Sandi Schaible and Kimberly Ehman, Ph.D., WuXi AppTec Medical Device Testing11.01.23
Whether it's a pre-submission meeting, a study risk determination or simply an informational chat, medical device manufacturers have various ways to interact with U.S. regulatory agencies about their products. And now, that guidance—the Q-submission (Q-Sub) program—has been updated.
In the rapidly evolving healthcare technology landscape, medical device manufacturers face a critical imperative—balancing innovation with safety and efficacy. The Q-Sub program is an integral conduit between U.S. regulatory agencies and manufacturers, enabling collaborative discussions that can shape the trajectory of device development, clearance or approval, and post-market surveillance. The primary goals of the Q-Sub program are threefold:
Often during the development process, device manufacturers fail to recognize evolving regulatory standards, instead relying on past processes and documentation practices. This can stop a submission in its tracks. Lab testing partners can (and should) consult on study designs and support manufacturers during regulatory discussions. Lab partners cannot predict which development approach reviewers will accept, but they can provide valuable insight into current regulatory trends.
There are several examples of savvy testing partners saving manufacturers time and money by recommending test plan revisions after receiving and interpreting regulatory feedback. However, there are also instances in which lab testing partners have recommended formal test plans and a pre-submission meeting and have been ignored. This inevitably led to costly repeat testing and submission delays for impatient manufacturers who chose to forego regulatory best practices.
The Q-Sub program is essential, given medical devices' increasingly complex and evolving nature and regulatory challenges. Manufacturers can gain valuable insights into current regulatory thinking, aligning their strategies with regulatory expectations and facilitating an efficient review process.
One notable update pertains to the procedure for requesting Q-Submissions meetings. The updated guidelines provide more precise instructions for requesting a meeting, specifying the documents to be submitted, and defining the timeframes in which the regulatory agency will respond. This enhanced clarity can assist manufacturers in planning and preparing for meetings, thereby facilitating more productive discussions.
The revised guidelines also emphasize the importance of including a clear statement of the specific purpose and expected outcome of the interaction. This allows regulators to understand the manufacturer's intent better, ensuring more focused feedback and minimizing the likelihood of miscommunications.
Furthermore, the updates provide a detailed explanation of the review and feedback process, outlining different members' roles within the review team. Understanding these roles can help manufacturers tailor their submissions to the appropriate audience, fostering clearer and more effective communication and improving their chances of regulatory clearance or approval.
Finally, the updates reiterate the agency's commitment to a timely response. The guidelines specify target timeframes for different stages of the process, providing manufacturers with a predictable timeline to aid in planning and decision-making.
These updates reflect U.S. regulatory agencies’ ongoing commitment to transparency, predictability, and efficiency in medical device manufacturing. Manufacturers should carefully review these updates and incorporate them into their communication strategy.
1. Pre-Submission (pre-sub): The pre-sub process provides a critical opportunity for early interaction between a U.S. regulatory agency and a device manufacturer. It allows manufacturers to seek regulatory feedback on device development and evaluation issues before the manufacturer makes a formal submission. This might include queries about proposed non-clinical or clinical testing, the relevance of recognized standards, the applicability of guidance documents or the suitability of device modifications.
Manufacturers can use pre-sub meetings to discuss such topics as investigational device exemption (IDE) studies, non-significant risk (NSR) determinations, humanitarian device exemption (HDE) applications, and device classifications. Early engagement with a regulatory agency can help refine device development strategies, optimize testing approaches, and clarify regulatory expectations, facilitating a smoother submission process.
2. Study Risk Determination: A study risk determination is sought when a manufacturer intends to conduct a clinical study on a medical device but is unsure whether a regulatory agency would consider the study a significant risk (SR), an NSR or an exempt study.
Risk determination is a crucial part of the device development pathway, as it significantly impacts the study’s regulatory requirements. In the United States, medical devices are classified into three risk categories—class I, II, and III. This classification system defines the level of regulatory control necessary to assure the device's safety and effectiveness.
SR studies must comply with the complete IDE regulations, including obtaining regulatory approval before the study can begin. NSR studies, on the other hand, are subject to abbreviated IDE regulations and do not require U.S. approval. Exempt studies, as the name implies, are exempt from the IDE regulations.
A risk-based approach to device regulation ensures that higher-risk devices undergo more rigorous evaluation, thereby protecting patient safety without impeding lower-risk device development.
3. Submission Issue Request: This is a type of Q-Sub used by manufacturers when they disagree with a decision a U.S. regulatory agency makes while reviewing a 510(k), PMA, HDE, or de novo request. This process provides a formal avenue for manufacturers to request additional review or reconsideration of decisions or requests, thereby ensuring a fair and transparent regulatory process.
4. Informational Meeting: These meetings allow manufacturers to discuss regulatory issues, new technologies or the regulatory agency’s policy on a specific topic. Unlike pre-sub meetings, informational meetings are not used to gather feedback on particular devices or intended submissions. Instead, they provide a platform for broad, open-ended discussions that can help manufacturers better understand the regulatory landscape and stay abreast of the latest developments. These meetings also help educate the regulatory agency’s review team, simplifying future discussions and reducing downstream delays.
When a proposed interaction with regulators does not fall into one of the above categories, and an appropriate Q-Sub type does not exist, the default designation is an informational meeting, and the U.S. regulatory agency will use this vehicle to document the interaction.
From facilitating early dialogue to resolving regulatory disagreements and clarifying study risks, the Q-Sub program offers many opportunities for manufacturers to engage with regulators, clarify queries, and navigate the regulatory process more efficiently.
Manufacturers should leverage the program to build a healthy relationship with the regulatory agency and streamline their approval process. The benefits of early and iterative feedback, guidance, and resolution of regulatory issues can significantly impact the speed and success of device development and approval.
Working with a knowledgeable lab testing partner further complements this process, providing the necessary scientific and technical expertise to meet regulatory requirements and optimize device design and evaluation. A reliable lab testing partner can offer a comprehensive understanding of regulatory expectations, support in conducting rigorous and effective testing, and assistance in preparing for Q-Sub interactions, thereby enhancing the chances of successful outcomes.
In the evolving field of medical device innovation, the Q-Sub program is an indispensable tool that bridges the gap between innovation and regulation, helping bring safe, effective devices to market.
Sandi Schaible is senior director of analytical chemistry and regulatory toxicology at WuXi AppTec Medical Device Testing, specializing in extractables and leachables studies. She is a U.S. delegate and international delegate for ISO 10993 part 18 in chemical characterization, and also a U.S. delegate for ISO 10993 part 13 and the particulates committee (TIR42).
Kimberly Ehman, Ph.D., is director of Regulatory Toxicology at WuXi AppTec Medical Device Testing. Before joining the company, she was a toxicologist for RTI International, Toxicology Regulatory Services, and Altria Client Services. She earned her Ph.D. in parasitology from McGill University and conducted postdoctoral research at the U.S. EPA in developmental neurotoxicology. In her current role, Dr. Ehman provides technical and regulatory support for biocompatibility test programs and conducts quantitative toxicological risk assessments to support product safety and risk management decisions.
In the rapidly evolving healthcare technology landscape, medical device manufacturers face a critical imperative—balancing innovation with safety and efficacy. The Q-Sub program is an integral conduit between U.S. regulatory agencies and manufacturers, enabling collaborative discussions that can shape the trajectory of device development, clearance or approval, and post-market surveillance. The primary goals of the Q-Sub program are threefold:
- Foster innovative advancements in healthcare technology.
- Ensure the highest level of patient safety.
- Expedite device development and approval.
Often during the development process, device manufacturers fail to recognize evolving regulatory standards, instead relying on past processes and documentation practices. This can stop a submission in its tracks. Lab testing partners can (and should) consult on study designs and support manufacturers during regulatory discussions. Lab partners cannot predict which development approach reviewers will accept, but they can provide valuable insight into current regulatory trends.
There are several examples of savvy testing partners saving manufacturers time and money by recommending test plan revisions after receiving and interpreting regulatory feedback. However, there are also instances in which lab testing partners have recommended formal test plans and a pre-submission meeting and have been ignored. This inevitably led to costly repeat testing and submission delays for impatient manufacturers who chose to forego regulatory best practices.
Q-Submission Program: The Basics
At its core, the Q-Sub program is an opportunity for interactive dialogue between U.S. regulatory agencies and a device manufacturer or sponsor. It provides a structured avenue for manufacturers to ask specific questions and seek regulatory input about device development and evaluation. This input could range from exploratory discussions about new technologies to specific queries about a study design or a forthcoming regulatory submission. The program provides manufacturers a systematic and predictable approach to navigating their device development and submission pathway.The Q-Sub program is essential, given medical devices' increasingly complex and evolving nature and regulatory challenges. Manufacturers can gain valuable insights into current regulatory thinking, aligning their strategies with regulatory expectations and facilitating an efficient review process.
Recent Q-Submission Program Updates
Several key program updates could influence how manufacturers navigate the device development and submission process. These changes aim to optimize the process by improving communication and interactions between regulators and manufacturers and enhance the program’s overall efficiency and effectiveness.One notable update pertains to the procedure for requesting Q-Submissions meetings. The updated guidelines provide more precise instructions for requesting a meeting, specifying the documents to be submitted, and defining the timeframes in which the regulatory agency will respond. This enhanced clarity can assist manufacturers in planning and preparing for meetings, thereby facilitating more productive discussions.
The revised guidelines also emphasize the importance of including a clear statement of the specific purpose and expected outcome of the interaction. This allows regulators to understand the manufacturer's intent better, ensuring more focused feedback and minimizing the likelihood of miscommunications.
Furthermore, the updates provide a detailed explanation of the review and feedback process, outlining different members' roles within the review team. Understanding these roles can help manufacturers tailor their submissions to the appropriate audience, fostering clearer and more effective communication and improving their chances of regulatory clearance or approval.
Finally, the updates reiterate the agency's commitment to a timely response. The guidelines specify target timeframes for different stages of the process, providing manufacturers with a predictable timeline to aid in planning and decision-making.
These updates reflect U.S. regulatory agencies’ ongoing commitment to transparency, predictability, and efficiency in medical device manufacturing. Manufacturers should carefully review these updates and incorporate them into their communication strategy.
Types of Q-Submissions
The Q-Sub program offers several types of submissions, each with a distinct purpose and use context: pre-submission (pre-sub), study risk determinations, submission issue requests, and informational meetings.1. Pre-Submission (pre-sub): The pre-sub process provides a critical opportunity for early interaction between a U.S. regulatory agency and a device manufacturer. It allows manufacturers to seek regulatory feedback on device development and evaluation issues before the manufacturer makes a formal submission. This might include queries about proposed non-clinical or clinical testing, the relevance of recognized standards, the applicability of guidance documents or the suitability of device modifications.
Manufacturers can use pre-sub meetings to discuss such topics as investigational device exemption (IDE) studies, non-significant risk (NSR) determinations, humanitarian device exemption (HDE) applications, and device classifications. Early engagement with a regulatory agency can help refine device development strategies, optimize testing approaches, and clarify regulatory expectations, facilitating a smoother submission process.
2. Study Risk Determination: A study risk determination is sought when a manufacturer intends to conduct a clinical study on a medical device but is unsure whether a regulatory agency would consider the study a significant risk (SR), an NSR or an exempt study.
Risk determination is a crucial part of the device development pathway, as it significantly impacts the study’s regulatory requirements. In the United States, medical devices are classified into three risk categories—class I, II, and III. This classification system defines the level of regulatory control necessary to assure the device's safety and effectiveness.
SR studies must comply with the complete IDE regulations, including obtaining regulatory approval before the study can begin. NSR studies, on the other hand, are subject to abbreviated IDE regulations and do not require U.S. approval. Exempt studies, as the name implies, are exempt from the IDE regulations.
A risk-based approach to device regulation ensures that higher-risk devices undergo more rigorous evaluation, thereby protecting patient safety without impeding lower-risk device development.
3. Submission Issue Request: This is a type of Q-Sub used by manufacturers when they disagree with a decision a U.S. regulatory agency makes while reviewing a 510(k), PMA, HDE, or de novo request. This process provides a formal avenue for manufacturers to request additional review or reconsideration of decisions or requests, thereby ensuring a fair and transparent regulatory process.
4. Informational Meeting: These meetings allow manufacturers to discuss regulatory issues, new technologies or the regulatory agency’s policy on a specific topic. Unlike pre-sub meetings, informational meetings are not used to gather feedback on particular devices or intended submissions. Instead, they provide a platform for broad, open-ended discussions that can help manufacturers better understand the regulatory landscape and stay abreast of the latest developments. These meetings also help educate the regulatory agency’s review team, simplifying future discussions and reducing downstream delays.
When a proposed interaction with regulators does not fall into one of the above categories, and an appropriate Q-Sub type does not exist, the default designation is an informational meeting, and the U.S. regulatory agency will use this vehicle to document the interaction.
From facilitating early dialogue to resolving regulatory disagreements and clarifying study risks, the Q-Sub program offers many opportunities for manufacturers to engage with regulators, clarify queries, and navigate the regulatory process more efficiently.
A Final Word
The Q-Sub program is a cornerstone in U.S. regulatory agencies’ commitment to promoting patient safety, healthcare innovation and regulatory science. Understanding and effectively utilizing this program is critical for manufacturers to successfully navigate the regulatory landscape.Manufacturers should leverage the program to build a healthy relationship with the regulatory agency and streamline their approval process. The benefits of early and iterative feedback, guidance, and resolution of regulatory issues can significantly impact the speed and success of device development and approval.
Working with a knowledgeable lab testing partner further complements this process, providing the necessary scientific and technical expertise to meet regulatory requirements and optimize device design and evaluation. A reliable lab testing partner can offer a comprehensive understanding of regulatory expectations, support in conducting rigorous and effective testing, and assistance in preparing for Q-Sub interactions, thereby enhancing the chances of successful outcomes.
In the evolving field of medical device innovation, the Q-Sub program is an indispensable tool that bridges the gap between innovation and regulation, helping bring safe, effective devices to market.
Sandi Schaible is senior director of analytical chemistry and regulatory toxicology at WuXi AppTec Medical Device Testing, specializing in extractables and leachables studies. She is a U.S. delegate and international delegate for ISO 10993 part 18 in chemical characterization, and also a U.S. delegate for ISO 10993 part 13 and the particulates committee (TIR42).
Kimberly Ehman, Ph.D., is director of Regulatory Toxicology at WuXi AppTec Medical Device Testing. Before joining the company, she was a toxicologist for RTI International, Toxicology Regulatory Services, and Altria Client Services. She earned her Ph.D. in parasitology from McGill University and conducted postdoctoral research at the U.S. EPA in developmental neurotoxicology. In her current role, Dr. Ehman provides technical and regulatory support for biocompatibility test programs and conducts quantitative toxicological risk assessments to support product safety and risk management decisions.
