed specifically to meet USP 28 <643> and <645> suitability test requirements for TOC and conductivity respectively. Also, as recommended by FDA, system alerts should be implemented to warn users if the system is performing outside the pre-determined specifications. Additionally, systems manufactured in an ISO 9001/ISO 14001 certified plant permit good traceability. Certificates of Conformity, Certificates of Quality, and Certificates of Calibration also should be available.

The USP specifies that operational qualification protocols be performed on-site after the system has been installed to meet USP validation requirements.

Conclusion Equipment validation is essential. Determining what equipment needs validating starts with ascertaining the requirements of the end user. It then proceeds to a risk analysis with careful attention paid to regulatory requirements. Careful choice of an equipment manufacturer that offers a comprehensive validation services program, incorporating specially-trained personnel, on-site qualification protocols, calibrated measuring instrumentation, and the relevant documentation in accordance with GMP requirements can facilitate the validation process and overall regulatory compliance.

Sean Murphy is worldwide validation product manager for the Lab Water Division of Millipore Corporation, Boîte Postale 307, 78054 St. Quentin en Yvelines Cedex, France, (33)1.3012.7232, sean_murphy@millipore.com