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Ombu Enterprises, LLC Design Control Pitfalls 1

Overcome the Pitfalls of

Design Control

Dan O’Leary CBA, CQA, CQE, CRE, SSBB, CIRM

President

Ombu Enterprises, LLC

[email protected]

www.OmbuEnterprises.com

603-209-0600

mailto:[email protected]

http://www.ombuenterprises.com/


Pitfalls

• Design control is required for most medical devices sold in the U.S. In addition, other regulatory venues, such as the EU and Canada, require design control for all devices.

• As postmarket surveillance demonstrates, many device problems result from design control deficiencies.

• Discuss how the FDA expects you to develop and implement design controls, then transfer product design to manufacturing operations.


How it Works • We will present four topics related to medical device

design control

• Each topic will include:

– Regulatory requirements

– Guidance on what it means

– FDA Warning Letters

– Questions for discussion

• We will have a discussion on the questions

• We will ask participants for other issues on the topic


How to Discuss • Use the microphone so everybody can hear

• Bring examples from your experience

– Issues raised by FDA Inspections, Form 483, or Warning Letters

– Issues raised by Notified Body audits

– Issued raised by colleagues

– Questions on how things should work

• Be polite – Don’t make disparaging remarks about Investigators, Auditors, and others


The Issues

• Design Transfer

– Production specifications

– Device Master Record (DMR) v. Quality System Record (QSR)

– Process validation in design transfer process,

– Production software validation in design transfer

• Risk Management

– RMS that doesn’t use ISO 14971:2007

– FMEA/FMECA is not a risk management system

– Content deviations in the EU (EN ISO 14971:2012)

– Proliferation of references to ISO 14971:2007


The Issues • Design Changes

– Design change control before and after design transfer

– Production and Process Changes are Design Changes

– Change evaluation for 510(k) devices

– Configuration management / form, fit & function definitions

• Design Verification

– The methods and number of items for design verification

– Design verification applied to packaging and labeling

– Tools to ensure complete input/output coverage


Design Transfer


Design Transfer

• 820.30(h) Design transfer

• Each manufacturer shall establish and maintain procedures to ensure that the device design is correctly translated into production specifications.

• 7.3.1 Design and development planning

• 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.


Production Specifications

• Design Control Guidance for Medical Device Manufacturers

• One normally associates the term “production specifications” with written documents, such as assembly drawings, component procurement specifications, workmanship standards, manufacturing instructions, and inspection and test specifications. While these types of documents are widely employed in medical device production, other equally acceptable means of conveying design information exist, and manufacturers have the flexibility to employ these alternate means of communication as appropriate.


Production Specifications

• QSIT – Design Controls – Determine if the design was correctly transferred.

• The transfer process must be a part of the design plan. It is not uncommon for the design to be transferred in phases. Production specifications typically consist of written documents such as assembly drawings, inspection and test specifications, and manufacturing instructions. However, they can also consist of electronic records, training materials such as video tapes or pictures, and manufacturing jigs and molds.

• Review how the design was transferred into production specifications. Review the device master record. Sample the significant elements of the device master record using the Sampling Tables and compare these with the approved design outputs. These elements may be chosen based on the firm's previously identified essential requirements and risk analysis.


Warning Letter Axis Health Care, LLC

October 20, 2010 • Failure to develop, conduct, control, and monitor

production processes to ensure a device conforms to its specifications, as required by 21 CFR §820.70(a).

• For example, your firm failed to establish and implement written process control procedures, including standard operating procedure and work instructions to ensure the PACS device conformed to established specifications.

• Your response states your firm " ...has procedures in place but has not followed a formal procedure with documentation. We will identify and plan production operations, which directly affect quality to ensure production process, are carried out under controlled conditions...”


Quality System Record

• Sec. 820.186 Quality system record

• Each manufacturer shall maintain a quality

system record (QSR). The QSR shall include, or

refer to the location of, procedures and the

documentation of activities required by this part

that are not specific to a particular type of

device(s), including, but not limited to, the

records required by 820.20. Each manufacturer

shall ensure that the QSR is prepared and

approved in accordance with 820.40.


Quality System Record • QSR Manual Chapter 8 Device Master Records

• Quality system record (QSR) (820.186) or general documents are used for many activities that are essential to operating a manufacturing establishment – these are not specific to any given product even if the company produces only one product. Thus, the quality system record includes general documents such as standard operating procedures (SOPs) and standard quality assurance procedures (QAPs). If the company added another product line, the basic content of these documents would undergo none or only minor changes.

• In a typical manufacturing operation, general QSR, SOP, and QAP documents may include the following (partial list):

• Employee training procedures Supplier assessment policy

• General design control procedures Cleaning procedures

• Component inspection procedures Calibration policy

• Design review policy/procedure Label review policy/procedure


Quality System Record

• QSR Preamble #189

• One comment stated that general quality system procedures and instructions should not be required in the DMR because the DMR is device specific, and many quality system procedures are not tied to a particular device.

• FDA agrees in part with these comments and has developed new Sec. 820.186 Quality system record. This section separates the procedures and documentation of activities that are not specific to a particular type of device from the device specific records.


Warning Letter X-Ray Support, Inc. September 23, 2011

• Failure to maintain a quality system record (QSR), as required by 21 CFR §820.186.

• For example, your firm has not established a quality system record.

• Upon request by the investigator for the above referenced procedures, you indicated the requested procedures were located in your head.


Process Validation

• 820.75(a) Process validation

• Where the results of a process cannot be fully

verified by subsequent inspection and test, the

process shall be validated with a high degree of

assurance and approved according to

established procedures. The validation activities

and results, including the date and signature of

the individual(s) approving the validation and

where appropriate the major equipment

validated, shall be documented.


Processes Validation • QSR Preamble #85

• The requirement for testing from the first three production lots or batches has been deleted. While FDA believes that three production runs during process validation (process validation may be initiated before or during design transfer) is the accepted standard, FDA recognizes that all processes may not be defined in terms of lots or batches. The number three is, however, currently considered to be the acceptable standard. Therefore, although the number requirement is deleted, FDA expects validation to be carried out properly in accordance with accepted standards, and will inspect for compliance accordingly.

• Revised Sec. 820.30(h) now contains a general requirement for the establishment of procedures to ensure that the design basis for the device is correctly translated into production methods and procedures.


Warning Letter Michigan Medical Innovations

June 5, 2012 • Failure to adequately ensure that, where the results of a

process cannot be fully verified by subsequent inspection and test, the process is validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR §820.75(a).

• For example, your procedure [require validation]. However, your firm has not validated in-process and finish device testing apparati and processes that ensure the device is being manufactured according to your specifications to include:

a. Valve Assembly Test Kit

b. Battery Tester

c. Final Functionality Testing

d. Proper Valve Installation


Warning Letter Millar Instruments, Inc.

May 7, 2012 • Failure to validate with a high degree of assurance and approve

according to established procedures, a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR §820.75(a).

• For example: Your firm has not validated to a high degree of assurance all processes involved in the manufacture of your re-usable and disposable cardiac, intracranial, and urological catheters.

• Your response further stated that your firm’s past focus was on verification of product design which included process verification rather than process validation. Your proposed actions were to validate the equipment identified in the observation and to investigate all other equipment to ensure adequate validation and/or verification. In addition, your response stated that Process Validation SOP-2632 will be reviewed and evaluated for adequacy.


Production Software Validation

• 820.70(i) Automated processes

• When computers or automated data processing

systems are used as part of production or the

quality system, the manufacturer shall validate

computer software for its intended use according

to an established protocol. All software changes

shall be validated before approval and issuance.

These validation activities and results shall be

documented.




• FDA has modified the requirement to mandate validation for the intended use of the software. In addition, the requirement that the software be validated by individuals designated by the manufacturer has also been deleted to make clear that validation may be performed by those other than the manufacturer. However, whether the manufacturer designates its own personnel or relies on outside assistance to validate software, there must be an established procedure to ensure validation is carried out properly.




• FDA has maintained the requirement for validation because the agency believes that it is necessary that software be validated to the extent possible to adequately ensure performance. Where source code and design specifications cannot be obtained, “black box testing” must be performed to confirm that the software meets the user's needs and its intended uses.




• FDA emphasizes that manufacturers are responsible for the adequacy of the software used in their devices, and activities used to produce devices. When manufacturers purchase “off-the-shelf” software, they must ensure that it will perform as intended in its chosen application.


Production Software Validation • QSIT – Production & Process Controls – If the process is

software controlled, confirm that the software was validated.

• If the process chosen is automated with software, review the software requirements document, software validation protocol, software validation activities, software change controls and software validation results to confirm that the software will meet user needs and its intended use.

• If multiple software driven systems are used in the process, challenge one based upon significance.

• An important linkage to consider at this point is Material Controls (820.50 Purchasing Controls). For example, for software developed elsewhere, confirm that appropriate software and quality requirements were established and provided to the vendor and that purchasing data (and validation results) support that the requirements were met.


Warning Letter Omron (Dalian) Co., Ltd. (Plant 1)

February 14, 2012 • Failure to validate computer software used as a part of

production or the quality system for its intended use according to an established protocol, as required by 21 CFR §820.70(i).

• For example, your firm could not provide any documentation to demonstrate that the software used for the 6111 PCB (Printed Circuit Board) check machine (b)(4) was validated for its intended use. Your firm’s Department Manager of Regulatory Affairs stated that the software used for the PCB check machine has not been validated.

• The adequacy of your firm’s response cannot be determined at this time. Evidence of implementation of your firm’s corrections and corrective actions referenced in your response were not provided.


Design Transfer Issues

• What methods, other than written documents do you use for “production specifications”?

• How do you decide what information goes into the Device Master Record (DMR) and what goes into the Quality System Record (QSR)?

• In the design transfer process, where do you determine the need for process validation, 820.75?

• In the design transfer process, where do you determine the need for production software validation, 820.70(i)?


Risk Management


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Risk Management

• 820.30(g) Design validation

• Design validation shall include software validation and risk analysis, where appropriate.

• 7.1 Planning of product realization

• The organization shall establish documented requirements for risk management throughout product realization. Records arising from risk management shall be maintained.

• NOTE 3 See ISO 14971 for guidance related to risk management.


Risk Management

• Presumably the QSR requirement means,

“Design validation shall include risk

management and, where appropriate,

software validation.”

• Risk management is always appropriate,

but some devices don’t have software.


Risk Management

• Preamble #83

• 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, for example, by redesign or warnings.

• An important part of risk analysis is ensuring that changes made to eliminate or minimize hazards do not introduce new hazards.

• Tools for conducting such analyses include Failure Mode Effect Analysis and Fault Tree Analysis, among others.


Risk Management Standard

• The International standard is ISO 14971:2007

• Some regional and national standards are:

– Canada: CSA-ISO 14971-07 Medical devices – Application of risk management to medical devices

– EU: EN ISO 14971:2012 Medical devices - Application of risk management to medical devices (ISO 14971:2007, Corrected version 2007-10-01)

– US: AAMI / ANSI / ISO 14971:2007/(R)2010 (Corrected 4 October 2007), Medical devices - Applications of risk management to medical devices


FMEA & Risk Management

• The FDA’s QSR expert, Kim Trautman, on risk management:

• “Are FMEA or FMECA… good tools? Yes. They are very good tools that can be utilized. Are they in and of themselves a risk management system? Absolutely not. I can’t tell you how many manufacturers I have seen that have tried to present their risk management system by simply presenting an FMEA — that is not a risk management system. Do not make the mistake of presenting FMEAs as your whole risk management system.”



• FMEA & FMECA deals with failures, i.e., fault conditions only.

• The preamble tells says, to identify possible hazards associated with the design in both normal and fault conditions and calculate the associated risks in both normal and fault conditions.

• ISO 14971:2007 4.3 Identification of hazards says, “The manufacturer shall compile documentation on known and foreseeable hazards associated with the medical device in both normal and fault conditions.”



Known Foreseeable

Normal

Condition

Fault

Condition

Hazard Classification from Clause 4.3


FMEA & Risk Management • IEC 60812:2006 Analysis techniques for system reliability –

Procedure for failure mode and effects analysis (FMEA)

• Some FMEA or FMECA applications form a risk priority number, RPN = S × O × D

– S is severity

– O is occurrence

– D is detectability

• 5.3.2 Risk, R, and risk priority number (RPN)

• Risk priority number may then be used for prioritization in addressing the mitigation of failure modes. In addition to the magnitude of the risk priority number, the decision for mitigation is primarily influenced by the severity of the failure mode, meaning that if there are failure modes with similar or identical RPN, the failure modes that are to be addressed first are those with the high severity numbers.


Warning Letter Amplivox Limited

May 2, 2012 • Failure to establish and maintain adequate procedures for validating

the device design. Design validation shall include risk analysis, where appropriate, as required by 21 CFR §820.30(g).

• For example, your firm’s procedure does not include or refer to the process to be used when conducting a risk analysis. Specifically, the design history file (DHF) for the Otowave102 Hand Held Tympanometer device included a risk management file document … However, your firm did not establish a process for identifying the potential hazards of the design project as required by the standard being used [redacted].

• We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it will revise the Design and Development Procedure to include adequate requirements for conducting risk analysis. Your firm did not provide any information about developing a new risk analysis procedure.


Warning Letter Blackstone Medical Inc.

March 13, 2009 • Failure to adequately establish and maintain a risk analysis of the

device as part of your design validation, as required by 21 CFR §820.30(g). In October 2007, after design changes to the ICON™ System were made and as a part of your design validation for that change, your firm failed to adhere to your own risk management procedures.

• For example, Failure Modes and Effects Analysis (FMEA) Risk Priority Numbers (RPNs) for the changed design fell within your predefined unacceptable zone for the set screws, multi axial body assemblies, off set body assemblies and multi axial screws. No actions to reduce the risk or to add additional risk control measures were identified or implemented as required by your firm's Risk Management Procedure.

• We have reviewed your responses and find your responses to be inadequate. Scientific justification for the revisions to the risk analysis process was not adequately explained nor evidence provided. Recalculating the RPNs without proper justification is not acceptable.


EU Content Deviations

• EN ISO 14971:2012 identifies seven places where the EU directives are more stringent than ISO 14971:2012

– Treatment of negligible risks

– Discretionary power of manufacturers as to the acceptability of risks

– Risk reduction "as far as possible" versus "as low as reasonably practicable“

– Discretion as to whether a risk-benefit analysis needs to take place

– Discretion as to the risk control options/measures

– Deviation as to the first risk control option

– Information of the users influencing the residual risk:


EU Content Deviations

Severity

Pro

ba

bil

ity

Unacceptable

Acceptable

Negligible ALARP

How do the

content deviations

affect this

traditional view of

risk?


Standards • Many standards and guidance documents call out an

ISO 14971:2007 Risk Management System

– IEC 60601-1 Medical electrical equipment – Part 1: General requirements for basic safety and essential performance

– IEC 62304 Medical device software – Software life-cycle processes

– FDA Guidance – Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications

– FDA Draft Guidance – Applying Human Factors and Usability Engineering to Optimize Medical Device Design


Risk Management Issues • Are you using a risk management Risk Management

System (RMS) that is not based on ISO 14971:2007 or one of its national or regional variants?

• We know that FMEA/FMECA is not an adequate Risk Management System (RMS)

– Have you moved from only failure evaluation to hazard evaluation?

– Have you shifted from a risk definition for failures using Risk Priority Numbers (RPNs) to a risk definition for hazards using

– What issues did you encounter in the transition?


Risk Management Issues • For CE Mark devices, the seven content deviations in

EN ISO 14971:2012 should have changed technical files and design dossiers

– What issues have you encountered in implementing the change?

– For devices with the CE Mark, what expectations do Notified Bodies present?

– For devices sold outside the EU, have you updated the Risk Management File (plans, hazard analysis, etc.) to match the EU requirements?

• Many standards and guidance documents now expect risk management and incorporate ISO 14971:2007. What issues does this create for risk management implementation?


Design Changes


Design Changes

• 820.30(i) Design changes

• Each manufacturer shall establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation.

• 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.


Design Change Records • Preamble #87

• Manufacturers are not expected to maintain records of all changes proposed during the very early stages of the design process. However, 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 evaluation and documentation should be in direct proportion to the significance of the change. Procedures must ensure that after the design requirements are established and approved, changes to the design, both pre- production and post-production are also reviewed, validated (or verified where appropriate), and approved.


Production & Process Control

• QSIT – Confirm that changes were controlled including validation or where appropriate verification

• The degree of design change control is dependent on the significance of the change and the risk presented by the device. Manufacturers may use their routine post-production change control procedure for pre-production design changes. However, most post-production change control procedures may be too restrictive and stifle the development process. Firms may use a separate and less stringent change control procedure for pre-production design changes.


Design Changes

Design Changes

Design Transfer

Pre-production Changes

820.30(i)

Post-production Changes

820.70(b)

820.30(i)

Separate and less formal change control allowed for pre-

production changes

Formal change control required including document control

review and approval (820.40)


Warning Letter Electric Mobility Corp

April 14, 2011 • Failure to establish and maintain adequate procedures

for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation as required by 21 CFR §820.30(i).

• Your firm's Design Controls procedure in effect at the initiation of this inspection, does not address how changes to the design are to be handled when they are made after design inputs have been approved but before the design is transferred into production.


Production & Process Control • QSIT – Confirm that changes were controlled including

validation or where appropriate verification

• The design change control section is linked to and is redundant with Section 820.70(b) Production and process changes of the regulation

• Post-production design changes require the firm to loop back into the design controls of Section 820.30 of the regulation. This does not mean that post-production changes have to go back to the R&D Department for processing. This track is dependent on what the firm specifies in their change procedure. It is acceptable for the manufacturing department to process the entire design change and to implement the controls of Section 820.30.


Warning Letter CPR Medical Devices, Inc.

December 13, 2011 • Failure to adequately establish and maintain

procedures for changes to a specification, method, process, or procedure, as required by 21 CFR §820.70(b).

• For example, your firm failed to follow its own procedure… Your firm has made specification changes to the device, Oxylator EMX, since the original design was transferred to production. The changes to the specifications to the device have not been validated or verified and were implemented without approval.


510(k) Change Analysis

• Preamble #87

• Note that when a change is made to a specification, method, or procedure, each manufacturer should evaluate the change in accordance with an established procedure to determine if the submission of a premarket notification (510(k)) under 21 CFR §807.81(a)(3)), or the submission of a supplement to a PMA under 21 §CFR 814.39 is required. Records of this evaluation and its results should be maintained.


510(k) Change Analysis

Enactment

July 9, 2012

Report

Receipt 18 Months

Dec. 9, 2013

Receipt +

12 Months

Report Due

Blackout for Draft

Guidance and Rules

Blackout for Final

Guidance and Rules

FDASIA instructed

FDA to revert to the

1997 guidance

document


Warning Letter Applied Medical Technology Inc

June 8, 2011 • Failure to establish and maintain adequate procedures for the

identification, documentation, validation or where appropriate verification, review and approval of all design changes before their implementation, as required by 21 CFR §820.30(i).

• Specifically, you are not following your “510(k) & Existing Device Changes” procedure, which requires that each design change be reviewed to determine if a new 510(k) is needed and if a new 510(k) is not required, a “note to file” must be documented. Your firm has made eight design changes since 2006, and there is no documented rationale why these changes did not requires a new 510(k).

• We cannot determine the adequacy of your response at this time. Your response states that more thorough documentation shall be implemented by June 1, 2011. Please provide a copy of the documented rationales.


Configuration Management

• MIL-STD-973 configuration Management offers

the following definitions:

– Fit – The ability of an item to physically interface or

interconnect with or become an integral part of

another item.

– Form – The shape, size, dimensions, mass, weight,

and other visual parameters which uniquely

characterize an item. For software, form denotes the

language and media.

– Function – The action or actions which an item is

designed to perform.


Configuration Management

• ISO 13485 Clause 7.5.3.2.1 General

• NOTE: Configuration management is a

means by which identification and

traceability can be maintained.

• ISO 10007:2003 Quality management

systems – Guidelines for configuration

management


Warning Letter Medtronic

November 9, 2009 • Failure to implement procedures for document control,

which is required by 21 CFR §820.40.

• Specifically, the Configuration Management and Document Control procedure states "Quality system documents shall be reviewed for adequacy and approved by designated individual(s) prior to release for use. *** The approval of the documents shall be documented and shall include the date, and signature of the individual(s)." However, there is no record of review or approval of the document entitled [redacted]: Fidelis Leads."


Design Changes Issues

• What are the common methods for informal control before transfer to production

• Do you handle all Production and process changes as design changes? – If so who responsibility: design engineering, manufacturing engineering,

quality engineering?

• For 510(k) devices, you perform an analysis and leave a quality record? Do you follow the 1997 flow charts, answer each applicable question for each change?

• What is the role of configuration management in design changes? – In particular, do you implement and use definitions of form, fit, and

function?

– What if any, automated tools do you use?


Design Verification


Design Verification • 820.30(f) Design verification

• Each manufacturer shall establish and maintain procedures for verifying the device design. Design verification shall confirm that the design output meets the design input requirements. The results of the design verification, including identification of the design, method(s), the date, and the individual(s) performing the verification, shall be documented in the DHF.

• 7.3.5 Design and development verification

• Verification shall be performed in accordance with planned arrangements 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.


Design Verification • QSIT – Determine if design verification confirmed that design

outputs met the design input requirements.

• Design verification activities are performed to provide objective evidence that design output meets the design input requirements. Verification activities include tests, inspections, analyses, measurements, or demonstrations. Activities should be explicit and thorough in their execution. It is the firm's responsibility to select and apply appropriate verification techniques. Complex designs can require more and different types of verification activities than simple designs. Any approach selected by the firm, as long as it establishes conformance of the output to the input, is an acceptable means of verifying the design with respect to that requirement.

• Review the documentation of the verification activities associated with a sample of inputs and outputs as determined using the Sampling Tables. If possible, select activities that are associated with outputs identified as essential to the proper functioning of the device. Confirm that design outputs met design input requirements.


Design Verification Methods

• ISO/TR 14969:2004 Medical devices — Quality management systems — Guidance on the application of ISO 13485:2003

• Design and development verification is necessary to ensure that the design and development outputs conform to specified requirements (design and development inputs).

• Verification activities can include, if appropriate,

– tests (e.g. bench tests, laboratory analyses),

– alternative calculations,

– comparison with proven design,

– inspections, and

– document reviews (e.g. specifications, drawings, plans, reports)


Design Verification Methods • ISO/TR 14969:2004 Medical devices — Quality management

systems — Guidance on the application of ISO 13485:2003

• If tests and demonstrations are employed at any stage of the design and development verification, the safety and performance of the product should be verified under conditions which are representative of the full range of circumstances of actual use.

• When alternative calculations or comparison with a proven design are employed as forms of design and development verification, the appropriateness of the alternative calculation method, and/or proven design, should be reviewed. This review should confirm that the alternative calculations or comparison with a proven design are actually scientifically valid methods of design verification for the design under consideration.


Packaging and Labeling

• 820.130 Device packaging

• Each manufacturer shall ensure that

device packaging and shipping containers

are designed and constructed to protect

the device from alteration or damage

during the customary conditions of

processing, storage, handling, and

distribution.


Packaging and Labeling

• Preamble #172

• Two comments on proposed 820.160 Device packaging, stated that the section should be changed to allow manufacturers to use third parties, if desired, for packaging. Another comment stated that it is very difficult if not impossible to protect from intentional damage, such as tampering.

• FDA agrees with the comments and has changed the requirement, now in Sec. 820.130, accordingly. FDA believes, however, that any intentional tampering would not be covered because the requirement states “during customary conditions.”


Warning Letter Prime Herbs Corporation

December 10, 2012 • Failure to ensure device packaging and shipping

containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution, as required by 21 CFR §820.130.

• During our inspection you told our investigator that you have received complaints from customers about your Precision TDP Lamp not functioning as it may have been damaged during shipping; however, you do not have procedures or documentation regarding any packaging validation to ensure the Precision TDP Lamp is not damaged during handling and distribution.


Labeling

• 820.120(a) Device labeling – Label

integrity

• Labels shall be printed and applied so as

to remain legible and affixed during the

customary conditions of processing,

storage, handling, distribution, and where

appropriate use.


Warning Letter Frantz Design, Inc.

June 5, 2009 • Failure to establish and maintain procedures to control

labeling activities, including labeling inspection, labeling storage, and labeling operations, in order to ensure that printed labels remain legible, as required by 21 CFR §820.120. See FDA 483 Item 15.

• Specifically, your firm has not established labeling procedures for how to label your packaged EMA devices and inspect the product label. There was no printed label on the device packaging. Your firm hand wrote the product description, quantity, and manufacturing dates on the bags.


What about bar

codes & UDI?

Labeling • Preamble #169

• A few comments stated that what is now Sec. 820.120(b), “Labeling inspections,” should allow automated readers to be used in place of a “designated individual(s)” to examine the labeling.

• FDA disagrees with the comments because several recalls on labeling have been attributed to automated readers not catching errors. The requirement does not preclude manufacturers from using automated readers where that process is followed by human oversight. A “designated individual” must examine, at a minimum, a representative sampling of all labels that have been checked by the automated readers. Further, automated readers are often programmed with only the base label and do not check specifics, such as control numbers and expiration dates, among other things, that are distinct for each label. The regulation requires that labeling be inspected for these items prior to release.


Design Verification Potential Issues

• What factors influence the methods and number of items used for design verification?

• FDA also expects that your design verification and validation is extended to your packaging and labeling because the finished product is the finished, packaged, and labeled device.

• Design verification confirms that design output meets the design input requirements. What tools do people use to ensure complete coverage of the design input?

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