compliance with applicable medical device regulations of … · 2018-04-02 · design history file...
TRANSCRIPT
M. Isabel Tejero MD, PhD Lead Consumer Safety Officer
Office of Compliance
FDA/OMPT/CDRH/OC
Compliance with Applicable
Medical Device Regulations
of Combination Products:
CDRH Expectations
Presentation Road Map
Who are we?
Regulatory Background: Part 4 rule
FDA Expectations:
Design Controls
Summary
CDRH Office of Compliance
To evaluate compliance with
applicable 21 CFR part 820 regulations
Regulatory Background
Combination Product GMP Rule
21 CFR Part 4
Key Messages
21 CFR part 4 Does Not Introduce Additional cGMP Regulatory Requirements
Manufacturers are required to comply with all the applicable regulations: drugs, biological products, devices, …
Provides clarification regarding alternative ways to meet regulatory GMP obligations: Streamlined Approach
21 CFR Part 4.4(b)(1)
Streamlined Approach: Declared GMP §210-211
21 CFR 820.20 Management Responsibility
21 CFR 820.30 Design Controls
21 CFR 820.50 Purchasing Controls
21 CFR 820.100 Corrective and Preventive
Actions
21 CFR 820.170 Installation*
21 CFR 820.200 Servicing*
FDA Expectations –
Design Controls
Design Controls
Ensure that specified design requirements are
met including user needs and intended use of
the finished product
Design Controls do not just involve the device
constituent parts
Design evaluation needs to include interactions
between the device part with the drug/biologic
part
Design Controls Applicability
Are Not retroactive to products already in
distribution prior to June 1, 1997.
Apply to new products with a device
constituent part designed after June 1, 1997,
and to design changes of pre-amendment
products done after June 1, 1997. QS Regulation Preamble p. 52616, Comment #64
Applicability
Design Controls Requirements
The design control procedures must address: • Design Input • Design Output • Design Review • Design Verification • Design Validation • Design Transfer • Design Changes • Must include Risk assessment
Design history file (DHF)
A compilation of records which describes the design history of the finished combination product. This includes all its constituent parts.
The DHF illustrates the history of the design, and is necessary so that
manufacturers can exercise control over and be accountable for the
design process, thereby maximizing the probability that the finished
design conforms to the design specifications.”
QS Regulation Preamble p. 52622, Comment #90
Design History File Requirements
Establish and maintain a DHF for each type of device (combination product).
Contain or reference the records maintained to demonstrate the design was developed in accordance with the design plan and requirements of design control.
Application of Design Controls
TIME
Design and Development Planning
Describe or reference design and development activities
Define responsibility for implementation
Identify or describe interfaces with different groups or activities
Plans kept up to date as design evolves
Design Inputs Established adequate procedures for
Design Inputs: Are appropriate
Address the intended use of the device
Include a mechanism for addressing incomplete, ambiguous, or conflicting requirements
Design Input Requirements
Sources used to identify the design inputs
Examples of Design Inputs
DRUG COMMON DEVICE
Efficacy Compatibility Function/performance parameters
Safety Regulatory Requirements
Safety
Formulation Labeling Reliability
Other Human Factors Environmental limits
Design outputs Established adequate procedures for design outputs
Specifications have been developed to meet design input requirements
Containing or referencing acceptance criteria
Ensuring design outputs essential for the proper functioning of the product are identified
Examples of Design Outputs
Device Component Part Specifications
Device Component Part Material Specifications
Drug Product Specifications
Closure System Specifications
Combination Product Assembly Drawings
Combination Product Manufacturing Procedures
Quality Control /Assurance Specifications
Sterilization Specifications
Design reviews
Formal documented reviews of the design results, planned
and conducted at appropriate stages of the product’s
design development.
Participants will include representatives of all functions
concerned with the design stage being reviewed and an
individual(s) who does not have direct responsibility for
the design stage being reviewed.
The results of a design review shall be documented in the
design history file (the DHF).
Design Verification
Design verification activities, including
identification of the design and methods used
Acceptance criteria for the design verification
Design verification activities confirm the
design outputs meet the design input
requirements
Examples of Design Verification
Clinical Tests
Safety Tests
Performance Tests
Sterility Test
Visual Inspection
Measurement Inspection
Design validation
Objective evidence that product requirements conform with user needs and intended use(s)
Risk Analysis / Risk Management
Under defined operating conditions
On initial production units, lots, or batches or their equivalents
Under actual or simulated use conditions
Predetermined acceptance criteria
Examples of Design Validation
Human Factors Studies
Evaluations (Clinical and Non-Clinical)
Clinical Trials
Scientific Literature Review
Historical Evidence and Performance
Risk Analysis
“... When conducting a risk analysis, manufacturers are expected to identify possible hazards associated with the design in both normal and fault conditions. The risks associated with the hazards, including those resulting from user error, should then be calculated in both normal and fault conditions. If any risk is judged unacceptable, it should be reduced to acceptable levels by the appropriate means ...”
Preamble p. 52620 Comment #83
Design Transfer
Product information and knowledge is transferred
from the design group to the manufacturing group
Examples of means to accomplished Design Transfer:
Assembly drawings
Test and Inspection Specifications
Training Materials
Manufacturing Specifications and Procedures
Design Changes
“... All design changes made after the design review that approves the initial design inputs for incorporation into the design, and those changes made to correct design deficiencies once the design has been released to production, must be documented. The records of these changes create a history of the evolution of the design...”
Preamble p. 52621 Comment #87
Design Change Controls, When & Why When:
Any time changes are made to new or existing designs during the product life cycle, and after the approval of the design inputs
Why:
To ensure that specified design requirements are still met (including user needs and intended use of the finished product)
To ensure that safety and effectiveness of the product is maintained
Examples of Applicability of Design Change Control
Changes to -
Any constituent part
Specifications
Materials
Packaging and Labeling
Testing (Acceptance Criteria or Test Methods)
How to Bring an existing Design Project into Compliance with 21 CFR 820.30
Use the CAPA system to evaluate the non-compliance,
find the cause and address it
The cause investigation should include both low-level
operational functions, as well as high-level systemic
functions
Evaluate any other design project subject to Design
Controls for compliance
Retrospectively create a DHF as complete as possible
How to Bring an existing Design Project into Compliance …..
Use risk to determine the timing, extent and
rigor of the activities
Identify and execute design control activities
necessary to fulfill requirements not
addressed by previous activities and to
mitigate additional identified risks
Document
Closing remarks
Design Controls apply to the combination
product, including packaging and labeling, and
should be applied to the designed system as a
whole, not just the device constituent
Non-compliance with 21 CFR 820.30:
Evaluated using the firm’s CAPA system
Include risk-based corrective and preventive actions
The corrective/preventive actions should include the
evaluation of other design projects subject to design
controls
Useful Contacts
A revised guidance to further clarify the application of part 4
is about to be published.
CDRH-Division of Industry and Consumer Education (DICE) (1-
800-638-2041, [email protected]) for questions regarding
applicable medical device regulations.
Office of Combination Products ([email protected]) for
General and implementation questions about part 4.
Product specific questions, contact the application project
manager.
