10 PURCHASING AND ACCEPTANCE
ACTIVITIES
INTRODUCTION
Components
Accessory Devices
Contractors and Consultants
COMPONENT SELECTION AND VERIFICATION
PURCHASING AND RECEIVING OF PRODUCT
Specifications
Supplier Qualifications
Acceptance Procedures
Acceptance Criteria
Testing and Inspection of Product
Acceptance and Rejection Records
Obsolete, Deteriorated, and Rejected
Components
Component Storage
Component Traceability
Written Test Procedures
Sampling Plans
Control Numbers
CONTRACTOR AND CONSULTANT ASSESSMENTS
Interface Requirements
Process Validation Requirements
Device Servicing Requirements
CONTRACT STERILIZATION
Labeling Requirements
Quality System Requirements for
Contract Sterilization
Information Transfer
Record Keeping
Process Validation
Bioindicators and Dosimeters
Loading Configuration
Preconditioning
Cycle Parameters and Process Control
Post-sterilization Handling and
Aeration
History Records and Review
Finished Device Release
Audits of Both Facilities
Training
Nonconformance
FINISHED DEVICE EVALUATION
Sampling Plans
Labeling and Packaging Inspection
Records
Product Release
EXHIBITS
Purchase of Components
Acceptance of Components
Material Receiving and Inspection
Procedure
Identification Decals and Forms
Receiving Rejection Notice
This chapter covers component specifications, supplier assessment,
receiving components and the services rendered in manufacturing
medical devices. Manufacturers of medical devices should maintain
a consistent, systematic quality system which, along with other
quality assurance activities, should assure that all components,
materials, and services involved with the manufacture of medical
devices are acceptable for their intended use. This control is
a combination of: component and supplier selection and verification;
data collection, analysis and corrective action; supplier, contractor,
and consultant assessment; identification and status of product
including labeling and/or quarantine; and operational procedures.
The establishment and maintenance of requirements, including quality
requirements, is essential for the manufacturer when dealing with
component suppliers, consultants, and contractors [820.50(a)].
The ability to meet specified requirements is important when evaluating
the suppliers and service providers. Assessments of these providers
shall be maintained and documented. Possible appropriate methods
of accomplishing these goals include audits, checking with other
clients, and previous performance data. If prior assessment is
not possible, then the manufacturer should assess the service
as it is being performed. Assessment shall be documented. Procedures
for accepting incoming product shall also be established and maintained.
Various acceptance activities may include inspections, tests,
and other forms of verification. Acceptance or rejection of components
and services shall be documented (820.80).
Components
"Component" is defined in 820.3(c) of the Quality System
(QS) regulation as any material, substance, piece, part, software,
firmware, labeling, or assembly, which is intended to be included
in the finished, packaged, and labeled device. For example, fasteners,
blood tubing assemblies and labels are components. This definition
excludes "manufacturing materials," which by definition,
are not intended to be included as part of the finished, packaged,
and labeled device.
According to 820.3(p), "manufacturing material" is any
material or substance used in or used to facilitate the manufacturing
process, a concomitant constituent, or a byproduct constituent
produced during the manufacturing process, which is present in
or on the finished device as a residue or impurity not by design
or intent of the manufacturer. Examples of manufacturing materials
include: cleaning agents, mold-release agents, lubricating oil,
or other substance used to facilitate a manufacturing process
which is not intended by the manufacturer to be included in the
finished device.
Manufacturers of components sold only for further manufacturing
of a medical device are not required to comply with the GMP requirements
for finished devices. Many components of devices, such as transistors,
containers, hardware, etc., are readily available in the marketplace
and are not manufactured exclusively for use in devices. Many
of these manufacturers supply only a small fraction of their production
to finished device manufacturers. However, section 820.1 of the
Quality System regulation encourages component manufacturers to
use applicable GMP elements as guidance.
If a component is manufactured in the same or proximal facility,
and produced for use in finished medical devices, then the component
is considered part of the production of the finished devices and
is subject to the applicable requirements of the GMP requirements.
If the component is manufactured in a separate plant owned by
the finished device manufacturer, then the manufacturer has flexibility
in handling the quality assurance activities related to the control
of components. One satisfactory approach is to have the plant
that builds the components operate in full GMP compliance. Under
this arrangement, the plant which does the final device assembly
would still be responsible for ascertaining that the quality and
integrity of incoming components have not been damaged during
shipment. Alternately, the component manufacturing plant may not
fully comply with Quality System regulation. Then the plant that
does final assembly should handle the acceptance of these components
with the same degree of control as if the components were purchased
from an outside supplier.
For components such as labels, package inserts, packaging, etc.,
there is additional information in chapter 11, Labeling; and chapter
13, Packaging.
Accessory Devices
The Quality System regulation applies to manufacturers who produce
finished accessories to devices intended to be used for health-related
purposes. An accessory is any finished unit distributed separately
but intended to be attached to or used in conjunction with another
finished device. Therefore, any manufacturer of accessory devices
should meet all FDA regulations for a finished device. These regulations
include 21 CFR Part 807 Subpart E, Premarket Notification; 21
CFR Part 807 Subparts B, C., and D, Registration and Listing;
21 CFR Part 820, Good Manufacturing Practices (GMP); 21 CFR Part
801, General Device Labeling; 21 CFR Part 809, In Vitro Diagnostic
Labeling (if applicable); etc.
Contractors and Consultants
Contractors and consultants generally provide a service rather
than a physical component. This service should be treated in basically
the same manner as physical components because these services
affect the quality of the finished device. The combination of
both services and physical components determines the quality of
the finished device. Services should be obtained per 820.50, Purchasing
Controls, and be controlled upon receipt using the applicable
requirements in 820.30, Design Controls, 820.70, Production and
Process Controls; 820.80, Receiving, In-Process, and Finished
Device Acceptance, etc., depending on the nature of the service.
COMPONENT SELECTION
AND VERIFICATION
Verification of physical components is a very important step toward
producing a high quality product. Verification of components consists
of determining through documented testing that a component will
perform its function reliably in the intended application and
under the most adverse environmental conditions in which the device
is expected to be used. These conditions shall consider the needs
of the user and patient [820.30(c)] and shall encompass the manufacturer's
labeling claims for the device.
Components have to be carefully selected, using the requirements
of the device as a guide. Components should be chosen so that
they will not be over-stressed and will be compatible with the
internal device environment, as well as the external environment
that the device is expected to encounter during manufacture, distribution,
and use. The components should then be appropriately tested, alone,
and as part of the device, utilizing the specifications established
for the component and the device. New components or components
used in an unusual application will usually need extensive evaluation.
This evaluation should include parameter and life testing as well
as compatibility testing for both the internal and external environment.
Well known industry standard components that are used in their
normal application and that are not over-stressed will need only
minor testing, which is usually an integral part of the verification
of the device design. A record of any component verification testing
should be maintained. This record should include the component
identity and the testing methods that were used, as well as the
actual test data and results.
PURCHASING AND
RECEIVING OF PRODUCT
Component quality is maintained through correct specifications,
procurement, incoming acceptance, storage, handling, installation,
and change control. To monitor the adequacy of these activities
and procedures, feedback from the quality system is needed. Corrections
are made if necessary. In addition to maintaining quality, the
manufacturer shall also establish and maintain procedures for
identifying product during all manufacturing stages from receipt
through installation (820.60 and 820.86). Product includes components,
manufacturing materials, in-process devices, finished devices,
and returned devices.
Specifications
Component specifications are required as part of the device master
record. Components are selected and their specifications are documented
during the design of the device. The specifications should be
well designed, achievable, and acceptable to suppliers. They should
adequately describe the quality characteristics, dimensions, design,
materials, performance, and any other features necessary to assure
receipt of the item desired. For unusual, vital, new or key components
the specification data is derived primarily from the verification
data with minor details from the catalog data. For routine components,
such as those that have been used for a long time or have a known
performance history, a catalog designation may be adequate to
describe a component and assure its purchase. For some components
such as transistors, the catalog number also may be used to obtain
complete specifications from a reference manual. Specifications
should reflect both design requirements and quality/reliability
needs. The quality level for each component should be specified.
Components usually are available in several quality levels such
as reagent grade, commercial grade, military grade, etc. In some
cases, a significant increase in component quality can be obtained
for a modest increase in cost by specifying a higher grade, thus
reducing the probability of future quality problems and the possibility
of significant associated costs.
Supplier Qualifications
A major factor in obtaining high quality components is the selection
of suppliers. Although a manufacturer's knowledge of supplier
operations may be limited and information about the operations
difficult to obtain, the GMP requirement that a manufacturer is
responsible for quality remains undiminished. To the maximum extent
feasible, selection and qualification of suppliers by audits,
performance analysis, etc., should be part of a quality system.
If the manufacturer does not have the capability to test components
for conformance to specifications, then supplier test data or
outside lab results are acceptable provided that components are
tested and inspected in a statistically valid manner to show their
acceptability for use in the finished device. Any outside test
results should be accompanied by relevant raw data used for the
test so that judgments of authenticity may be made by the finished
device manufacturer. Excluding a supplier whose components are
unreliable from supplying components may help prevent problems
with the final device and is certainly worthwhile as a cost reduction
effort.
It is important to remember that raw components acquire cumulative
value as they are processed through receiving, assembly, test,
inspection, and as they ultimately become part of the finished
device. If a component fails during assembly, or as part of the
device, additional costs will be incurred for fault isolation,
removal, replacement, inspection, testing, etc. When field failures
occur, the ultimate cost of the component becomes even higher
because its replacement requires travel, trouble-shooting, and
retrofit. In addition, customer dissatisfaction, user injury,
product liability action, medical device reporting, or regulatory
action may result. Usually, the initial cost of a component is
relatively insignificant compared to the later cost should the
component prove to be defective or improper for the selected use.
Many recalls occur because manufacturers fail to qualify components
properly or to assure that a supplier's manufacturing methods
and quality system are adequate.
Acceptance Procedures
Written instructions are necessary to assure that components,
manufacturing materials, etc. are properly identified, processed,
and stored when received. Written inspection and test procedures
are necessary to prescribe the:
Before acceptance, all components should be either physically
separated (quarantined) or clearly identified as not yet accepted.
The decision to separate or tag not-yet-accepted product should
be made based on the characteristics of the device, the potential
for mixups, plant conditions, and manufacturing practices.
Although 820.80 requires a written procedure for accepting components,
the Quality System regulation in 820.5 allows discretion in the
quality system. Thus a very small manufacturer, usually 10 or
fewer employees, may only need very brief written acceptance procedures
referencing the purchase orders and receiving tickets. As the
size of the operation, the numbers of activities, and number of
people involved increase, the need for comprehensive written instructions
generally increases.
Acceptance Criteria
Manufacturers should have specific acceptance criteria for components.
Acceptance criteria are the attributes of a component that determine
its acceptability, such as appearance, dimension, purity, performance
characteristics, etc. Typically, acceptance criteria are made
a part of the inspection/test procedure. For example, if component
specifications or a drawing adequately describe the attributes
needed in order for the component to perform in its intended manner,
these may be used as the acceptance criteria. If components or
the suppliers of the components have a history of good performance,
the components may be accepted for use after a visual check to
assure they are the items intended and that they are not damaged
or contaminated. Components, which need only a visual inspection,
may be accepted using the purchase order data as acceptance criteria.
The purchase order and/or receiving ticket should at a minimum
contain the following information:
For a standard component, the catalog number may be used as a
description. QA personnel should determine whether the use of
any "abbreviated" criteria are adequate during their
audit of production rework, history records, complaint files,
and service records.
Testing and Inspection of Product
The minimum acceptance activity per current practice requires
that all incoming components and other product receive at least
a visual inspection for contamination and/or damage and be identified
as the component specified on the purchase order. A manufacturer
accepting the product has the discretion to determine when and
where product should be inspected, sampled, and tested for conformance
to specifications depending upon the risk that failure of that
component may pose. As appropriate, product may be tested and/or
inspected by:
If components are tested as part of the finished device, the testing
should be able to reveal failed and "out-of-spec" components
and not just that the finished device does not meet specifications.
This determination, of course, may be performed after removing
the component from the device. The rejection shall be documented
[820.80(b)].
Manufacturers who decide not to sample or test specific components
should be able to justify that decision based on such factors
as knowledge of the supplier's previous performance in providing
high quality components, the component performance history, and
application of the components in the device. Manufacturers may
rely on component suppliers to conduct testing if the manufacturer
specifies or is knowledgeable about the supplier's quality system,
particularly the inspection and test programs and the supplier
has specifications that properly define the manufacturer's acceptable
limits for the component or material parameters. These specifications
may be used to meet the device master record requirements for
component specifications, if these accurately reflect the parameters,
composition, and configuration required for the component to perform
the function for which it was selected. Supplier specifications
are usually adequate for standard components. However, a manufacturer
who relies on supplier specifications usually has no control over
changes in these and, therefore, should assure at an appropriate
point in the manufacturing process that the components received
meet the desired specifications.
If components are tested by the supplier, acceptance of components
can be based on certification and review of test data submitted
by the supplier for the specific components provided. Certification
should accompany each lot of components. When certification is
used, the manufacturer should periodically verify the validity
of the certification through an assessment of the supplier.
Where historical data shows that certain components or other product
have been substandard and resulted in a device failing to meet
specifications, or where performance history has not been established,
specific steps should be taken to assure components meet specifications.
Typically, this task is accomplished by sampling and testing each
lot of components to assure that the components meet specifications.
Where appropriate, all significant or high risk components should
be sampled and tested.
Manufacturers may test entire assemblies of components rather
than individual components. If, however, testing an assembly cannot
assure fitness-for-use of the components, then components should
be tested on an individual or lot basis, whichever is appropriate.
For example, assemblies with an internal feedback circuit could
have a very marginal component. Because of the circuit design,
the condition of the marginal component might not be detected
by testing the entire assembly. Therefore, the feedback loop in
the assembly should be opened during one of the tests, or the
individual components should be tested.
When using a contract laboratory to test production components,
the laboratory becomes an extension of the device manufacturer's
quality system. The device manufacturer is responsible for assuring
that the contractor's test and inspection procedures are acceptable.
This assurance maybe obtained by audits of the laboratory, by
the lab staff, and by the finished device manufacturer.
Inspection and testing will not improve the quality of components
or other product; however, if the inspection and testing is appropriate
and performed adequately, these activities can be used to prevent
or significantly reduce the use of low-quality or defective product.
Through feedback into the overall quality system, data on products
will help identify basic causes of problems and lead to solutions
(820.100). If problems are found, actions such as design changes,
tighter acceptance criteria, supplier assessments, or change of
suppliers may be appropriate.
Acceptance and Rejection Records
Adequate records shall be maintained to provide objective evidence
that components were inspected and accepted, or rejected. These
records are a part of the device history record and should be
maintained in a format that facilitates review. The records, however,
are not required to be maintained in a single file with other
production history records, and are typically filed in the receiving
or quality control area according to part number or component
nomenclature. Small manufacturers may use purchase orders or packing
slips to record acceptance and rejection if they contain adequate
information.
The Quality System regulation specifies in 820.80(b) that a record
of component acceptance and rejection be maintained. Typically,
acceptance/rejection records should contain:
Obsolete, Deteriorated, and Rejected Components
Obsolete, deteriorated and rejected components shall be identified
(820.60, 820.86, and 820.150) as such and be placed in a separate
quarantine area or specially identified area to prevent mixups.
If practical, components should be individually identified as
rejects. Where it is not feasible to tag each rejected component,
as in the case of transistors, bolts, bottles, etc., containers
or packages of rejected lots should be clearly marked and otherwise
appropriately segregated from accepted components. See 820.86
for clarification. Manufacturers should determine the need for
a separate written procedure for handling these components based
on the size of the manufacturer and complexity of their devices
and operations. Disposition of nonconforming product shall be
documented [820.90(b)].
Records for rejected components should state whether the components
were returned, scraped, reworked, etc. In very small manufacturers,
disposition can be recorded directly onto the purchase order,
receiving ticket, or other associated document. Small-to-medium
sized manufacturers generally record disposition on the form used
to receive components. Most large manufacturers record disposition
of rejected components on standard forms such as a Nonconforming
Material Report (NMR).
When components, materials, etc., become obsolete, many manufacturers
assign new identification numbers to the new version of these
components etc. The obsolete items are retained for other uses,
such as repair parts, engineering projects, etc. In these cases,
the old and new items should be adequately segregated and/or identified
to prevent inadvertent use of obsolete components in production.
Component Storage
Each manufacturer shall establish and maintain procedures for
control of storage areas and stock rooms for product to prevent
mixups, damage, deterioration, contamination, or other adverse
effects pending use or distribution and to ensure that no obsolete,
rejected, or deteriorated product is used or distributed. When
the quality of product deteriorates over time, it shall be stored
in a manner to facilitate proper stock rotation, its condition
shall be assessed as appropriate. 820.150 procedures shall be
established and maintained that describe methods for authorizing
receipt from, and dispatch to, storage areas and stock rooms.
Although not a direct requirement, all raw materials and components
used in the finished device should be received through a central
control point. Centralized receiving leads to orderly storage,
limits access to stored material, and aids a manufacturer in meeting
other GMP requirements. Components and other product should be
identified or stored so that it is obvious at all times that product
has been accepted, rejected, or is awaiting a disposition decision.
A quarantine area can be either a physically secure area or simply
limited access area identified as a quarantine area. If special
environmental storage conditions are required such as for many
biologically derived components, these conditions should be controlled
and monitored and the associated specifications included in the
device master record.
When the device is to be sterilized, storage conditions should
be selected, as appropriate, to prevent contamination of components
and packaging by bacteria or filth. Also, temperatures should
be controlled as necessary to prevent or reduce the growth of
bacteria. The higher bioburden (bacteria, etc.) levels may challenge
the sterilization cycle to an extent greater than the capability
established during process validation and, thereby, result in
a sterility assurance level that may not meet the finished device
specification. Some components, particularly those used in the
manufacture of in vitro diagnostic devices, if not stored properly,
may support growth of bacteria.
Component Traceability
The criteria as stated in 820.65 for determining the need to have
traceability via a unit, lot, or batch control number of a device
specifies devices intended for surgical implant into the body
or those that support or sustain life and whose failure to perform,
when properly used in accordance with instructions for use provided
in the labeling, can be reasonably expected to result in a significant
injury to the user. Identification of traceable devices should
be based on the health hazard presented if a device fails to meet
its performance specifications when operated as intended. Because
of the design control requirements (820.30), user error and the
environment are not considered by FDA as a means for excusing
the lack of device performance. User error is not a performance
failure, although it could be considered a result of inadequate
directions for use, other inadequate labeling, or poor human factors
design. The environment could result in failure of a device but
it should not effect the result of the device failure.
FDA is concerned about the failure of components that would result
in sudden or catastrophic device failure, which can reasonably
be expected to result in significant injury to the user, such
as:
A manufacturer should know in detail how the device functions
and the purpose of each component in the finished device. If as
a result of a failure, the performance, lack of performance, or
effect on safety or effectiveness of the finished device could
result in significant injury to the user when the device is properly
used in accordance with instructions in the labeling, the component
under consideration may require increased control and traceability.
The effect that each component will have on finished device performance,
should the component fail to perform as intended, should be determined.
Thus, manufacturers should carefully study the possible failure
modes of their devices and decide which components are truly critical
under the various modes. This determination may be time-consuming
with respect to some devices, but it is necessary. It will, in
the long run, save manufacturers liability, repair, and replacement
costs. To make such a determination, manufacturers should conduct
reliability tests and failure effects analyses during the design
phase in order to accurately identify critical components.
The number of components that need to be considered as potentially
needing to be handled as traceable components can be reduced by
considering the reliability of components and whether they "reasonably"
can be expected to fail. For example, power cords, clamps, plugs,
etc. seldom fail. Therefore, manufacturers may not need to consider
extensive tracing requirement of these components. Also, manufacturers
can consider a subassembly as a component and, thereby, reduce
the number of identification and record keeping activities, but
all rationale and justification should be documented.
Written Test Procedures
A device manufacturer shall establish and maintain procedures
to ensure that all purchased and otherwise received product conforms
to specified requirements (820.50) and establish and maintain
procedures for acceptance activities [820.80(a)]. The manufacturer
shall assure that all lots of components or other products are
accepted, sampled, tested and/or inspected using written procedures.
The inspection/test procedure for each component shall be correct
[820.30(d), Design Output and 820.30(h) Design Transfer], dated,
and approved. The design verification procedures usually may be
used to develop production test procedures. The procedure should
specify, as appropriate,:
Sampling Plans
When assuring that components and other products meet acceptance
criteria, manufacturers may test either all components or may
test a portion of the components using a sampling plan based upon
an acceptable statistical rationale (820.250). A manufacturer
shall be prepared to demonstrate the statistical rationale for
any sampling plan used. Plans should be developed by qualified
mathematicians or statisticians, or be taken from established
standards such as ANSI Z1.4. It should be recognized that all
sampling plans have a built-in risk of accepting a bad lot.
This sampling risk is typically determined in quantitative terms
by deriving the "operating characteristic curve" for
the selected plan. Each sampling plan has a characteristic curve.
ANSI Z1.4 contains operating characteristic curves for sampling
plans presented in the standards, and it can be used to determine
the risk a sampling plan presents. A manufacturer should be aware
of the risks the chosen plan presents. Operating characteristic
curves are a means of graphically showing the relationship between
the:
Control Numbers
Manufacturers of surgically implantable or life sustaining devices
whose failure to perform when properly used can be reasonable
expected to result in a significant injury shall establish and
maintain procedures for identifying with a control number each
unit, lot, or batch of finished devices and when appropriate components.
Control numbers should be assigned to each unit, lot or batch
of components that were manufactured under similar conditions
over the same time period so that defects can be traced to the
component manufacturer and the cause of the defects determined
and corrected. If a subassembly is regarded as a traceable component
by the manufacturer, a control number for that traceable subassembly
shall be recorded in the device history record.
CONTRACTOR
AND CONSULTANT ASSESSMENTS
Manufacturers shall establish and maintain the requirements, including
quality requirements, that will be met by contractors/consultants
that perform a service for them. To aid in accomplishing this
task each manufacturer shall:
Contractors and consultants often provide information or a service
rather than a physical component. However, the thought and control
processes are similar whether one is working with services or
with physical product. The input from contractors and consultants
have a definite impact on the finished device. Services may include:
design activities, various product verification/validation activities,
sterilization, routine maintenance, and calibration of equipment.
Each manufacturer shall provide adequate resources and trained
personnel to properly assess the activities of their contractors
and make adjustments as necessary. Contractors and consultants
maybe assessed based on their applicable education, experience,
ability, resources such as facilities and equipment, list of clients,
patents, technical reports, etc. Assessment may include conducting
internal quality audits [820.20(b)(2)]. Therefore, each manufacturer
that is having important work done by a contractor should inform
the contractor that their quality system and activities may be
audited. These services may include janitorial, consultants, design
work, calibration, sterilization, laboratory, and maintenance.
Interface Requirements
At various stages of product development the manufacturer may
need to interface with different groups. If a need for this interface relationship arises during
the design phase, a plan shall be developed describing the interface
with different groups or activities during the design process
[820.30(b)]. By planning for outside services, and including these
providers in selected design review meetings, a manufacturer increases
the probability of receiving a service that meets requirements.
Also the manufacturer is held responsible for work done by outside
contractors or consultants. Thus, it is in the manufacturer's
best interest to keep providers adequately informed and to monitor
contractors to ensure that the correct design, production, or
process controls are applied to contractor services to ensure
the service or finished product conforms to its specifications
(820.30, 820.50, 820.70, and 820.80).
Process Validation Requirements
Regardless of whether a manufacturer or a contractor performs
the actual work, the manufacturer is responsible for establishing
and maintaining control of the process parameters for the validated
process (820.75). Established procedures for validation and the
validation results should offer a high degree of assurance that
the process consistently produces an output that meets pre-established
specifications. Validated processes shall be performed by a qualified
person(s) and be documented regardless of whether the manufacturer
or an outside contractor performs the validation activities. For
more information see Process Validation, chapter 4.
Device Servicing Requirements
If a manufacturer contracts for device service with another party,
the assessment and selection of such contractors shall be done
according to 820.50 Purchasing Controls. Such service activities
and reports should be periodically reviewed to assure that the
service activities meet GMP servicing requirements as briefly
described below.
Device servicing performed by contractors and/or consultants shall
be conducted using established procedures for performing and verifying
that the service meets specified requirements (820.50 and 820.200).
A written report on the servicing shall include:
1. the name of the medical device serviced;
2. any device identification(s) and control number(s) used;
3. the date of service;
4. the individual(s) servicing the device;
5. the service performed; and
6. the test and inspection data.
Each manufacturer should analyze the service reports they receive
directly, as well as the ones they receive from contractors, using
the appropriate statistical methodology referenced in 820.100.
It is important that this service data be collected and organized
such that it can be analyzed to determine if quality problems
exist. See Chapter 15, Complaints, for more details. If the report
represents an event which is reportable to FDA under medical device
reporting (MDR) requirements in 21 CFR part 803 or 804, these
reports shall be handled as complaints using 820.198.
Contract agreements between the manufacturer and contractors and/or
consultants will vary in their degree of complexity. The most
comprehensive is probably the agreement between the manufacturer
and the contract sterilizer. Thus, the contract sterilization
agreement is an excellent example of what is involved in setting
up a contract between the device manufacturer and a contractor.
The steps necessary for an agreement may be less extensive with
other contracts than it is with the sterilization contract; however,
the sterilization contract does provide a good basis for understanding
this contractual agreement.
Manufacturers of medical devices frequently use contract sterilizers
to provide sterilization processing for their devices prior to
distribution. Contract sterilization of medical devices shall
be performed so that the device manufacturer and the contract
sterilizer meet the applicable parts of both the QS regulation
and the labeling requirements of 21 CFR 801.
Labeling Requirements
Manufacturers of sterile devices commonly label devices as sterile
at one establishment and ship them to another facility or to a
contract sterilizer for sterilization. Shipments of nonsterile
devices labeled as sterile are clearly misbranded and adulterated,
and they may be diverted into consumer channels, thus creating
a health hazard. FDA recognizes that this longstanding practice
is an economic necessity for many manufacturers. Therefore, to
meet the needs of these manufacturers in a way that will also
assure the protection of the public health, FDA added Part 801.150(e)
to the Code of Federal Regulations (CFR). This part identifies
the necessary markings for such shipments and requires a written
agreement which specifies the sterilization process. Part 801.150(e)
It is reprinted below:
(e) As it is a common industry practice to manufacture and/or
assemble, package, and fully label a device as sterile at one
establishment and then ship such device in interstate commerce
to another establishment or to a contract sterilizer for sterilization,
the Food and Drug Administration will initiate no regulatory action
against the device as misbranded or adulterated when the nonsterile
device is labeled sterile, provided all the following conditions
are met:
(1) There is in effect a written agreement which:
(i) Contains the names and post office addresses of the manufacturers
involved and is signed by the person authorizing such shipment
and the operator or person in charge of the establishment receiving
the devices for sterilization.
(ii) Provides instructions for maintaining proper records or otherwise
accounting for the number of units in each shipment to insure
that the number of units shipped is the same as the number received
and sterilized.
(iii) Acknowledges that the device is nonsterile and is being shipped for further processing, and
(iv) States in detail the sterilization process, the gaseous mixture
or other media, the equipment, and the testing method or quality
controls to be used by the contract sterilizer to assure that
the device will be brought into full compliance with the Federal
Food, Drug and Cosmetic Act.
(2) Each pallet, carton, or other designated unit is conspicuously
marked to show its nonsterile nature when it is introduced into
and is moving in interstate commerce, and while it is being held
prior to sterilization. Following sterilization, and until such
time as it is established that the device is sterile and can be
released from quarantine, each pallet, carton, or other designated
unit is conspicuously marked to show that it has not been released
from quarantine, e.g., "sterilized awaiting test results"
or an equivalent designation.
Quality System Requirements for Contract Sterilization
The sterilization process are performed in compliance with applicable
parts of the Quality System regulation for medical devices because
sterilization is a manufacturing process. Thus, the contract sterilizer
is a manufacturer [(820.3(o)] and the device master record (DMR)
shall contain, or refer to, the location of sterilization process
specifications. Process specifications may be generated by either
the manufacturer, contract sterilizer, or by both parties, although
overall responsibility rests with the finished device manufacturer.
The device manufacturer is ultimately responsible for assuring
that its devices are sterile. The responsibility for specific
tasks may be delegated to a contract sterilizer, but the device
manufacturer retains the ultimate responsibility. The contract
sterilizer is subject to those parts of the QS regulations that
apply to the operations that it performs for the finished device
manufacturers, e.g., equipment maintenance and calibration, in-process
controls, and associated record keeping, etc. Thus, both the manufacturer
and the contract sterilizer share the responsibility to comply
with the QS regulation in assuring effective sterilization.
Because the responsibility for effective sterilization is shared
between the device manufacturer and the contract sterilizer, it
is essential that the two parties clearly define in writing the
division of responsibility for every aspect of the sterilization
process. The QS arrangements between the manufacturer and the
contract sterilizer may be in the same written agreement used
to cover the 801.150(e) labeling requirements. It is the manufacturer's
and contractor's responsibility to assure the agreement is a workable
practical document and is followed by both parties. FDA inspects
finished device manufacturers and contract sterilizers to determine
compliance. The following is QS related information that should
be in the written agreement for contract sterilization and implemented
during production, sterilization, and release.
Information Transfer
The manufacturer and contract sterilizer should designate the
individual(s) at each facility responsible for coordinating the
flow of information between establishments and for approving changes
in procedures. All technical, procedural, and other information
that pertains to the sterilization process and associated activities
should pass through these designees. The manufacturer and the
contractor shall agree to inform one another of any device or
process changes, especially those that may require cycle requalification.
Record Keeping
Documentation such as device master record procedures, device
history records, etc., to be used and maintained should be specified.
If changes are made to the documentation, both parties should
agree on the manner in which the changes are to be made. These
documentation changes shall comply with QS requirements in 820.70(b)
and .75(c) for manufacturing and process specification changes,
and with 820.40(b) for changes in device master records.
Process Validation
The device manufacturer has primary responsibility for the validation
of the process used to sterilize its devices. Commonly, responsibility
for portions of the validation study are delegated to the contract
sterilizer in the written agreement. The manufacturer should work
with the contract sterilizer to assure that the facilities, equipment
and processing parameters (including preconditioning and aeration
steps) will provide for effective sterilization and will not adversely
affect the devices or their packaging. Validation is required
for every device or device family. The written agreement should
identify responsibility for all aspects of validation and define
the criteria, frequency, and responsibility for requalification.
Likewise, the agreement should identify the documentation that
is maintained for validation studies.
Bioindicators and Dosimeters
The agreement should specify responsibility for placement, retrieval,
handling, and processing of product samples and any biological,
chemical, or physical indicators. The agreement should include
instructions for packaging and shipment of indicators and samples
to test laboratories for analysis.
Loading Configuration
The loading parameters for each lot of device(s) or device family
should be specified. The routine product load configuration should
conform to the validated load configuration. It is not recommended
that a contract sterilizer mix products from different manufacturers
in processing cycles unless validation studies have proven the
effectiveness of the cycle for those mixes or worst case mixes,
and the customers are informed about the practice.
Preconditioning
The agreement should address preconditioning requirements for
external preconditioning and/or in-chamber conditioning if required
by the sterilization process.
Cycle Parameters and Process Control
The written agreement should specify the cycle parameters to be
achieved during processing. After the process is qualified, the
contract sterilizer is responsible for maintaining control over
the process to make certain that process specifications are routinely
achieved. Cycle parameters should be clearly defined in written
specifications, accurately monitored, and the actual parameter
values achieved during each run should be recorded.
The primary manufacturer should produce the product under a quality
system, which includes appropriate environmental control procedures
such as bioburden control. Thus, the product is the "same"
product as that for which the original process was developed or
specified.
Post-sterilization Handling and Aeration
The agreement should address procedures for post-sterilization
quarantine of the product before release for distribution. While
waiting for release, the pallets, cartons, or designated unit
shall be marked to indicate the status of the product; for example,
"sterilized: awaiting test results," or an equivalent
statement. If an aeration period is required, it should be specified.
Both parties should acknowledge that the product is not to be
shipped for commercial distribution until it is properly approved
for distribution in accordance with procedures in the agreement.
If correctly labeled, a device that has been sterilized may be
shipped to a controlled distribution point before final
release by the manufacturer. Routine distributors are NOT
considered to be "controlled distribution points." Shipments
to a company warehouse or to another finished device manufacturer
may be acceptable as long as the manufacturers are able to show
that they have control of the product until final release and
could recall it if necessary. See CFR 801 Subparts A & E and
QS sections 820.160, Distribution, and 820.80(d), Final Acceptance
Activities.
History Records and Review
Both the manufacturer and contractor should agree on the procedures
and responsibility for reviewing and approving the device history
records.
Finished Device Release
The agreement should include device release procedures. Individuals
responsible for approving device release for distribution should
be identified. A contract sterilizer may handle the final release
of a batch of sterilized devices. The manufacturer should make
sure, however, that this agreement is part of a written contract.
In addition, the manufacturer should: audit or have a consultant
audit the contract sterilizer; review the contractor's own QA
audit report; or obtain written certification of compliance to
assure that personnel and procedures are adequate to meet the
requirements of 820.160, Distribution, and, 820.80(d), Final Acceptance
Activities.
Audits of Both Facilities
The device manufacturer should audit his quality system and assure
by audits or other means such as a review of the contractor's
own QA audit that the contractor has adequate control over the
sterilization process. The agreement should cover the extent and
frequency of the audit, corrective actions, records, confidentiality,
and the auditor(s).
Training
The manufacturer should assure that the entire sterilization process
is performed and controlled by properly trained operators. The
agreement should provide the manufacturer access to applicable
training records during agreed upon audits.
Nonconformance
Both parties should mutually agree to inform one another if the
device or process deviates from the agreed upon specifications.
As appropriate, the nonconformance should be investigated, evaluated,
and, if necessary, corrective actions should be instituted. The
parties should consider and agree on conditions requiring corrective
action and document all reprocessing. The agreement should specify
the individuals that should be contracted regarding any changes
or deviations in the manufacturing or sterilization process. It
should also specify the individual at the manufacturer that should
be contacted when product is damaged to determine how the product
should be handled at the contract sterilizer.
It is highly recommended that manufacturers of sterile medical
devices read Sterile Medical Devices-A GMP Workshop Manual. This
publication may be obtained from National Technical Information
Services (NTIS), phone: 703-487-4650. The ordering number is:
PB84188713. As of 7/96 the price is $71.50 for a paper copy and
$12.50 for a microfiche copy.
Finished device inspection is typically a final test and review
of safety, performance, labeling, appearance, and configuration
characteristics to assure the device meets the acceptance criteria
established in the DMR. For many medical devices this assurance
requires an analysis, electrical test, mechanical test, or other
technical tests. For some simple devices, however, such as eyeglass
frames, a visual or dimensional check may be sufficient to prove
acceptability. For both simple and complex devices the manufacturer
shall have written specifications or criteria for determining
the acceptability of the finished device. It is important that
the device characteristics to be evaluated are defined and also,
where applicable, the equipment, environment, and handling procedure
should be defined and established.
Sampling Plans
To show the manufacturing process is operating in a state-of-control,
the process may need to be validated as explained in chapter 4,
Process Validation. Testing product by using a sampling plan based
upon an acceptable statistical rationale may demonstrate that
the process continues to operate in a state of control. A manufacturer
should be prepared to demonstrate the statistical rationale for
any sampling plan used. Plans should be developed by qualified
mathematicians or be selected from established standards such
as ANSI Z1.4. Copies of this standard may be obtained by writing
to: American National Standards Institute, 11 West 42nd Street,
13th Floor, New York City, NY 10036, or phone 212-642-4900.
All sampling plans have a built-in sampling risk of shipping devices
that do not meet product specifications. Each sampling plan can
be graphically illustrated to show the relationship between: the
quality of lots submitted for sampling inspection and the probability
that the sampling plan will yield a decision to ship the lot.
ANSI Z1.4 contains operating characteristic curves for sampling
plans presented in them. These curves can be used to determine
the risk each sampling plan presents.
When sampling plans are used, there exists the possibility that
a few defective devices will be shipped to the user. Thus, manufacturers
should be aware of the risks a particular plan presents to the
manufacturer and to the user. Questions such as those listed below
should be considered before selecting a sampling plan.
Manufacturers should recognize that straightforward logical answers
to these questions may not always be suitable. Acceptance status
for devices may be influenced by the price the user is willing
to pay -- 100 percent testing usually costs more than sampling.
Destructive testing makes 100 percent testing impossible. Whether
sample testing and inspection of a particular family of devices
is acceptable to the user also changes with technology. Where
100% valid automatic testing is not feasible, validation of the
process and the product with a follow up sampling plan is usually
the preferred method of establishing and maintaining a quality
system, which can continuously produce a device that meets specifications.
Each manufacturer shall establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that it meets its current approved specifications. Rework and reevaluation activities, including a determination of any adverse effect from the rework upon the product, shall be documented in the device history record (DHR) [820.90(b)(2)].
When a device fails testing, it should not be repeatedly retested
until it passes. The problem should be corrected. If a manufacturer's
acceptance procedures allow acceptance after repeated testing
and rework, there should be a valid basis for such an acceptance
procedure. Failed devices shall be identified and segregated from
acceptable devices and from the flow of the production process.
Labeling and Packaging Inspection
The manufacturer shall establish and maintain procedures to control
labeling. This control includes the label's integrity, inspection,
storage, control numbers, and labeling related operations (820.120).
The manufacturer shall control labeling and packaging operations
to prevent labeling mixups. The label and labeling used for each
production unit, lot, or batch shall be documented in the DHR
[820.120(d)]. Where a control number is required by 820.65, that
control number shall be on, or shall accompany, the device through
distribution [820.120(e)]. The DHR shall include or refer to the
location of the primary identification label and labeling used
for each production unit [820.184(e)].
The manufacturer shall ensure that the 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 (820.130, Device Packaging).
This may include containers and packaging examination as applicable
to assure they are not damaged or misbranded. All devices shall
have the correct labels, package inserts, and/or manuals as specified
in the DMR.
Records
A DHR is a compilation of records containing the production history
of a finished device [820.3(i)]. However, procedures for establishing
and maintaining DHR shall be developed. These records demonstrate
the device is manufactured in accordance with the DMR. The DHR
shall include or note the location [820.80(e), 820.184] of:
The DHR should be reviewed before distribution because these records
are used to show that finished devices are manufactured in accordance
with, and meet, the specifications in the DMR.
Beside these requirements, some device manufacturers should fulfill
an additional traceability requirement if their device is intended
for surgical implant into the body or to support or sustain life
and whose failure to perform when properly used in accordance
with the label instructions for use can be reasonably expected
to result in a significant injury to the user. For these devices
procedures shall be established and maintained to identify a control
number for each unit, lot, or batch of finished devices and, where
appropriate, components. The control number is used to trace a
defective lot and facilitate corrective action. Identification
of devices shall be documented in the DHR (820.65).
Product Release
Finished device manufacturers shall have sufficient controls to
assure that only devices that have passed test and inspection
are released as discussed in chapter 14, Storage, Distribution
and Installation. The manufacturer shall establish and maintain
procedures for identifying product during all stages of receipt,
production, distribution, and installation to prevent mixups (820.60).
Each manufacturer shall establish and maintain procedures for
finished device acceptance to ensure that each production run,
lot, or batch of finished devices meets acceptance criteria. To
prevent mixups, not-yet-accepted and rejected devices shall be
controlled to prevent mix up with devices that have been through
final evaluation and accepted for release [820.80(d)]. Methods
of controlling non-releasable product include storage location,
boxing, or manifest tagging. The desired end result is to assure
operations are in a state-of-control. Finished devices should
not be released for distribution until:
Examples of forms that may be used for purchasing, accepting,
receiving, and inspecting components are exhibited at the end
of this chapter. These examples show the types of information
required by the Quality System regulation. Procedures and forms
for a particular situation may be more or less comprehensive than
these, and may assume other formats or arrangements according
to need.
Purchase of Components
This exhibit is a specification for purchasing a zener diode and
is typical of device master record documents that are used to
purchase components. This spec describes the diode in sufficient
detail for the correct part to be procured.
Acceptance of Components
This example is intended as an acceptance procedure that may be
followed by a small to medium size manufacturer. The procedure
has space for the number, revision level, and a blank for "ECN
History." The history blank is for adding brief notes about
changes that have been made to this procedure. Included as part
of this procedure is a "Receiving History Log" which
immediately follows the procedure. The other forms mentioned in
the procedure are not reprinted; however, similar forms are included
with the "Procedure for Receiving and Inspection of Material"
described below with the example located immediately following
the "Receiving History Log."
Material Receiving and Inspection Procedure
This document is a more extensive receiving procedure than the
one discussed above and it can be used by a medium to large manufacturer.
As part of this procedure you will note an extensive revision
record section. Also, part of the procedure is a flow chart which
outlines the steps in the procedure and the branches for each
step. Next is a "Daily Report of Goods Received" which
includes the supplier name, quantity received, lot number or item
number, purchase order or requisition number, and information
on where the item was sent. The next item in the procedure is
a "Receiving and Inspection Report" which contains information
about the item and the sampling and testing performed on the item.
The report includes an acceptance or rejection slot along with
a space for the cause for rejection. The procedure continues with
a "Daily Inspection Log" which is a summary of the items
received and their disposition, either accepted or rejected. Finally,
as part of the procedure, we find examples of the decals to be
used to accept, reject, or quarantine the incoming items.
Identification Decals and Forms
Examples of decals and travelers used to identify materials, components
and in-process assemblies are exhibited. Two of the decals deal
with components and can be used as a means of assuring proper
disposition of these items. A "Material Lot Identification"
is exhibited which is used to identify components in a container.
This form has space for, among other information, lot number,
expiration date, quantity in the subject container, date it was
issued to stock, and the person who received the container. The
final example in this group is a "Stock Requisition"
form, used whenever items are being released from stock to production.
This form contains information such as, part number, quantity
ordered and issued, and lot number. Note that part of this form
is used to indicate if the issued item is to replace a defective
item.
Receiving Rejection Notice
This form is used when incoming components and materials are rejected
and includes sections for the inspector's report listing the sampling
plan, specification tested for, number of defects, and a description
of the defects. There is a section for a preliminary review, if
necessary, and finally a section for the Material Review Board
(MRB) decision on the disposition of the rejected lot. A MRB may
accept temporary deviations that do not affect safety and effectiveness.
These deviations or changes should be approved by the MRB or other
designee. MRB activities should be performed per a written procedure
and otherwise meet GMP requirements. The MRB should not change
a device master record (DMR) drawing or be used as a substitute
for the primary change control system of a manufacturer.
Sheet 1 of 1
TITLE: IN4278 ZENER DIODE SPECIFICATION NUMBER
Drafted by App. Date
REV. ECN History Date
1. SCOPE: This specification describes a onewatt zener diode
used for voltage reference in the XYZ Stimulator.
2. ELECTRONIC CHARACTERISTICS
2.1 Zener Voltage: 3.1 vdc @ 76 madc
2.2 Maximum Zener Impedance: 10 ohms @ 76 madc
2.3 Reverse Leakage Current: (25%) 100 microamps (max) @ l vdc
3. TESTING: All diodes shall meet the requirements of JANTX IN4278
as specified in MILS19500/127G.
4. PHYSICAL CHARACTERISTICS
4.1 Diodes shall be packaged in a voidfree silicone case.
4.2 Leads shall be readily solder able.
5. MARKING
5.1 The cathode shall be identified by a color band.
5.2 An identification number and lot number or date code shall
represent a specific manufacturing period.
5.3 All markings shall be permanent such that cleaning solutions
will not remove the markings.
6. CERTIFICATION
6.1 A certification of compliance with this specification and
a test data sheet must accompany each lot shipped.
6.2 Certification must include a statement that no changes have
been made in materials or physical or electrical characteristics.
7. APPROVED SUPPLIERS
7.1 XXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXX
TITLE: ACCEPTANCE OF COMPONENTS Sheet 1 of 3
No. Rev. ECN History
_______________________________________________________________________________
Drafted by App. by Date
1.0 SCOPE
These procedures are to be followed in the receipt, inspection,
and storage of product such as raw materials, components, parts,
manufacturing materials, etc., used in the manufacture of the
XYZ Stimulator, a device that does not require traceability per
820.65.
2.0 RECEIVING
2.1 All incoming shipments must be examined for external signs
of damage. If the shipment is damaged, immediately notify Purchasing
and move the shipment to the unloading Hold area until disposition
is decided by Purchasing.
2.2 Upon receipt, check each shipment against the corresponding
purchase order and verify identity and quantity. The purchase
order may include, reference, or have attached purchase specifications.
2.3 Enter the appropriate data into the Received Goods Log for
each shipment received.
2.4 After completing the data entry, attach a yellow "HOLD"
tag to the product and immediately move the products to the receiving
quarantine area. The pink copy of the purchase order must accompany
the product.
2.5 Notify Quality Control when materials requiring inspectionare
received in the quarantine area. This information is obtained
from the device master record specification for the item ordered.
2.6 Quality control shall, after examining the product for damage
and identity, move the product, etc., to be inspected to the Receiving
Inspection area.
3.0 INSPECTION
3.1 Pull the inspection history file for the product to be inspected.
This file contains the Receiving History form and inspection procedure.
Enter the appropriate data from the purchase order onto the Receiving
History form and perform the inspection per the procedure.
Sheet 2 of 3
3.2 The QC manager shall assign a five digit lot number to each
supplier lot received and enter the number on the Receiving History
form.
3.3 After the inspection is completed, enter on the Receiving History form:
a. the quantity accepted and sent to stock;
b. the quantity rejected; and
c. your signature and the date.
4.0 DISPOSITION
4.1 Receiving and test data for each shipment are sent to the
designated individual for review and the decision regarding the
acceptability of the lot.
4.2 For accepted product, enter the quantity accepted, date accepted,
and lot number on a green "ACCEPTED" tag, attach the
tag to the product, etc., and move it the stockroom.
4.3 For rejected product attach a red "REJECTED" tag
to the rejected product and complete a Rejected Material form.
Place all rejected product in the rejected quarantine area and
forward the Rejected Material form to Quality Engineering for
disposition.
5.0 STOCKROOM
5.1 All items entering the stockroom must be accompanied by a
green "ACCEPTED" tag.
5.2 Components and other materials shall be stored and issued
per SOP 17320.
5.3 Components and other materials will be issued from the stockroom
on a first-in, first-out basis. All materials with a limited shelf
life or requiring controlled storage conditions will be stored
appropriately per SOP 17321.
Note: Sheet 3 is the Receiving History log for this procedure.
The other forms mentioned in this procedure are not reprinted.
However, similar forms are included with another procedure located
later in this chapter.
Updated January 1, 1997
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