BIOE 4420 – Senior Design

BIOE 4420 – Senior Design Pre-Market Testing and Validation K. Lang A. Pinkie 18 Feb 2014

Overview • Verification and Validation • Standard Testing • Testing Equipment • Biocompatibility Testing • Software Verification and Validation • Drug Development • Clinical Trials

Verification and Validation • Verification Ensures design outputs = design inputs • Validation Ensures user needs are met • Specific tests depend on the function of the device

Verification and Validation Test Method Commonalities • The verification process requires a stable and defined life cycle. • To create a cohesive and efficient verification and validation effort, a definition of the “cradle to grave” development of the software must be produced. • Setbacks should be handled but should not change the defined process unless absolutely necessary, otherwise inconsistency will place doubt in the users and erodes your confidence in the process. • Validation requires that verification is working.

Verification and Validation Test Method Commonalities • Creating an efficient verification and validation organization is done by producing salient results during the validation effort and permeating a common test approach. • Perform a survey of each product line and test equipment that the verification and validation group will support. • Implement a Common Test Set with a suit of static and dynamic test tools to run on the products and equipment using verification and validation.

Techniques, Methodologies and test approach Test approaches should be selected based on categorization of the life cycle of the product/equipment. • Full development life cycle – • Is applied when new products = high level of concern. • Accelerated enhancement development life cycle – • If the product is based on existing products then majority of the faults are already taken care of.

Techniques, Methodologies and test approach The test approach to any product/equipment should be a combination of requirements testing and safety testing. • Requirements testing: • Consists of development efforts that include a production of requirements design specifications. • Safety testing: • Validation in the focus consists of preventing harm to the user. • hazard analysis – i.e. medical products • surveying of the environment

Verification and Validation Reporting • Test documentation that is generated for a particular product/equipment also depends on life cycle and level of concern. • The verification and validation report summarizes the results of verification and validation activity. • The reports should contain: • Purpose • Scope • Background • Worst case rationale • References • Definitions • Responsibilities • Materials • Equipment • Deviations • Including justifications for any deviations • Results • Discussion • Acceptance Criteria • Conclusion • Appendices (as necessary)

Standard Testing • Standard tests are conducted at room temperature with no acceleration of any parameters. • Examples include: • Cycle testing • Typical use testing • 10 x 10 testing

Standard Testing Cycle Testing • Conducts tests on individual components • Passing the state of operation and non-operation of a component or device. • Example: A power supply could be cycled on for 8 hours and off for 16 hours.

Standard Testing Typical Use Testing • Testing the device as it will be operated in its typical environment • Helps show product reliability • Also used to calculate a long-term mean time between failures value (product lifetime)

Standard Testing 10 x 10 Testing • Ten samples tested for a particular parameter, ten different times. • The mean and standard deviation values are then calculated for each of the ten recordings and ten units.

Testing Equipment • Instron/MTS • Mechanical or hydraulic testing machines • Tensile • Tear • Shear • Compression • Peel • Flexure • Scales/calipers • Length • Diameter • Width • HALT Chamber • Accelerated Aging

Biocompatibility Testing • For devices which are to come in contact with the body “Biocompatibility is the capability of a material implanted in the body to exist in harmony with tissue without causing deleterious changes”

Software Verification & Validation Software verification and validation must be performed when the quality or effectiveness of the product cannot be adequately tested or evaluated in the final product • Ex: design testing through FEA • Software verification is performed during product development to make sure that the development process, methodology and design have been met. • Software developed according to procedure • Software validation is the end activity to development and demonstrates that the software satisfies its goals. • Product and software requirements satisfied

Software Verification & Validation • Testing final products is no longer adequate, one must assure quality during the design and development phase • Verification and Validation • Maximize assurance of quality • Minimize testing necessary

Medical Product Software Development • In order to satisfy the requirements of regulatory agencies, international communities, and corporate commitments, an effective systematic approach to medical product software is necessary. • A software quality assurance program will minimize redundancy, assure access to information and integrate information.

Steps of Software Testing • Software Designers should: • Record design activities and store resultant design • Generate tests to specify the testing to be conducted to validate the design • The tests should target: • Integrated software components • Interfaces between integrated tasks/functions • Path testing between tasks/functions

Steps of Software Testing • Design given to programmers to generate the code and create the tests. Results are reviewed, signed, and archived according to GDP • Test priority: • Safety • Reliability • Effectiveness or performance • Any other relevant criteria

Software Testing Process

Validation and Test Overview • Medical companies are faced with validating both products and test/manufacturing equipment. • Phases of Software Development • Code and Test – development of the code and debugging the implemented code by the software developers. • Integrate and Test – integration of the software components and the testing of the integrated parts. • Software System Testing – verification and validation testing that is performed by the engineers on the fully integrated software and hardware.

Edward Kit • Edward Kit is founder and president of Software Development Technologies (SDT). • He is well known as an industry leader, test expert, author, and keynote speaker at testing conferences. • His best-selling book, Software Testing in the Real World: Improving the Process, has been adopted as a standard by companies around the world such as Sun Microsystems, Exxon, Chase Manhattan Bank and Cadence Design Systems.

Edward Kit’s Six Essentials for Software Testing • The quality of the test process determines the success of the test effort. • Prevent defect migration by using early life-cycle testing techniques. • The time for software tools is NOW! • A real person must take responsibility for improving the test process. • Testing is a professional discipline requiring trained, skilled people. • Cultivate a positive team attitude of creative destruction.

Drug Development Drugs are created in one of three ways: • Trial and error • Computer modeling of the chemical structure • Acquiring/testing unusual fungi, viruses, and molds. • After a drug has made it past test tube stages, tests are done on two relevant animal models. • Primarily rats, mice and other rodents are used.

Drug Development Testing facility must follow government regulations for good laboratory practice in order to run properly and for accurate results For example: • animal care and testing procedures • test and reporting procedures • requirement for quality assurance

Drug Development Clinical Trial • If effective in animal studies, the FDA can approve a drug to move to clinical trials • A committee of medical and lay personnel study the proposed drug’s test and protocol. • Committee approval allows for Phase 1 clinical trials to begin

Drug Development Clinical Trial • Phase 1 of a clinical trial involves 20-100 people, typically healthy volunteers or patients. • This phase is designed to assess the drug for acute adverse effects and examine the size of doses that patients can take safely without a high incidence of side effects. • Phase 1 lasts a few months • ~70% of drugs pass this first test. • Phase 2 of a clinical trial tests several hundred patients to determine short term safety and effectiveness. • Phase 2 takes months to years to perform • ~ 50% of the drugs fail here.

Drug Development Clinical Trial • Phase 3 tests the drug on several thousand patients with primary questions about drug safety, dosage, and effectiveness are being addressed. • Large samples are usually performed in order to obtain good statistics which will be used in the literature that accompanies the prescription. • About 60-70% of drugs pass this phase. • After phase 3, the FDA is petitioned for a new drug approval. • Which takes an additional two years. • Phase 4 investigates the continued efficacy and long term effects of the drug in use.

Thank You Presented by: Kacie Lang Alex Pinkie

BIOE 4420 – Senior Design