Introduction to Due Process for Medical Product Manufacturers

It may not be immediately apparent to those who have not studied law and/or history, but the concept of due process has been ingrained in much of the Western world for about 700 years, and it is of particular historical and current interest in the United States. The Fifth Amendment to the U.S. Constitution requires the federal government to refrain from denying a person “life, liberty or property without due process of law.”

An example of Fifth Amendment due process is the Takings Clause that applies to eminent domain actions. The federal government is prevented from seizing private property without notice and just compensation therefor. The term due process is again used in the Fourteenth Amendment to impress the same legal requirement for the state governments. The clause’s words and substance reflect the concepts from thirteenth-century Great Britain in the Magna Carta, which required that the English monarchy, the Church, and feudal barons follow a legal process or procedure to maintain legal order and consistency for all accused persons. The discussion about the effectiveness, implementation, or modern respect of these rights is reserved for a law school class or a glass of wine with friends and is not applicable here.

This is where most of you are either bored or wondering why you are reading this in MPO—likely both. Stay with me a few minutes longer: There is a beautiful rug to be woven from these seemingly incongruent topics—legal due process and medical product quality.

I am a biomedical engineer who cut my teeth in orthopedic device manufacturing engineering before moving into development, quality, and regulatory affairs. I recently graduated from law school as a 48-year-old bantling and approached my law studies with an engineering mind that was likely more focused on the concept of due process than my fellow non-engineer law school students. Many of the younger and more idealistic students would bypass the due process discussions and jump to what they thought the “fair” or “right” outcome of a case should be. This observation made me realize my time as an engineer gave me a greater appreciation for the adage “focus on the journey, not the outcome.” Sidestepping due process can lead to the conviction of the innocent or release of the guilty because each step in the process from arrest to evidence to hearings serves a specific and important purpose.
Now I’ll start to weave the rug I have promised.

Just as due process brings consistency and fairness to the legal system, standardized processes bring consistency and objectivity to the various aspects of the medical product lifecycle. In the U.S., we attempt to guard our Constitutional rights with the vigor and verve that personifies the American culture. The internal processes and standard operating procedures at a medical product company should be implemented and followed with nearly the same enthusiasm because the importance of consistency and objectivity cannot be overstated in this industry. Patient safety and regulatory compliance depend on it.

This new column will include discussions about processes critical to the success of medical product lifecycles. I will examine some tried and true processes such as CAPA, design controls (product realization), and complaint handling, but also more obscure or new processes like additive manufacturing, patient-specific devices, and intellectual property.

Many regulations and laws the industry attempts to follow are vague, at best, and provide no information about how requirements should be met. The responsibility for establishing appropriate procedures for each of the processes rests with the manufacturer, contract manufacturer, and each of the departments therein. For example, 21 CFR §820.75 outlines the entire legal requirement for process validation in medical device manufacturing. For those of us who no longer carry the pocket notebook of 21 CFR 820 provided by so many suppliers and auditors in the 1990s (you know who you are, and you know that you did), here is the regulation’s verbiage:

(a) Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented.

(b) Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure the specified requirements continue to be met.

1. Each manufacturer shall ensure that validated processes are performed by qualified individual(s).
2. For validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented.
3. When changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate. These activities shall be documented.

As discussed by Ranica Arrowsmith in The Philosophy of Process Validation,¹ “Process validation conducted in the ‘proper’ way, with painstaking documentation of each manufacturing step, detailed master control documents, statistical process control (SPC) documentation, and comprehensive historical data, easily starts to seem like overkill. However, if as a manufacturer you don’t validate your process, you inevitably will end up with an unreliable product.” Companies spend tens to hundreds of thousands of dollars on process validations; that time and money are wasted if internal validation processes are not properly developed and rigorously followed. Requirements like phase-gating are put in place to protect the company and the patient, and circumventing a phase of a process validation can lead to ineffectuality of the finished validation.

There are highly publicized and secretly known instances of failures that were likely caused by either poor procedural development or shortcutting process validation procedures. REDICA Systems published an article—Incorrect Specifications, Process Validation Issues at CMO Lead to Adverse Events, Recall²—that summarized several case studies from recent drug GMP inspections. While these studies are specific to the drug industry, there are valuable lessons to be learned. One of the referenced case studies relates to process validation issues, including the “poor choice” of performing concurrent process validations instead of prospective validations. This is an example of either not implementing an adequate process or shortcutting the prescribed process, and the result was detrimental to patients and the company. More discussion of process validation will be included in a future article; this is one of many examples of the importance of having and following a consistent process.

We have all sat in team, management, or supplier meetings where the conversation revolves almost entirely around timelines and cost. While these aspects of a project are indeed critical, they are literal or figurative Ghant charts of all actions that must be taken to reach the end goal of selling or shipping the product. Each of the actions within the project Ghant chart represents the output of a process that should already be clearly explained in the document control system pyramid: quality manual, policies, procedures, work instructions.

Do you have the applicable documents in place? Are they being followed? Are shortcuts being made in these processes to get to the end goal of selling the product faster? After commercialization, do you have documented procedures for obtaining and evaluating feedback? Are you pulling quality data out of sources like nonconformances and CAPAs to feed back into the design development and change the process? Do you have a documented process of exactly what actions are required in a crisis? How is your patent portfolio being created and managed? Is there a formula to decide which aspects of a product should be patented and which might be infringing? How does your company determine which trademarks require registration?

In this series of articles, we will answer these questions and delve into the critical aspects of the expected processes for medical product manufacturing lifecycle management: legal requirements, unwritten expectations that have become industry standards, examples of successes and failures, familiar challenges, and common solutions. These examples might be anecdotes I have heard in social settings (company and employee names kept confidential, of course), published articles, or information gleaned from the FDA website. I hope this information will be beneficial for those new to the industry and those like me who are more seasoned. 

References

1. tinyurl.com/due010124
2. tinyurl.com/due020124

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Meredith P. Vanderbilt is an internationally known medical device regulatory affairs consultant unafraid to communicate directly and honestly with regulatory bodies and clients about strategies and submissions to provide compliant and high-quality devices to the market. She is an industry influencer through workshops, networking, presentations, articles, textbook chapters, and (coming soon) an orthopedic industry book about additive manufacturing. She has decades of experience in performing and managing medical device development, commercialization, and marketing activities. She has a high success rate for gaining regulatory clearances in relatively short periods of time and is a participant in all aspects of quality management systems and post-marketing activities.