RTI InternationalRTRP Informatics

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications July 12th, 2006
Software Solutions for Critical Applications. TM
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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Agenda July 12th, 2006
• 800 805 Introductions Food
• 805 820 Presentation Overview
• Regulated Applications
• The Food and Drug Administration
• Medical Devices Software
• 820 840 Developing Safe Software for
  Regulated Industries
• Medical Devices vs. Consumer Products
• So you want to sell your device to a Big
  Company?
• Design Controls
• Software Development Life Cycles
• 840 900 Regulatory Affairs for Device
  Submissions
• 900 915 Automated Sampling Pooling System
  for Blood Banks
• 915 930 QA

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Introductions and Food
• Meeting Moderators
• John Geikler, RTI International, Informatics
  Cluster
• Scott Mladsi, RTI International, Advanced
  Healthcare Cluster
• Matt Harris, RTI International, Cluster Meeting
  Coordinator
• Presenters
• Samir Dandekar, Director of Business Development,
  Code Refinery
• Greg Godlevski, Director of Software Development,
  Code Refinery
• Mike Brown, Director of Operations, Code Refinery
• Tammy Carrea, Director of Regulatory Affairs,
  Sicel Technologies

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Presentation Focus
• Industries that are regulated by the Food and
  Drug Administration where software development
  and computerized systems are subject to the
  medical device Quality System regulation.
• Regulated Applications
• Definition of regulated
• The American Heritage Dictionary
• regulate (v.) To control or direct according to
  rule, principle, or law.
• regulate (v.) To adjust to a particular
  specification or requirement regulate
  temperature.
• regulate (v.) To adjust (a mechanism) for
  accurate and proper functioning
• regulate (v.) To put or maintain in order
  regulate one's eating habits.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Food and Drug Administration (FDA)
• Who is the FDA?
• Agency within the Department of Health and Human
  Services
• Regulates a host of products - From the most
  common food ingredients to complex medical,
  surgical devices, lifesaving drugs, and
  radiation-emitting products
• These products are worth about a trillion dollars
  a year and make up 25 of all consumer spending.
• Agencys nearly 10,000 employees are scientists,
  consumer safety officers, medical officers, and
  other professionals.
• FDAs budget is 1.6 billion a year, or about 4
  a year per taxpayer.
• FDA is the oldest consumer protection agency and
  in 2006 is the 100 year anniversary of its
  founding law, the 1906 Pure Food and Drugs Act.
• FDAs Mission Statement
• The FDA is responsible for protecting the public
  health by assuring the safety, efficacy, and
  security of human and veterinary drugs,
  biological products, medical devices, our
  nations food supply, cosmetics, and products
  that emit radiation.
• The FDA is also responsible for advancing the
  public health by helping to speed innovations
  that make medicines and foods more effective,
  safer, and more affordable and helping the
  public get the accurate, science-based
  information they need to use medicines and foods
  to improve their health.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications
What IS regulated by the FDA?

• Medical Devices
• premarket approval of new devices
• manufacturing and performance standards
• tracking reports of device malfunctioning and
  serious adverse reactions
• Radiation-Emitting Electronic Products
• radiation safety performance standards for
  microwave ovens, television receivers, diagnostic
  
• x-ray equipment, cabinet x-ray systems (such as
  baggage x-rays at airports), laser products,
• ultrasonic therapy equipment, mercury vapor
  lamps, and sunlamps
• accrediting and inspecting mammography facilities
  
• Veterinary Products
• livestock feeds
• pet foods
• veterinary drugs and devices

• Biologics
• product and manufacturing establishment licensing
  
• safety of the nation's blood supply
• research to establish product standards and
  develop improved testing methods
• Cosmetics
• safety
• labeling
• Drugs
• product approvals
• OTC and prescription drug labeling
• drug manufacturing standards
• Foods
• labeling
• safety of all food products (except meat and
  poultry)
• bottled water

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• FDA Centers
• Center for Biologics Evaluation and Research
  (CBER)
• Center for Devices and Radiological Health (CDRH)
• Center for Drug Evaluation and Research (CDER)
• Center for Food Safety and Applied Nutrition
  (CFSAN)
• Center for Veterinary Medicine (CVM)
• National Center for Toxicological Research (NCTR)
• Office of the Commissioner (OC)
• Office of Regulatory Affairs (ORA)

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications
Medical Devices

• Simple tongue depressors and bedpans to complex
  programmable pacemakers with micro-chip
  technology and laser surgical devices
• In vitro diagnostic products, such as general
  purpose lab equipment, reagents, and test kits,
  which may include monoclonal antibody technology.
• FDAs Definition of a Medical Device
• If a product is labeled, promoted or used in a
  manner that meets the following definition in
  section 201(h) of the Federal Food Drug
  Cosmetic (FDC) Act it will be regulated by the
  Food and Drug Administration (FDA) as a medical
  device and is subject to pre-marketing and
  post-marketing regulatory controls.
• FDC Act Section 201 (h)
• The term "device" (except when used in paragraph
  (n) of this section and in sections 301(i),
  403(f), 502(c), and 602(c)) means an instrument,
  apparatus, implement, machine, contrivance,
  implant, in vitro reagent, or other similar or
  related article, including any component, part,
  or accessory, which is
• Recognized in the official National Formulary, or
  the United States Pharmacopeia, or any supplement
  to them,
• Intended for use in the diagnosis of disease or
  other conditions, or in the cure, mitigation,
  treatment, or prevention of disease, in man or
  other animals, or
• Intended to affect the structure or any function
  of the body of man or other animals, and which
  does not achieve its primary intended purposes
  through chemical action within or on the body of
  man or other animals and which is not dependent
  upon being metabolized for the achievement of its
  primary intended purposes.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications
Medical Device Health Law Milestones

• Medical Device Amendments, 1976
• Required all devices to be classified into one
  of three device classes based on extent of
  controls necessary to provide necessary
  assurances of safety and effectiveness.
• Safe Medical Device Act, 1990
• Required reporting of any medical device causing
  or contributing to the death, serious illness or
  injury of a patient as well as post-market
  surveillance of implanted devices.
• FDA Modernization Act, 1997
• Established framework for efficient premarket
  review. Changed device tracking, reporting,
  PMAs, 510 (k)s and required FDA to identify
  recognized standards and institute new approaches
  to labeling claims and intended uses.
• Medical Device Fee and Modernization Act, 2002
• Allowed FDA to collect fees to review medical
  device submissions.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications
Medical Device Classifications

• Class I General Controls
• Subject to least regulatory control
• Minimal potential for harm to user
• Examples Elastic bandages, examination gloves,
  tongue
• Class II Special Controls
• General controls alone are insufficient to assure
  safety and effectiveness
• Special controls may include special labeling
  requirements, mandatory performance standards
  postmarket survellance.
• Existing methods are available to assure safety
  and effectiveness
• Examples Powered wheelchairs, infusion pumps,
  surgical drapes
• Class III Premarket Approval
• Most stringent category
• Insufficient information exists to assure safety
  and effectiveness through General or Special
  controls
• Usually support or sustain human life, or
  substantial importance in preventing impairment
  of human health.
• Examples Replacement heart valves, implantable
  pacemaker pulse generators, implanted cerebella
  stimulators.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications
Software Device, Component, Accessory

• FDAs Definition of Types of Software
• Software (ANSI) Programs, procedures, rules and
  any associated documentation pertaining to the
  operation of a system.
• Application Software (IEEE) Designed to fill
  the specific needs of a user.
• Operating System (ISO) Software that controls
  the execution of programs and that provides
  services such as resource allocation, scheduling,
  input/output control and data management.
• System Software (ISO) Application independent
  software that supports the running of application
  software. (IEEE) Software designed to facilitate
  the operation and maintenance of a computer
  system and its associated programs.
• FDAs Definition of Medical Device Software
• Used as a component, part or accessory of a
  medical device
• Standalone software considered a medical device
  (e.g., blood establishment software, records
  medical information for later recall analysis,
  designed to assist in the clinical diagnosis of a
  patient).
• Used in the production of a device (e.g., PLCs
  used in manufacturing, automation equipment).
• Used in the implementation of the device
  manufacturer's quality system (e.g., software
  that records and maintains the device history
  records)
• Key difference for Medical Device Software
  SAFETY.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Developing Safe Software for Regulated Industries
• Medical Devices vs. Consumer Products
• So you want to sell your device to a Big
  Company?
• Design Controls

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Developing Medical Devices vs. Consumer Products
• Similarities
• Identifying a market need
• Developing specifications
• Building prototypes
• Building devices
• Testing
• Selling

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Developing Medical Devices vs. Consumer Products
• Differences for a medical device
• Requires a quality system to support development.
• Requires a design control system to guide
  development.
• Requires detailed traceability between
  development steps.
• Requires formally addressing risk.
• Requires pre-approval by the government before
  selling.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Most Common Mistakes
• Waiting too long to treat the idea as a medical
  device
• Focusing the requirements effort on a component
  rather than the system
• Treating risk management as an after thought
• Underestimating testing effort
• Failing to adhere to procedures
• Lack of management commitment
• Bending to time pressures
• Lack of oversight

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• What does it take to be a Medical Device
  Manufacturer?
• A lot of procedures, people, and money
• Quality System Regulations

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• So you want to sell your Device to a Big
  Company?
• Minimum Set of Supporting Systems
• Document control system
• Version control system
• Change control system
• Training system
• System SOP and maybe a software program
• Why? Due Diligence.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Design Controls 21 CFR 820.30
• Design and development planning
• Design input
• Design output
• Design review
• Design verification
• Design validation
• Design transfer
• Design changes
• Design history file
• Each manufacturer shall establish and maintain
  procedures to

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Software Development Life Cycle

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Blood Bank Software Application
• Lessons Learned
• If the behavior of the system, when it performed
  without error, was all that must be specified and
  tested, then life would be easy.
• In the case of a successful medical device, the
  vast majority of the design, specification,
  development and testing resources will be
  spent handling error conditions.
• One of the best tools to identify those error
  conditions is the risk analysis.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Overview of Typical Blood Bank Applications
• Runs in Windows.
• Controls an automated pipettor.
• Pools samples or runs an assay.
• Replace a general-use application with one
  specifically designed for the intended
  environment, operator, and use.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Software Requirement Specification
• Unreadable Tube Barcode ID
• For each rack position which contains a tube
  without a readable barcode ID, an error message
  shall be displayed along with the grid position
  and rack position where the error occurred. 
• The error message shall provide the operator the
  option to rescan the tube position. 
• The error message shall provide the operator the
  option to ignore the tube position. 
• The error message shall provide the operator the
  option to execute the manual entry function. 
• If a barcode ID is successfully entered then the
  application shall use the returned barcode value
  as if it was read from the tube. 
• The message and its resolution shall be recorded
  in the Session Log.

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Test Case Specification
• This script tests the Unreadable Tube Barcode ID
  during the scan-only sequence of two pool sets.
  Testing includes
• Verification that when the system reports that a
  tube barcode ID cannot be determined because the
  barcode cannot be read, the Unreadable Tube
  Barcode ID error message is displayed and logged
  appropriately.
• Verification that selecting Retry from the error
  message causes the system to reread the tube
  barcode.
• Verification that scanning continues from the
  point at which the error was detected if the
  barcode was successfully reread.
• Verification that selecting Ignore from the error
  message causes only the unreadable tube to be
  ignored.
• Verification that selecting Manual Entry from the
  error message causes the Barcode ID Data dialog
  box to be displayed.
• Verification that, if the barcode ID is
  successfully entered manually, the returned
  barcode value is used as if it was read from the
  tube.
• Verification that, if the barcode ID is
  successfully entered manually, the sequence
  continues from the point at which the error was
  first detected.
• Verification that only Codabar and Code 128
  barcode types are accepted. 

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Traceability Matrices
• Upward Traceability
• Downward Traceability

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Test Script

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Risk Analysis

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• References
• Guidance for the Content of Premarket Submissions
  for Software Contained in Medical Devices, FDA,
  May, 2005
• General Principles of Software Validation Final
  Guidance for Industry and Staff, FDA, January,
  2002
• Guidance for Off-The-Shelf Software Use in
  Medical Devices, FDA, September, 1999
• Glossary of Computerized System and Software
  Development Terminology, FDA, http//www.fda.gov/o
  ra/inspect_ref/igs/gloss.html

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RTI International/RTRP Informatics Advanced
Healthcare Cluster Meeting
Developing Systems for Highly Regulated
Applications

• Thank You!

Software Solutions for Critical Applications. TM
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