Premarket Testing and Validation

1. Premarket Testing and Validation Alena Barga Chase Maag Ashley Muszynski Nick Oblizajek

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

3. Verification and Validation • Verification  Checking to make sure design outputs=inputs • Validation  Checking to make sure user needs are met • Specific tests depend on the function of the device

4. Standard Testing • Standard tests are conducted at room temperature with no acceleration of any parameters. • There are several types of tests such as cycle testing, typical use testing, and 10 x 10 testing.

5. Standard Testing • Cycle testing is conducting tests on individual components. • Or it could consist of passing the state of operation and non-operation of a component or device. • An example being a power supply could be cycled on for 8 hours and off for 16 hours.

6. Standard Testing • Typical use testing is testing the device as it will be operated in its typical environment. • This testing can help show reliability. • It can also be used to calculate a long term mean time between failures value.

7. Standard Testing • 10 x 10 testing: There are ten samples that tested for a particular parameter at ten different times. • The mean and standard deviation values are then calculated for each of the ten recordings and ten units.

8. Standard Testing 10 x 10 testing The horizontal rows of data show the repeatability of the results. The vertical columns of data show the variability among the units measured.

9. Common Testing Equipment • Instron • Tensile, tear, shear, compression, peel and flexure testing • Scales/calipers • Length, diameter, width • HALT Chamber • Accelerated Aging

10. Biocompatibility • For devices in contact with the body, biocompatibility testing must be conducted.

11. Software Verification & Validation • Evidence needs to be collected to demonstrate that the process and products have met specifications. • Done by use of software. • Software verification is performed during product development to make sure that the development process, methodology and design have been met. • Software validation is the end activity to development and demonstrates that the software satisfies its goals.

12. 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. • Design Testing through FEA • In summation, software verification is roughly assuring that the software was developed according to a documented process, and validation assures that the product and software requirements were satisfied.

13. Software Verification & Validation • Testing final products for compliance according to regulations is no longer adequate in assuring the quality of the product. • Assuring the quality of the product during the design and development phase is a must. • Verification and Validation should be designed to maximize the assurance of quality, however, verification and validation should try to minimize testing necessary.

14. 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.

15. Allocation of Software Testing • In order to achieve consistent and sufficient software test coverage, the software designers should record their design activities and store the resultant design. The designers should also generate tests that will specify the testing to be conducted to validate the design. • The tests should target integrated software components, interfaces between the integrated tasks/functions and path testing between various tasks/functions.

16. Allocation of Software Testing • The design is then given to programmers who generate the code and make tests for the code. • The tests for the code should be prioritized by safety, reliability, effectiveness or performance, and then any other relevant criteria. • After the code has been created, the formal testing can begin. The tests will be based on the tests created from the programmers and designers, and the results will be reviewed for adequacy, completeness and coverage. Then signed and archived.

17. Software Testing Process

18. Verification and Validation Test Method Commonality • 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.

19. Verification and Validation Test Method Commonality • 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 software 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 software verification and validation.

20. 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.

21. Techniques, methodologies and test approach Test approaches should be selected based on categorization of the life cycle of the product/equipment. • Full software 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.

22. 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

23. 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 summary contains: • Description of tasks performed • Number of cycles • Summary of task results • Summary of errors and their resolutions • Description and location • Impact • Criticality • Rational for resolution • Results of re-test • Assessment of the software reliability

24. 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.

25. 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.

26. 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.

27. Drug Development • The structure and function of the testing facility doing the research must follow government regulations for good laboratory practice. • For example: • animal care and testing procedures, • test and reporting procedures, • requirement for quality assurance. • This helps assure that the laboratories are run properly and the results of the activities are correctly documented.

28. Clinical Trials • If a drug has been proven to be effective on animal models, the test of the drug may proceed to clinical trials if the FDA believes that the testing has shown potential value for the disease under study. • Before the testing process begins, a committee of medical and lay personnel study the proposed drug’s test and protocol. • Once the committee approves the drug for testing, phase 1 of clinical trials starts.

29. Clinical Trials • 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.

30. ClinicalTrials • 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.

31. Questions?