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.

1. The Rise of the Medical Device/Pharmaceutical Product
combination and how it affects traditional
Pharmacovigilance
German Pharmacovigilance Day
02. June 2015

2. 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

3. In the past …
Medical Devices and Pharmaceutical products
were well separated
Different companies
Different regulations

4. Device Classification
Class I: lowest potential for harm and are
simpler in design

5. Device Classification
Class II

6. Device Classification
Class III

7. THERAC-25
Linear accelerator to
deliver x-rays and
electron beams for
the treatment of
cancer
Released in 1985

8. What went wrong?
Within 2 years, 6 patients received
massive radiation overdose due to a
software failure

9. 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

10. 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>

11. 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

12. 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 postmarket
regulation.

13. 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>

14. Endeavor Drug-Eluting Stent
Scaffold coated with a drug to prevent scar
tissue from growing in an artery

15. Exubara
Inhaled Insulin Combination
Product for Treatment of Diabetes

16. Ionsys
Fentanyl HCl Patient-Controlled Iontophoretic
Transdermal System

17. 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)

18. 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.

19. 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.

20. 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

21. Additional Information to be captured
Model #, Serial #, Lot #
Expiration Date
Who operated the device
Evaluation of Device
 Interaction with
Manufacturing department

22. 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