Use of Standards Premarket Submissions Auditing Packaging Process - - PowerPoint PPT Presentation

Committee F02 on Flexible Barrier Packaging

Use of Standards –

Premarket Submissions

Auditing Packaging Process – Medical Device Inspections

FDA’s Involvement with Standards

Food, Drug and Modernization Act 1997 – section 514

 Requires CDRH to be involved in standards

recognition.

 Develop a system which recognizes all or part of

a national and international standard established by recognized standards development

• rganizations.

FDA’s Involvement with Standards

 FDA publishes in the Federal Register the

standards that are being recognized as well as standards that will be withdrawn.

 FDA maintains a database of recognized

consensus standards.

 Firms can reference recognized consensus

standards in a Declaration of Conformity, which can satisfy a premarket submission requirement.

FDA’s Involvement with Packaging Standards

 Latest edition of ISO 11607 addresses the

ASTM test methods that may be used to validate the packaging process.

 32 ASTM Packaging test methods/standards are

referenced in ISO 11607.

 ASTM’s F02 standards provide detailed

guidance and industry practices in regard to packaging testing.

 Keeps FDA informed of current best practices.

Recognition of Packaging & Shipping Standards

CDRH’s Sterility Standards Task Group has recognized:

 ANSI/AAMI/ISO 11607-Parts 1 & 2.  19 ASTM Test Methods, Standard Practices, etc

regarding packages and packaging material.

 D4169-09 - Standard Practice for Performance

Testing of Shipping Containers and Systems.

Device Premarket submissions

Using Standards in Premarket Submissions Premarket Notifications – 510(k) Submissions Premarket Approval Submissions - PMA

Premarket Submission

 Premarket Notification Submission –

Demonstrating device to be marketed, is substantially equivalent to a device already on the market. (510k submissions - typically are Class II devices)

Premarket Submissions

Medical device firms:

 Will voluntarily state conformance with

recognized consensus standards.

 When a device manufacturer decides to

recognize a consensus standard to meet a premarket requirement (i.e. sterilization validation), they must provide a declaration of conformance for the standard.

Recognition of Standards for Premarket Submissions

 Must maintain data to demonstrate

conformance.

 This data may be requested by FDA at any time

(typically during inspections).

 Failure to demonstrate or falsify conformance to

a standard is a prohibited act. Devices will be considered misbranded.

Declaration of Conformity

Benefits of stating Declaration of Conformity to a standard.

 Recognition of standards can minimize the data

needed in premarket submissions.

 Less data to review can streamline the premarket

submissions review.

510(k) Submissions for Sterile Devices

What CDRH Reviewers look for:

 Sterilization method that will be used ( i.e.

radiation or moist heat).

 The method that will be used to validate the

sterilization cycle, but not the validation data itself.

510(k) Submissions for Sterile Devices

What CDRH Reviewers look for:

 A description of the packaging to maintain the

device’s sterility, not including package integrity testing data.

 For "pyrogen free” labeling, a description of the

method used to make the determination, e.g., limulus amebocyte lysate (LAL).

 The sterility assurance level (SAL).

510(k) Submissions

 Declaration of Conformance to Test Methods:  When a standard describes a test method but

does not specify a performance limit or acceptance criteria, the manufacturer should submit the test results.

Declaration of Conformity

 Identify the recognized consensus standards.  State all requirements met. Identify and explain

inapplicable requirements or deviations from the standard.

 Specify any differences between tested device

and the device to be marketed.

 Laboratory and certification body information

used to determine conformance with the standard.

Premarket Approval

 Premarket Approval (PMA) – Evaluate the

safety and effectiveness of a Class III device - Life supporting/Life Sustaining devices.

 Actual sterilization procedures and validation

data will need to be submitted.

 Quality System procedures (Design controls,

Purchasing (supplier) controls, Process controls, Calibration, etc.)

PMA Devices

 PMA submissions are more voluminous and

take longer to review than 510(k) submissions.

 Premarket inspections of the sterilization facility

may be needed.

Inspection Considerations

Inspection of the Packaging Process Documents reviewed Quality System requirements evaluated

FDA Inspection of Packaging Process

 Evaluate Procedures – Ensure procedures meet

FDA requirements and provide adequate instructions to complete the task.

 Personnel – Adequate resources. Experienced

and trained personnel.

 Procedures are being implemented. Review

testing done on sterile barrier system. Testing is done according to procedures.

FDA Inspection of Packaging Process

 Evaluate process controls procedures - When a

non-conformance could occur, making sure process controls are implemented.

 Ensuring test equipment is calibrated (pressure

gauges, timers) and routine maintenance is identified for equipment.

FDA Inspection of Packaging Process

 Confirm packaging process has been validated.  Review production records from routine

processed lots/batches to ensure the sterile barrier system or packaging system are within the validated parameters.

 Appropriate records are maintained, reviewed

and approved before releasing product.

FDA Inspection of the Packaging Process

 Adequate controls established for

nonconforming product.

 Purchasing/Supplier controls – for packaging

material supplier or contract packager.

Inspecting the Packaging Process

 FDA inspections of the packaging process in

medical device manufacturers often focus on process validation - 21 Code of Federal Regulation (CFR) 820.75.

 Packaging can be evaluated throughout the

Quality System (QS) regulation:

Inspecting the Packaging Process

 21 CFR 820.22 – Quality Audit

 Ensuring packaging process is being reviewed during

quality audits. If a contract packager is used, ensure they are adequately evaluated and complying with the QS regulation.

 21 CFR 820.25 – Personnel

 Training is documented. Personnel made aware of

device defects which may occur from improper

• performance. Personnel that perform verification or

validation – need to be aware of defects or errors that may be encountered from their job function.

Inspecting the Packaging Process

 21 CFR 820.30 – Design Controls

 Packaging needs to be considered early in the design

• process. (Packaging engineers part of the design

team, ensure packaging will protect the device, maintain sterile barrier, ensure packaging materials are not affected the sterilization process; design changes – do the impact the packaging.)

FDA inspection of the Packaging Process

 21 CFR 820.50 - Purchasing Controls

 Establish procedures to ensure purchased or

• therwise received product and services conform to

specifications.

 Evaluate & select potential suppliers, contractors,

and consultants on the basis of their ability to meet specified requirements (quality requirements).

FDA inspection of the Packaging Process

 Purchasing Controls

 Define the type and extent of control to be exercised

• ver the product, services, contractors, and

consultants, based on the evaluation results.

 Establish and maintain records of acceptable

suppliers, contractors, etc.

FDA inspection of the Packaging Process

 Purchasing Data

 Establish and maintain data that clearly describe or

reference the specified requirements.

 Where possible, an agreement that the suppliers,

contractors, or consultants agree to notify the manufacturer of changes in the product or service to determine if the change may affect the quality of the finished device.

Purchasing Control Problems

 Quality requirements are not established.  List of acceptable suppliers or contractors not

maintained.

 Inadequate controls implemented

 No assurance contract packaging process has been

validated.

 Manufacturer assumes contractor performing

packaging, however the packaging is outsourced to a third party.

FDA inspection of the Packaging Process

 21 CFR 820.70 – Production and Process

Controls

 Where deviations from a device specification could

• ccur from manufacturing process, the manufacture

shall establish process control procedures. (includes Production and process changes, Environmental Controls, Personnel, Contamination Control, Buildings, Equipment - Maintenance schedule, inspection, adjustment, manufacturing material, automated process)

FDA inspection of the Packaging Process

 21 CFR 820.72 – Inspection, Measuring and test

equipment

 Control of inspection, measuring and test equipment

capable of producing valid results; Calibration - Calibration standards; Calibration records.

FDA inspection of Packaging Process

 21 CFR 820.75 – Process Validation

 Sterilization and packaging process has been

validated according to procedures.

 Validation results and activities, including the date

and signature of the individuals approving the validation, and where appropriate major equipment validated shall be documented.

Process Validation

 Establish procedures for monitoring control of

process parameters to ensure that specified requirements continue to be met.

 Ensure that validated processes are performed

by qualified individuals.

 Monitoring and control methods and data, the

date performed and where appropriate, the individuals performing the process or major equipment used shall be documented.

Process Validation

 When changes or process deviations occur, the

manufacturer shall review and evaluate the process and perform revalidation, where appropriate.

 Document these activities.

Packaging Validation deviations

 Packaging validation not conducted.  Failure to revalidate the packaging process when

changes are made to the equipment or packaging material.

 Monitoring and Control of process parameters

not maintained. No assurance packaging equipment is operating within parameters.

35

FDA inspection of the Packaging Process

 21 CFR 820.80 – Acceptance Activities –

Receiving, In-process, and Finished device acceptance

 Inspection of packaging material, conducting in-

process test on seals.

 21 CFR 820.90 – Nonconforming Product

 Establish controls for product that do not meet

specified requirements. (i.e. seal specifications not met, compromised seals observed )

FDA inspection of the Packaging Process

 21 CFR 820.100 – Corrective and Preventive

Action

 Analyze sources of quality data to identify existing

and potential causes of nonconforming product. Analyze data→Investigate cause →Identify actions to correct and prevent nonconformance →Verify &/or Validate →disseminate information to those directly responsible for quality…

 For example, analyze complaints for packaging

deviations.

FDA inspection of the Packaging Process

 21 CFR 820.130 – Device Packaging

 Designed and constructed to protect the device

during processing, storage, handling, and distribution.

 Validation of the packaging process is if often

inspected for sterile devices. Packaging issues are the reason for most recalls due to lack of sterility assurance.

FDA Inspection of the Packaging Process

 21 CFR 820.140 – Handling

 Ensure mixup, damage, deterioration, contamination

to product do not occur during handling.

 21 CFR 820.150 – Storage

 Control of storage areas and stock rooms for

product to prevent mixups, damage, deterioration, or

• contamination. Ensure obsolete, rejected or

deteriorated product is not used or distributed.

2011 Inspectional Observation data

 Reviewed 128 medical device inspections in

which sterilization was reviewed.

 22 inspections identified inspectional

• bservations in which packaging process was

identified in the inspectional observation.

2011 Inspectional Observations

# of Observations

2 4 6 8 10 12 14 Interna Audit Design Control Doc Control Purchasing

• Prod. Process

Acceptance Validation Nonconform CAPA Packaging Storage DMR Complaint

• Stat. Sampl

# of Observations

2011 Sterile Packaging System Recall Data

 For the year 2011, I searched for recalls in which

sterility, packaging, or seals may have been identified in the cause of the recall.

 Medical Device firms notified FDA 51 times of

their intentions to voluntary recall devices due to problems with the sterile barrier system. May compromise sterility of the medical device.

 230 device recalls were classified by FDA.

(Example- one firm recalled 33 different kits)

2011 Sterile Packaging System Recall Data

 Separated the recalls into 4 categories of where

the problems appear to have originated.

 Suppliers (contract packagers or suppliers of

packaging material), Design, Production & Process Controls, and Personnel.

Supplier Problems

 Total of 63 device recalls classified due to

supplier problems.

 Equipment causing stress on trays.  New supplier and new material used.  Packaging process was not validated.  Used expire adhesive.

Recalls due to Supplier Problems

Reasons Devices Recalled

N = 63

Delaminations 2 (3%) Cracks 7 (11%) Seals 9 (14%) Pin Holes 45 (72%)

Design Problems

 Total of 79 device recalls classified due to design

problems.

 Device gets in way of seal.  Burrs & sharp edges puncture SBS.  Protective packaging too small, stressed SBS.  Protective package changed, cracked trays.  Wrong packaging configuration.

Packaging Design Recalls

Reasons Devices Recalled

N = 79

Pkg Config 3 (4%) Other 4 (5%) Tears/Abrasions 34 (43%) Cracks 19 (24%) Seals 2 (3%) Pin Holes 17 (22%)

Production & Process Control Problems

 Total of 62 device recalls classified due to

production & process control problems.

 Wrong parameters used on sealing machine.  Building layout or storage controls allowed for

sealed and unsealed SBS to be mixed.

 Changes made to equipment and changes not

properly validated or verified before production.

 Packaging Process not validated.

Production & Process Control Recalls

Reasons Devices Recalled

N = 62

Other 6 (10%)

Tears/Abrasions 2 (3%) Seals 25 (40%) Pin Holes 29 (47%)

Personnel Problems

 Total of 26 device recalls classified due to

personnel problems.

 Not following procedures.  Not aligning equipment properly.  Did not receive adequate training.

Recall due to Personnel Issues

Reason Device Recalled

N = 26

Seals

100%

Thank You!

Patrick Weixel Patrick.Weixel@FDA.HHS.GOV Phone: 301-796-5537