Recent FDA Guidances

FDA Biocompatibility Guidance

Use of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process

After over three years of review, the FDA’s new biocompatibility guidance will be going into effect on September 14, 2016. This guidance clarifies and expands on how the FDA expects manufacturers of medical devices that come into contact with the human body should comply with the ISO 10993-1 standard for biological evaluation of devices within a risk management framework. It includes new recommendations for manufacturers in terms of risk-based biocompatibility approaches, chemical assessment, and biocompatibility test article preparations for devices. It is important to keep in mind that though the guidance is based on and very similar to ISO 10993-1, there are differences.

The guidance incorporates new ideas regarding toxic chemicals (e.g. color additives) not previously addressed in a standard. It focuses on safety concerns associated with chemicals that can leach from medical devices and impact patient safety. It also recommends manufacturers evaluate the need for chronic toxicity and carcinogenicity testing for permanent implant devices and recommends more extensive testing for blood contacting devices, regardless of contact duration, or to provide justification for forgoing those tests. The new guidance requires organ specific devices to undergo additional testing for the target organ. The FDA’s new guidance puts more emphasis on scientific analysis and contains ideas on how to justify biocompatibility and limit animal testing. Biocompatibility testing and/or adequate chemical characterization in conjunction with supplementary biocompatibility testing may be acceptable to minimize animal testing.

Additionally, the document provides guidance for performing a risk assessment for materials that are found to be toxic. The material may either be eliminated or accepted based on the results of the risk assessment. The FDA lays out the steps it recommends for risk-based biocompatibility evaluations as follows:

  1. Risk assessment
  2. Risk identification – including risks other than chemical toxicity
  3. Available risk information – literature, clinical data, etc.
  4. Submission – clear connections between applicants’ identified biocompatibility risks and data available to mitigate those risks should be included.

The FDA will now require full reports be provided in FDA submissions. Master files are an insufficient basis for replacing biocompatibility testing in submissions as the same materials may be processed differently in different medical devices. The guidance stresses that the FDA approves final devices (including sterilization), so the manufacturers cannot only test raw materials for biocompatibility. They must also evaluate the impact of the production process on the materials. The FDA recommends discussing biocompatibility tests with them prior to performing tests in order to avoid expensive and time-consuming surprises on review by the FDA.

AlvaMed is here to help guide you and your organization through the new biocompatibility requirements.

To read the guidance in its entirety:


FDA Draft Risk-Benefit Guidance

Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions

The FDA released a draft guidance on factors to consider regarding benefit-risk in medical device product availability, compliance, and enforcement decisions on June16, 2016. The FDA hopes that describing the factors they use for evaluating risk versus benefits will lead to a more consistent and transparent approach. The guidance applies to diagnostic and therapeutic medical devices and is intended to compliment, not supplant, other guidance regarding risk assessments.

The FDA is focusing on maximizing patient benefits while reducing patient risk and improving medical device quality. They may consider information regarding patients’ perspectives on what constitutes a meaningful benefit or risk and what tradeoffs patients are willing to accept. The FDA may take into account benefits and risks to caregivers and healthcare providers, as well.

The draft guidance documents three categories of factors the FDA considers in a risk-benefit assessment, but does not explain how the factors are weighted and evaluated. The three categories include:

Benefit Factors

  • Type of benefit(s)
  • Magnitude of benefit(s)
  • Likelihood of patient experiencing benefit(s)
  • Duration of effects
  • Patient preference on benefit
  • Benefit factors for healthcare professionals or caregivers
  • Medical Necessity

Risk Factors

  • Risk severity (includes three levels and a duration component)
  • Likelihood of risk (includes three factors related to the number of patients at risk)
  • Nonconforming product risks
  • Duration of exposure to population
  • False-positive or false-negative results
  • Patient tolerance of risk
  • Risk factors for healthcare professionals or caregivers

Additional Factors

  • Uncertainty
  • Mitigations
  • Detectability
  • Failure mode
  • Scope of the device issue
  • Patient impact
  • Preference for availability
  • Nature of violations/nonconforming product
  • Firm compliance history

Upon evaluation of these factors, the FDA may choose to work with the manufacturers to address problems rather than initiate formal compliance or enforcement action for devices found to have high benefit and low risk. Additionally, the FDA will likely conclude it appropriate for patients to have access to a nonconforming device while long term corrective action is taken, if no alternative treatments are available. Devices found to be high risk and low benefit will most likely have formal action taken by the FDA to address the issue.

It is important for manufacturers to be aware of these factors. Manufacturers can advocate for favorable FDA decisions by using the FDA’s factors to illustrate the high benefits and low risks of the device.

AlvaMed is here to help guide you and your organization through all of the upcoming changes.

To read the draft guidance in its entirety:


IDE Draft Guidance

FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions.

On June 1, 2016, the FDA released a draft guidance for sponsors, clinical investigators, industry, institutional review boards and food and drug administration staff concerning the categorization of IDE devices for Medicare and Medicaid coverage decisions.  The guidance is available for comments and suggestions within 60 days of the issue date.

The intention of this guidance is to modify the current policy on categorizing investigational device exemption devices for Medicare and Medicaid to determine whether or not an IDE device should be covered (reimbursed) by CMS.  Following IDE device approval (approved or approved with conditions) by the FDA, the FDA reviews the intended use of the device and assigns it to a CMS category (A or B).

Category A devices are experimental devices with no PMA approval, 510(k) clearance or de novo request and does not have clinical or non-clinical data that resolves initial questions of safety and effectiveness.  Category A devices also differ (have no substantial equivalence) from current, legally marketed devices.  Category B devices are nonexperimental/investigational IDE devices where the “incremental risk is the primary risk in question and initial questions of safety and effectiveness of that device type have been resolved.”

The 1995 interagency agreement for Medicare and Medicaid reimbursement still applies: Category B IDE devices qualify for Medicare reimbursement, only services related to Category A devices are covered, not the devices themselves.

This guidance adjusts the language of Category A and Category B IDE devices, their categorization path and how IDE devices can move from Category A to Category B once there is enough relevant data to justify moving the device.

AlvaMed is here to help guide you and your organization through all of the upcoming changes.

To read the draft guidance in its entirety: