This guidance was written prior to the February 27, 1997 implementation of FDA's
`Good Guidance Practices, GGP's. It does not create or confer rights for or on any person
`and does not operate to bind FDA or the public. An alternative approach may be used if
`such approach satisfies the requirements of the applicable statute, regulations, or both.
`This guidance will be up dated in the next revision to include the standard elemnt s of GGP 's .
`
`ALL 2078
`PROLLENIUM V. ALLERGAN
`IPR2019-01505 et al.
`
`

`

`SHELF LIFE OF MEDICAL DEVICES
`
`April 1991
`
`Geoffrey S. Clark
`Microbiologist
`Division of Small Manufacturers Assistance
`Office of Training and Assistance
`Center for Devices and Radiological Health
`Food and Drug Administration
`
`

`

`TABLE OF CONTENTS
`
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`
`INTRODUCTION
`
`STABILITY CRITERIA AND VARIABLES
`
`RECOMMENDATIONS
`
`REGULATIONS
`
`FDA POLICIES
`
`CDRHGUIDANCE
`
`GLOSSARY
`
`REFERENCES
`
`NOTE :
`
`The excerpts of documents included throughout this
`
`paper have been edited .
`
`

`

`INTRODUCTION
`
`The potential benefit from the use of a medical device ranges
`from relieving minor irritations to correcting life threatening
`conditions. If the device design and manufacturing processes are
`done adequately, there is a high probability that the device will
`perform as desired at the time it is manufactured. However,
`there are many naturally occurring factors that can affect how
`long after manufacturing the device will maintain the ability to
`fully perform the intended function.
`
`Shelf life is the term or period during which a commodity remains
`suitable for the intended use. An expiration date is the
`termination of shelf life, after which a percentage of the
`commodity, e.g., medical devices, may no longer function as
`intended. To determine if a particular device requires a shelf
`life and assign an expiration date, there are a number of
`different parameters that must be considered. The device must be
`analyzed to determine if it is susceptible to degradation that
`would lead to functional failure and the level of risk that the
`failure would present. For some devices, e.g., tongue
`depressors, it is not reasonable to assign a shelf life because
`of the small likelihood of time-dependant product degradation and
`the lack of serious consequences if it did fail to perform as
`designed. For certain devices susceptible to degradation that
`are intended to treat life-threatening conditions, e.g.,
`pacemakers, the failure rate should approach zero within the
`labeled shelf life.
`
`The purpose of this document is to:
`
`inform readers of the Food and Drug Administration (FDA)
`regulations and policies relating to shelf life of medical
`devices.
`
`discuss the various parameters that determine the length of
`time a particular device will remain within acceptable
`specifications;
`
`outline the different activities that can be undertaken to
`establish the shelf life of a device; and
`
`STABILITY CRITERIA AND VARIABLES
`
`The United States Pharmacopoeia (USP) defines stability as "the
`extent to which a product retains, within specified limits, and
`throughout its period of storage and use, i.e., its shelf life,
`the same properties and characteristics that it possessed at the
`time of manufacture." There is no one exhaustive set of criteria
`that would apply equally to all medical devices. The USP has a
`section <1191> entitled "Stability Considerations in Dispensing
`Practicen that supplies general information on this topic. It
`includes a list of five sets of criteria for acceptable levels of
`stability for drug products as follows on the next page:
`
`

`

`1. chemical,
`physical,
`2.
`microbiological,
`3.
`therapeutic, and
`4 .
`5. toxicological.
`
`Although this set of criteria applies specifically to the
`evaluation of drug product stability, it is useful as a starting
`point in developing a set of criteria to evaluate the stability
`of medical devices.
`
`The following outline may be useful in identifying parameters
`that could significantly affect the shelf life of a device, even
`though all of the criteria will not apply to every device. This
`outline is based on the criteria listed above with the addition
`of biocompatibility.
`
`Chemical
`
`Degradation: Do any active ingredients or components of the
`device degrade over time in a manner which adversely affects
`device safety or performance?
`
`Interactions: Do ingredients or components interact to
`alter the device? Does the device have interactions among
`the various components that cause degradation of the ability
`to perform the intended function?
`
`Device and Packaging Interaction: Is there interaction
`between the device and package that has undesirable affects?
`
`Radioactive Decay: Does the device contain radioactive
`material with a relatively short half-life? Do the
`radioactive decay by-products alter the safety or
`effectiveness of the device either by themselves or through
`further interaction?
`
`Manufacturing: Do any of the manufacturing processes alter
`the chemistry of the raw materials, components, or finished
`device in a manner which adversely affects device Safety or
`performance?
`
`Physical
`
`Physical Characteristics: Does the device have physical
`characteristics that vary with time; e.g., appearance,
`viscosity, elasticity, tensile strength, burst strength, or
`electrical resistance? In some cases, a significant change
`in appearance may cause concern to the user even though the
`performance of the device is not affected.
`
`

`

`2.2 Manufacturing Process: Do the different steps in the
`manufacture of the device affect the physical
`characteristics of the individual components or the finished
`device in a manner which adversely affects device safety or
`performance?
`
`2.3 Storage Conditions: Do the storage conditions, e.g.,
`temperature, humidity, light, etc., have an affect on the
`device in a manner which adversely affects device safety or
`performance?
`
`3.
`
`Microbiological
`
`3.1 Sterility: Do sterile devices remain sterile? Maintenance
`of sterility is primarily determined by the maintenance of
`package and seal integrity.
`
`3.2 Environmental Control: Is an environmental control program
`needed during manufacturing or storage to monitor and adjust
`the microbial load in or on the device and packaging below
`an established tolerance level to prevent adverse
`degradation of the product?
`
`3.3 Antimicrobial Effectiveness: Does the device lose the
`ability to perform the intended antimicrobial function?
`
`3.4 Integrity: Do the device's barrier characteristics change?
`
`3.5 Preservative Effectiveness: If the device uses a
`preservative system, how long does the preservative system
`retain effectiveness within tolerance levels?
`
`4 .
`
`Therapeutic: Does the ability of the device to perform the
`intended therapeutic or diagnostic function change under
`storage or use conditions?
`
`5. Toxicological: Do device degradation by-products form
`during storage or use that produce an adverse toxic effect?
`
`6. Biocompatibility: Does the biocompatibility of the product
`change adversely during storage or use?
`
`There are numerous variables that affect the shelf life of a
`medical device. Some of these were discussed in the stability
`criteria outline above while additional product dependent
`variables are listed below. Although manufacturers may not be
`able to control all of the variables, their affect on device
`performance can be minimized if properly considered. Each of the
`categories listed below should be addressed during the
`preproduction estimation of product shelf life and the actual
`determination of the shelf life for normal production units. A
`written procedure for determining the necessity of a shelf life
`and setting the shelf life of a finished medical device should be
`used to avoid missing an important aspect and to provide needed
`
`

`

`documentation. While developing these written procedures for
`determining a shelf life of a device, the stability criteria and
`the product specific variables that follow should be assessed.
`
`1. Storage conditions, e.g.! temperature variations, relative
`humidity, ventilation, a n pressure, air-borne
`contamination, visible light and other radiation, etc.
`
`2.
`
`3.
`
`The nature of the device and intended use, e.g., medical
`gloves are made of latex because of the intended use even
`though latex deteriorates with age.
`
`The components used to manufacture the device, e.g., some
`devices contain a battery or other components that would
`suffer degradation of function with the passage of time.
`
`4. Method of manufacture, e.g., an in vitro diagnostic device
`that is aseptically packaged may have a shorter shelf life
`than one that is terminally sterilized.
`
`5. Packaging, e.g., products that are packaged in different
`size containers may each have a different stability shelf
`life due to the different ratio of product to package
`surface area contact.
`
`6. Transportation conditions; e.g., vibration, shock,
`temperature, humidity, etc.
`
`RECOMMENDATIONS
`
`The concept of shelf life or expiration dating should be
`incorporated into product reliability during the process of
`developing or improving a device for commercial distribution.
`The result is to make sure that, if the device is used in
`accordance with the labeling, the device will perform in the
`intended manner. Developing an appropriate set of specifications
`for the device's characteristics and assigning tolerance values
`for these characteristics is essential to the process of shelf
`life determination. The events that can cause a device to no
`longer perform in the intended manner may originate:
`
`a
`
`a
`
`internally, e.g., device component interactions or
`degradation can cause the device operating characteristics
`to fall outside of the prescribed tolerances; or
`
`externally, e.g., the shipping or storage conditions can
`cause a breakage in the device, a failure of the barrier
`properties of a sterile package or degeneration of the
`device itself.
`
`A device's "shelf lifew should not be confused with a device's
`"useful life.'' The useful life of a device is the duration of
`actual use or the number and duration of repeat uses before some
`change results in the device's inability to achieve its intended
`function.
`
`

`

`Establishing a Shelf Life
`
`The best time to begin considering device shelf life is during
`preproduction planning and review while the device is being
`formulated before any concrete decisions about the device have
`been made and changes can be readily adapted. When design,
`material and process factors that influence shelf life are
`identified early in the process, redesigning the device
`parameters involve the least cost. The materials, components and
`packaging that are to be used in the manufacture of the device
`may need to be examined for their individual shelf life
`characteristics in addition to their effect on the shelf life of
`the finished device. Some materials and components may need
`special handling to maintain their characteristics within the
`desired specifications. Also, the intended use of the device is
`an important consideration because this will greatly influence
`the tolerance level of shelf life or other failure of the device.
`
`Begin by establishing a target shelf life for the finished device
`that allows adequate time for shipping, storage and use.
`Evaluate the proposed materials and components used to produce
`and package the device. Also, a review of the literature should
`be conducted and, where feasible, data for similar devices
`collected. The method of manufacturing may need to be tailored
`to the materials or different materials may need to be selected
`that don't interfere with, and are not affected by, the
`manufacturing process. For devices that are found to have good
`stability characteristics, larger production runs may be
`practical to permit savings in production costs. With all
`devices there must be sufficient inventory control to produce,
`ship and sell the device within the shelf life period to avoid
`the monetary losses associated with recovering an out-of-date
`product, reworking a product, or otherwise disposing material to
`prevent unnecessary health risks for the consumer. If the shelf
`life considerations are implemented properly, they will add to
`product quality and actually decrease total production cost.
`
`For devices that are intended to be sterilized, the affect of the
`sterilization procedure on both the device and the package must
`be considered. It is much easier to rule out a package with
`water soluble sealants and select packaging that is compatible
`with steam sterilization, if steam sterilization is selected as
`the most desirable procedure before a contract with a package
`supplier is signed. There are numerous reference works available
`that cover packaging technology and various sterilization
`technologies.
`
`Procedure for Testing Shelf Life
`
`A written procedure for establishing and monitoring shelf life of
`medical devices should include the following:
`
`1. Organizational units responsible for the various phases of
`the shelf life testing program should be included in the
`written procedure.
`
`

`

`A Finished Device Sampling Plan, including the purpose for
`collecting the samples, the number of finished devices to be
`collected, frequency of sampling, sample selection criteria,
`and lots to be sampled.
`
`Raw Materials, Components and Packaging Evaluation Plan, to
`determine if any of these have their own individual shelf
`life considerations and how they affect the shelf life of
`the finished device. This plan should include obtaining
`data from suppliers, obtain new data as appropriate, and
`recording data for current and future designs.
`
`A Plan for Storage of Shelf Life Samples, including storage
`conditions and the environmental conditions to be
`controlled, monitored and recorded. .
`
`Accelerated Aging Parameters, including information that
`validates the accelerated system. The results need to be
`supported by real time testing of shelf life samples to
`confirm the tentative shelf life data collected from the
`accelerated tests.
`
`Simulation of Shipping and Handling Stresses Plan, including
`vibration tests, temperature extremes challenge, actual
`shipping and intentionally mishandling the device to
`determine the affect of unusual circumstances.
`
`Follow-up procedures should be included in the written plan
`that outline the steps to be taken based upon the results of
`the shelf life testing. These procedures must also cover
`conspicuously placing the expiration date on appropriate raw
`materials in storage and on the finished device to aid in
`stock rotation. The results of the shelf life testing may
`indicate a need to set limits on the time the device is held
`in storage, redesign the packaging of the device, or control
`the environmental conditions to minimize the degradation.
`
`REGULATIONS
`
`The Code of Federal Regulations (CFR) is a codification of the
`general and permanent rules published in the Federal Register by
`the Executive Departments and Agencies of the Federal Government.
`FDA regulations are grouped in Title 21 of the CFR, and the
`regulations that govern medical devices are contained in Parts
`800 to 1299. The regulations that apply specifically to shelf
`life and expiration dating of medical devices are listed below:
`In Vitro Diagnostic Regulation - 21 CFR Part 809
`1. The paragraph below outlines the labeling requirements for
`the primary container or wrapper of the retail package.
`
`21 CFR 809.10(a)(5): For a reagent, appropriate storage
`instructions adequate to protect the stability of the
`product. When applicable, these instructions shall include
`
`

`

`such information as conditions of temperature, light,
`humidity, and other pertinent factors. For products
`requiring manipulation, such as reconstitution and/or mixing
`before use, appropriate storage instructions shall be
`provided for the reconstituted or mixed product which is to
`be stored in the original container. The basis for such
`instructions shall be determined by reliable, meaningful,
`and specific test methods such as those described in
`211.166 of this chapter.
`
`2.
`
`The paragraph below outlines the information that is to be
`included in the package insert or other labeling that
`accompanies the product.
`
`21 CFR 809.10(b)(5)(iv): Appropriate storage instructions
`adequate to protect the stability of the product. When
`applicable, these instructions shall include such
`information as conditions of temperature, light( humidity,
`and other pertinent factors. For products requiring
`manipulation, such as reconstitution and/or mixing before
`use, appropriate storage instructions shall be provided for
`the reconstituted or mixed product. The basis for such
`instructions shall be determined by reliable, meaningful,
`and specific test methods such as those described in §
`211 .I66 of this chapter.
`
`3.
`
`The paragraph below describes a requirement for the labeling
`of Itgeneral purpose laboratory reagentsM.
`
`21 CFR 809.10(d)(l)(v): Appropriate storage instructions
`adequate to protect the stability of the product. When
`applicable, these instructions shall include such
`information as conditions of temperature, light, humidity,
`and other pertinent factors. The basis for such
`instructions shall be determined by reliable, meaningful,
`and specific test methods such as those described in §
`211.166 of this chapter.
`. The paragraph below from the drug regulation is referred to
`
`in the three regulations above and specifically requires a
`written stability testing program that may include
`accelerated shelf life testing, but also indicates that real
`time testing must be performed to verify the validity of the
`accelerated testing results.
`
`21 CFR 211.166: (a) There shall be a written testing
`program designed to assess the stability characteristics of
`drug products. The results of such stability testing shall
`be used in determining appropriate storage conditions and
`expiration dates. The written program shall include: (1)
`Sample size and test intervals based on statistical criteria
`for each attribute examined to assure valid estimates of
`stability; (2) Storage conditions for samples retained for
`testing; (3) Reliable, meaningful, and specific test
`methods; ( 4 ) Testing of the drug product in the same
`
`

`

`c o n t a i n e r - c l o s u r e s y s t e m a s t h a t i n which t h e drug product
`i s marketed; ( 5 ) T e s t i n g o f d r u g p r o d u c t s f o r r e c o n s t i t u t i o n
`a t the t i m e o f d i s p e n s i n g ( a s d i r e c t e d i n the l a b e l i n g ) a s
`w e l l a s a f t e r t h e y a r e r e c o n s t i t u t e d .
`(b) An adequate
`number o f b a t c h e s o f e a c h drug product s h a l l be tested t o
`d e t e r m i n e an a p p r o p r i a t e e x p i r a t i o n d a t e and a record o f
`s u c h d a t a s h a l l be m a i n t a i n e d . A c c e l e r a t e d s t u d i e s ,
`combined w i t h b a s i c s t a b i l i t y i n f o r m a t i o n on the components,
`d r u g p r o d u c t s , and c o n t a i n e r - c l o s u r e s y s t e m , may be used t o
`s u p p o r t t e n t a t i v e e x p i r a t i o n d a t e s provided f u l l shelf l i f e
`s t u d i e s a r e n o t a v a i l a b l e and a r e b e i n g c o n d u c t e d . Where
`d a t a from a c c e l e r a t e d s t u d i e s a r e used t o p r o j e c t a
`t e n t a t i v e e x p i r a t i o n d a t e t h a t i s beyond a d a t e s u p p o r t e d b y
`a c t u a l shelf l i f e s t u d i e s , there m u s t be s t a b i l i t y s t u d i e s
`c o n d u c t e d , i n c l u d i n g d r u g product t e s t i n g a t a p p r o p r i a t e
`i n t e r v a l s , u n t i l the t e n t a t i v e e x p i r a t i o n d a t e i s v e r i f i e d
`or the a p p r o p r i a t e e x p i r a t i o n d a t e d e t e r m i n e d .
`
`5. The paragraph below requires an expiration date based upon
`the recommended storage conditions for the reagent unless
`there is a visible alteration of the product or a simple
`test method by which the user can determine if the reagent
`meets appropriate specifications.
`
`An e x p i r a t i o n d a t e based upon t h e
`21 CFR 809.10(a)(6)(i):
`s t a t e d s t o r a g e c o n d i t i o n s .
`Premarket Approval (PMA) - 21 CFR Part 814
`The PMA requirements concerning shelf life do not stipulate which
`devices require a shelf life nor do they stipulate the parameters
`that must be considered in establishing a shelf life. It is the
`responsibility of the sponsor of the PMA to make the initial
`determination of whether their device requires a shelf life and
`the device characteristics that will be considered.
`
`1. The paragraph below outlines the information that is to be
`contained in a PMA and requires a section of the PMA to
`include the results of nonclinical laboratory studies
`including studies of shelf life.
`
`A section c o n t a i n i n g r e s u l t s o f t h e
`21 CFR 814.20(b)(6)(i):
`n o n c l i n i c a l l a b o r a t o r y s t u d i e s w i t h the device i n c l u d i n g
`m i c r o b i o l o g i c a l , t o x i c o l o g i c a l , immunological,
`b i o c o m p a t i b i l i t y , stress, wear, s h e l f l i f e , and o t h e r
`l a b o r a t o r y or animal t e s t s a s a p p r o p r i a t e .
`
`2. Paragraph (a) below covers the type of changes to a device
`that require a supplemental PMA application, and expiration
`dating is specifically covered in section (8). It is
`advantageous to have a protocol for extending shelf life
`approved by FDA in the original PMA, since the change in
`product expiration date can be made as soon as the
`evaluation is completed instead of having to submit an
`additional PMA supplement and awaiting FDA approval.
`
`

`

`21 CFR 814.39(a) (8): Extension o f the e x p i r a t i o n d a t e o f
`the d e v i c e based on d a t a o b t a i n e d under a new or r e v i s e d
`s t a b i l i t y or s t e r i l i t y t e s t i n g protocol t h a t h a s not been
`approved by FDA.
`I f the p r o t o c o l h a s been approved, the
`change s h a l l be r e p o r t e d t o FDA under paragraph ( b ) o f t h i s
`section.
`
`3. The Center for Devices and Radiological Health (CDRH) has
`determined that if a protocol for testing the shelf life of
`a device has been approved by FDA in the original PMA or a
`PMA supplement, revising the shelf life of the device based
`on data collected according to the protocol is a change that
`does not affect the device's safety or effectiveness.
`Therefore, the change can be made and FDA notified in the
`next periodic report.
`
`21 CFR 814.39(b): An a p p l i c a n t may make a change i n a
`d e v i c e a f t e r F D A ' s approval o f a PMA for a device w i t h o u t
`s u b m i t t i n g a PMA supplement i f the change d o e s n o t a f f e c t
`the device's s a f e t y or e f f e c t i v e n e s s and the change i s
`r e p o r t e d t o FDA i n postapproval p e r i o d i c r e p o r t s r e q u i r e d a s
`a c o n d i t i o n t o the approval o f the d e v i c e , e .g., a n
`e d i t o r i a l change i n the l a b e l i n g which d o e s not a f f e c t t h e
`s a f e t y or e f f e c t i v e n e s s o f the device.
`Good Manufacturing Practices (GMP) - 21 CFR Part 820
`The GMP requirements outline elements of a quality assurance
`system that point to the desired goals, not as an intricate set
`of instructions. This approach is beneficial to manufacturers
`that may have already implemented quality control procedures
`which include shelf life; or who are contemplating a new device
`that has unique aspects which would not fit into a l'cookbookv
`approach. Some GMP elements that impact on shelf life are
`reprinted below.
`
`1. The paragraph below requires the establishment of a quality
`assurance program that would include an expiration date if
`appropriate.
`
`21 CFR 820.5: Every f i n i s h e d device m a n u f a c t u r e r s h a l l
`prepare and implement a q u a l i t y assurance program t h a t i s
`a p p r o p r i a t e t o the s p e c i f i c device manufactured and meets
`the r e q u i r e m e n t s o f t h i s p a r t .
`
`2.
`
`This section requires an environmental control program when
`it is necessary to prevent contamination of the device and
`to provide proper conditions for the operations performed to
`manufacture, store and distribute the device.
`
`21 CFR 820.46: Where environmental c o n d i t i o n s a t the
`m a n u f a c t u r i n g s i t e c o u l d have an a d v e r s e e f f e c t on a
`device s f i t n e s s f o r u s e , these environmental c o n d i t i o n s
`s h a l l be controlled t o p r e v e n t c o n t a m i n a t i o n o f t h e device
`and t o p r o v i d e proper c o n d i t i o n s for each o f the o p e r a t i o n s
`
`

`

`8 2 0 . 4 0 . Conditions t o be considered
`performed pursuant t o
`f o r control are l i g h t i n g , v e n t i l a t i o n , temperature,
`humidity, a i r pressure, f i l t r a t i o n , airborne contamination,
`and other contamination. Any environmental control system
`shall be periodically inspected t o v e r i f y t h a t t h e system i s
`properly functioning. Such inspections shall be documented.
`
`3.
`
`Both the manufacturing specifications and the manufacturing
`processes must be written and include a formal method to
`control changes to these procedures. This GMP requirement
`includes an evaluation of any change to the shelf life
`characteristics of the device resulting from a specification
`or process change.
`
`21 CFR 820.100: Written manufacturing s p e c i f i c a t i o n s and
`processing procedures shall be established, implemented, and
`controlled t o assure t h a t t h e device conforms t o i t s
`original design o r any approved changes i n t h a t design.
`(also, see subparts F and J)
`4. The paragraph below requires written procedures for
`warehouse control and distribution. This could include
`controlled storage; e.g., refrigeration, humidity control,
`etc., and first-in, first-out shipping, as needed to protect
`the device.
`
`21 CFR 820.150: There shall be written procedures for
`warehouse control and d i s t r i b u t i o n o f finished devices t o
`assure t h a t only those devices approved f o r release are
`d i s t r i b u t e d . Where a d e v i c e ' s f i t n e s s for use or q u a l i t y
`deteriorates over time, there shall be a system t o assure
`t h a t the oldest approved devices are distributed f i r s t .
`
`FDA POLICIES
`
`CDRH has issued various policy and internal guidance documents to
`assist CDRH employees and the regulated industry in understanding
`what information will be required to satisfy the regulatory
`requirements for commercial distribution of a medical device.
`The policies that are in effect for the applications submitted to
`satisfy these premarketing clearance and distribution
`requirements are discussed below.
`
`Premarket Notification (510(k))
`
`There currently is no written policy concerning the determination
`of shelf life for a device that is the subject of a 510(k)
`submission. However, CDRH has issued an internal guidance
`document, 510(k) Sterility Review Guidance #K90-1, to set forth
`the procedure to be used by the Office of Device Evaluation (ODE)
`and the Office of Compliance and Surveillance (OCS) in reviewing
`510(k)s for sterile devices. The 510(k) Sterility Review
`Guidance document lists the information that is to be included in
`a 510(k) for a sterile device regardless of how the device is
`labeled for shelf life. The guidance also acknowledges that
`certain sterilization processes have a deleterious effect upon a
`
`

`

`nonsterility aspect of the device, e.g., the shelf life of the
`sterilized device could vary due to the use of different
`sterilization procedures. The 510(k) Sterility Review Guidance
`document can be used by medical device manufacturers when
`preparing a 510(k) application for a sterile medical device to
`make sure the application contains all the information required
`by CDRH. An excerpt of #K90-1 follows:
`
`The following information concerning the s p e c i f i c a t i o n s related
`t o s t e r i l i t y should be collected and reviewed by ODE during t h e
`review o f the 510 ( k ) for a s t e r i l e device:
`-
`t h e s t e r i l i z a t i o n method t h a t w i l l be used;
`-
`a description o f t h e method t h a t w i l l be used t o validate
`t h e s t e r i l i z a t i o n cycle, but not t h e validation data i t s e l f ;
`-
`t h e s t e r i l i t y assurance l e v e l (SAL) f o r the device which t h e
`f i r m intends t o meet;
`-
`a description o f t h e packaging t o maintain t h e device's
`s t e r i l i t y ( t h i s i s not t o include packaging i n t e g r i t y
`t e s t i n g data) ;
`i f s t e r i l i z a t i o n involved ETO, the maximum l e v e l s o f
`residues o f ethylene oxide, ethylene chlorohydrin, and
`ethylene glycol which remain on t h e device;
`whether the product i s "pyrogen free1' and a description o f
`t h e method used t o make t h e determination;
`t h e radiation dose, i f radiation s t e r i l i z a t i o n w i l l be used.
`
`-
`-
`Only t h i s information w i l l be collected regardless o f how t h e
`device i s labeled, i . e . , whether it i s labeled s t e r i l e , s t e r i l e
`u n t i l opened or damaged, or s t e r i l e u n t i l a stated expiration
`date.
`
`-
`
`We recognize t h a t certain s t e r i l i z a t i o n processes have
`deleterious e f f e c t upon a n o n s t e r i l i t y aspect o f t h e device.
`These e f f e c t s have t o be factored i n t o t h e equivalency decision.
`
`The pilot program that is outlined in #K90-1 with the Division of
`Cardiovascular Devices (DCD), 510(k) Staff and OCS participating
`is still in effect. As of March 1991, there have been no
`decisions made regarding expanding the program to the other
`divisions, modifying or removing this portion of the guidance or
`evaluating the effectiveness of the program.
`
`Investigational Device Exemption (IDE)
`
`There currently is no written policy concerning the determination
`of shelf life for a device that is the subject of an IDE. The
`current CDRH policy for shelf life determination for devices
`undergoing clinical investigation allows each of the operating
`divisions within ODE to determine:
`
`which devices require an established shelf life prior to the
`clinical study; and
`
`the methods to be used for validating a shelf life of a
`particular device.
`
`

`

`Premarket Approval (PMA)
`
`The current policy concerning the determination of shelf life for
`a device that is the subject of a PMA is entitled I8Office of
`Device valuation Shelf-Life Policy for PMAs8' issued
`March 7 , 1984. This policy for shelf life determination for
`devices marketed through the PMA process allows each of the
`operating divisions within ODE to determine:
`
`which devices require an established shelf life; and
`
`the adequacy of the proposed methods for validating a shelf
`life for a particular device.
`
`The policy also requires that the labeling for the device include
`the shelf life and discusses the process for extending the shelf
`life by submitting a PMA supplement or following an approved
`protocol as previously discussed. The text of the policy
`follows:
`
`The ODE Divisions have the r e s p o n s i b i l i t y t o determine
`whether t h e sponsor must submit data i n support o f s h e l f
`l i f e dating o f a PMA device. The Divisions have the
`r e s p o n s i b i l i t y for maintaining a l i s t o f generic classes o f
`devices which require s h e l f l i f e dating and supplying t h e
`l i s t t o t h e PMA s t a f f .
`
`The Divisions have t h e r e s p o n s i b i l i t y f o r evaluating t h e
`data t o determine whether they are appropriate and adequate
`and t o reach a conclusion regarding t h e s h e l f l i f e o f t h e
`device.
`
`The approval order (approval l e t t e r ) shall include the s h e l f
`l i f e o f t h e device. This i s an