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

http://www.anteris-medical.com/




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: THE CASE OF TNF INHIBITORS

„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 OF TNF INHIBITORS

...of course, we know what happened next:

2000 1998 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





(ALMOST COMPLETE LIST OF) SUCCESS FACTORS

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





ADDITIONS TO THE LIST OF 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





WHAT DOES THIS 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 OPTIONS TO 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 PART 4 ??





THE CASE OF THE AMGEN WARNING LETTER

Products found adulturated:

Prolia prefilled syringe

Enbrel lyo vial

Enbrel Sureclick autoinjector











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 [email protected] www.anteris-medical.com

THANK YOU !




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Health & Medicine

Medical devices for biosimilars