Stability - Definition:
How the quality of an API or FPP varies with time under factors such as temperature, humidity and light.Studies also show how product-related factors influence stability: the properties of API/excipients, FPP composition, manufacturing process, and container-closure system.
API: Active Pharmaceutical Ingredient
FPP: Finished Pharmaceutical Products
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Definition: re-test period:
API: Active Pharmaceutical Ingredient
FPP: Finished Pharmaceutical Products
Stability - purpose:
a) To establish a re-test period* for the API or a shelf-life for the FPP.
b) To establish storage conditions.
Before starting assessment of stability data:
Is there a valid CEP (EDQM Certification Database)
If yes: was the valid version provided and does it include a retest date? If yes, this retest is acceptable without further review. If the applicant is requesting a longer retest (see label/specifications) then data must be assessed.
The period of time during which the API is expected to remain within its specification and, therefore, can be used in the manufacture of a given FPP, provided that the API has been stored under the defined conditions. After this period, a batch of API destined for use in the manufacture of an FPP should be re-tested for compliance with the specification and then used immediately. A batch of API can be re-tested multiple times and a different portion of the batch used after each re-test, as long as it continues to comply with the specification. For most substances known to be labile, it is more appropriate to establish a shelf life than a re-test period. The same may be true for certain antibiotics. [New Guide = Q1A]
Problem: The applicant has proposed a 12 month re-test period and a 60 month expiration period. They have provided data to support the re-test period, but not the shelf-life. Now what?
Answer: Except in exceptional situations, the shelf-life is not required and is considered an extra assurance. Since a re-test period is defined, the applicant must re-test the API immediately prior to its use once the re-test period has been exceeded. The re-test period, which is supported by data, is approved.
"The expiration date of an excipient cannot be extended. The Retest Date for an excipient is the date indicated by the supplier after which the excipient should be re-evaluated to ensure continued compliance with appropriate specifications. An excipient retest date may be extended based upon appropriate testing. The re-evaluation of the excipient may include physical inspection and/or appropriate chemical, physical, or microbiological testing."
Date Retested:
If retesting is performed by an excipient supplier and the results are used by the supplier to extend the length of time that the material may be used, then the Date Retested should also be reported preferably on the COA but alternative communication means are acceptable. The specific tests that were subject to retesting should be clearly identified and the results obtained upon retesting should be reported. After retesting, a new Recommended Retest Date should be reported on the COA.
Reference from 21CFR211:
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER C--DRUGS: GENERAL
PART 211 -- CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS
Subpart E--Control of Components and Drug Product Containers and Closures
Sec. 211.87 Retesting of approved components, drug product containers, and closures.
Components, drug product containers, and closures shall be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit in accordance with 211.84 as necessary, e.g., after storage for long periods or after exposure to air, heat or other conditions that might adversely affect the component, drug product container, or closure.
For industry Standard operating procedure Retest for API can be defined 6 monthly basis and 1 year for API based on vendor COA and provided stability data. Retesting of packaging material can be done yearly basis. Retest period can be assigned in label from the date of sampling of material
For more information regarding specifics per your application, please refer to the following sources:
1. ICH Q1A(R2), Stability Testing of New Drug Substances and Products
2. ICH Q1E, Evaluation for Stability Data
3. ICH Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products.
4. IPEC Excipient Information Package (EIP): Template and User Guide 2009
The Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients, 2006.
5. IPEC Good Distribution Practice Guide for Pharmaceutical Excipients 2006
6. IPEC-Americas Certificate of Analysis Guide for Bulk Pharmaceutical Excipients, 2000.
7. IPEC Excipient Composition Guide 2009.
CPMP/QWP/609/96/Rev 2, Guideline on Declaration of Storage Conditions
CPMP/QWP/4359/03 - EMEA/CVMP/205/04, Guideline on Plastic Immediate Packaging Materials
8. Commission Directive 2002/72/EC, Plastic materials intended for coming in contact with foodstuffs
Problem: The applicant has proposed a 12 month re-test period and a 60 month expiration period. They have provided data to support the re-test period, but not the shelf-life. Now what?
Answer: Except in exceptional situations, the shelf-life is not required and is considered an extra assurance. Since a re-test period is defined, the applicant must re-test the API immediately prior to its use once the re-test period has been exceeded. The re-test period, which is supported by data, is approved.
"The expiration date of an excipient cannot be extended. The Retest Date for an excipient is the date indicated by the supplier after which the excipient should be re-evaluated to ensure continued compliance with appropriate specifications. An excipient retest date may be extended based upon appropriate testing. The re-evaluation of the excipient may include physical inspection and/or appropriate chemical, physical, or microbiological testing."
If retesting is performed by an excipient supplier and the results are used by the supplier to extend the length of time that the material may be used, then the Date Retested should also be reported preferably on the COA but alternative communication means are acceptable. The specific tests that were subject to retesting should be clearly identified and the results obtained upon retesting should be reported. After retesting, a new Recommended Retest Date should be reported on the COA.
Reference from 21CFR211:
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER C--DRUGS: GENERAL
PART 211 -- CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS
Subpart E--Control of Components and Drug Product Containers and Closures
Sec. 211.87 Retesting of approved components, drug product containers, and closures.
Components, drug product containers, and closures shall be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit in accordance with 211.84 as necessary, e.g., after storage for long periods or after exposure to air, heat or other conditions that might adversely affect the component, drug product container, or closure.
For industry Standard operating procedure Retest for API can be defined 6 monthly basis and 1 year for API based on vendor COA and provided stability data. Retesting of packaging material can be done yearly basis. Retest period can be assigned in label from the date of sampling of material
For more information regarding specifics per your application, please refer to the following sources:
1. ICH Q1A(R2), Stability Testing of New Drug Substances and Products
2. ICH Q1E, Evaluation for Stability Data
3. ICH Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products.
4. IPEC Excipient Information Package (EIP): Template and User Guide 2009
The Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients, 2006.
5. IPEC Good Distribution Practice Guide for Pharmaceutical Excipients 2006
6. IPEC-Americas Certificate of Analysis Guide for Bulk Pharmaceutical Excipients, 2000.
7. IPEC Excipient Composition Guide 2009.
CPMP/QWP/609/96/Rev 2, Guideline on Declaration of Storage Conditions
CPMP/QWP/4359/03 - EMEA/CVMP/205/04, Guideline on Plastic Immediate Packaging Materials
8. Commission Directive 2002/72/EC, Plastic materials intended for coming in contact with foodstuffs
Nice article. Every excipient has expiry period, after that it should be re-test. Last test date is mentioned on COA i.e Certificate of Analysis.
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