Translating cell therapies:Academic versus Industry model

Alexey Bersenev, MD, PhD

Advanced Cell Therapy Laboratory,Yale-New Haven Hospital, Yale University www.celltrials.info

The BioProcessing Summit, Boston, Aug. 4, 2015

• Academia vs. industry – clinical trials global trends

• Key differences between academic and industry models

• Gaps and solutions

Outline of the talk:

Global trends: sponsorship of clinical trials

http://dx.doi.org/10.6084/m9.figshare.1504124

Global trends: Total number of MSC trials

http://dx.doi.org/10.6084/m9.figshare.1504131

Global trends: Total number of trials, involved adipose-derived cells

http://dx.doi.org/10.6084/m9.figshare.1504586

Is industry in favor of allo- model?

NO!

Total number of registered clinical trials

http://dx.doi.org/10.6084/m9.figshare.1504311

Measuring output: published results of clinical studies in regenerative medicine –

2014 sample (n=116)

• focus on “first-in-human”, pilot studies

• early stages of development

• delivery: cell therapy as procedure

• favored model – auto?

• favored medical innovation regulatory path

• diseases with low prevalence

• low scale

• no attention to pharmacoeconomics, relies on “efficacy boost”

• focus on commercialization and technology transfer

• delivery: cell therapy as mass-produced drug

• favored model – allo?

• all phases of trials under FDA

• diseases with high prevalence

• large scale

• pharmacoeconomics will determine product development

Academic versus industry cell models – key differences:

academic industry

Medical Research

Personalized Medicine

First-In-Human

Serum

Cell Culture

Patient File/ Binder

Scale Out

Closed System

Cost of Goods

Automation

Large Scale

Bioprocess

Batch/ Lot

Unit Operations

Academia vs. Industry – cultural/ language difference:

Academia Industry

developer

FDA

local IRB

FACT

AABB

Traditional academic and industrial pathways

CAP

HCT/P

biologic/ drug

361

351

No GMP

cGMP

need for cell culture/ gene modifications

• Booming of stem cell and maturity of cell-based technologies on research side – ready for translation!

• Clinical resources in big academic hospitals – pioneering physician are eager to be the first

• Technological tools for clinical cell processing are available

• Pharma and Biotech are reluctant to enter the field on early stages

The need for academic GMP cell therapy facilities:

Academic GMP cell therapy facilities:

• Trend: increase number of academic facilities

• AABM – Association of Academic Biologics Manufacturers

http://www.aabmonline.org ~ 45 registered, mostly in US

• AGORA: ATMP GMP Open Access Research Alliance

http://agora-gmp.org/ - 8 centers listed

• EATRIS: European Infrastructure for Translational Medicine ATMP

Platform http://www.eatris.eu/ – 14 GMP facilities in EU

• Estimated total # of facilities in US 50-100 and EU – few

hundreds

• Usually not a subject of FDA inspection not always follow strict GMP standards

• Scale and capacity: much smaller than industry

• Acting as a hospital core facility must to accommodate all types cell/gene therapy trials

• Usually under-funded data not publishable, so no return

Academic GMP facilities – key differences:

Thermoscientific.com

Octaneco.com

Talking of scale:

Academia

Industry

Centralized vs. decentralized cell manufacturing facilities

cGMPcGMP

decentralized centralized

collection/ processing

OR/ APH

closed system/ automation

OR/ APH

releasedelivery

collection

delivery

processing

release

• Licensing —> Tech Transfer

• Contract manufacturing

• Validation studies

Academic GMP – Industry interactions:

Key to success in tech transfer:

1. Academics must understand needs of industry for

successful commercialization and regulatory

compliance

2. Industry to leverage the knowledge of academics

Academic GMP - more gaps:

• Lack of QC, QA and Regulatory

• Research-like mindset

• Training

• Funding: The cost of GMP compliance is underestimated in academia

Advice for academics:

• Invest time in developing cell therapy programs in academia – training, GMP facilities, QA/ regulatory affairs teams

• Start pre-clinical design and Phase 1 with pharmacoeconomics analysis think of cost-effectiviness, COGS, BLA, reimbursement

• Utilize (1) translational centers to help and (2) industry consultants

• Get involved in industry collaborations and tech transfers huge experience!

Advice for industry:

• It will be slow —> be patient

• Educate academics for your own benefit

• Invest early —> product/ process development. Phase 2 could be too late

• Utilize academics more for validation studies