Question & Answer on Quality Control Part -III AS PER EU Guidelines (EudraLex)

Question & Answer on Quality Control Part -III AS PER EU Guidelines (EudraLex)

Question:

What is the purpose of the ongoing stability programme for medicinal products according to the EU GMP?

Answer:

The purpose of the ongoing stability programme is to monitor the product over its shelf life and ensure that it remains, and can be expected to remain, within specifications under the labeled storage conditions. This programme aims to detect any stability issues associated with the formulation in the marketed package.

Question:

What considerations should be made regarding the inclusion of bulk product in the stability programme according to the EU GMP?

Answer:

Consideration should be given to the inclusion of bulk product in the stability programme. For instance, when bulk product is stored for a long period before being packaged and/or shipped from a manufacturing site to a packaging site, the impact on the stability of the packaged product should be evaluated and studied under ambient conditions. Additionally, intermediates stored and used over prolonged periods should also be considered.

Question:

How should the ongoing stability programme be described and formalized according to the EU GMP?

Answer:

The ongoing stability programme should be described in a written protocol following the general rules outlined in Chapter 4. The results of the programme should be formalized as a report.

Question:

What requirements apply to the equipment used for the ongoing stability programme according to the EU GMP?

 Answer:

The equipment used for the ongoing stability programme, such as stability chambers, should be qualified and maintained following the general rules described in Chapter 3 and Annex 15.

Question:

What parameters should be included in the protocol for an ongoing stability programme according to the EU GMP?

Answer:

The protocol for an ongoing stability programme should extend to the end of the shelf life period and include parameters such as the number of batches per strength and different batch sizes, relevant physical, chemical, microbiological, and biological test methods, acceptance criteria, reference to test methods, description of the container closure system(s), testing intervals (time points), description of the storage conditions, and other applicable parameters specific to the medicinal product.

Question:

What is the purpose of monitoring reconstituted product stability according to the EU GMP?

Answer:

The stability of reconstituted product is monitored when relevant, although stability studies on reconstituted product are performed during product development and need not be monitored on an ongoing basis. However, when relevant, the stability of reconstituted product can also be monitored.

Question:

What criteria should be considered for the acceptance of parameters in the ongoing stability programme according to the EU GMP?

Answer:

Acceptance criteria should be established for the ongoing stability programme based on relevant guidelines and regulations, ensuring that the product remains within specified limits throughout its shelf life.

Question:

Why is it important to include relevant physical, chemical, microbiological, and biological test methods in the protocol for an ongoing stability programme according to the EU GMP?

Answer:

Including relevant test methods in the protocol ensures comprehensive monitoring of the product’s stability, allowing for the detection of any changes in physical, chemical, microbiological, and biological attributes over time.

Question:

What conditions should be described for the storage of products in the ongoing stability programme according to the EU GMP?

Answer:

The conditions of storage described in the ongoing stability programme should be consistent with standardized ICH/VICH conditions for long-term testing and should align with the product labeling. These conditions should be accurately documented and adhered to throughout the stability testing period.

Question:

How should the stability of intermediates be addressed in the ongoing stability programme according to the EU GMP?

Answer:

The stability of intermediates should be considered in the ongoing stability programme, and appropriate testing protocols should be established to ensure their stability over prolonged periods. This ensures that the quality of intermediates used in the production process is maintained, contributing to the overall quality of the final medicinal product.

Question:

How can the protocol for the ongoing stability programme differ from the initial long-term stability study submitted in the marketing authorisation dossier, and what requirements are there for such differences?

Answer:

The protocol for the ongoing stability programme can be different from that of the initial long-term stability study submitted in the marketing authorisation dossier, provided that this is justified and documented in the protocol. Differences may include changes in the frequency of testing or updates to ICH/VICH recommendations.

Question:

What criteria should be considered for determining the number of batches and frequency of testing in the ongoing stability programme according to the EU GMP?

Answer:

The number of batches and frequency of testing in the ongoing stability programme should provide a sufficient amount of data to allow for trend analysis. Unless otherwise justified, at least one batch per year of product manufactured in every strength and every primary packaging type should be included in the stability programme, unless none are produced during that year. The frequency of testing may also consider a risk-benefit approach, particularly for products requiring testing using animals with no appropriate alternative validated techniques available.

Question:

Under what circumstances should additional batches be included in the ongoing stability programme according to the EU GMP?

Answer:

Additional batches should be included in the ongoing stability programme in certain situations, such as after any significant change or deviation to the process or package, or when any reworking, reprocessing, or recovery operation occurs.

Question:

Who should have access to the results of ongoing stability studies according to the EU GMP?

Answer:

Results of ongoing stability studies should be made available to key personnel, particularly the Qualified Person(s). If ongoing stability studies are conducted at a site other than the site of manufacture of the bulk or finished product, there should be a written agreement between the parties concerned. Results of ongoing stability studies should also be available at the site of manufacture for review by the competent authority.

Question:

What action should be taken in response to out of specification or significant atypical trends in the ongoing stability programme according to the EU GMP?

Answer:

Out of specification results or significant atypical trends identified in the ongoing stability programme should be investigated. Any confirmed out of specification result or significant negative trend affecting product batches released on the market should be reported to the relevant competent authorities. The possible impact on batches on the market should be considered in accordance with Chapter 8 of the GMP Guide and in consultation with the relevant competent authorities.

Question:

What requirements are there for summarizing the data generated in the ongoing stability programme according to the EU GMP?

Answer:

A summary of all the data generated, including any interim conclusions on the programme, should be written and maintained. This summary should be subjected to periodic review.

Question:

What steps should the transferring site take prior to transferring a test method, according to the EU GMP?

Answer:

Prior to transferring a test method, the transferring site should verify that the test method(s) comply with those described in the Marketing Authorization or the relevant technical dossier. The original validation of the test method(s) should be reviewed to ensure compliance with current ICH/VICH requirements. Additionally, a gap analysis should be performed and documented to identify any supplementary validation that should be performed before commencing the technical transfer process.

Question:

What documentation should be provided in the transfer protocol according to the EU GMP?

Answer:

The transfer protocol should include, but not be limited to, several parameters such as the identification of the testing to be performed and the relevant test method(s) undergoing transfer, identification of additional training requirements, identification of standards and samples to be tested, identification of any special transport and storage conditions of test items, and the establishment of acceptance criteria based upon the current validation study of the methodology and in line with ICH/VICH requirements.

Question:

What action should be taken if there are deviations from the transfer protocol according to the EU GMP?

Answer:

Deviations from the transfer protocol should be investigated before the closure of the technical transfer process. The technical transfer report should document the comparative outcome of the process and identify any areas requiring further test method revalidation, if applicable.

Question:

What consideration should be given to specific requirements from European Guidelines for the transfer of particular testing methods, as mentioned in the EU GMP?

Answer:

Where appropriate, specific requirements described in other European Guidelines should be addressed for the transfer of particular testing methods, such as Near Infrared Spectroscopy. This ensures that the transfer process adheres to relevant regulatory standards and guidelines.