Anyone involved in medical device manufacturing knows that their industry is highly regulated. Almost every medical device manufacturer or pharmaceutical supplier uses materials testing systems in their quality control and research laboratories or outsources their testing to approved third-party laboratories. Though there are several different regulatory standards that testing laboratories often need to meet, the two most common are 21 CFR Part 11 (Electronic Records; Electronic Signatures – Scope and Application) and 21 CFR part 820 (Quality System Regulation/Medical Device Good Manufacturing Practices). Although these standards have broad-ranging requirements, materials testing suppliers offer products and services that focus on the specific elements associated with testing in these regulated environments.

21 CFR Part 11 for the Materials Testing Supplier

21 CFR Part 11 was first introduced in 1997. Although comprehensive, the standard created a great deal of tension within the medical device and pharmaceutical industries, with the most common concern being the potential cost of achieving compliance. Furthermore, there was considerable confusion regarding implementation processes and procedures. Several guidance documents were written by the FDA in 1999 (Guidance for Computerized Systems…), 2003 (Guidance for Industry Part 11, electronic Records: Electronic Signatures), and 2007 (Guidance for Computerized Systems replacing the 1999 version) in hopes of clarifying the situation.

Along with many other companies, materials testing suppliers were challenged to supply testing systems and software that could comply with the broad scope of the regulation. Part 11 includes a glossary that provides additional guidelines and definitions for clarification. For example, materials testing suppliers make closed systems, meaning that information and data is controlled by the persons responsible for content. At the time Part 11 was introduced, most laboratories continued to use hard copies of test methods and reports since those could be “authoritative documents” for the lab. In the 20 years since the regulation debuted, many laboratories have transitioned, or are transitioning in some manner, to electronic records and signatures as outlined in Part 11. Several features are now typically included with systems and software that help facilitate compliance to the standard. These include:

• the ability to generate copies of electronic records of test methods
• robust security that limits access to authorized software users
• unique e-signatures with printed name, date, time, and reason stamps
• secure, computer-generated, time-stamped audit trails of ALL electronic records
• use of authority checks for important operations associated with system use, e-signatures, and altering records

Despite the relatively slow ramp-up of 21 CFR Part 11, inspectors from FDA now visit laboratories and perform audits to ensure that they are in compliance with the regulations. If processes and procedures are found to be out of compliance, a warning letter (Form 483) could be issued. Data from the FDA shows that over 5,000 Form 483s were issued in 2018 alone. Poor audit results can mean delays in product delivery, time lost in preparation for audit follow-up, fines (sometimes into the millions of dollars), and time lost chasing paper records errors. In the current environment, non-compliance is not an option.

Reviewing requirements materials testing suppliers can create efficiency when developing 21 CFR Part 11 processes.

21 CFR Part 820 (and ISO 13485) for the Materials Testing Supplier

The differences between 21 CFR Part 820 and ISO 13485 are subtle, but recent revisions (2016 for ISO and 2018 for Part 820) now have them well aligned. While both of these standards focus on quality systems, conformance to ISO 13485 is an internal decision while 21 CFR Part 820 is an FDA-mandated system of product design quality. Because of their similarities, organizations can use the implementation of ISO 13485 to establish compliance to 21 CFR Part 820. Some requirements of 820 might not be fully covered by 13485, but simple gap analysis and proposed actions to fill those gaps can ensure compliance to 820. In the end, like with 21 CFR Part 11, non-compliance is not an option.

The Focus of the Testing Supplier

All of a laboratory’s product development and manufacturing processes are subject to Part 820 validation. Materials testing suppliers will typically assist companies in the required creation of a qualification plan. This plan typically includes several phases: performance specifications, risk analysis (RA), design qualifications (DQ), installation qualifications (IQ), operational qualifications (OQ), and performance qualifications (PQ). Most materials testing suppliers provide independent assessments and documentation for the IQ and OQ which typically includes system checks, transducer and system verifications, functional checks of test software, and validation of calculations. Recent trends show laboratories working collaboratively with testing suppliers to assist in the development of robust RA and DQ documentation as well as fulfillment of the PQ. These collaborative approaches can save valuable time as well as internal costs associated with the validation process.

Load cell verification is another critical activity for 21 CFR Part 820 compliance.

Challenges for the Materials Testing Supplier in the Regulated Laboratory

Because every laboratory will likely approach compliance somewhat differently, materials testing suppliers must provide testing software that will conform to regulatory requirements while remaining flexible enough to meet the wide variety of application needs. Furthermore, interpretations of the standards have varied within different organizations, and the standards themselves have gone through several iterations which included follow-up guidance documents from the FDA in hopes of clarifying. With all of this complexity at play, the process can be daunting for medical device and pharmaceutical companies, and potentially overwhelming for materials testing companies that are not under the direct mandate of the regulations, but which must provide systems that operate successfully within those environments.

Verification services should utilize traceable and well-documented calibration standards provided by ISO 17025 certified laboratories.

Further complicating the situation is the fact that laboratories often test highly confidential materials, drugs, or devices that carry a significant amount of intellectual property with them. Materials testing suppliers need to focus discussions around processes and testing without interfering with the proprietary nature of the products themselves. Understanding these fine subtleties is paramount to being able to provide the most efficient and effective services for the laboratory. Non-disclosure agreements are often employed to protect the laboratory and provide the security necessary to work in the most effective collaborative manner. These collaborations can incorporate the strengths of both organizations to make sure the validation process is completed smoothly and without conflict.

Challenges for the Regulated Laboratory with Materials Testing Systems

One common fallacy is the notion that materials testing systems manufacturers can provide “21 CFR Part 11 compliant software.” In reality, it is up to the user to establish processes and procedures that lead to compliant actions and activities. The materials testing software company must provide the appropriate software structure and features that allow the user to create those processes and procedures that meet the requirements of the standards. This may seem like a subtle distinction, but a software package that can create a hard copy test method and hard copy results reports that can be printed, signed, and stored according to company operating procedures could be called “21 CFR Part 11” compliant. There are file cabinets across the globe filled with documents that can be difficult to find during an audit. The real intent of the regulation was to begin eliminating these types of processes and to move to a more efficient, effective and secure electronic process. The goal of “eliminating paper” continues to be broadcast across regulated organizations around the globe. In order to achieve a compliant process, materials testing software should provide the user the capability of transitioning to the preferred electronic record approach with the security of knowing they have all of the required traceability, date-stamped audits trails, and secure authority checks for all e-signatures and record alterations.

All elements of your testing system should be verified including displacement and strain measurements.

How Best to Collaborate in the Regulatory Environment

In the beginning, both regulated companies and materials testing suppliers operated in their own respective industrial silos. Device and pharmaceutical companies struggled to understand how to apply 21 CFR Part 11 and Part 820 to their materials testing equipment while material testing suppliers wrestled with understanding their role in the process and incorporating appropriate capabilities into their products. As both education and experience have evolved, both sides now have a better understanding of how to create processes that can comply with 21 CFR Part 11 and 820.

 Through upfront collaboration, regulated companies can define requirements associated with their qualification plans and their 21 CFR Part 11 strategy and work with materials testing companies to determine best approaches and practices related to the different steps in their plan. Sometimes, regulated companies will want to own the majority of the validation plan, but they increasingly see the benefits of collaborating with materials testing suppliers in overlapping areas like performance qualification and risk analysis. Through these types of collaborations, regulated companies can save significant amounts of time delivering solid validation plans as well as creating robust and compliant processes that will delight auditors and simplify their lives.