The European Agency for the Evaluation of Medicinal Products
7Westferry Circus,Canary Wharf,London,E144HB,UK
英文网名伤感London,1March 2001
CPMP/QWP/2934/99COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)NOTE FOR GUIDANCE ON IN-USE STABILITY TESTING OF HUMAN MEDICINAL PRODUCTS DISCUSSION IN THE QUALITY WORKING PARTY (QWP)
January/October 1999TRANSMISSION TO THE CPMP
December 1999RELEASE FOR CONSULTATION
December 1999DEADLINE FOR COMMENTS
June 2000ADOPTION BY CPMP
February 2001DATE FOR COMING INTO OPERATION September 2001
NOTE FOR GUIDANCE ON IN-USE STABILITY TESTING OF HUMAN
MEDICINAL PRODUCTS
Objective
The purpo of in-u stability testing is to establish-where applicable-a period of time during which a multido product can be ud whilst retaining quality within an accepted specification once the container is opened.
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This guideline refers to medicinal products in multido containers which-by nature of their physical form and chemical composition-due to repeated opening and closing,may po a risk to its content w
ith regard to microbiological contamination,proliferation and/or physico-chemical degradation once the system has been breached.
Introduction
The continued integrity of products in multido containers after the first opening is an important quality issue.While this principle is acknowledged in the Ph.Eur.and EU Guidelines,no specific guidance is available on defining test design and conduct of studies to be undertaken to define in-u shelf life in a uniform fashion.Therefore,this document attempts to define a framework for lection of batches,test design,test storage conditions, test parameters,test procedures etc.,taking into consideration the broad range of products concerned.
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Nevertheless should this Note for guidance also be read in connection with the Notes for guidance on Development pharmaceutics(CPMP/QWP/155/96),Stability testing of existing active substances and related finished products(CPMP/QWP/556/96)and Stability testing of new drug substances and products(CPMP/ICH/2736/99).
The registration dossier for a multi-do product should include either the in-u stability data on which the in-u shelf life is bad or a justification why no in-u shelf life is established. This justifi
cation can also be bad on experimental results.
Selection of batches
A minimum of two batches,at least pilot scale batches,should be subjected to the test.At least one of the batches should be chon towards the end of its shelf life.If such results are not available,one batch should be tested at the final point of the submitted stability studies. The batch number,date of manufacture and size of each batch should be stated.The container and closure of the product and,if prent,the medicinal device should be equivalent to that propod for marketing.
If the product is to be supplied in more than one container size or in different strengths,the in-u stability test should be applied to the product which the greatest susceptibility to change.The choice of the tested product should always be justified.
黑板报主题Test design
As far as possible the test should be designed to simulate the u of the product in practice taking into consideration the filling volume of the container and any dilution/reconstitution before u.At intervals comparable to tho which occur in practice appropriate quantities should be removed by t
he withdrawal methods normally ud and described in the product literature.Sampling should take place under normal environmental conditions of u.
The appropriate physical,chemical and microbial properties of the product susceptible to change during storage should be determined over the period of the propod in-u shelf life.
鲱鱼罐头那么臭为什么还有人吃If possible,testing should be performed at intermediate time points and at the end of the propod in-u shelf life on the final remaining amount of the product in the container.
Test storage conditions
The product should be stored under the conditions as recommended in the product literature (SPC and PIL)throughout the in-u stability test period.
Any other storage conditions should be justified.
Test parameters
The appropriate physical,chemical and microbial properties of the product susceptible to change during u should be monitored.The tests ud must be appropriate to individual dosage forms,however,examples of parameter types which may need to be studied are given below:
Physical:colour,clarity,closure integrity,particulate matter,particle size
Chemical:active substance assay(s),antimicrobial prervative and antioxidant content(s),degradation product level(s),pH
Microbial:Total viable count,sterility
Analytical procedures
The analytical procedures ud in the study should be described and fully validated.Stability indicating assays should be employed.
Prentation of the results
The results should be summarized and tabulated.
If relevant,the results should be prented graphically.
Evaluation
Conclusions reached bad on the data provided should be stated.In the ca of anomalous results 善解人意近义词
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息开头的成语the should be explained.
Where applicable and justified an in-u shelf life specification should be given.
In-u stability data should be ud to determine whether or not a declaration of an in-u shelf life and additional storage conditions are necessary.
Labelling of the primary container
The in-u shelf life should be stated on the label.In addition(if space allows)there should be a space for the ur to write the date of opening or the"u-by"date.
SPC,leaflet and labelling of the condary container
The in-u shelf life and in-u storage recommendations-if applicable-should be included in SPC,leaflet and outer carton text.
