Beeston Engineering Consulting1 An Engineer Dive in the Bio and Medical Devices World Presentation by: Amer El-Hage 11/20/2006.

Beeston Engineering Consulting

1

An Engineer Dive in An Engineer Dive in the Bio and Medical the Bio and Medical

Devices WorldDevices World

Presentation by:

Amer El-Hage 11/20/2006


2

Outline

A bit about myself, Beeston Engineering

and this industry

What my Engineering education missed!

What is Art, Science and what is

Engineering?

Common Engineering issues

Project management!

Summary


3

My Qualifications25 years in scientific instrument development at Beckman, Varian, LJL Biosystems and Molecular Devices

Over 30 product development programs experience. Several products carried from concept to full production

Directed product development projects in meeting their specification, budget and schedule goals

Involved in several instrument designs (fifteen issued patents), product validation and risk assessment programs

Developed at Varian, LJL and MDC their product development process

ASME Silicon Valley volunteer for over five years, chair 2006

U.C. Berkeley M.S. 1980, Mechanical Engineering- Design and Automation


4


Independent evaluation of product or devices at any stage in the development cycle

Identify necessary technical skills and tools to execute a product development project successfully

Program Management: Develop tasks, budget, and resources

Develop plans to validate prototypes to relevant standards and regulatory systems

Draft engineering, quality and processes to efficiently transfer or release your product to manufacturing


5

California and Bay area Bio-Space

Some Statistics and Graphs


6

Defining the Industry

The Biotech & Biomedical (Life-science) Industry in California is comprised of many sectors, with employment today exceeding 250,000.

Employment breaks down as follows:Biopharmaceuticals (34%)Medical devices, instruments and diagnostics (33%)Academic research (18%)Laboratory services (12%)Other (3%)

Source: CHI, California’s Biomedical Industry, 2004


7

A Few Figures for California

Total biomedical companies: 2,600 (90% founded since 1980 and 80% privately owned)

Total world-wide revenues: $32.3 billion

Total employment: 230,100 (This exceeds the number employed by the computer industry in the same time frame!)

Total wages and salaries paid: $14 billion

These companies serve as powerful economic drivers in the 7 regional clusters in which they are located.



8

Biomedical Industry Wages in CA



9

Employment Growth

23% growth from 1990 to 200223% growth from 1990 to 2002Source: CHI, California’s Biomedical Industry, 2004


10

Some of my Instrumentations and Medical Devices Experience

Chemical and Immunodiagnostics – Design audit, Project planning and transfer to manufacturingCombinatorial Chemistry systemsDNA, HIV and other detection systemsBiology and cell based assaysPulmonary drug delivery device – Plastic moldingGlaucoma, Bone density - Technical reviews and project development for medical devices measurement, Insulin inhaling deviceCatheters and Stents – SLA models, and coating processesQuality Engineering, Design Control and process validation


11

A Typical Automated Laboratory Setting

Automated Liquid Handler “Dispensers”

Microplate Reader

Robot Arm

Microplate Hotel or Storage

Other Mechanical Laboratory Gizmos


12

Microtubes Moved Into 96 Well Microplates


13


14

Time and Dollars scale

It usually takes 8 -10 years to get a pharmaceutical product or drug to market and $500-900M investment

Medical Devices require 4 - 6 years and $40-100M to develop

Scientific Instruments require 3-4 years and ONLY $5 - 10M to develop!


15

What about the Bay Area?

750+ companies *86,000+ employees30+ academic and research institutions

The Bay Area has the largest concentration of medical device start-ups in the U.S., and the largest concentration of companies bought out by medical device giants.

* Excludes the 98 companies and 5,000 employees in the Sacramento area



16

Example of some Scientific and medical Devices companies


17

BD BiosciencesDivision of Becton Dickinson Company

Medical Device company - Regulated industryParent company well established > 100 yrs IVD products Research products

Approximately 15,000 employees (1,000 BA) Revenue of $4B ($300-400M) per year

Figures in (parenthesis) are my estimates


18

A BD Diagnostic Instrument Made Possible by “Engineers”


19

Molecular Devices Corp.

Scientific and Bio-analytical solution company – Non Regulated (yet!)

Company well established > 20 yrs Drug discovery tools, includes reagents Research, and Analytical instruments

Approximately 600 employees Revenue of $160-200M per year Wide portfolio, steady growth mostly by

acquisitions Operate several independent companies worldwide


20

Microplate Reader

5 Detection modalities: Absorbance, Fluorescence intensity, Fluorescence

Polarization (FP), Time-Resolved Fluorescence (TRF), Luminescence


21

Inside a Microplate Reader


22

Predicant Biosciences

Medical Device company- will have to be FDA regulated

Startup - about 3 yrs old IVD products

System that analyzes protein patterns in blood to correlate with disease state.

Approximately 40 employeesNo revenue…yet


23

A “Mechanical” Medical Device


24

Areas that I learned something about after graduation…

Program and Project managementInstruments, device design – Mechanical, fluidics, and opto-mechanicalPlastics, labware and consumables – Co-chair SBS/ANSI Microplate Standards

Quality, Audit, QMS and Regulatory (CE and ISO, too)MEMS and special processes – Member on SEMI Fluid Interface Task force


25

What my Berkeley Education missed!

All data is NOT created EQUAL! How to design “in-tolerance”… and promote

probabilities The problems with diversity and dependencies, DOE

Freedom of choice is great…” as long as it is my choice!”

Write your processes or you’re Left with regulators

Do not create every design… buy the wheel!

Talking and making friends with business


26

What is Art and What is Science?

This stuff is organic… and it really stinks!

What’s the matter with this material? Polymers and the slippery, sticky, and non-linear stuff…

Give Precision to the Scientist, and leave the Accuracy to the Gods...

Lab-On-A-Chip, Microfluids, MEMS, and the uncharted murky nano-waters

Time, Temperature, and Temper of Biological entities large and small.


27

Errors !!!Random or Systematic Deviation from the mean (DFM) is used to

define or distinguish the type

False Negatives: Appearance of a negative value or “No result” when a positive or some value is expected.

False Positives: Appearance of a positive value or result when a negative value is expected.


28

Accuracy is a measure of the result in comparison to the intended or ideal value.

Expressed usually as a percentage bias or measure of deviation from the absolute or ideal. Inaccuracy (%) = [(Va-Vm )/ Vm ] x 100

Precision is a measure of the variability or variance. Usually expressed as percent deviation from the mean, or a % coefficient of variation of the data.Precision (%CV) = [Standard Deviation /(mean)] x100

*

Accuracy & Precision


29

What’s Art and What’s Engineering

Rules of Thumb (ROT) and fundamentals are always helpful, but watch the unexpected in MEMS and living entities

Tiny Mechanical gadgets .. that can do (work) on nothing

Optics Galore – Not just Snell your Beer’s law?

Fluidics… Reynolds and the Junk There will be always a bubble or a leak Carryover, cross contamination… How do you clean this Atto-

mole junk?

CAD-CAM, SLA, RPT and other fine acronyms


30

Common Engineering Issues

Fluid dynamics (not what you learned at your Alta Mater)Material properties (not only Stainless)

Galvanic (ions are everywhere) Polymers AdhesivesSurface Chemistry ( especially when things get smaller and need to be sensitive)Manufacturing and cost issuesPackaging and Sterility


31

Schedules and Projects from Hell ! Get the requirements first, the

specs (speck-less) and agreed on early! Typical project equation = 2t x

2$<spec/2

Watch for Creeping Elegance The many distinct Phases of

Product Development - Three times (min.) is a charm…


32

Responsibilities and Contributors

Phase 0 - R&D and Business DevelopmentPhase 1 – R&D, Marketing, and QAPhase 2 - Engineering, Marketing and R&DPhase 3 - Engineering, Marketing, QA and ManufacturingPhase 4 - Manufacturing, QA/QC, service and sales supportPhase 5 – Operation, QC and Production


33

Product Development Steps


34

Summary High Level Areas

Interaction with Biological matrix and the nature of small and “large living species”

QSR regulatory and FDA – QA is part of Development

Management types: Optimistic (marketing driven) or conservative and inefficient (Scientific and technical driven)

Collaborations, Finance, VC, IP and legal issues

Discipline and focus


35

Conclusions

Biomedical Device Engineering is a true multidisciplinary activityIt is the best “continuous learning” career

Creativity is not bounded by the laws of Physics, but by the laws of Business!

Driven by desire to do products for industry, society’s health and its patients (self interest)


36

Q&A

Contact: [email protected]


37

Supporting slides


38

Startup Medium Medium Transition

Large

Establishing processes

Wearing many hats Innovation Long term security

Choices


39

Target Selection

Lead Identification

Lead Optimization

DiscoveryDevelopment

Target ID (e.g. Protein families as drug targets from Genomics and Proteomics research)

Assay Development Lead Generation and Target Validation (Using small molecules or antibodies from combinatorial synthesis, natural extracts as drug candidates)

Assay Screening

Medicinal Chemistry

In Vivo cell Biology and Animal Medicinal Pharmacology

Clinical Trials

Commercialization

Drug Discovery Process and its functional elements


40

SBS and the Microplate Standards History

First annual meeting held in Philadelphia, Sept. 1995 Working Groups formed to address variety of issues relevant to

its members A group was to address issues where standardization would

improve performance of automation Top on the list of issues was standardizing the 96 well

microplate

In 1998, SBS Board re-opened the standard Email ListServ started in March 1998 First meeting held in Boston in August 1998

The Microplate Standards Development Committee Became an Accredited ANSI Standards Developer in July, 2002

4 Standards submitted and approved by ANSI in Jan 2004

Beeston Engineering Consulting1 An Engineer Dive in the Bio and Medical Devices World Presentation by: Amer El-Hage 11/20/2006.

Documents

engineering education

mechanical engineering

automation slide

summary slide

computer industry

product development

product validation

total employment