Frequently Asked Questions
Most Commonly Asked Questions
I’d like a quote for finished device packaging and sterilization; what information do you need?
- Estimated production volume, quarterly and annually
- Package configuration plan or drawing, aka the top-level assembly drawing*
- Bill of Material for the complete device including packaging*
- Product labeling plan or drawing*
- Desired/known sterilization modality*
- Cleaning, disinfection, and validation requirements
* Eagle can provide guidance and contracted services for these items and will include them in your quote upon request
What are the basic steps to manufacture at Eagle if my packaging is already designed?
- Thermoforming & Sealing Tooling
- Thermoforming qualification
- Sealing qualification
- Device assembly qualification with pilot builds
- Label development/artwork integration
- Perform packaging validation per ISO 11607
- Work instruction/DHR initiation
Sealing and Manufacturing Process Development, as applicable: (16-24 weeks for thermoformed trays, 8-20 weeks for pouch systems)
What annual volume of product is needed for outsourcing to Eagle?
Eagle will develop and implement manufacturing processes to accommodate annual volumes from thousands to one million units. Flexible cleanroom formats and a variety of production methods enable us to provide scalable and efficient contract manufacturing and packaging services across a range of volumes.
Package Design and Validation
What package design services does Eagle offer?
- Documenting requirements for the medical device package, which includes usability issues and aseptic transfer requirements, as well as labeling preferences.
- Packaging system requirements that consider storage and transportation conditions, cleanliness, bioburden, and expected environmental stresses and constraints.
- Evaluation of appropriate sterility methods and material compatibility.
Eagle offers turnkey package design and validation processes that are ISO/FDA compliant and can be easily integrated into the corresponding technical files. Our process follows the basic steps below:
Based on these inputs, we design both the medical device sterile barrier system that will prevent microbial contamination and the protective packaging that will protect both the product and the sterile barrier system during shipment. Next, we manufacture the packaging prototypes under worst-case manufacturing conditions. Next, we test the feasibility of these designs to ensure a high probability they will pass simulated distribution testing. Then, the customer approves the medical device packaging prototypes. Finally, we test usability.
All of our medical device package design work is conducted under an ISO 13485 quality system including requirements, specifications, test protocols, validation plans, and test reports, which are provided to the customer for their technical files. We also manage all outside testing services.
How is medical device packaging validated?
Packaging validation is complex and there are several processes that must be completed. The manufacturing process to produce the packaging’s sterile barrier system must be validated. This requires an Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) to be conducted on the manufacturing equipment.
Packaging performance testing must be completed. This includes manufacturing and sterilizing under worst-case conditions and subjecting the packaging system to simulated distribution testing.
A stability study must be completed and is done with both accelerated and real-time aging studies. Both the performance testing and stability study require tests for seal integrity and an evaluation of product protection.
Do orthopedic implants need to be double-packaged?
Short Answer: Not Always.
Richer answer: A dual or double pouch is typically used for providing a dual sterile barrier because the delivery of the device to the sterile field requires that the inner package be “dropped” into the sterile field. This is known as “good aseptic transfer technique.” There is no requirement from the FDA that all devices have a dual barrier; rather, it depends on the clinical application of the device, the physical features of the device, and nurse/surgeon preference. As a general rule, implants are most often packaged in a double barrier, while instruments and auxiliary devices are packaged in a single barrier, dependent on the risk profile defined by the customer.
How long does a medical device package design and validation take from start to finish?
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Package System Requirements
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Sterile Barrier Design
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Protective Package Design
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Prototyping
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Verification Testing
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Thermoforming & Sealing Tooling
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Thermoforming IQ/OQ/PQ
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Sealing IQ/OQ/PQ
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Device Assembly IQ/OQ/PQ
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Label Development
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Build OQ-Low for Transit Test
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Expose to Worst-Case Sterilization
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Transit Simulation
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Accelerated Aging Testing
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Seal Integrity Test
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Product and Packaging Stability Test
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Real-Time Aging Testing
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Seal Integrity Test
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Product and Packaging Stability Test
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Manufacturing PQ
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Single Lot Verification 1
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Single Lot Verification 2/3 (Additional 16 Weeks)
Package Design: 13-30 Weeks***
Sealing and Manufacturing Process Development: 16-24 Weeks for thermoformed trays, 8-20 weeks for pouch systems***
Transit Testing, Aging and Sterilization Testing: 13 Weeks – Real Time***
Transit Testing
Aging Testing
Sterilization Testing: 10-16 Weeks
*** Contact EMPS for detailed current duration estimates; post-pandemic market conditions fluctuate significantly and require current market spot-verification.
Are microbial challenges required for medical device packaging validation?
There is no universally accepted method of demonstrating microbial barrier properties, although there are efforts to address this that may eventually be incorporated into a standard. ISO 11607 Part 1 Section 5.2.2 indicates only that the microbial barrier requirement can be demonstrated by showing the material is impermeable. Annex C requires that impermeable materials for sterile barrier systems shall be tested for air permeance in accordance with ISO 5636-5. Contact Eagle to discuss your specific needs regarding this topic for more information.
Cleaning Validation
How does Eagle perform a cleaning validation?
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Process FMEA to determine possible sources of contaminants, including suppliers that touch the device
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Benchmarking non-cleaned parts
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Establishing acceptance criteria
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Grouping of samples by material type/family, cleaning process
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Identification of worst-case conditions to test
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Establishing a statistical rationale for sample size
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Establishing the cleaning process steps and parameters
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Post cleaning testing
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Establishing Alert and Action Levels
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Establishing post validation sampling plan and change control plan
Eagle uses approved protocols for all validations, including cleaning. The medical device cleaning validation is designed to show that contaminants that come in contact with the product during manufacturing and packaging are safely removed. These contaminants include organic residues such as oils/greases/lubricants, inorganic residues such as leftover particulates from processing, and microbiological contaminants such as airborne or surface acquired bioburden. The key components of the validation are:
What tests are used for a cleaning validation?
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Cytotoxicity: a test for overall safety, measuring if the device material or residuals are cytotoxic.
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Bacterial Endotoxin: a test of harmful endotoxin contamination, which is typically introduced by water and can be very dangerous to patients.
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Bioburden: a test of fungal or bacterial contamination.
Typically, testing covers three areas:
Is cleaning validation required for orthopedic implants?
If the orthopedic implant is cleaned prior to packaging, the cleaning process must be validated to ensure a high probability that the cleaning specifications are met (FDA CGMP). There have been numerous recalls in orthopedics caused by insufficient cleaning processes, which left patient harming contaminants on the product. A cleaning validation should be evaluated starting with a product and process FMEA that shows possible sources of contamination and their impact and severity.
Testing
Should the medical device packaging performance qualification (distribution simulation) be done at the same time as the product stability study (accelerated aging)?
This is a project cost-based answer. If the project can afford the expense and risk of a parallel packaging test failure, then yes, simultaneous testing is possible. If the answers are no, then a sequential test series is safer and minimizes the costs of test failure. ISO 11607-1 Section 6.4.4 indicates that stability testing and performance testing are separate entities. Stability testing tests the sterile barrier system and will demonstrate the shelf life of the sterile barrier. Performance testing tests how the packaging system responds to shipping and handling stresses and must demonstrate that expected shipping stresses do not compromise the sterile barrier.
Can Eagle perform additional testing required for product releases such as endotoxin or bioburden?
While Eagle does not perform the actual testing of the samples, we do have a laboratory that is on our approved alliance partner list that performs any required testing.
How does “worst case” manifest itself to package performance testing?
Per ISO 11607-1, section 8.2.2: performance testing shall be conducted on packaging systems comprised of the worst-case sterile barrier system as well as the worst-case protective packaging when your organization has multiple shipping configurations or product families that may or could be utilized. Industry wide best practice further leans toward the worst-case product configuration be contained within the WC system/package. A few things to consider when understanding or evaluating your “worst case” shipping configuration scenario:
• Mass of the product
• Geometry of the product (surface asperity, roughness, etc.)
• Weight of the entire packaging system
• Typical quantities that are shipped to customers
Ultimately, you may identify that you have competing worst-case scenario(s) that needs to be evaluated for performance testing. In some cases, you may be able to generate rationales based upon overall weight and mass. Eagle can help with your process, through Configuration Analysis, so the option you choose effectively proves that your sterile barrier system is safe and effective for transport.
Why does the standard separate accelerated aging and real-time aging from performance/dynamics testing?
ISO 11607-1 defines stability testing and performance testing as separate processes, evaluating different aspects of the sterile barrier package. Stability testing is accomplished through accelerated aging and real-time aging while performance testing focuses on environmental and distribution simulation. This allows separate testing and the option to perform testing either as a sequential series of tests on the same packages or simultaneously depending on your project budget. In real-time aging, test samples are pulled from the aging populations in target-specific interval order to evaluate physical package integrity for desired expiration dating. Evaluations using standard test methods such as ASTM F2096, “Standard test method for detecting gross leaks in porous medical packaging by internal pressurization (bubble test),” ASTM F1929, “Standard test method for detecting seal leaks in porous medical packaging by dye penetration,” and ASTM F88, “Standard test method for seal strength of flexible barrier materials” are then performed. These tests yield valuable advance knowledge of the behavior and performance of the selected packaging materials through accelerated aging. Using the sequential approach to testing allows the interaction between the packaging system and the protected product(s) to be evaluated as they respond to the stresses imposed by the manufacturing processes, sterilization processes, and the handling, storage, and shipping environments. Protocols such as ASTM D4169 followed by whole package and seal integrity testing on the same packages provide valuable advance knowledge of the behavior and performance of the selected packaging materials through the distribution environment at market release. The data obtained as a result of separating stability and performance testing provides the packaging engineer with valuable information on the packaging materials’ integrity performance over time and the packaging system’s integrity performance throughout the manufacturing process, sterilization process, and the subsequent handling, storage, and shipping environments. If you are having difficulty choosing between a sequential aging and package performance protocol or a separate entity protocol, contact Eagle. We’ll provide a risk-based evaluation of your proposed system and product that will help your team create a very rigorous validation of the packaging process.
Why do you need to include the Instructions for Use (IFU) when testing?
The IFU is a component within the package system that is typically inserted into the protective package. It is frequently loose and thereby allowed to move around within the package. We’ve seen instances where the IFU causes damage to the sterile barrier system or becomes damaged itself, potentially rendering the product incomplete for the User. If costs for IFU’s are a concern, consider using folded or stapled paper in the same configuration as the intended IFU.
Assembly and Manufacturing
Does Eagle offer Design for Manufacturing (DFM) services?
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Process FMEA analysis of your assembly needs
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Fixturing and assembly accuracy needs for your product’s optimal performance
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Electrical test for powered devices
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Software/firmware test for self-powered, software-driven devices
As your manufacturer of choice, we will always conduct DFM services for any project prior to launch. We believe it is in the best service to our customers and our production team to ensure that all designs are streamlined for manufacturing and can be assembled/produced as designed. Eagle provides support in the form of:
What is contract assembly?
Many medical device companies want to focus on what they do best, which is design life-saving medical devices. However, when it comes to assembling and producing the final device, it is inefficient for them to invest the resources and time to build, maintain, and staff a cleanroom environment which may only be operating for a fraction of the work week. That’s where a medical device contract manufacturing company like Eagle comes in. We operate cleanrooms with existing production lines available to assemble the most complex products. With medical device contract assembly, you only pay for the production time, and custom fixtures needed to assemble your device.
Do you offer distribution services for contract manufacturing customers?
Not presently. We feel it is more important to maximize our manufacturing space over finished goods storage in order to continue to expand our capabilities and capacity. Therefore, we do not offer distribution services for our contract manufacturing customers currently.
Can Eagle provide expedited services for manufacturing?
Yes, Eagle can provide expedited manufacturing services. This is just one of many offerings our customers benefit from and may utilize when needed. Inquire with your Eagle representative about our expedite schedules and costs.
Is Eagle capable of longer production runs or mass production?
Our Medical Device Manufacturing Team works with all sizes and levels of organizations and has flexible and scalable production lines to accommodate NPI volumes from intermediate to mass production. Depending on your volume forecast for product build(s), Eagle can flexibly manage your production capacity to build quantities that meet your goals.
Quality System
How fast can changes be made in your quality system?
For urgent situations, changes can be implemented within 48 hours of the request, as long as it does not impact the supply chain or require new material orders.
Is Eagle's quality system certificated?
Our quality system is an integrated system of documents, specifications, procedures, other records, and systems that are compliant to FDA and ISO 13485 (2016). We use external auditing via Notified Body to assure our compliance to our quality system. We also undergo routine and frequent supplier audits.
FDA Guidelines
How do we conduct a quality audit according to the FDA?
Each manufacturer shall establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited. Corrective action(s), including a reaudit of deficient matters, shall be taken when necessary.
What does the FDA say about production and process controls?
(a) General. Each manufacturer shall develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications. Where deviations from device specifications could occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications. Where process controls are needed they shall include:
(1) Documented instructions, standard operating procedures (SOP's), and methods that define and control the manner of production;
(2) Monitoring and control of process parameters and component and device characteristics during production;
(3) Compliance with specified reference standards or codes;
(4) The approval of processes and process equipment; and
(5) Criteria for workmanship which shall be expressed in documented standards or by means of identified and approved representative samples.
(b) Production and process changes. Each manufacturer shall establish and maintain procedures for changes to a specification, method, process, or procedure. Such changes shall be verified or where appropriate validated according to § 820.75, before implementation and these activities shall be documented. Changes shall be approved in accordance with § 820.40.
(c) Environmental control. Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions. Environmental control system(s) shall be periodically inspected to verify that the system, including necessary equipment, is adequate and functioning properly. These activities shall be documented and reviewed.
(d) Personnel. Each manufacturer shall establish and maintain requirements for the health, cleanliness, personal practices, and clothing of personnel if contact between such personnel and product or environment could reasonably be expected to have an adverse effect on product quality. The manufacturer shall ensure that maintenance and other personnel who are required to work temporarily under special environmental conditions are appropriately trained or supervised by a trained individual.
(e) Contamination control. Each manufacturer shall establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality.
(f) Buildings. Buildings shall be of suitable design and contain sufficient space to perform necessary operations, prevent mixups, and assure orderly handling.
(g) Equipment. Each manufacturer shall ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use.
(1) Maintenance schedule. Each manufacturer shall establish and maintain schedules for the adjustment, cleaning, and other maintenance of equipment to ensure that manufacturing specifications are met. Maintenance activities, including the date and individual(s) performing the maintenance activities, shall be documented.
(2) Inspection. Each manufacturer shall conduct periodic inspections in accordance with established procedures to ensure adherence to applicable equipment maintenance schedules. The inspections, including the date and individual(s) conducting the inspections, shall be documented.
(3) Adjustment. Each manufacturer shall ensure that any inherent limitations or allowable tolerances are visibly posted on or near equipment requiring periodic adjustments or are readily available to personnel performing these adjustments.
(h) Manufacturing material. Where a manufacturing material could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures for the use and removal of such manufacturing material to ensure that it is removed or limited to an amount that does not adversely affect the device's quality. The removal or reduction of such manufacturing material shall be documented.
(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.
What are the FDA’s rules regarding process validation?
(a) 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.
(b) Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met.
(1) Each manufacturer shall ensure that validated processes are performed by qualified individual(s).
(2) For validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented.
(c) When changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate. These activities shall be documented.
Now that’s the formal stuff of law and regulation; contact your Eagle representative to ask how this gets translated into our DHR structure, Work-Instructions, and Process Documentation.
What are the requirements for a Unique Device Identifier (UDI)?
A unique device identifier (UDI) must:
(a) Be issued under a system operated by FDA or an FDA-accredited issuing agency.
(b) Conform to each of the following international standards:
(1) ISO/IEC 15459-2, which is incorporated by reference at § 830.10
(2) ISO/IEC 15459-4, which is incorporated by reference at § 830.10 and
(3) ISO/IEC 15459-6, which is incorporated by reference at § 830.10.
(c) Use only characters and numbers from the invariant character set of ISO/IEC 646, which is incorporated by reference at § 830.10.
Eagle has deep and vast knowledge in the area of label symbology, layout, and production to meet your UDI needs.