The FDA Center for Devices and Radiological Health (CDRH) recently published new guidance for medical device priorities in 2023. The FDA CDRH guidance looks to evolve away from the COVID-19 pandemic and transition toward digital health, medical device software and regulated software as a medical device (SaMD).

 

Cybersecurity for Medical Devices

 

Among topics the FDA guidance considers “A-List” priorities is cybersecurity for medical devices. Two initial priorities of fda medical devicethe FDA guidance will include a deeper study of quality system (QMS) considerations and premarket submission (PMA) content.

 

Additional FDA software guidance was published earlier this year (September 2022) that described how software functions meet the definition of a medical device and risks to the public. The change industry should keep an eye on is FDA product specific guidance that applies to regulating software development that impacts risk to patient safety.

 

Quality Management System

 

Quality management system regulation currently falls under 21 CFR 820, so it will be interesting to see how new updates are developed based on discussion with industry. Every medical device manufacturer is required to have a compliant QMS system that includes the necessary QMS documentation for regulatory approval.

 

As digital healthcare integrates the physician-patient relationship, FDA continues to scrutinize device software functions and healthcare mobile apps. These insights may provide additional feedback on software functions not subject to FDA regulatory requirements relevant to a QMS audit.

 

Remanufacturing Medical Devices

 

FDA is taking a deeper look at reusable medical devices and how preventive maintenance increases the life of a medical device. Currently, there are separate regulations for both industry manufacturers and 3rd party service companies. FDA will look to clarify the differences between “servicing” and “remanufacturing”, and the impact on medical device safety for either. This will likely impact the regulatory responsibilities of companies who perform these activities for health care providers.

 

Premarket Authorization (PMA)

 

Software as a medical device continues to grow across the health care industry. Updated premarket authorization guidance will focus on software devices with consideration to how the software is delivered to the end user. This can include factory-installed healthcare software or platforms installed by a third-party vendor.

 

New information is anticipated for different types of firmware and software-based control of medical devices. Industry employees should also anticipate greater clarity for stand-alone software applications and general purpose computers. Leadership at FDA has included subtle hints that accessories to medical devices that include software may also be included in future FDA guidance for industry.

 

COVID-19 Emergency Use Authorization (EUA)

 

There has been discussion around the 180-day timeline proposed for notice of ending a medical device EUA due to COVID-19. Final guidance should be available in 2023 that provides more detail about on the appropriate transition period. FDA is considering industry recommendations that avoid disruptions to product shortage and supply chain.

 

Consideration is also being given to medical device manufacturer and healthcare providers to adjust from policies adopted during the public health emergency (PHE). For example, an EUA issued under section 564 of the FD&C Act will remain in effect. Primary changes will be based on if FDA chooses to revoke the EUA because the criteria for issuance is no longer met. 

 

Voluntary Improvement Program

 

FDA and the Medical Device Innovation Consortium (MDIC) continue to advance their pilot program launched in 2018. Select medical device manufacturing sites were chosen to review key business processes using a series of integrated best practices. The Capability Maturity Model Integration (CMMI) Institute certified select team to conduct and review quality system maturity of these sites.

 

2023 will likely bring even more data surrounding the MDIC program. This could include public info for industry about continuous improvement through quarterly check-in progress with participating medical device companies. The program is designed to report industry baseline metrics after the check-in and monitor operational excellence.

 

Breakthrough Devices Program

 

New information from FDA will arrive in 2023 for updates to the Breakthrough Devices Program. Early updates suggest the guidance will clarify how the program may be more applicable to certain devices than others. FDA breakthrough designation often benefits populations that are more likely to be impacted by health care disparities. New clarity may include breakthrough therapy designations and how medical device companies can educatee sponsors to submit for proposed indications of use. 

 

An important facet of the breakthrough devices program is the type of evidence needed for FDA approval. Clarity should help to determine whether a device is reasonably expected to increase the treatment or diagnosis efficacy. Early indications suggest that the intended use of the device, technology and features, and the available standard of care alternatives will all play a role.

 

About RCA®

 

Regulatory Compliance Associates® (RCA) provides healthcare consulting services to the following industries for resolution of compliance and regulatory challenges:

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. Our life science consultants are used to working on the front lines and thriving in the scrutiny of FDA and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

 

Things to remember when scaling your Design History Files (DHF):

  • One size does not fit all
  • All classes of devices need design controls
  • The process is scaled based on the complexity of the device and the size of the company
  • Don’t wait for the regulators to identify any gaps

 

When you scale your Design Controls appropriately to the complexity and size of your company, it makes it easier to manage the scope of everyday work needed to keep your files current.

 

Also, identifying your gaps up front, closing them upon identification, then wrapping them into your entire DHF process with your team or with a third-party consultant like RCA helps ensure you have a rock-solid DHF and that you will be prepared when the regulators ask questions.

 


Listen to the full DHF & Design Control episode Here!


 

DHF Support – From Launch to Lifecycle, RCA Assists in Ensuring Device Design History

We offer expertise in helping you navigate through new product development and remediating legacy Design History Files (DHF) within the complex and evolving regulatory environment. From launching a new product to market in accelerated timeframes to updating the design information necessary to validate and maintain the device throughout its lifecycle, we have a thorough understanding of the specific design history requirements for U.S. and international medical device industries to ensure regulatory compliance and drive business best practices.

 

In addition to DHF content, development, and management, download our handout to view more of our DHF-related support services, including:

  • Quality System Regulation, 21 CFR Part 820
  • The Design Control requirements of the CGMPs, 21 CFR 820.30
  • Device Master Records (DMR) and Device History Record (DHR)
  • The EU’s Medical Device Regulations (MDR) including Technical File / Design Dossier
  • Risk management (ISO 14971) for medical devices including risk analysis, FMEA, risk evaluation, and risk controls through Corrective and Preventive Action (CAPA) plan and design control requirements
  • IEC 60601-1-11 (2010) including Programmable Electrical Medical Systems (PEMS) (Clause 14)
  • Total product life cycle (TPLC)

 

About RCA

Regulatory Compliance Associates®  (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory challenges:

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA-and globally-regulated companies.

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage.

 

In this soundbite from RCA Radio, Erika Porcelli, CEO of Regulatory Compliance Associates® (RCA), provides examples of how different size companies leverage the stage of business they’re in to accelerate development with outsourced staff.

 

Start ups vs Large Companies

 

Using Staff augmentation to bring in SMEs gives companies the ability to scale up and scale down quickly without taking away people from other projects.

Start-ups are typically not ready to bring on a full-time employee. In cases like these, we can bring in a subject matter expert (SME) that can help work through any regulatory, compliance, or quality problem and assist on an as-needed base.

 

Larger companies typically need help when they are performing a project such as adding a new manufacturing line into a facility. They don’t do this all of the time and only need the extra resources for this particular project. In cases like these, we will put together a team with the right skillsets that can complete the particular project. Once completed, RCA perform a hand-off with the client, and our team steps away from the project. 

 


Listen to the full episode “Outsourcing and Staff Augmentation” now!


 

All companies experience staffing support issues whether they are transient and short-lived, chronic and unplanned, or intrinsic to your business model. RCA has consultants that develop a solution to your specific needs; we can help “right-size” your team when and where you need it most.

 

Outsourcing has become an increasingly common practice in the life science industry. The quality assurance (QA) and regulatory affairs (RA) functions create extra complexity for large and small life science companies because needs may vary greatly depending on the life cycle of the organization. These companies turn to outsourcing to manage operations and tactical skills, and also help adopt best practices.

 

Successful execution comes through project monitoring, issue resolution, and risk management of the process through clear leadership. RCA’s team of experienced project management professionals organize and manage resources to ensure that projects are completed successfully, on time, and within budget.

 

RCA Outsourcing Services

 

Project Management

outsourced staffTo be successful in the field of manufacturing, you must have a proper project management plan in place. Not only do project management procedures keep your projects on time and on schedule, but they also ensure your devices’ compliance with stringent national and international regulations. RCA can help you develop an effective plan, and we can even lead these tasks so that you can run more projects at one time more efficiently.

 

Our outsourced staff capabilities for project management capabilities include:

 

  • On-site Project Leadership or Project Management Support
  • Design and Implementation of a Project Management Office
  • FDA Workshops
  • Project Assessment, Remediation, and Follow-up
  • Advanced Schedule Optimization and Management
  • Development and Implementation of Compliant Methods
    • Risk Management
    • Issues Resolution and Decision Tracking
    • Change Management
    • Performance Measurement and Tracking
  • Tool Selection for Program Portfolio and Resource Management

 

Staff Augmentation

Many companies need the assistance of a professional with specific skills and expertise when completing a project but might not have the need or resources to hire this expert as a full-time employee. Instead, you can add experienced professionals to your staff for a short- or long-term project through our medical device staffing support capabilities. RCA’s outsourcing solutions can help you manage even your most complex projects with experts trained in areas such as:

 

  • Quality Assurance
  • Regulatory Affairs
  • Validation
  • Operations
  • Product Development

 

Consulting Support

Maybe your company is struggling to complete projects on time, or perhaps you often face challenges associated with product compliance. Whatever your situation, our consultants will work with you to ensure your business’ success with consulting support services. By getting to know more about your business and goals, we’ll tailor our approach to best meet your particular needs.

 

Advantages of Outsourcing

 

When you hit a snag in your project’s development, you need to design and develop the best solution to create a timely, quality finished product. RCA’s quality assurance and regulatory affairs consultants can help you define the specific problem, generate ideas for a potential solution, and implement that solution for the utmost success in your project’s completion.

 

Our goal is to help you get your projects to completion on time and on budget — all while outsourced staff keeps superior quality at the forefront of your every task. And with a team of more than 500 pharmaceutical consultants and industry experts with an average of 25 years of experience in the life science industries, we have the extensive resources and expertise needed to meet this goal.

 

Strategic Outsourcing

 

Medical device manufacturers face the challenging task of creating top-quality products quickly with minimal personnel and growing compliance regulations to adhere to. With these increasing challenges, it’s no wonder so many local startups and Fortune 100 companies alike choose RCA for outsourced staff and strategic outsourcing services.

 

About RCA

Regulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA-and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

 

Since 2018, FDA has been working to align its quality system regulation for medical devices with ISO13485, with the goals of reducing burdens on medical device companies with global products that face different international regulations and updating its quality system requirements. On February 23, 2022, the FDA issued the proposed rule to amend the current good manufacturing practice (CGMP) requirements of the Quality System Regulations (21 CFR 820) to harmonize and align more closely with international requirements, specifically those of ISO 13485: 2016.

 

The FDA proposed to do so primarily by incorporating the 2016 edition of the international standard specific for medical device quality management systems ISO13485. Through this rulemaking, the FDA is also proposing additional requirements that help connect and align ISO13485 with existing requirements in the FD&C Act and its implementing regulations. This will include making conforming edits to 21 CFR Part 4 to clarify the device CGMP requirements for combination products.


Do you need ISO13485 compliance support? Contact us now to get started.


The most noticeable difference between the current quality systems regulation and ISO13485 is that the risk management requirements integrated throughout the aspects of the quality management system in ISO13485. This differs from 21 CFR 820, in that the only risk-specific requirement in the QS regulation is listed in §820.30(g), as it relates to risk analysis as a part of design validation.

 

These revisions are intended to supplant the existing ISO13485 requirements with the specifications of an international consensus standard for medical device manufacturers. The revisions are expected to reduce device manufacturers’ burdens, specifically aspects of compliance and recordkeeping through the harmonization of domestic and international requirements. FDA intends to issue a final rule after reviewing comments and feedback from the proposed rule. The final rule will become effective 1 year after the date of publication in the Federal Register.

 

About RCA

pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA-and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

The FDA recently updated guidance for clinical trial design (2022). This update stems from an objective of the 21st Century Cures Act (Cures Act). It includes recommendations for how industry sponsors of pharmaceuticals or biologics should design and conduct clinical trials. The guidance provides a greater explanation of how biologic and oncology trial design can simultaneously evaluate more than one investigational drug.

 

FDA Guidance

 

The guidance goes into depth about the clinical research milestones of master protocol design. Data integrity considerations are also mentioned for biomarker co-development and trial statistical analysis. Traditionally, oncology clinical trials are designed to assess multiple investigational drugs at the same time. Clinical data in this type of design is analyzed across multiple cancer types during the same trial to find all sources of patient efficacy and commercial value.

 

Another primary driver is the CDMO race due to testing multiple drugs and sub-populations under the same protocol. Pharmaceutical consultants like RCA Inc. have witnessed a shortening of client commercialization timelines across the life sciences industry. This directly adds incremental pressure on project sponsors. Clinical teams are being tasked to discover late-stage drug success faster than ever before. Every trial must simultaneously ensure patient safety while producing data that satisfies the regulatory safety and effectiveness.


Need help with your Clinical Trials? Contact Us Now!


Investigational Drugs (IND FDA)

 

The FDA concisely describes this unique protocol design and clinical trial planning for IND filings and multiple sub-studies. Sub-studies may have separate goals and require aligned efforts across the data science team. For example, collaboration is needed in order to appropriately value multiple investigational drugs. Consideration should be given that therapeutic value may be in one or more disease sub-types in the clinical trial.

 

With these considerations in mind, the FDA goes on to describe the benefits of a master protocol across the study design. This provides the project sponsor design flexibility via electronic data capture (EDC) in an EDC system (e.g. shared control arm, adaptive designs, centralized data capture).

 

Clinical Trial Design

 

This new FDA guidance also provides insights on potential challenges the industry should consider when using master protocols. These unintended consequences can include greater difficulty when assigning detailed adverse events to an investigational drug if numerous products are being investigated across the clinical study.

 

Any lack of adverse event reporting clarity can impact the safety profile of an investigational drug. This directly makes the clinical analysis for FDA approval more complicated for the regulatory body. Multiple study groups can also increase the overinterpretation of study findings. For example, signs of positive product efficacy for cardiac biomarkers could be different than from cancer biomarkers. Biomarker discovery for one subpopulation could also be identified as false if based a different ad hoc patient group.

 

Basket Trials

 

Basket trial design includes assessing an investigational drug blend by including a dose-finding or safety lead-in component. The goal is to identify safe quantities of the combination early in the clinical trial before progressing with an efficacy activity-estimating factor. The FDA proposes therapeutic efficacy for sub-studies within basket trials are constructed as single-arm, activity-estimating trial. The primary endpoint would be recorded as total response rate.

 

The guidance goes on to elaborate on sub-study objectives, including study rationale for each population. A comprehensive statistical analysis plan (SAP) with reasoning for sample size and unique stopping rules based on ineffectuality should also be included in the program documentation.

 

Umbrella Trials

 

A master protocol designed to evaluate multiple drugs is commonly referred to as an umbrella trial. These umbrella trials are often administered as a single drug or as a combination product. Umbrella trials are often a randomized controlled trial to evaluate the mechanism of action of the investigational drug/drugs with a common control arm. Study design for an umbrella trial can include sub-studies based on a patient biomarker or to a separate therapeutic sub-study inside the trial.

 

Clinical Study Design

 

As the clinical study focus, the FDA provides a clear understanding of how project sponsors improve the efficiency of master protocols. For example, using a common control arm during an Umbrella Trial has proven to help evaluate multiple drugs simultaneously for a single disease state.

 

Control Arm

 

For clinical trials, the FDA now recommends a project sponsor use a common control arm when numerous drugs are evaluated simultaneously in a single illness (e.g. umbrella trials). The FDA guidance elaborates in the use of a control arm be the current standard of care (SOC) so trial results are understandable from the perspective of the biologic and oncology medical community.

 

Changes in SOC can also take place during the trial because of an FDA approval or the latest scientific data. The Statistical Analysis Plan (SAP) would need to be revised before any data analysis occurs if this is the case.

 

Novel Drugs

 

When a project sponsor uses sub-studies to assess two or more investigational drugs, the FDA advocates for providing a thorough scientific motivation for the combination. This includes the clinical trial sponsor defining the Recommended Phase 2 Dose (RP2D). Analysis should include each novel drug and ensuring the appropriate dosage has been identified for each individual drug.

 

Targeting Biomarkers

 

The FDA goes on to elaborate on digital biomarkers to help validate the patient selection and recruiting for clinical trials. Biomarkers should be clearly identified based on the intended therapeutic response.

 

For example, an oncology biomarker for tumor size can help predict the response to the investigational drug. This type of study biomarker might demonstrate how the mechanism of action succeeded or failed. There needs to be a consensus among the clinical study team on how biomarkers are justified. Understanding study measures for showing marker positivity before patients enter the trial is critical.

 

Data Monitoring

 

One final important note about the master protocol in the updated FDA guidance describes the independent radiologic review committee. This committee medical research should include blinded tumor-based assessments to provide a charter for the independent data monitoring committee (IDMC).

 

The IDMC charter would guide the committee through ad hoc trials, such as patient efficacy and drug futility. The IDMC can also recommend clinical trial protocol actions. This often includes changes in sample size or modification of a sub-study based on overwhelming futility or efficacy evidence.

 

About RCA

 

Regulatory Compliance Associates® Inc. (RCA) provides healthcare consulting services to the following industries for resolution of compliance and regulatory challenges:

 

We understand the complexities of running a life science business. Our team possesses areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA-and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

 

In this soundbite from RCA Radio, Dr. Helin Raagel and Dr. Matthew Jorgensen from Nelson Labs explain why the Cytotoxicity test during a biocompatibility evaluation is the most important test you will run.

 

cytotoxicity

What is Cytotoxicity? – Cytotoxicity is the degree to which a substance can cause damage to a cell. A substance or process that causes cell damage or death is referred to as cytotoxic, “cyto” meaning cell and “toxic” meaning poison. (Will the device kill or harm the cells it comes in contact with?)

 

There are three reasons why the cytotoxicity test is the most important test you run during a biocompatibility evaluation.

  1. The test can be run quickly.
  2. It is the most cost-effective test in an evaluation.
  3. Most evaluation concerns come from the cytotoxicity results.

Listen to the full episode “What is Cytotoxicity?” now!


About Nelson Labs

 

Every year, hundreds of medical device, pharmaceutical, and tissue companies make Nelson Labs their testing laboratory of choice. For them, the decision is easy. Nelson Labs is a clear leader in the microbiology and analytical chemistry testing industry, offering more than 800 laboratory tests and employing more than 500 scientists and staff in state-of-the-art facilities. We are known for exceptional quality and rigorous testing standards, but it is our focus on the bigger picture that sets us apart. We look beyond test results and partner with you to achieve your long-term business goals — mitigating risk, being first to market, and succeeding with your customers.

 

About RCA®

 

Regulatory Compliance Associates® (RCA) provides healthcare consulting services to the following industries for resolution of compliance and regulatory challenges:

 

Life Science consultantsWe understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. Our life science consultants are used to working on the front lines and thriving in the scrutiny of FDA and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and private equity due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

 

To begin the RCA® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

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