With its numerous steps and intricacies, the process of receiving FDA approval can easily be seen by those working with medical devices as the proverbial brick wall waiting at the end of the development cycle. Achieving approval requires a comprehensive understanding of the governing agencies and specific regulatory documents relevant to a particular device and an exact application of the practices and requirements they define. This can be especially daunting considering the number and length of official documents that exist today. Yet, in truth, familiarizing oneself with and meeting the standards pertaining to a specific device is not an insurmountably difficult process.
Preparing for U.S. Medical Device Submission
For manufacturers and development teams aspiring to create new medical devices, the depth and range of applicable standards can easily be overwhelming. Fortunately, the process can be made more manageable by reducing it to three primary steps:
Ultimately, it is up to the manufacturers and developers to identify and apply the FDA's standards and guidelines relevant to their devices.
General U.S. Standards
Of course, performing these steps begins with awareness of the most prominent documents relating to users, devices, usability research, and human factors engineering. However, the list is not as long as one might think. In the U.S., two major regulatory standards extend to all medical devices applying for FDA submission. The first is the FDA CDRH's final guidance document, Applying Human Factors and Usability Engineering to Medical Devices, published February 3, 2016. This document intends to encourage proper human factors and usability engineering practices to improve device designs and minimize use errors, preventing potential harm to users. The second is ANSI/AAMI HE75:2009/(R) 2013, entitled Human Factors Engineering- Design of Medical Devices. This document is recognized by the FDA as a comprehensive reference for industry best practice, providing detailed HFE principles of design, usability engineering guidance, management of use error risk, design elements, integrated human factors solutions, examples, and inventories for the development of medical devices. The 500-pg document also helps developers provide evidence to regulators to verify that a human factors design process has been utilized and supports the device's usability and safety while increasing development efficiency.
One document applying to many devices is the FDA CDRH's Guidance on Medical Device Patient Labeling: Final Guidance for Industry and FDA Reviewers, specifically regulating labeling intended for the patient or provider use. It assists manufacturers in developing and providing critical information to end-users clearly and concisely and aids reviewers in evaluating such labeling.
Device Specific U.S. Standards
Some regulatory guidelines apply only to particular device types, dictated by purpose, use setting, components, and other various factors. For example, a reusable device must follow guidance regarding proper human factors application in sterilization processes, whereas devices utilizing software need to mind their relevant documents.
Combination products are examples of such devices, therapeutic and diagnostic products combining multiple treatment methods or products. These devices must follow two primary documents. First, the FDA CDER's Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development, published February 2016, dictates the underlying principles of human factors studies in the development process. Second, the April 2016 FDA CDER document Safety Considerations for Product Design to Minimize Medication Errors, which provides best practices for improving drug products and container closure designs, as well as examples of designs that have resulted in post-market medication errors.
Another example of these devices is those intended for home use or in a non-clinical setting. November 2014's FDA CDRH guidance Design Considerations for Devices Intended for Home Use assists in designing and developing home-use devices that comply with applicable standards of safety and effectiveness, along with other relevant regulatory requirements. Meanwhile, the AAMI TIR 49:2013 document titled Design of Training and Instructional Materials for Medical Devices Used in Non-Clinical Environments identifies special considerations for non-clinical use settings, mainly relating to the design of training and instructional materials.
Next, reusable devices are beholden to the FDA CDRH and CDER document Reprocessing Medical Devices in Healthcare Settings: Validation Methods and Labeling, issued March 2015. This document relates to the development and validation of instructions for reprocessing both reusable devices and single-use devices that arrive non-sterile.
Finally, infusion pumps specifically must adhere to guidelines laid out in the FDA CDRH's Infusion Pumps Total Product Life Cycle, Guidance for Industry, published December 2014, which identifies device features and use-related considerations manufacturers must address throughout the product life cycle.
International Standards Applicable to U.S. Devices
Along with U.S. standards, there are several internationally based, human factors related regulatory documents issued by the IEC and ISO, recognized by the FDA, ANSI, and AAMI as applying to U.S. devices.
One such standard, which specifies the process by which a manufacturer should analyze, define, develop, and evaluate a device's usability relating to safety, is the ANSI/AAMI/IEC 62366-1:2015 document titled Medical Devices Part 1: Application of Usability Engineering to Medical Devices. This process allows for the analysis and mitigation of risks associated with correct use and use errors but excludes those related to abnormal usage. ANSI/AAMI/IEC 62366-1:2015 Annex C: Evaluation of a User Interface of Unknown Provenance, a document recognized by the FDA as applicable to legacy devices, applies the tools provided in the former to user interfaces or parts thereof that have already been released to market before the standard's publication. Also related to 62366 is 62366-2:2016 Medical Devices Part 2: Guidance on the Application of Usability Engineering to Medical Devices, which is a prescriptive technical report containing background information and providing guidance regarding specific areas in which human factors and usability engineering may become relevant, supporting safety as well as non-safety-related goals.
Another FDA recognized international standards document is the ANSI/AAMI HA60601-1-11:2015 – Medical Electrical Equipment-Part 1-11: General Requirements for Basic Safety and Essential Performance, which applies to all medical devices with electrical components and outlines collateral requirements for these devices and systems as related to a home-use setting. Within the HA60601 arena is IEC 60601-1-6:2010, Collateral Standard: Usability, which establishes a bridge connecting IEC 60601-1 and ANSI/AAMI/IEC 62366, specifying a process for evaluating usability as it relates to basic safety and essential performance. The FDA also recognizes this as applying to devices with electrical components.
One 60601 standard relates specifically to medical devices with alarm systems: IEC 60601-1-8 Edition 2.1 2012-11, General Requirements, Tests, and Guidance for Alarm Systems in Medical Electrical Equipment and Medical Electrical Systems. As its name suggests, this is a prescriptive standard for designing these alarms. Another specific electrical standard applies to home use devices, IEC 60601-1-11:2015 Requirements for Medical Electrical Equipment and Medical Electrical Systems Used in the Home Healthcare Environment. This regulatory standard applies regardless of whether the intended user is a lay operator or a trained medical professional.
The FDA and AAMI also recognize some ISO guidance documents as applicable to U.S. devices, such as ANSI/AAMI/ISO 14971-1:2007/(R) 2016, Medical Devices- Application of Risk Management to Medical Devices, a standard detailing the process by which device hazards should be identified and associated risks quantified, as well as how control effectiveness should be monitored. One acknowledged ISO standard applying to symbol labeling is ISO 15223-1:2016 Medical Devices- Symbols to be Used with Medical Device Labels, Labeling, and Information to be Supplied, more specifically Part 1. This outlines the requirements for symbols used to convey information to users and lists those acceptable.
An ISO standard applying to those devices that require sterilization procedures are regulated under ISO 14937:2009 (Sterilization of Health Care Products), a document specifying general requirements for the identification of appropriate sterilizing agents and for the development, validation, and routine monitoring of the process, in which microorganisms must be inactivated by physical and chemical means. It must be applied by process developers, sterilization equipment manufacturers, manufacturers of devices requiring sterilization, and responsible organizations.
Some ISO standards are recognized by AAMI and ANSI specifically, such as ISO 9186-1:2014, Graphical Symbols- Test Methods Part 1: Method for Testing Comprehensibility, which prescribes measuring how well graphical symbols communicate their intended meaning. This standard ensures that symbols are easily understood as presented without supplementary information, such as explanatory text. Another of these standards applies to computer-based interactive systems. ISO 9241-210:2010 Ergonomics of Human-System Interaction Part 210: Human-Centered Design for Interactive Systems outlines the required human factors elements necessary when designing interactive systems and recommends activities to be performed throughout its life cycle. Finally, ISO/TR 16982:2002 Ergonomics of Human-System Interaction- Usability Methods Supporting Human-Centered Design is a standard presenting various human-centered usability methods and their advantages and disadvantages and other relevant considerations.
While not a comprehensive examination of all human factors guidance, we have covered here the most prominent documents developers must abide by for successful FDA submission. The list itself is not as comprehensive as one might initially expect; however, what makes meeting regulatory requirements a complicated matter lies in the details of recommended practices and prescribed methods as outlined in documents such as ANSI/AAMI HE75. In our next episode, we will examine these specifics and contribute to effective human factors engineering medical device development implementation. Stay tuned.