The Rise of the Medical Device/Pharmaceutical Product combination and how it affects traditional

Pharmacovigilance

German Pharmacovigilance Day 02. June 2015

Abstract

Medical Devices and Pharmaceutical products have long been separate worlds with distinct regulations. Advances in technology continue to create new opportunities by merging devices with drugs or biologics to provide previously impossible benefits to patients. As these combination products involve components that are normally regulated under different types of regulatory authorities, they raise several challenges to traditional pharmaceutical companies, not previously exposed to Device regulations. Compared to drug regulations, device regulations are more diverse depending on the classification of the device. But the safety of Medical Devices has recently become the focus of regulatory activities in Europe following the scandal about industrial silicone breast implants in France, leading to changes in regulations that follow Pharmacovigilance principles. In this presentation Dr Marc Zittartz, Chief Quality Officer at pharmasol, provides an overview on drug-device combinations, the recent regulatory developments, and how this affects the traditional Pharmacovigilance activities of pharmaceutical companies.

Abstract

In the past …

Medical Devices and Pharmaceutical products were well separated

Different companies

Different regulations

Device Classification

Class I: lowest potential for harm and are simpler in design

Device Classification

Class II

Device Classification

Class III

THERAC-25

Linear accelerator to deliver x-rays and electron beams for the treatment of cancer

Released in 1985

What went wrong?

Within 2 years, 6 patients received massive radiation overdose due to a software failure

Recent Device Safety issues

DePuy Hip Replacements

- Approved without Clinical Trials in 2005

- 12% of patients who received the device needed “revision surgery.”

Poly Implant Prothèse

- Breast implants from industrial-grade silicone

- 500% higher risk of rupturing or leaking

- implicated in at several deaths due to systemic toxicity and several cases of induced breast cancer

Combination Product Definition (FDA)

(1) A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are … combined or mixed and produced as a single entity;(2) Two or more separate products packaged together… and comprised of drug and device products, …;(3) A drug, device, or biological product packaged separately that … is intended for use only with an (approved) individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect

From <http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm118332.htm>

What is the problem?

Technological advances continue to merge product types

Combination products contain components that individually would be regulated by different types of Authorities

Biologics FDA CBER

Pharmaceuticals CDER

Devices CDRH

The FDA solution: OCP

Office of Combination Products (OCP)

Established in 2002

Ensure

• Identify PMOA (Primary Mode of Action)

• prompt assignment of to FDA Centers,

• timely and effective premarket review,

• consistent and appropriate postmarketregulation.

Advantages Of Developing Combination Products

Approximately one-third of all medical products under development today are combination products. According to data published by Research and Markets, the drug-device combination products segment alone will grow to $115 billion by 2019.”

From <http://www.meddeviceonline.com/doc/combination-products-a-primer-for-medical-device-makers-0001>

Endeavor Drug-Eluting Stent

Scaffold coated with a drug to prevent scar tissue from growing in an artery

Exubara

Inhaled Insulin CombinationProduct for Treatment of Diabetes

Ionsys

Fentanyl HCl Patient-Controlled IontophoreticTransdermal System

Combination Product Safety

How is the product approved (Drug, Device, Biologic)?

Which regulations apply?

Which regulations should apply?

Postmarket Safety Reporting for Combination Products - Concepts for Comment (PDF - 41KB)

How to manage different reporting obligations?

Device Malfunction Reporting

- Reporting of device malfunctions where no death or serious injury occurred, but it would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur.

How to manage different reporting obligations?

5-Day MDR Reporting

- (1) any reportable event that necessitates remedial action to prevent an unreasonable risk of substantial harm to the public health, and

- (2) any MDR reportable event for which FDA has made a written request for the submission of a 5-day report.

How to manage different reporting obligations?

Drug and Biological Product “Alert” Reporting

- adverse events that are both serious and unexpected.

- Device safety reporting requires 30- day reports of any serious injury, the reports would not necessarily flag an event as both serious and unexpected

Additional Information to be captured

Model #, Serial #, Lot #

Expiration Date

Who operated the device

Evaluation of Device

Interaction with Manufacturing department

In a nutshell

Combination Products are on the rise

Provide benefits to patients

Medical Device regulations are getting tighter

Gaps in regulations between Drugs and Devices become apparent