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 .  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 
Page 
. . . . . . . . . . . . . . . . . . . .  
INTRODUCTION  1 
. . . . . . . . . .  
STABILITY CRITERIA AND VARIABLES  1 
. . . . . . . . . . . . . . . . . . .  
RECOMMENDATIONS  4 
. . . . . . . . . . . . . . . . . . . . .  
REGULATIONS  . 6  
. . . . . . . . . . . . . . . . . . . .  
FDA POLICIES  10 
. . . . . . . . . . . . . . . . . . . .  
CDRHGUIDANCE  13 
. . . . . . . . . . . . . . . . . . . . . .  
GLOSSARY  23 
. . . . . . . . . . . . . . . . . . . . .  
REFERENCES  24 
NOTE :  The excerpts of documen.t s 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, 
2.  physical, 
3.  microbiological, 
4.  therapeutic, and 
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.  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. 
3.  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  internally, e.g., device component interactions or 
degradation can cause the device operating characteristics 
to fall outside of the prescribed tolerances; or 
a  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  container-closure  system  as that in which  the drug product 
i s  marketed;  (5) Testing of drug products  for reconstitution 
a t  the time of dispensing  (as directed in the labeling) as 
well  as after they are reconstituted.  (b) An  adequate 
number of batches of each drug product  shall  be  tested  to 
determine  an appropriate  expiration date and  a record  of 
such  data shall  be  maintained.  Accelerated  studies, 
combined  with basic stability information on  the components, 
drug products,  and  container-closure  system,  may  be  used  to 
support  tentative expiration dates provided  full  shelf  l i f e  
studies are not available and  are being conducted.  Where 
data from  accelerated  studies are used  to project  a 
tentative expiration date  that is beyond  a date supported  by 
actual  shelf l i f e  studies,  there must be  stability studies 
conducted,  including drug product  testing a t  appropriate 
intervals,  until the tentative expiration date is verified 
or the appropriate expiration date determined. 
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. 
21 CFR 809.10(a)(6)(i):  An expiration date based  upon  the 
stated  storage  conditions. 
- 
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. 
21 CFR 814.20(b)(6)(i):  A section  containing results of the 
nonclinical  laboratory studies with the device including 
microbiological,  toxicological,  immunological, 
biocompatibility,  stress,  wear,  shelf  life, and  other 
laboratory or animal  tests as appropriate. 
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  of the expiration date of 
the device based  on data obtained  under a  new  or revised 
stability or sterility testing protocol  that has not been 
approved  by FDA.  I f  the protocol  has been approved,  the 
change  shall  be reported  to FDA  under paragraph  (b) of this 
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  applicant may  make  a  change  in a 
device after FDA's  approval  of a  PMA  for  a  device without 
submitting a  PMA  supplement  if the change  does not affect 
the device's safety or effectiveness and  the change  i s  
reported  to FDA  in postapproval  periodic  reports required  as 
a  condition to the approval  of the device,  e .g.,  an 
editorial change  i n  the labeling which does not  affect the 
safety or  effectiveness of 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  finished  device manufacturer shall 
prepare  and  implement  a  quality assurance program  that i s  
appropriate to the specific device manufactured  and  meets 
the requirements  of this part. 
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  conditions a t  the 
manufacturing site could have  an adverse effect on  a 
device s  fitness for  use,  these environmental  conditions 
shall  be  controlled  to prevent  contamination of the device 
and  to provide  proper  conditions for each of the operations  performed  pursuant  to  820.40.  Conditions  to be  considered 
for  control  are lighting,  ventilation,  temperature, 
humidity,  air pressure,  filtration,  airborne  contamination, 
and  other contamination.  Any  environmental  control  system 
shall  be periodically  inspected  to verify that the 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 specifications and 
processing  procedures  shall  be  established,  implemented,  and 
controlled  to assure  that  the device conforms to its 
original  design or any  approved  changes  in that 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  distribution of finished  devices  to 
assure  that only those devices approved  for release  are 
distributed.  Where a  device's fitness  for  use  or quality 
deteriorates  over  time,  there shall  be  a  system  to assure 
that  the oldest  approved  devices are  distributed  first. 
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 specifications related 
to sterility should  be  collected and  reviewed  by ODE  during  the 
r-e view of the 510 (k) for a sterile device: 
the sterilization method  that w i l l  be  used; 
- 
a description of the method  that w i l l  be used  to validate 
-  the sterilization cycle,  but not  the validation data  itself; 
the sterility assurance  level  (SAL) for  the device which  the 
firm  intends to meet; 
- 
a description of the packaging  to maintain  the device's 
sterility  (this i s  not  to include packaging  integrity 
testing data) ; 
- 
if sterilization involved ETO,  the maximum  levels of 
residues of ethylene oxide,  ethylene  chlorohydrin,  and 
ethylene glycol  which  remain  on  the device; 
- 
whether  the product  i s  "pyrogen free1' and  a  description of 
-  the method  used  to make  the determination; 
the radiation dose,  if radiation sterilization w i l l  be  used. 
Only this information w i l l  be  collected  regardless of how  the 
device  i s  labeled,  i.e.,  whether  it i s  labeled  sterile,  sterile 
until  opened  or damaged,  or sterile until  a  stated  expiration 
date. 
We  recognize  that certain sterilization processes  have 
deleterious effect upon  a nonsterility aspect  of  the device. 
These effects have  to be  factored  into the 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 responsibility  to determine 
whether  the sponsor  must  submit  data  in support  of shelf 
l i f e  dating of a PMA  device.  The Divisions  have  the 
responsibility for maintaining a list of generic  classes of 
devices which  require  shelf l i f e  dating  and  supplying  the 
list to the PMA  staff. 
The Divisions  have  the responsibility for evaluating  the 
data  to determine whether  they are  appropriate  and  adequate 
and  to reach a conclusion regarding  the shelf  l i f e  of the 
device. 
The  approval  order  (approval letter) shall  include  the shelf 
l i f e  of the device.  This i s  an  important  element  of the 
record  of approval  of the device and  the shelf l i f e  must  be 
officially noted. 
The  sponsor  may  extend  the shelf  l i f e  of an  approved  device 
through the use  of methods  and  tests described  in the PMA 
which  were  reviewed  and  approved  by FDA  to establish the 
shelf  life.  Under these conditions,  the sponsor  need  only 
advise FDA  of the extension in routine reports  submitted 
under  the PMA. 
The  sponsor  must  submit  a supplement  if the sponsor  proposes 
to extend  the shelf  l i f e  based  on methods  or tests other 
than  those used  in the approved  PMA  and  the sponsor  may  not 
extend  the shelf  l i f e  without FDA  approval  of the 
supplement. 
The  device  labeling must  include an  expiration date based 
upon  an  approved  shelf  l i f e  period.  CDRH GUIDANCE 
The following documents are issued by CDRH and contain guidance 
on the methods to be used in determining a shelf life for various 
medical devices.  It is important to note that only the first 
document is a true guidance document that has undergone the 
process of announcement in the Federal Register and response to 
comments received, while each of the others is a draft guidance 
document. 
1.  "Guidance Document for Class I11 Contact Lensesw; April 
1989; issued by the Division of Ophthalmic Devices (DOD) 
within ODE.  Contact Lenses may be stored up to 20C above 
room temperature to simulate accelerated passage of time. 
The guidance includes a mathematical formula for calculating 
the simulated age of the subject devices.  Stability of 
physical, chemical and optical specifications must be 
determined along with a test for sterility.  An excerpt from 
the Shelf life section follows: 
"A. Shelf  life: 
The manufacturer must  demonstrate  the stability of the 
parameters  of the finished  lens over t i m e  as packaged  and 
stored  under the proposed  storage  conditions. 
The  aging of the lens in its storage container can be 
extrapolated  to the proposed  storage  temperature.  As  a  rule 
of thumb,  every 10C increase for  the tested  temperature 
above normal  storage  temperature will enhance  the expiration 
date b y  a  factor  or two.  A  total of 10-20 lenses randomly 
selected  from  2-3 lots are required  for shelf  l i f e  tests. 
The stability tests should  include physical  and  optical 
parameters  and  the physical  appearance  of the lens i n  
addition to sterility data.  In  addition,  additional 
parameters  should  be  monitored  for lenses containing color 
additives,  ultraviolet absorbers,  or other chemicals during 
the testing period. 
3.  Sterility Stability  (shelf life) 
The manufacturer must  demonstrate  that lenses will remain 
sterile for  the recommended  shelf  l i f e  as packaged.  This 
applies to all hydrophilic lenses as well  as hydrophobic 
lenses that will  be  labeled  as sterile.  This requirement 
does not  apply to hydrophobic  lenses where  the sterilization 
requirement  has been waived. 
To f u l f i l l   this requirement,  the manufacturer should  test 
10-20 lenses that have been packaged  and  stored  for  the 
proposed  shelf  li fe.   Samples  from  two or three lots of 
approximately  the same  age should  be  tested for  sterility 
using methods  such  as USP XXI  sterility testing.  Method for calculation of shelf life (expiration date) is 
included in Micro Appendix D. 
MICRO APPENDIX D 
MICROBIOLOGY REQUIREMENTS FOR ESTABLISHMENT OR EXTENSION OF SHELF 
LIFE (EXPIRATION DATE) FOR CONTACT LENSES 
Shelf life sterility stability must be demonstrated by one 
of the following two tests: 
I.  Sterility tests, lenses stored at ambient temperature, 
or 
II.  Accelerated shelf life sterility study, lenses stored 
at elevated temperature to 4S0 C. 
Protocols : 
I.  Conduct sterility re-check tests according to USP XXI 
(Sterility Tests pp. 1156-1160) on 10-20 shelf life 
samples which have been stored at ambient temperature, 
preferably from several different lots of the 
approximate age for which shelf life is requested. 
Examples:  Six month old lenses stored at ambient 
temperature (generally 23-2SC), with an additional 6 
months customarily added to actual shelf life age, are 
granted a 12-month (1 year) expiration date if they 
have passed the sterility stability testing and the 
other (physical/chemical)s tability requirements.  One 
year old lenses, stored at ambient temperature, 
similarly are given an 18 month expiration date if they 
have passed the sterility stability testing and the 
other stability requirements. 
II.  Accelerated shelf life studies may be run by storing 
samples at higher temperatures for a shorter period of 
time and mathematically correlating increased 
temperature with time. 
a.  Raise temperature a maximum of 20-2SC above 
ambient temperature (45OC.m aximum). 
b.  The acceleration factor for 10C rise is 1.8. 
c.  Sterility tests according to USP XXI are run on 
these samples. 
Example of calculation: 
3 month old lenses, stored entire 3 months at 40C. 
1.  Age of lens = 3 months 
2.  Ambient temperature = 25OC 
3.  Q,, = 1.8  4.  Acceleration factor (based on lSO temperature 
difference) : (1.8)'.' = 2 .41 
5.  Length of time at elevated temperature = 3 months 
6.  Estimation of shelf life 
a.  age x acceleration factor  = accelerated age 
3 months x 2.41  =  7.2 months 
b.  accelerated age + actual age  shelf life 
= 
7.2  + 3  = 10.2 months 
NOTE:  The customary "additional 6 months "is not given 
for accelerated shelf life." 
2.  '#Testing Guidelines for Class I11 Soft (Hydrophilic) Contact 
- 
Lens Solutionsw; Draft  July 15, 1985; issued by DOD within 
ODE.  Contact Lens Solutions may be stored up to 20C  above 
room temperature to simulate accelerated passage of time. 
The guidelines include a mathematical formula for 
calculating the simulated age of the subject devices. 
Stability of Ph, viscosity, ingredient concentrations, 
appearance, preservative concentration, and preservative 
effectiveness must be determined along with a test for 
sterility.  An excerpt from the Guidelines concerning shelf 
life follows: 
"b. Solution Stability Testinq 
The manufacturer must demonstrate the stability of the 
solution over time as packaged and stored unde; the proposed 
storage conditions. 
The size of the container tested should be the same as that 
intended to be marketed.  Generally, if the solution is 
susceptible to chemical oxidation or reduction, the greater 
the internal contact of the solution with the container 
surface the greater the chance of chemical degradation.  The 
degradation therefore, is more likely to occur in smaller 
containers because the ratio of solution to internal surface 
area increases as the container size decreases.  For this 
reason, it is our policy to approve a solution for marketing 
in a container larger than that used for stability testing, 
but not a container smaller than tested.  FDA believes that 
this policy should extend to containers not more than 8 
times the size tested provided that containers are 
constructed of the same material. 
The aging of the solution in the storage container should be 
initiated as soon as possible.  The stability tests should 
include pH, viscosity, preservative concentration, physical 
. . 
appearance, and concentrations of major ingredients (e g , 
surfactant, enzyme, etc.).  Stability results obtained at 
the corresponding storage temperature of the solution are 
the basis for the establishment of an expiration date. 
Accelerated aging up to 50 C may be used as supporting 
evidence of stability.  As a rule of thumb, every 10" C 
increase for the tested temperature will enhance the  expiration date by a factor of two compared to the normal 
storage temperature e.g.,  testing solution at 4SC for 3 
months corresponds to the normal storage temperature e.g., 
testing solution at 2S0 C for 12 months (2x2~3). A total of 
3 containers of solution randomly selected from 3 lots are 
required for shelf life tests of each container size.  The 
analytical methodology for all tests should be described in 
detail.  FDA does not restrict the method used; however, all 
analytical methods should be scientifically sound.  The 
following is a suggested protocol: 
1.  Number of Samples:  3 containers of solution randomly 
selected from 3 lots for each storage temperature and 
storage container size. 
2.  Parameters monitored:  pH; viscosity*; preservative 
concentration; physical appearance : (color, clarity, 
and integrity.**); and concentration of other major 
ingredients: (e.g., enzyme activity, *** 
surfactants****) 
3.  Test method: 
a)  Measure and record pH, viscosity, preservative 
concentration, physical appearance, and major 
ingredients before study. 
b)  Record lot number, beginning date, and storage 
temperature for the study. 
c)  Measure and record pH, viscosity, preservative 
concentration, physical appearance, and major 
ingredients after study. 
d)  Record terminating date, lot number and storage 
temperature 
e)  Determine how many parameters have fallen beyond 
their specifications and discuss their impact on 
safety and effectiveness of the solution. 
f)  Calculate the expiration date. 
q)  Summary of results and proposed shelf life. 
4.  Appendix 
a)  Analytical methodology of parameters monitored. 
b)  Ethylene oxide residues (ethylene oxide, ethylene 
chlorohydrin, ethylene glycol) of plastic 
bottle/closure if sterilized by ethylene oxide 
gas.  Aeration time and temperature should be 
specified and residues should be below the 
proposed FDA guidelines (Federal Register, vol. 
43, no. 122, June 23, 1978: ethylene oxide, 10 
ppm; ethylene chlorohydrin, 20 ppm; ethylene 
. 
glycol, 60 ppm) 
*  Not applicable for solution without thickening 
. 
agents and polymers 
**  The physical and chemical integrity of the plastic 
. 
bottle (e g., discoloration, solution leakage, and 
surface cracks with or without repeatedly applying 
a light pressure on bottle) should be a part of  the stability program if the bottle is sterilized 
by gamma radiation. 
*** 
For enzyme tablet or solution. 
**** Not applicable for solution without surfactants. 
Shelf 1i fe Testinq Reuuirements (Second Microbiolocrv 
Requirement) : 
1.  Shelf Life Sterility 
The manufacturer must demonstrate that the contact lens 
solution (s) will remain sterile for the recommended shelf 
life as packaged.  This applies to all solutions that will be 
labeled as sterile. 
To fulfill this requirement, the manufacturer should test 10- 
20 samples (of one type) that have been packaged and stored 
for the proposed shelf life.  Samples from two or three lots 
should be tested for sterility using methods such as USP XX 
sterility testing.  A separate shelf life sterility test must 
be performed for each type of lens solution manufactured. 
2.  Shelf Life Preservative Effectiveness 
For any preserved solution, the preservative effectiveness 
must be demonstrated for the proposed shelf life.  Samples 
from two or three lots to total a minimum of ten samples are 
tested according to the FDA modification of the USP 
Preservative Effectiveness Test. 
3.  Extension of Shelf Life protocol- see Appendix K 
APPENDIX K 
Protocol for Shelf Life Extensions 
Microbiolocrical Reuuirements 
Shelf life sterility stability must be demonstrated.  Also 
for a preserved solution, the shelf life stability of the 
preservative must be demonstrated. 
A.  Shelf life sterility stability must be demonstrated by 
one of the following two tests: 
I.  Sterility tests, solutions stored at ambient 
temperature. 
or 
II. Accelerated shelf life sterility study, solutions 
stored at elevated temperature to 50 C. 
B.  For preserved solutions, the Preservative Effectiveness 
Test is requires in addition to the sterility test. 
I.  Preservative Effectiveness Test, solutions stored at 
ambient temperature.  or 
II. Accelerated preservative Effectiveness study, 
solutions stored at elevated temperature to 50 C. 
Protocols: 
A.  Sterility Stability Tests 
I .   Conduct sterility re-check tests according to USP XXI 
(Sterility Tests pages 1156-1160) on at least 20 
shelf life samples which have been stored at ambient 
temperature.  Samples may be of different sizes and 
should be from several different lots of the 
approximate age for which shelf life is requested. 
Each sample should be properly identified in the raw 
data as to lot number and package size. 
Example:  Six month old solutions, stored at ambient 
temperature, with an additional 6 months customarily 
added to the actual shelf life age, are granted a 12 
month (1 year) expiration date if they have passed the 
sterility stability testing and the other stability 
requirements. 
II. Accelerated shelf life studies may be run by storing 
samples at higher temperatures for a shorter period 
of time and mathematically correlating increased 
temperature with time. 
a)  Raise temperature a maximum of 20-25O C above 
. 
ambient temperature (50 c maximum) 
b)  For microbiol ogy, the acceleration factor for 
* 
each 10  C rise is 1.8. 
O 
c)  sterility tests according to USP XXI are run on 
these samples. 
Example of calculation: 
6 month old solution stored at 45O C 
1.  Age of solution = 6 months 
2.  Ambient temperature = 25O C 
3.  Q,, = 1.8 
4.  Acceleration factor (based on a 20 C temperature 
difference):  (1.8)' = 3.24 
5.  Length of time at elevated temperature =  6 months 
6.  Estimation of shelf life 
a)  time at elevated temperature x acceleration factor = 
accelerated age  6 months x 3.24 = 19.44 months 
b)  accelerated age + actual age = shelf life 
19.44  +  6  = 25.44 months 
approximately 2 years 
Note:  The customary additional 6 months is not given for 
accelerated shelf life.  B.  Preservative Efficacy Test 
For shelf life stability any preserved solution must pass 
the FDA modification of the USP Preservative 
Effectiveness Test against all five of the challenge 
organisms.  Refer to page 53 of the FDA Guidelines for 
Testing Contact Lens Solutions; also to USP XXI, page 
." 
1151 
3.  "GuiBelines for Intraocular Lensesw; Draft - June 9, 1980; 
issued by DOD within ODE.  The Intraocular Lenses guidelines 
allow accelerated aging but do not give parameters to be used 
in designing an accelerated aging program and also state that 
room temperature storage is usually the most valuable. 
Stability of the mechanical and optical properties are to be 
measured against the original measurements along with a test 
for sterility. 
#Id. Storage Stability 
The storage stability of the intraocular lens is an 
important factor in the overall investigation of a new 
lens material.  A study of the aging of the lenses and 
their containers must be initiated as soon as possible. 
These stability tests made at regular intervals should 
include all parameters cited previously. [The parameters 
are as follow: 1.  permeability (small molecules, 
proteins, oxygen); 2. chemical and physical stability 
(ultra-violet, boiling water, steam, ethylene oxide, 
radiation, caustic solution); 3. light transmittance 
(white light); 4. extractables (if none, state 
methodology); 5. physical property profile (elongation, 
deformation, tensile strength); 6. average molecular 
weight, molecular weight distribution; 7 .   infrared 
spectroscopy, ultraviolet spectroscopy; 8. nuclear 
magnetic resonance spectroscopy; 9. melting point, glass 
transition temperature; 10. solubility in water, saline, 
selected solvents; 11. refractive index; 12. elemental 
analysis of metals and nonmetals; 13. surface microscopy 
(scanning electron microscopy); 14. biocompatibility 
(i.e. tissue culture); and 15. heat deformation 
temperature].  Special importance should be given to 
monitoring change in mechanical and optical properties. 
Accelerated aging may be used as supporting evidence of 
stability.  Stability results obtained at the storage 
temperature of the device are the basis for the 
establishment of an expiration date.  In the case of 
packaged lenses, room temperature is usually the most 
valuable.  Other temperatures, low and elevated (below 
freezing and approximately 50 degrees C.) are helpful for 
the determination of product stability.  Some plastics 
may be susceptible to temperature variations.  Freezing 
of the aqueous phase may seriously alter the structure of 
the lens.  In view of the temperature fluctuations  that can occur 
during shipment  of the lens,  the manufacturer should  make 
an effort to provide  a method  to monitor  the 
environmental  extremes incurred during transit.  A 
disposable,  maximum-minimum  temperature  indicator, 
serving as a package  insert,  to warn  the surgeon  of 
potential  temperature related  alterations of  the lens, 
." 
should  be  considered 
4.  88GeneralG uidance for Modifying Condom Labeling to Include 
- 
Shelf Lifeo8;D raft  October 1989; issued by the Division of 
Obstetrics/Gynecology, Ear, Nose, Throat, and Dental Devices 
(DOED) within ODE.  The Condoms guidance references test 
methods specified in American Society for Testing and 
Materials (ASTM) Standard Specifications for Rubber 
Contraception (Condoms), D 3492-89.  This includes 
accelerated aging at 70C  and testing the tensile strength 
and ultimate elongation of the material after the aging 
process.  Excerpts from these two documents follow: 
4.1 Excerpt from "General Guidance for Modifying Condom Labeling 
to Include Shelf Lifeog: "If a manufacturer,  repacker or 
importer of condoms  intends to modify the product  labeling t o  
include a  shelf  l i f e  or expiration date,  a premarket 
notification (510 (k))   must be  submitted  t o  the FDA.  FDA 
requires data from  real  time aging of condoms  to support  the 
labeling modification.  FDA,  in the absence  of real  time 
aging data,  will  allow a  tentative expiration date based  on 
accelerated  aging data,  provided  the manufacturer also 
initiates studies to determine  the real  shelf  life. 
Appropriate  records are  t o  be maintained  for FDA  inspection 
and  also,  when  real  time shelf  l i f e  is confirmed,  the 
manufacturer should  notify FDA  in a  supplement  to the 510(k). 
In  the event  that the real  time aging data does not  support 
the tentative expiration date,  the manufacturer should 
immediately inform FDA  and  take all necessary steps to 
correct  the labeling.  In  addition,  a  supplement  to the 
510 (k) must be  submitted  amending  the expiration date.  FDA 
will accept  test methods  specified in American  Society for 
Testing and  Materials  (ASTM)  Standard  Specifications for 
RUBBER  CONTRACEPTIVES  (CONDOMS),  D  3492,  or any other 
demonstrably valid method  for accelerated  testing.  For non- 
latex condoms,  and  for  condoms  that contain a  spermicidal 
lubricant,  details of the shelf  l i f e  test methodology need  t o  
be  provided. " 
-- 
4.2  Excerpt from ASTM #  D 3492-89:  "6.3  Accelerated  Aging 
Heat  condoms  to be  aged  i n  original  packages  a t  70  f 2OC  for 
166  f Z h  in accordance  with test Methods  D  573  or D  865. 
Determine  tensile properties  not less that 16h or more  than 
96h after heating." 
5.  "Guideline for the Manufacture of In Vitro Diagnostic 
- 
 device^^^; Second Draft  February 1990; issued by the 
Division of Compliance Programs (DCP) within OCS.  The  in vitro diagnostic products guidance allows the use of 
accelerated shelf life studies if followed by real time 
studies.  The procedure to be used in establishing the shelf 
life of an in vitro diagnostic device should be discussed 
with the Division of Clinical Laboratory Devices (DCLD) 
within ODE before initiating the studies, since DCLD did not 
issue the in vitro diagnostic products guidance document. 
"3.9  STABILITY  STUDIES  AND  EXPIRATION  DATING 
Section 820.100 (a) (1) requires  that procedures  for 
specification control  measures be  established  to assure  that 
the design basis for  the device,  components,  and  packaging  is 
correctly translated  into approved  specifications.  When  N D  
stability i s  a design concern,  appropriate procedures  such  as 
stability studies are  conducted  and  an expiration date, 
supported  by the studies,  is established  to define the period 
in which stability is assured.  The expiration date i s  
included as part  of the product  specifications for  the N D  
. 
and  its components,  as required by 820.181 (a) 
Stability studies for a l l  W D s  are.  required by Sections 
809 -10 (a)(  5) and  809.10 (b)( 5)(  iv)  These regulations require 
that storage instructions be  stated on  the immediate con- 
tainer label,  k i t  or  outer container label,  and  i n  the 
product  insert for  the product  in its initial state and  for 
products  which are mixed  or reconstituted  prior  to use. 
Where applicable,  storage instructions should  include 
temperature,  light and  humidity or other conditions.  The 
immediate container label,  and  the kit or outer container 
label,  are required  by 809.10(a)(6)  to state a means  by which 
the user i s  assured  the N D  meets appropriate standards  of 
identity,  strength,  quality,  and  purity  a t  time of use.  This 
assurance can be  an expiration date,  an observable indication 
of product  alteration,  such  as turbidity,  or instructions for 
a  simple function  test.  The following  are means  of complying 
with these regulations  for  establishing stability studies  and 
expiration dating: 
An  expiration date is the usual  method  used  to indicate 
stability for  N D s .   The l a s t  date for  the product  to be  used 
by the customer  i s  defined as the expiration date. 
The  storage  instructions and  the expiration date are 
determined  as part  of product  development  for  the proposed 
container/closure system.  The  device package  and  shipping 
container are evaluated  as part  of this development  phase. 
For example,  during product  development  an N D  labeled for 
storage  a t  Z0  to 8OC  was  found  to be  stable for 24  months. 
Studies were performed  by the manufacturer which subjected 
the N D  to adverse shipping  temperatures of - 5 O C   and  37OC for 
one week  each;  however,  the IVD was  stable for  only 6  months 
a t  2" to 8C  after being subjected  to these adverse shipping 
Conditions.  A  shipping  container was  then designed  to 
maintain  the IVD product  a t  2"  to 8OC  during adverse  environmental  conditions that might be  encountered  during 
shipping to support  the 24  month  expiry period.  This type of 
design effort supports the type of adequate package  design 
requirements of section 820 .l30. 
Storage instructions for W D s  are required  by 809.10(a) (5) to 
have  reliable,  meaningful,  and  specific test methods  such as 
those in 21 CFR 211.166.  Section 211.166  requires  sample 
sizes and  test intervals to be  based  on  statistical criteria 
for  each attribute examined  to assure valid  estimates of 
stability and  also requires reliable,  meaningful  and  specific 
test methods.  Performance and  identity testing on  a l l  N D  
reagents and  systems is included  i n  the stability testing 
program.  In addition,  sterility testing on sterile labeled 
N D s ,   and  microbial  l i m i t s  testing on  a l l  microbiologiCally 
controlled N D s ,   i s  included  in the stability testing 
program.  The finished  N D p  roduct  is held  under appropriate 
conditions to support  the expiry period  and  storage 
instructions determined  during the development  phase.  These 
are normally  taken from  the first  three production  batches. 
Accelerated  studies  (i.e.,  a t  high temperature and  humidity) 
are acceptable  for  some  products  to support  tentative dates 
and  storage conditions,  as long as they are followed  and 
supported  by real  time studies.  Accelerated  studies may not 
be  appropriate  for  some  products  because  of  their complexity, 
because  there i s  no  adequate methodology to conduct  acceler- 
ated  studies,  or because  they are new products  and  there i s  
insufficient historical  data available. 
Each  N D  i s  evaluated  for additional stability studies if 
there is any significant change which may affect stability i n  
the manufacturing process  or equipment,  the components 
including the container/closure system,  or shipping 
container. " 
6.  Medical Gloves:  Two separate CDRH documents concerning 
medical gloves contain references to shelf life.  Excerpt 
from these are included in the following subsections. 
6.1 "United States FDA Pre-Marketing and Labeling Requirements 
for Medical Glovess~;M arch 1990; issued by DSMA within the 
Office of Training and Assistance.  This document describes 
the activities that must be completed to import and market 
medical gloves in the US.  In the section that discusses the 
labeling requirements of medical gloves is stated "Finally, 
Part  820, The  Good  Manufacturing  Practices  (GMP)  regulation 
does not require lot numbers  for surgical  gloves.  However, 
it is customary for surgical  gloves  to have  a lot number,  an 
expiration date,  and  data  to support  the expiration date. 
The GMP  regulation does  require manufacturers  t o  establish a 
quality assurance  program  appropriate for  the device being 
manufactured.  6.2 "Guidance for the Content and Organization of a Premarket 
Notification [510(k)] for Surgeon's  Glovesw; August 1989; 
issued by the General and Plastic Surgical Devices Branch, 
Division of Surgical and Rehabilitation Devices within ODE. 
This document details the information that should be included 
in a 510(k) for surgeon's gloves and states that "If a  shelf 
life is t o  be  included  on  the label  of the  finished  gloves, 
the applicant must  provide  data supporting  the proposed 
shelf  l i f e . "  
Additionally, DCD within ODE, has begun drafting a guidance 
document for determining the shelf life of products that are the 
subject of applications reviewed in DCD.  This guidance document 
has not yet been issued in final or draft form.  Their current 
policy is to determine if a shelf life is appropriate on a case- 
by-case basis for PMA products (class I11 devices).  DCD is also 
participating in the pilot program that is outlined in the 510(k) 
Sterility Review Guidance mentioned previously. 
The Division of Small Manufacturers Assistance (DSMA) was 
established to meet the requirements of the Medical Device 
Amendments that FDA establish an office to provide technical and 
other nonfinancial assistance to medical device manufacturers. 
The guidelines and other documents referenced throughout this 
paper are available from DSMA by calling 800-638-2041 (or 
301-443-6597 in Maryland).  DSMA is also ready to answer requests 
for other information or guidance concerning the obligations of 
medical device establishments. 
GLOSSARY 
510 (k)  Premarket Notification 
ASTM  American Society for Testing and Materials 
CDRH  Center for Devices and Radiological Health 
CFR  Code of Federal Regulations 
DCD  Division of Cardiovascular Devices 
DCLD  Division of Clinical Laboratory Devices 
DCP  Division of Compliance Programs 
DOD  Division of Ophthalmic Devices 
DOED  Division of Obstetrics/Gynecology, Ear, Nose, Throat, and 
Dental Devices 
DSMA  Division of Small Manufacturers Assistance 
FDA  Food and Drug Administration 
GMP  Good Manufacturing Practices 
IDE  Investigational Device Exemption 
OCS  Office of Compliance and Surveillance 
ODE  Office of Device Evaluation 
PMA  Premarket Approval 
USP  United States Pharmacopoeia  REFERENCES 
Accelerated Aging of packaging: ~onsiderations, ~uggestions, and 
Use in Expiration Date verification, Robert R.  Reich et.al., 
MDDI, March 1988 
ASTM method D 3492-89 
Accelerated Testing, Wayne Nelson, 1990 
Guideline for Submitting Documentation for the Stability of Human 
Drugs and Biologics, Center for Drugs and Biologics, FDA, 
February 1987 
Guideline on General Principles of Process Validation, Division 
of Manufacturing and Product Quality (HFN-320), Center for 
Drugs and Biologics, FDA, May 1987 
Medical Device Packaging Handbook, Joseph D.  OtBrien, Marcel 
Dekker, Inc.,  1990 
MIL STD 105E, 10 May 1989 
Preproduction Quality Assurance Planning &  Recommendations for 
Medical Device Manufacturers, FDA 90-4236, 1990 
Quality Planning and Analysis, J.M.Juran  &  Frank M. Gryna Jr., 
1980 
Sterile Package Validation Guidance Document (DRAFT), AMMI, 
04/05/90 
The Five PIS of Package Design, David L.  Seitelman, MDDI, March 
1988 
USP XXII  pages 1678, 1679, 1703-1705