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Expanded Access Programs for Medical Devices

Posted 23 April 2018 | By Sharon Perez 

Expanded Access Programs for Medical Devices

Expanded access, also referred to as compassionate use, is a vital pathway for patients with life-threatening diseases to gain early access to unapproved investigational medical devices. This article summarizes expanded access programs for medical devices in the US, Europe, Japan, Canada and Australia.

Background

The average time from medical device concept to marketing approval has been reported as three to seven years.1 This long-time lag is problematic for patients with serious or life-threatening diseases if alternative treatments are not available. Expanded access permits patients with life-threatening conditions who are not eligible to participate in clinical trials to receive investigational devices before formal product approval. Expanded access of medical devices varies widely by country.

US Expanded Access Programs for Medical Devices

The US Food and Drug Administration (FDA) has three categories of expanded access programs depending on the urgency, number of patients, and whether prior FDA approval is required - Table 1.

Table 1. FDA Expanded Access
Authority Food and Drug Administration
Program Emergency Use Compassionate Use Treatment Use
Laws and Regulations 21 CFR 812.35 (only devices with IDEs) 21 CFR 812

21 CFR 812.36

21 CFR 56

21 CFR 50

Number of Patients Individual Individual or Group Group
Applicant Physician Manufacturer or Physician Manufacturer
Authority Approval Required Prior to Device Use No Yes Yes

All medical devices must meet the following criteria regardless of the expanded access pathway:

  • Device is intended for diagnosis, monitoring or treatment of a life-threatening or serious disease/condition.
  • No generally acceptable alternative therapy exists.
  • The risk from the disease or condition is equal to or less than the probable risk from the device.
  • There is sufficient safety and effectiveness evidence for the intended use.

FDA expects physicians to weigh the seriousness of the patient's condition and the possible benefit from use of the unapproved device against any device-associated risks.

Emergency use is intended to treat patients with life-threatening or serious diseases or conditions for which there is no available alternative and no time to obtain FDA approval. Physicians treating a patient via emergency use must obtain:

  • informed consent from the patient or legal representative
  • approval from their institution
  • approval of their Institutional Review Board (IRB) chairperson
  • an independent assessment from an uninvolved physician
  • authorization from the device manufacturer (Note: manufacturers are under no obligation to provide devices for emergency use).

Emergency use must be reported to FDA. If there is already an Investigational Device Exemption (IDE) for the device, the treating physician must notify the IDE sponsor and the IDE sponsor must inform the FDA within five days through an IDE report. The content of the IDE report is described in 21 CFR 812.35—IDE Supplemental Applications.2 If there is no IDE, the physician should submit a report describing the use of the device directly to FDA and to his or her IRB within five days.

A second expanded access program in the US is compassionate use. There are two categories of compassionate use—for individual patients or for small groups of patients. In contrast to emergency use, FDA approval is needed prior to device  use. Physicians must first obtain approval from the manufacturer to provide the device; however, the manufacturer is under no legal obligation to either give approval or provide the device. If there is already an IDE for the device, the IDE sponsor of must submit an IDE supplement which includes:

  • description of the patient's condition and the circumstances necessitating treatment
  • discussion of why alternative therapies are unsatisfactory and why the probable risk of using the investigational device is no greater than the probable risk from the disease or condition
  • identification of any deviations in the approved clinical protocol that may be needed in order to treat the patient
  • a draft of the informed consent document that will be used

Treating physicians must get approval from their institution, IRB and an independent physician. If there is no IDE, the treating physician or the manufacturer must submit all the information required for an IDE supplement along with a description of the device. Physicians may make compassionate use requests for a small group of patients in the same manner by also including the number of patients to be treated. Patients being treated under compassionate use should be actively monitored by the treating physician and a summary report detailing patient outcomes must be submitted to the IRB and FDA once all patients have been treated.

If a device is under investigation in a clinical trial and the manufacturer is pursuing market approval, expanded access also may be pursued through the treatment use IDE pathway. In this case, the device must be used for the same indication studied in the active (or completed) clinical trial. Patients treated should have a serious or immediately life-threatening disease (defined as a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without treatment). Content for the treatment use IDE application must include:

  • criteria for patient selection
  • a written protocol describing the treatment use
  • description of clinical procedures, laboratory tests or other measures that will be used to evaluate the effects of the device and to minimize risk
  • written procedures for monitoring the treatment use and the name and address of the monitor
  • instructions for use for the device and device labeling
  • information on safety and effectiveness of the device for the intended use
  • If the device is to be sold, the price to be charged and a statement indicating that the price is based on manufacturing and handling costs only.3

Physicians approved for a treatment use IDE are considered "investigators" under the IDE regulations and are responsible for meeting all applicable IDE investigator responsibilities.4 Sponsors of treatment use IDEs must submit semi-annual progress reports to their IRB and FDA until such time as the device's marketing application is submitted. These reports should follow the format of an IDE Progress Report and include the number of patients treated, the names of participating investigators and a brief description of the manufacturer's efforts to obtain marketing approval.5 Other IDE reporting requirements under 21 CFR 812.150 also apply, including unanticipated device adverse effects and final reports.6

Expanded access is a "hot button" issue in the US and has been included in recent and proposed legislation. The 21st Century Cures Act, passed in December 2016, requires manufacturers to provide information on expanded access, including application procedures, anticipated time to acknowledge receipt of requests and general criteria for evaluating requests to the public. However, manufacturers are still not required to provide product though expanded access. On 3 October 2017, FDA Commissioner Scott Gottlieb announced that the IRB approval process was being simplified to require only one IRB member to approve treatment rather than the full IRB.7 As of January 2018, 38 states have passed Right to Try laws allowing terminally ill patients to use unapproved devices that have passed Phase I testing.8 However, these state laws rely on passage of a federal Right to Try law. As of March 2017, a federal Right to Try bill had been passed by the Senate and was under review with Congress.

Europe Expanded Access Programs for Medicinal Products

The European Medicines Agency (EMA) defines compassionate use as a medicinal product being made available for compassionate reasons to a group of patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening and who cannot be treated satisfactorily by an authorized medicinal product.9 Although the EMA has mechanisms for compassionate use of drugs in the EU, there is no equivalent medical device compassionate use program because Conformité Européenne (CE) marking must be affixed to medical devices before use. However, medical device compassionate use programs may be coordinated and implemented by EU Member States (MS) according to national rules and legislation. For example, in the United Kingdom (Table 2), there is a humanitarian use exemption which allows for exceptional use of non-CE marked medical devices in order to protect a patient's health if there is no legitimate alternative available. Treatment is on a single named patient basis and the following criteria must be met:

  • The treating physician must contribute to the manufacturer's application.
  • There must be no alternative CE marked device available.
  • It must be demonstrated that the mortality or morbidity of the patient is significantly reduced if the device is used compared to alterative approved treatment.10
Table 2. United Kingdom Humanitarian Use of Device
Authority Medicines and Healthcare Products Regulatory Agency (MHRA)
Laws and Regulations Medical Devices Regulations
Number of Patients Individual
Applicant Physician and Manufacturer
Authority Approval Required Prior to Device Use Yes

Japan Expanded Access for Medical Devices

Information on Japan's expanded access program for medical devices can be found here (written in Japanese).

Table 3. Japan Physician Direct Import Program
Authority Pharmaceutical and Medical Device Agency (PMDA)/Ministry of Health, Labour and Welfare
Laws and Regulations Pharmaceutical and Medical Device Act (PMD)
Number of Patients Individual
Applicant Physician
Authority Approval Required Prior to Device Use No

Canada

Canada's Special Access Programme (SAP) allows HealthCare Professionals (HCPs) to obtain custom made or unlicensed medical devices for emergency use or when conventional therapies have failed, are unavailable, or are unsuitable to provide appropriate treatment for patients under their care (Table 4). An "emergency" is defined as a situation posing immediate risk to a patient's life or long-term health.12

Table 4. Canada Special Access Programme
Authority Health Canada
Laws and Regulations

Medical Devices Regulations Part 2

Food and Drugs Act subsections 3(3), 30(1) and 37(1)

Number of Patients Individual or Group
Applicant Physician
Authority Approval Required Prior to Device Use Yes

The SAP is administered by the Special Access Unit (SAU) of the Medical Devices Bureau in the Therapeutics Products Directorate of Health Canada. In addition to risk assessment review prior to approval of a SAP application, the SAU conducts periodic reviews of the benefit-risk profile and continued clinical need of medical devices used under the SAP for an extended period of time (typically one year or more).

SAP applications may be made for individual patients or by batch request. Patient-specific requests are for an identified patient. Batch requests may be appropriate when shipping delays could result in adverse patient outcomes. HCPs must provide an estimate of the number of devices required to treat patients in a one month period. HCPs must prepare and submit applications with only administrative support from the manufacturer (e.g., providing model numbers, instructions for use, etc.) Manufacturers cannot provide medical or clinical rationale in support of the application. The application must include:

  • diagnosis, treatment or prevention for which the device is required
  • reasons why the device was chosen
  • risks and benefits associated with device use
  • clinical reasons why conventional methods or approved devices are not appropriate
  • known safety and effectiveness information for the device
  • agreement that the HCP will inform the patient of the risks and benefits associated with the device
  • manufacturer's instructions for use for the device13

Physicians must report all serious adverse events associated with the device to Health Canada and to the manufacturer or importer of the device within 72 hours of their occurrence. HCPs also are encouraged to submit voluntary reports of clinical outcomes for patients treated with devices under the SAP.

Australia Expanded Access Programs for Medical Devices

Unapproved medical devices not included on the Australian Register of Therapeutic Goods (ARTG) but may be legally accessible through three mechanisms: the Special Access Scheme (SAS), the Authorised Prescriber Scheme and Personal Importation.

The Special Access Scheme (SAS) allows medical practitioners to import unapproved devices for single patients. Devices may be imported under a range of circumstances, such as:

  • Early access for terminally ill patients
  • The device was provided initially to patients through a clinical trial while a marketing application is being considered.
  • The device is available overseas, but not in Australia.

There are three pathways in the SAS:

  • Category A (notification pathway)—patients which are seriously ill with a condition from which death is reasonably likely to occur within a matter of months or from which premature death is reasonably likely to occur in the absence of early treatment.
  • Category B (application pathway)—patients that do not fit Category A using a device that does not have an established history of use per the Therapeutic Goods (Authorised Supply of Specified Medical Devices) Rules.
  • Category C (notification pathway)—devices deemed to have an established history of use per the Therapeutic Goods (Authorised Supply of Specified Medical Devices) Rules.

Prior approval from TGA is only required for Class B patients. Medical practitioners treating patients under the SAS must inform TGA of adverse device events or defects. Manufacturers are under no obligation to supply an unapproved device requested under the SAS. However, if a device is supplied the manufacturer is required to report the number of unapproved devices shipped to Australia, report to the TGA serious unanticipated device related adverse events, and inform TGA of any change to the benefit-risk assessment of the device.14

Medical practitioners may obtain access to an unapproved device for specified individual patients with a particular medical condition in their immediate care without further approval from TGA by becoming an "Authorised Prescriber."

Devices may be imported by Authorised Prescribers under a range of circumstances, such as:

  • The device was provided initially to patients through a clinical trial while an application for inclusion on the ARTG is under consideration.
  • The device is available overseas, but not in Australia.
  • No suitable alternative approved device is available in Australia.

Patients treated with devices by an Authorised Prescriber must be suffering from an illness or condition that is either life-threatening or serious. Authorised Prescribers must get endorsement from an Ethics Committee in addition to TGA approval prior to treating patients. Once approved, the Authorised Prescriber is responsible for reporting the number of patients treated (on a six-monthly basis) and adverse device events to TGA. Manufacturers are under no obligation to supply an unapproved device just because it was requested by an Authorised Prescriber. However, if a device is supplied, the manufacturer is required to report the number of unapproved devices shipped to Australia, report to the TGA serious unanticipated device related adverse events, and inform TGA of any change to the benefit-risk assessment of the device.15

Individuals may import unapproved devices for personal use. In this case, the device must be used by that individual or a member of his/her immediate family and cannot be sold or supplied to any other person. For Class IIa or higher devices, the quantity imported cannot exceed the amount required for three months' treatment. There are additional restrictions on devices which incorporate tissues, cells or blood derivatives. Individuals also must ensure they adhere to Customs and Quarantine laws.16

Table 5. Australia Special Access Programme
Authority Therapeutic Goods Administration
Laws and Regulations Therapeutic Goods (Medical Devices) Regulations
Therapeutic Goods Act
Program Special Access Scheme Authorised Prescriber Scheme Personal Importation
Number of Patients Individual Individual or Group Individual
Applicant Physician Physician Patient/Family Member
Authority Approval Required Prior to Device Use

Class A – No

Class B – Yes

Class C - No

Yes No

Discussion

Expanded access programs are not intended as an early market access route for medical devices still under development, in clinical trials, or awaiting marketing approval. Manufacturers are expected to pursue traditional approval routes in conjunction with compassionate use. Sales, advertising, and promotion of unapproved devices is not permitted under these programs. Expanded access is also not meant to subvert the clinical trial process and devices should only be made available to patients which are not eligible to participate in ongoing clinical trials. Devices used in expanded access may still be under development and the efficacy and safety of the device has not been fully vetted though the marketing approval process. Therefore, patients treated under expanded access should be carefully monitored to ensure a continued clinical need and benefit to the patient. When used appropriately and responsibly, expanded access is a vital tool for getting patients the quickest possible access to new treatments before it is too late to benefit.

References

  1. Fargen KM, Frei D, Fiorella D, McDougall CG, Myers PM, Hirsch JA, Mocco J. The FDA Approval Process for Medical Devices. J Neurointervent Surg. 2013;5:269-275.
  2. FDA. 21 CFR 812.35. Investigation Device Exemptions—Supplemental Applications. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=812.35. Revised 1 April 2017. Accessed 19 April 2018.
  3. FDA. 21 CFR 812.36. Investigation Device Exemptions—Treatment Use of an Investigational Device. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=812.36. Revised 1 April 2017. Accessed 19 April 2018.
  4. FDA. 21 CFR 812. Investigation Device Exemptions. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=812. Revised 1 April 2017. Accessed 19 April 2018.
  5. FDA. 21 CFR 812.150. Investigation Device Exemptions—Reports. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=812.150. Revised 1 April 2017. Accessed 19 April 2018.
  6. Ibid.
  7. Gottlieb S. Expanded Access: FDA Describes Efforts to Ease Application Process. FDA Voice. 3 October 2017. https://blogs.fda.gov/fdavoice/index.php/2017/10/expanded-access-fda-describes-efforts-to-ease-application-process/. Accessed 19 April 2018.
  8. About Right to Try. http://righttotry.org/about-right-to-try/. Accessed 19 April 2018.
  9. Committee for Medicinal Products for Human Use (CHMP). Guideline on Compassionate Use of Medicinal Products, Pursuant to Article 83 of Regulation (EC) No 726/2004. 19 July 2007.http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf. Accessed 19 April 2018.
  10. Medicines and Healthcare Products Regulatory Agency. Guidance–Exceptional Use of non-CE Marked Medical Device. 18 December 2014. https://www.gov.uk/guidance/exceptional-use-of-non-ce-marked-medical-devices. Accessed 19 April 2018.
  11. Japan MDC. Private Import With Doctor's License of Unapproved Medical Devices. https://www.j-mdc.com/private.html. Accessed 19 April 2018.
  12. Health Canada. Guidance for Healthcare Professionals on Special Access and Custom-Made Medical Devices. 18 February 2016. https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/hpfb-dgpsa/pdf/acces/sap-md-dg-as-im-ld-eng.pdf. Accessed 19 April 2018.
  13. Ibid.
  14. Therapeutic Goods Administration. Special Access Scheme—Guidance for Health Practitioners and Sponsors. September 2017. https://www.tga.gov.au/sites/default/files/special-access-scheme-guidance-for-health-practitioners-and-sponsors.pdf. Accessed 19 April 2018.
  15. Therapeutic Goods Administration. Authorised Prescriber Scheme—Guidance for Medical Practitioners, Human Research Ethics Committees, Specialist Collages and Sponsors. July 2017. https://www.tga.gov.au/sites/default/files/authorised-prescriber-scheme.pdf. Accessed 19 April 2018.
  16. Therapeutic Goods Administration. Access to Unapproved Therapeutic Goods—Personal Importation. October 2004. https://www.tga.gov.au/sites/default/files/access-personal-import-guidelines.pdf. Accessed 19 April 2018.

About the Author

Sharon Perez obtained her PhD in molecular and cell biology in 1998 from the University of Maryland at Baltimore. She has worked in pharmacovigilance and medical device safety for 15 years. She is currently director of global medical device safety at Novocure. Perez is an active member of RAPS and a current Regulatory Exchange Community Ambassador. She may be reached at sperez@novocure.com.

Cite as: Perez S. "Expanded Access Programs for Medical Devices." Regulatory Focus. April 2018. Regulatory Affairs Professionals Society.


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