Medical devices for biosimilars

MEDICAL DEVICES FOR BIOSIMILARS –
BURDEN OR CHANCE?
London, 01 Oct 2015

2 | Introduction to anteris medical www.anteris-medical.com
1. Brief Introduction to αNTERIS mEDICAL
2. Biosimilars – Opportunities and Challenges
3. Combination or Borderline Products
4. Three Reasons why Developers of Biosimilars can Benefit
from Medical Devices
5. Case Studies
6. Conclusions
AGENDA

Brief Introduction to
αNTERIS
mEDICAL
1

αNTERIS mEDICAL
• Founding motive: „We can do this better“
• Service offering of non-core capabilities to Biopharma, Biotech, and Medical
Device industries
0
2
4
6
Employees
• Dual company background of life sciences
and engineering
• Broad and diverse customer base
• Growing and expanding in scope

αNTERIS mEDICAL
What is it we can do better than
the customer?
• Integration into client‘s teams
• Independent, and fully focused on medical device
regulations and requirements
• Good access to resources with relevant background
• Flexible with regard to location and timing of services
• Broad network of partners in Engineering, Clinical
Development, and Manufacturing

Biosimilars –
Opportunities and
Challenges
2

BIOLOGICS: THECASE OF
TNFINHIBITORS
„TNF inhibitors will never become commercial
products“
John Doe, M.D., 1995
Head of a leading research organization in TNF research
Publications in Nature, Science, PNAS, ….

BIOLOGICS:
THE CASE OFTNF INHIBITORS
...of course, we know what happened next:
20001998 1999 2001 2002 2003 2004 2005 2006 2007 2008 2009
Worlds best-selling drug 2014
IMS Health

BIOLOGICS ARE HUGELY
SUCCESSFUL PRODUCTS

SLOW START WITH GREAT
POTENTIAL

UNPRECEDENTED WAVE
OF PATENT EXPIRIES

(ALMOSTCOMPLETE LISTOF)
SUCCESS FACTORS
Source: The Biosimilars Market Today And Tomorrow, Pharmaceutical Technology Europe, Volume 22, Issue 9 (Sep 2010)

ADDITIONSTOTHE LISTOF
SUCCESS FACTORS
1. Regulatory Competence: Track record will allow regulatory
agencies to „borrow“ from earlier products and other markets
• Point in case: Zarxio approval by US FDA
2. Ability to convince KOLs and decision makers
3. Ability to develop and clear medical devices

Combination
products
and
borderline
products
3

From 21 CFR part 4 comments and clarification:
A syringe is a device used to deliver another medical product (e.g., a drug) (see, e.g.,
21 CFR 880.5860). Accordingly, a prefilled syringe is a combination product and
subject to this rule.
21 CFR Part 4 – cGMP for Combination Products
As set forth in part 3 (21 CFR Part 3), a combination product is a product
comprised of any combination of a drug and a device; a device and a biological
product; a biological product and a drug; or a drug, a device, and a biological
product.
Rule 21 CFR Part 4 became final in January 2013 and became effective 180 days later
DRUG / DEVICE
COMBINATION PRODUCTS

WHATDOESTHIS MEAN
FOR BIOSIMILARS ?
• Biosimilars are treated like any other biologic
• Any product classified as combination product needs to fulfill both, requirements
for medicinal products (drugs) AND requirements for medical devices
• Biosimilars in the US are reviewed by CBER
• The device part of a submission may include review by CDRH
• Where unclear, the Office of Combination Products assigns to either CBER or
CDRH

21 CFR PART 4
• Most biosimilars are combination products like any other biologic
• Any product classified as combination product needs to fulfill both, requirements
for medicinal products (drugs) AND requirements for medical devices
• Biosimilars in the US are reviewed by CBER
• The device part of a submission may include review by CDRH
• Where unclear, the Office of Combination Products assigns to either CBER
or CDRH

21 CFR PART 4 –TWO
OPTIONSTO COMPLY
Product developed according to drug
CGMPs (21 CFR 211)
Product developed according to device QSR (21
CFR 820)
820.20: Management responsibility 211.84: Testing and approval or rejection of components,
drug product containers, and closures
820.30: Design controls 211.103: Calculation of yield
820.50: Purchasing controls 211.132: Tamper-evident packaging requirements for over-
the-counter (OTC) human drug products
820.100: Corrective and preventive actions 211.137: Expiration dating
820.170: Installation 211.165: Testing and release for distribution
820.200: Servicing 211.166: Stability testing
211.167: Special testing requirements
211.170: Reserve samples
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM429304.pdf

BUT…. IS FDA REALLY
ENFORCING PART4 ??

THE CASE OFTHEAMGEN
WARNING LETTER
Products found adulturated:
 Prolia prefilled syringe
 Enbrel lyo vial
 Enbrel Sureclick autoinjector

THE CASE OFTHEAMGEN
WARNING LETTER

THE CASE OFTHEAMGEN
WARNING LETTER
Conclusion for the US:
1. A prefilled syringe is not considered a medical device
2. In the U.S., a PFS is regulated as a combination product
3. A Design History File needs to be established
4. Safety and performance requirements must be met (as for a medical device)
5. Design control needs to be applied (based on ISO 13485, chapter 7.3 and 21 CFR Part 820.30)

http://ec.europa.eu/consumers/sectors/medical-devices/files/meddev/2_1_3_rev_3-12_2009_en.pdf
BORDERLINE
PRODUCTS

BORDERLINE
PRODUCTS
Conclusion for Europe:
 A prefilled syringe is not considered a
medical device
 In Europe, a PFS is regulated as a
medicinal product
o A technical dossier needs to be
established
o Safety and performance
requirements must be met (as for a
medical device)

SO…HOW DO YOU
ACHIEVE COMPLIANCE?
Stupid answer: …you comply with medical device regulations…
A bit more useful answer:
 Choose a modular approach (generate modules of documentation
for reuse you suspect you will need in the future
 Describe the combination product as
(1) the medicinal product with it’s indication for use
(2) the medical device components and their
performance criteria
(3) the combination of the medicinal product and the
medical device components, including
demonstration of performance criteria and usability

 A well maintained DHF for a medical device contains
dozens of documents referencing each other
 Subject to audits by regulatory agencies or Notified
Bodies
 The TFTOC is more or less prescribed within 21 CFR
820 and ISO 13485
 There must be a smarter way to comply
A COMPLETE DHF ?
FOR A SYRINGE ??

1. A modular approach is the easiest way to address the
need to conform with the essential requirements for
medical devices
1. For a prefilled syringe with NSD three components of the
Technical File are required:
Module describing the PFS
Module describing the NSD
Combination module
MANAGING THE BURDEN OF
TECHNICAL DOCUMENTATION

1. Biosimilars, like any combination product have to fulfill the essential
requirements for safety and performance of the device used in the
combination
2. Increasingly important: the usability of the product has to be built into
the design (usually done by performing formative usability studies) and
demonstrated/validated (usually in a summative handling study)
3. Biosimilars may not be superior to the originator, however the device
used in the combination may be under certain conditions
GENERAL CONSIDERATIONS
FOR THE USE OF MEDICAL
DEVICES WITH BIOSIMILARS

DO BIOSIMILARS HAVE TO
USE THE SAME DEVICES
AS THE ORIGINATOR?
Guidance for Industry on Biosimilars: Q & As Regarding Implementation of
the BPCI Act of 2009: Questions and Answers Part I
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm259809.htm

How Biosimilar
Developers Can
Benefit from
Medical Devices
4

ACHIEVING COMPETITIVE
ADVANTAGE THROUGH
DEVICE IMPROVEMENTS
Trend from vials to prefilled syringes to autoinjectors:
1. Better usability, especially in indications with tactile and sensory impairments
2. Higher perceived and actual value
3. Better branding and brand recognition
4. IP protection around the device
5. Long changeover periods

DEVICE IMPROVEMENTS IN
THE SAME CATEGORY
Concrete example: Needle Safety Device (NSD)
Areas of improvement:
 Finger flange: ensure better grip
 Shape and size of plunger rod base: ensure
better grip
 Shape and size of window: improve
readability
 Additional safety features: NSD housing
snaps into plunger rod base
 All changes supported by human factors
studies and documentation available to
customer

DIFFERENTIATION AND
BRANDING
Example: Human Growth Hormone Market – Which ones are the biosimilar
products??
(1)
(2)
(3)
(4)
(5)
(6)

Case Studies
5

CASE 1:
IMPROVED NSD
Biosimilar may have an edge over competition
Case of a biosimilar developer:
• Originator markets one of the devices to the left in
combination with the biologic
• The device manufacturer now offers an improved
version of the NSD, complete with supporting
documentation (performance data, usability data)
• Originator AND biosimilar competiion face several
hurdles:
• Regulatory hurdle
• Cost of change-over
• Finding a CMO for a relatively new device

CASE 2: IMPROVED
AUTOINJECTOR
Improved device for a human growth hormone biosimilar:
Benefits from the change:
 Higher attractiveness attracts new patients
 New features improve usability (pre-set
dose)
 Helpful in tender markets where device
aspects are considered
 Marketing argument
 IP around the device

CASE 3: IMPROVED
DISPOSABLE PEN
Disease Area: Rheumathoid Arthritis (RA)
• Obvious and significant differences in usability
• Many products on the market allow for significant improvements
• Opportunity to improve, differentiate, and leverage a success factor other than price and date of entry

Conclusions
6

CONCLUSIONS
1. Regulators support improvements under certain
conditions
2. Biosimilars can (and are) improving within product
categories, gaining a competitive edge over
biosimilar and originator competitors
3. Biosimilars can improve across categories (for
example replace prefilled syringes with
autoinjectors)
4. Improvements on the device level are accepted,
effective differentiators, and provide a sustainable
competitive advantage

Any questions?
You can find me at dk@anteris-medical.com
www.anteris-medical.com
THANKYOU !

Medical devices for biosimilars

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