1. 1. Medical Device Design & Development Presented by : Pankaj Bhatia Head Quality Mechanical Engineer IIT Roorkee MBA Operations Amity University Lead Auditor : ISO13485 & ISO9001 Certified for 21 CFR 820, 21 CFR part 11, ISO14971, IEC 62304 Six Sigma Green Belt
2. 2. Agenda Definitions Drug Vs. Device design Importance of design controls Elements of design controls Planning Inputs Outputs Review Verification Validation Transfer Changes History file Inspection & audit of D&D process Things to remember Further reading/ Reference material Questions
3. 3. Definitions Medical device (ISO13495 SEC 3.5) any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of diagnosis, prevention, monitoring, treatment or alleviation of disease, diagnosis, monitoring, treatment, alleviation of or compensation for an injury, investigation, replacement, modification, or support of the anatomy or of a physiological process, supporting or sustaining life, control of conception, disinfection of medical devices, providing information for medical purposes by means of in vitro examination of specimens derived from the human body, and which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means. NOTE This definition has been developed by the Global Harmonization Task Force (GHTF). See bibliographic reference [15].
4. 4. Definitions Medical Device ( as per Proposed The Drugs & Cosmetics (Amendment) Bill, 2013 ) (i) any instrument, apparatus, appliance, implant, material or other article, whether used alone or in combination, including the software, intended by its manufacturer to be used specially for human beings or animals for one or more of the specific purposes of, (A) diagnosis, prevention, monitoring, treatment or alleviation of any disease or disorder; (B) diagnosis, monitoring, treatment, alleviation of, or assistance for, any injury or handicap; (C) investigation, replacement or modification or support of the anatomy or of a physiological process; (D) supporting or sustaining life; (E) disinfection of medical devices; (F) control of conception, and which does not achieve its primary intended action in or on the human body or animals by any pharmacological or immunological or metabolic means, but which may be assisted in its intended function by such means; (ii) an accessory to such an instrument, apparatus, appliance, material or other article; (iii) a device which is reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment or system whether used alone or in combination thereof intended to be used for examination and providing information for medical or diagnostic purposes by means of in vitro examination of specimens derived from the human body or animals; (iv) any new medical device;
5. 5. Drug Vs. Device Design Many devices are first designed and developed as tools to accomplish a task that is already established practice. Intended patient population and anticipated effects of the device are known / understood beforehand. This is in contrast to the drug development process, in which a new molecular entity may be identified prior to the identification of any of its potential clinical applications. For devices developed as tools, Regulatory evaluation may most appropriately focus on assessing the ability of the device to perform its intended function safely and effectively. Use of a new device may be challenging for the practitioner. Patient selection may also prove challenging. Therefore, developing instructions for use(IFU) and physician training are critical to the safe and effective use of a novel device. This is in contrast to drug development and evaluation. Whether in the clinical trial setting or in practice, relatively few drugs require extensive clinician training in methods of administering the drug. Clinical trials for devices include evaluation of the delivery technique and of physician training.
6. 6. Drug Vs. Device Design Complex Medical Device Small-Molecule Compound Physical, engineering-based object or components Chemical formulation Direct mechanism of action and, usually, readily apparent, near-term response Indirect biochemical mechanism of action via blood, other body fluids, or tissue diffusion Site- or organ-specific therapy Usually systemic treatment Patient responses to therapy generally similar and not dependent on dose response Patient responses variable (benefits and adverse effects) and dose dependent High initial product costs amortized over service life Costs for product accumulate over the course of treatment Application often requires professional expertise (e.g., surgical implantation); patient use might involve complex instructions Application or use is often simple and patient controlled (e.g., taking a pill) Continuing product refinement and short product life cycle that may improve effectiveness and reduce costs Product (basic molecule) not modified, long product life cycle Moderate to high development cost High development cost Few basic patents, many incremental patents Basic patent, fewer incremental patents or products SOURCES: Adapted from Linehan et al., 2007; Citron, 2008; see also Feigal et al., 2003.
7. 7. Importance of Design Controls FDA found that approximately 50% of the quality problems that led to voluntary recall actions during 2003 ~ 2010 period were attributed to errors or deficiencies that were designed into particular devices and may have been prevented by adequate design controls.
8. 8. Importance of Design Controls FDA had issued 89 warning letters to medical Device companies for QS/GMP deficiencies in 2010. QS Subsystem # WL %age WL CAPA 81 91 Production & process controls 69 78 Design controls 49 55 Management controls 43 48 Documents controls 33 37 Source : http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHTransparency/UCM256354.pdf
9. 9. Importance of Design Controls YEAR # WLs $WL with DC %age 2010 89 49 55 2009 77 36 47 2008 98 54 55 2007 74 42 57 2006 79 47 60 2005 97 49 51 2004 113 57 50 2003 69 39 57 Source : http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHTransparency/UCM256354.pdf
10. 10. Importance of Design Controls Most Frequent Quality Systems Warning letters Cites 2010 Ref Details No 21 CFR 820 198(a) Complaints 42 21 CFR 820 100(a) CAPA 30 21 CFR 820 75(a) Process Validation 28 21 CFR 820 22 Quality Audit 26 21 CFR 820 184 Device History File 21 21 CFR 820 20(c) Management Review 19 21 CFR 820 30(i) Design Changes 18 21 CFR 820 90(a) NCEP 18 21 CFR 820 30(g) Design Validation 17 21 CFR 820 50 Purchasing 17 Source : http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHTransparency/UCM256354.pdf
11. 11. Importance of Design Controls ISO13485 Similar elements to 21CFR820.30 ISO13485 Section 7.3 Design & Development Design & development planning Design & development inputs Design & development outputs Design & development review Design & development verification Design & development validation Design & development changes
12. 12. Design & Development Planning 7.3.1 Design and development planning The organization shall establish documented procedures for design and development. The organization shall plan and control the design and development of product. During the design and development planning, the organization shall determine a) the design & development stages b) the review, verification, validation and design transfer activities (see note) that are appropriate at each design and development stage, and c) the responsibilities and authorities for design and development. The organization shall manage the interfaces between different groups involved in design and development to ensure effective communication and clear assignment of responsibility. Planning output shall be documented, and updated as appropriate, as the design and development progresses ( see 4.2.3) NOTE Design transfer activities during the design and development process ensure that design and development outputs are verified as suitable for manufacturing before becoming final production specifications.
13. 13. Design & Development Planning Product concept is usually outlined in a set of marketing requirements and included the wish list for device features and functionality Is there a market opportunity for the device ? Where will the new device be used and who will use it? How will the new device be used? How long will the new device be used? Once the project moves forward, a project plan is drawn up to guide and control design & development of the device Implementation of design controls is initiated.
14. 14. Design & Development Planning Elements include: Major tasks Deliverables Responsible individuals , including interfaces with suppliers, contractors Resources Project timelines, milestones Major reviews and decision points Review items Design documentation Planning method Flow diagram Spreadsheet Gantt chart
15. 15. Design Inputs 7.3.3 Design & Development Inputs Inputs relating to product requirements shall be determined and records maintained (see 4.2.4). These inputs shall include a) Functional, performance and safety requirements, according to the intended use, b) Applicable statutory and regulatory requirements, c) Where applicable, information derived from previous similar designs, d) Other requirements essential for design and development, and e) Output(s) of risk management (see 7.1) These inputs shall be reviewed for adequacy and approved. Requirements shall be complete, unambiguous and not in conflict with each other.
16. 16. Design Inputs Are the starting point for product design Categories: Functional requirements specify what the device does. operational capabilities Performance requirements specify how much or how will the device must perform. Addressing speed, strength, response time, accuracy, limits of operation includes device reliability and safety requirements. Interface requirements specify characteristics critical to compatibility with external systems, outside the control of the developers.
17. 17. Design Inputs Types of Design Inputs Intended use User Needs Physical/Chemical Characteristics Performance characteristics Safety Reliability Environmental limits User interfaces Regulatory requirements Labelling Human factors Maintenance Compatibility with other devices Sterilization Energy sources Toxicity and biocompatibility
18. 18. Design Inputs Sources of Design inputs Customer input through focus groups, surveys etc. Comparison testing of competitor product or other benchmarking activities Review of similar product histories to include production data for scrap, rework , testing Review of complaints , MDRs, FDA enforcement reports, recall of earlier generations of the product. Performance requirements stipulated by the regulators , voluntary standards or other regulatory agencies. Literature review Input from cross-functional teams ( R&D, Quality, Regulatory, Marketing, Sales, Manufacturing, Servicing etc.)
19. 19. Design Outputs 7.3.3 Design and development outputs The outputs of design and development shall be provided in a form that enables verification against the design and development input and shall be approved prior to release. Design and development outputs shall a) Meet the input requirements for design and development, b) Provide appropriate information for purchasing, production and for service provisions, c) Contain or reference product acceptance criteria, and d) Specify the characteristics of the product that are essential for its safe and proper use. Records of the design and development outputs shall be maintained ( see 4.2.4) NOTE Records of the design and development outputs can include specifications, manufacturing procedures, engineering drawings, and engineering or research logbooks.
20. 20. Design Outputs Results of a design effort at each design phase and at the end of the total design effort. Forms basis for the device master record. Consists of the device, its packaging and labelling, and the device master record. drawings, production and quality assurance specifications and procedures. Procurement specifications used to procure components, fabricate, inspect, install, maintain and service the device. Flow charts Software codes Procedures Work Instructions Risk Management File Acceptance criteria Other materials that are necessary for establishing conformance : Biocompatibility test results Bio-burden test results
21. 21. Design Review 7.3.4 Design and development review at suitable stages, systematic reviews of design and development shall be performed in accordance with planned arrangements ( see7.3.1) a) to evaluate the ability of the results of design and development to meet requirements, and b) to identify any problems and propose necessary actions. Participants in such reviews shall include representatives of functions concerned with the design and development stage(s) begin reviewed, as well as other specialist personnel ( see5.5.1 and 6.2.1) Records of the results of the reviewed and any necessary actions shall be maintained. (see 4.2.4)
22. 22. Design Review Consideration for design review Formal process to evaluate design, resolve concerns and implementation of corrective actions Required for phase approval Formal review prior to release for manufacturing and distribution Determine frequency of review and design phases Responsibility and authority for decision-making Cross functional team involvement including manufacturing, sales, marketing, regulatory, quality, major suppliers Competency of reviewer(s) in terms of background and experience Controlling documentation and record keeping
23. 23. Design Review How to conduct the review Internal focus Feasibility of design Produce ability of design Service and Installation capabilities External Focus Evaluate the Adequacy of the Design requirements Evaluate the capability of the design to meet the Design requirements Identify potential problems and solutions Independent and objective review Bring all functions together to use collective wisdom Resolution of concerns
24. 24. Design Verification 7.3.5 Design and development verification Verification shall be performed in accordance with planned arrangements (see 7.3.1 ) to ensure that the design and development outputs have met the design and development input requirements. Records of the results of the verification and any necessary actions shall be maintained ( see 4.2.4)
25. 25. Design Verification Establish and maintain procedures for verifying the device design Confirm design output meets design input requirements Types of verification activities include: Inspection Tests Analyses
26. 26. Design Verification Examples of Design verification Activities Evaluation of physical characteristics Mechanical/ chemical/ electrical testing Failure mode and effect analysis (FMEA) Packaging integrity testing Biocompatibility testing Sterility testing Comparison against predicate device with successful history
27. 27. Design Verification vs. Validation Design verification Did I make the product right? i.e. specified requirements have been fulfilled. Design Validation Did I make the right product? i.e. device specification conform with user needs and intended use(s)
28. 28. Design Validation 7.3.6 Design and development validation Design and development validation shall be performed in accordance with planned arrangements ( see 7.3.1) to ensure that the resulting product is capable of meeting the requirements for the specified application or intended use. Validation shall be completed prior to the delivery or implementation of the product ( see note 1). Records of the results of validation and any necessary actions shall be maintained ( see 4.2.4). As part of design and development validation, the organization shall perform clinical evaluations and/or evaluation of performance of the medical device, as required by national or regional regulations (see Note 2). NOTE 1 If a medical device can only be validated following assembly and installation at point of use, delivery is not considered to be complete until the product has been formally transferred to the customer. NOTE 2 Provision of the medical device for purposes of the clinical evaluations and/or evolution of performance is not considered to be delivery.
29. 29. Design Validation Examples of design validation activities Clinical studies Consumer preference testing Bench testing under simulated conditions Review of labeling and packaging Environmental testing ( i.e. stress during shipping and installation) Testing that distinguishes between customers, handlers, physicians, nurses, technicians and patients.
30. 30. Design Transfer 7.3.1 Design & Development Planning NOTE Design transfer activities during the design and development process ensure that design and development outputs are suitable for manufacturing before becoming final production specifications. 21 CFR 820.30 (h) Design Transfer Each manufacturer shall establish and maintain procedures to ensure that the device design is correctly translated into production specifications.
31. 31. Design Transfer Design transfer ensures : Repeatability Reproducibility Reliability Within the Production capabilities Design transfer includes Qualitative assessment of the completeness and adequacy of production specifications. Review and approval of all the documents drawings, process and test methods, digital data, CAM files, and articles molds, Jigs & fixtures, master samples, inspection gauges etc. Must ensure that only approved specs and materials is used in manufacturing.
32. 32. Design Changes 7.3.7 Control of design and development changes Design and development changes shall be identified and records maintained. The changes shall be reviewed, verified and validated, as appropriate, and approved before implementation. The review of design and development changes shall include evaluation of the effect of the changes on constituent parts and product already delivered. Records of the results of the review of changes and any necessary actions shall be maintained ( see 4.2.4).
33. 33. Design Changes Considerations for design changes Document decisions for change requests identifies possible design matters Document change order following acceptance of change requests identifies relevant documents and revision of content. May include assignment to designers for further evaluate the problem and develop corrective actions Review and assess impact of design change on design input requirements and intended uses.
34. 34. Design Changes Design change review The effect of the changes on products already in commercial or clinical use Whether prior design verification and validation results are impacted Changes are implemented in such a manner that the original problem is resolved and no new problems are created.
35. 35. Design History File 21 CFR 820.30 (j) Design History File Each manufacturer shall establish and maintain a DHF for each type of Device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part. Cross- reference to ISO 9001:1994 and ISO13485 section 4.16 Control of Quality records.
36. 36. Design History File Elements of Design History File Design & Development plan Design input documents Risk analysis documents Design outputs Pre-production design change records Engineering/ laboratory notebooks V&V protocols and results Design review records Design transfer records Copies of controlled documents i.e. SOPs Includes in the DHF all relevant records to demonstrate that the device was developed in accordance with the design plan and regulatory requirements. Tells the story of device development from beginning to end. Maintains knowledge base after design decisions have been made, employees leave, company reorganizes or subcontractors unavailable etc.
37. 37. Inspection/Audit of D&D Process Select a single design project. For the design project selected, verify that design control procedures have been defined and documented. Review the design plan to understand the scope including assigned responsibilities and interfaces. Confirm that design inputs were established. Verify that the design outputs that are essential for the proper functioning of the device were identified. Confirm that acceptance criteria were established prior to the performance of verification and validation activities. Determine if design verification confirmed that design outputs met the design input requirements.
38. 38. Inspection/Audit of D&D Process Confirm that design validation data show that the approved design met the predetermined user needs and intended uses. Confirm that the completed design validation did not leave any unresolved discrepancies. If the device contains software, confirm that the software was validated. Confirm that risk analysis was performed. Determine if design validation was accomplished using initial production devices or their equivalents. Confirm that changes were controlled. Determine if design reviews were conducted. Determine if the design was correctly transferred.
39. 39. Things To Remember Design Controls does not end with the transfer to production. Design controls applies to all changes to the device or manufacturing process design, including those occurring long after a device has been commercialized. The changes include evolutionary changes ( performance enhancement) as well as revolutionary changes (CAPA, field actions ). The changes are part of a continuous , ongoing effort to design and develop a device that meets the needs of the user and/or patients. Thus, the design controls in revisited many times during the life of the product. Source : Design Control Guidance for Medical Device Manufacturers : March 11, 1997, FDA, CDRH
40. 40. Further Reading/ Reference Material FDA guidance Document (http://www.fda.gov/downloads/medicaldevices/deviceregulationandg uidance/guidancedocuments/ucm070642.pdf) Medical Device Directive (http://eur- lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:247:0021:0055: en:PDF) ISO13485 (http://www.iso.org/iso/catalogue_detail?csnumber=36786) ISO14971(http://www.iso.org/iso/catalogue_detail.htm?csnumber=381 93) Quality System Inspection techniques (http://www.fda.gov/downloads/ICECI/Inspections/InspectionGuides/U CM085938.pdf) Points to consider when preparing for an FDA inspection under the QSIT Design Controls Sub-system (http://www.compliance- alliance.com/wp-content/uploads/2010/05/points-design.pdf)
41. 41. Questions ? Thank you very much. For further queries : pankaj.bhatia@bsci.com # +91 9818400941