Quality systems v3

Quality Systems 101
or
The Most Boring Topic in the World Made Fun and Easy

Ravi Pamnani
BioE 141 Biodesign Capstone
2012 Feb 23

Who am I and what am I doing here?
Background
• Guidant → Boston Scientific → Maquet Cardiovascular
• Eberhard Grube Fellow, 2010-2011
• ExploraMed, Transcend Medical
• By no means an expert – more of a discussion facilitator

Goals
• Not put you to sleep
• “Why” as opposed to “What”
• Hands-on

R. Pamnani Quality Systems v3.pptx 2

Overview
• What is a Quality System?
Why should you care?

• Components of a Quality
System

• Start-ups – What do I really
need to do?

• Pop Quiz

3

R. Pamnani Quality Systems v3.pptx

Quality Systems, in a nutshell

Manufacturers establish and follow quality systems to help ensure
that their products consistently meet applicable requirements and
specifications.

Link to 21 CFR 820

Federal Register Vol 61 No 195 Oct 7 1996 Rules and Regulations
4


A short of history of Quality
1200s European craftsmen formed guilds and developed strict product quality rules
1800s The birth of the factory and the standardization of product inspections
1906 President Roosevelt signs Food and Drugs Act
1920s Shewhart, “processes”, and statistical quality control
1937 Elixir of Sulfanilamide incident
1938 Federal Food, Drug, and Cosmetic Act is passed – first regulation of medical devices
1940s WWII
1950s Deming, Juran, and Japan
1953 The Factory Inspection Amendment
1961 Thalidomide Incident
1962 Kefauver-Harris Amendments – Good Mfg Practices (GMPs) for drugs
1976 Medical Device Amendments – establishment of pre-market registration, cGMPS for devices
1984 Congressional committee investigates deaths related to design of cardiac pacemaker leads
1989 FDA publishes a study on device recalls – 44% attributed to design issues
1990 Safe Medical Devices Act – better reporting, design controls
1997 FDA Modernization Act – the birth of the QSR as we know it today
http://www.gmp-quality.com/FDA_history.html
http://asq.org/learn-about-quality/history-of-quality/overview/overview.html
http://www.mdiconsultants.com/Publishing/article12.htm
http://www.mddionline.com/article/ba-brief-history-fda-good-manufacturing-practicesb


Why does it matter?

• FDA can order a recall
• FDA can shut you down
• DOJ can charge you with
criminal violations
• If done wrong, can slowly
suck the life out of your
company – or worse, hurt
someone
• If done right, can improve
product safety and efficacy

http://biomed.brown.edu/Courses/BI108/BI108_2007_Groups/group05/pages/guidant_stent.html
R. Pamnani

Quality Systems v3.pptx 6

Components of a Quality System

CFR Title 21 Part 820
• Management responsibility • Process validation
• Quality audit • Acceptance activities
• Personnel • Nonconforming product
• Design controls • Corrective and preventive
• Document controls action
• Purchasing controls • Labeling and packaging
• Identification and traceability • Handling
• Production and process , Storage, Distribution, and
controls Installation
• Inspection, measuring, and
test equipment • Records
• Servicing
R. Pamnani
• Statistical Techniques

Management responsibility

• Establish quality policy
• Commit
– Organization
– Authority
– Resources
• Management rep
• Quality system procedures
• Ultimate responsibility


Quality audit

• Not only will FDA audit you –
you have to audit yourself
• Someone unbiased to the
subject matter
– Someone not on your project
– Often a specialized role, if a
large company
– Consultants
• You decide when and how
often (FDA will decide if
you’re being reasonable
when they audit you)


Personnel

• Sufficient, smart people (this is actually in the law)
• Training


Design Controls

• Affects Class II and III (and a few Class I) devices
• “… ensure specified design requirements are met.”

• A framework manufacturers MUST USE when designing
new medical devices
• A lot of flexibility, some best practices
• People usually screw themselves over


Waterfall Process


Design Control Example
• User need
– Catheter guidewire for stroke treatment needs
to be able to enter the lenticulostriate arteries
from the middle cerebral artery (MCA).
• Design input
– Can you quantify this? What “engineering”
requirements would you consider to meet the
user need?
• Design process
– The actual physical, iterative process of design
• Design output and design verification
– How do we check if your design meets your
design input?
• Medical device and design validation?
– How do we check if the device meets the user
need?


Document controls

• Document approval and
distribution Signature requirements for a
• Document changes change to a part, pre-launch
• A great opportunity to: • R&D Eng, Quality Eng, Project
– Hold projects hostage Mgr., Buyer/Ops
– Stonewall
– Delay something you don’t Signature requirements for a
understand
– Use as a substitute for good change to a part, post-launch
communication • R&D Eng, Quality Eng, Supplier
• Really though: Quality Eng, Mfg Eng,
– Hold people accountable Buyer/Ops, Finance, R&D Mgr,
– Make sure you don’t do something
stupid Quality Mgr, Dir. of Ops,
Project Mgr,


Purchasing controls

• Evaluate your suppliers
– How will you control the quality of your supply chain?
– More audits
• Purchasing data
– Quality requirements for suppliers


Identification and traceability
Identification
• Prevent mixups

Traceability
• In case something goes wrong
• Know:
– which components
– which suppliers
– which manufacturing lots
– which days
– which operators
– which processing


Production and process controls

She is building an implantable device.

What’s wrong with this picture?


Inspection, measuring, and test
equipment


Process validation

Electrical resistance of
Strength of spot weld
assembled circuit

vs.


Acceptance activities and non-
conforming product
Acceptance Activities Non-conforming product
• Receiving • Control
• In-process • Review and disposition
• Finished device acceptance
• …
• Records!


Corrective and preventive action

• What you do with all of those audit findings
• Can also come from anywhere
– Product complaints
• Gives you a little bit of breathing room if you accidentally
broke the rules, but you pay later…


Labeling

• Labeling includes:
– Indication statement
– Intended use
– Instructions for use
– Warnings & Precautions
– Storage & Handling
– Traceability info
– Shelf life

• Changes must be cleared
with FDA


Packaging
• Make sure device can safely get
from A to B
• The #1 Project Delayer, in my
experience


Handling , Storage, Distribution, and
Installation
• Mixups, damage, deterio
ration, contamination, o
r other adverse effects


Records

• Keep records of EVERYTHING
– As long as the device is
being sold
– Device Master Record (DMR)
– Device History Record (DHR)
– Quality system records
(SOPs, Training
records, everything)
• Complaint files
– Very specific requirements
– Must report the really bad
ones to FDA


Servicing
• For capital equipment, document servicing procedures
• Servicing is a selling point, and often a revenue driver

Intuitive Surgical’s remote monitoring and servicing of the da Vinci

http://www.intuitivesurgical.com/support/onsite.html


Statistical techniques

• Statistical rationales for test
sample sizes
• Often based on risk level
• Up to you to determine and
justify what is appropriate…
just like everything else


Start-ups: What do you do?

Entire quality system at a local start-up


When do the QSRs apply?

QSR starts
“RESEARCH” here “ENGINEERING”


Clinical / Regulatory implications

• Are you preparing for a clinical trial?
• Are you preparing for investigational device
exemption application?
• Are you preparing for GLP animal studies that will
eventually be part of a regulatory submission?
• Are you developing the device design that will
eventually be used above?
• Are you doing an animal study as a proof-of-
concept / feasibility test?
• Are you cobbling together things you bought from
Walgreen’s to test on each other?


Planning ahead

• Where will you make devices that will be for human use?
• You can use contract manufacturing facilities for early
growth – but you are still the finished good
manufacturer, according to FDA!
• The laws are flexible – but justify any decisions or
exemptions you make for yourself
• What kind of equipment are you using to
build, measure, test devices? Why didn’t you calibrate
that ruler?
• Risky devices will need larger investment up front
• Non-significant risk devices can find simpler ways to
show safety


Scaleability: Think about it, but don’t
let it slow you down
SOP SOP SOP SOP
SOP
SOP
SOP SOP SOP SOP
SOP SOP
SOP
SOP
SOP SOP SOP SOP
SOP SOP
SOP SOP
SOP SOP SOP SOP
SOP SOP
SOP
SOP SOP SOP
SOP SOP
SOP SOP
SOP SOP
SOP SOP SOP SOP
SOP SOP
SOP
SOP SOP SOP SOP SOP
SOP SOP
SOP SOP SOP
SOP SOP
SOP
32


Pop quiz
• Ancure device, used for abdominal aortic aneurysms (AAA)


Pop quiz
• Guidant received approval for Ancure device and began selling it
• Implanted device designd well
• Catheter, on the other hand, not so much
• Catheter would become lodged and could not be removed by
conventional means
– Extensive surgery would be required to remove the device
• Guidant still sold it; advised “handle-breaking technique” to remove
catheter
• Of 7,632 devices shipped, there were close to 3,000 injuries, including
12 deaths and 57 conversions to traditional open surgical repair
– 34% failure rate
– Mortality rate of 0.2% (interestingly, compare with surgical mortality rate of
3.5% at the time)
• Guidant submitted only 172 reports to FDA during this period
• Did Guidant break the law?
http://biomed.brown.edu/Courses/BI108/BI108_2007_Groups/group05/pages/guidant_stent.html


Pop quiz
"Guidant's EVT division violated
the fundamental trust that
exists between the medical
device
industry, doctors, patients, and
the public at large. Because of
the company's
conduct, thousands of patients
underwent surgeries without
knowing the risks they
faced, and their doctors -
through no fault of their own -
were unprepared to deal with
those risks. These actions were
criminal, and I am happy to say
that today, for the first time in
more than three years, the
public will be able to learn the
truth."

Recall Exercise


Recall Exercise

CFR Title 21 Part 820
• Management responsibility • Process validation
• Quality audit • Acceptance activities
• Personnel • Nonconforming product
• Design controls • Corrective and preventive
• Document controls action
• Purchasing controls • Labeling and packaging
• Identification and traceability • Handling
• Production and process , Storage, Distribution, and
controls Installation
• Inspection, measuring, and
test equipment • Records
• Servicing
R. Pamnani
• Statistical Techniques

Quality systems v3

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