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    Home > Medical News > Latest Medical News > One question and one answer! ANDA API and preparation stability test, you want to know, here!

    One question and one answer! ANDA API and preparation stability test, you want to know, here!

    • Last Update: 2020-08-01
    • Source: Internet
    • Author: User
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    Guide: What are the recommendations for the stability test of slow-release products?
    Q1: The scope and implementation date of the Stability Guide?
    A1: The Stability Guide applies to all new ANDA applications filed under Article 505(j) of the Federal Food, Drug and Cosmetic Regulations, and DMF applications (class II medicinal substances supporting ANDA). Not applicable to post-marketing changes. Implementation date June 20, 2013.
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    . Q2: How does this guide affect the Presidential Emergency Act on AIDS Relief (PEPFAR) and POSD ANDA?
    A2: For chemical, production and control (CMC) information, PEPFAR ANDA should comply with the guidelines for fixed-dose formulations, combination packaging drugs, monochemicals for approved antiretroviral products for AIDS treatment.
    for PET ANDA, authorities recommend at least three batches with the highest or nearest radiation intensity. If a different synthesis method is used (synthetic method), it is recommended that each synthesis method have three batches with the highest or nearest radiation intensity. Each batch does not need to be synthesized in the same plant. For additional production sites, even if the submission of declarations using orthogonal methods is used, the applicant shall provide at least one batch of stability data for each site. For the additional information, the administration has published the industry guide "FDA Regulation of PET Products: Question and Answer".
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    . Q3(i): Can ANDA submit only 6 months of accelerated testing and 6 months long-term stability test data?
    A3(i): Yes. The request is for six months of accelerated stabilization tests and six months of long-term stability test data. However, if the six-month data show significant changes or any signs of failure, the recommendation is submitted with six months of intermediate condition data.
    Q3 (ii): If the acceleration condition fails, when will the intermediate condition stability test begin?
    A3 (ii): We recommend conducting intermediate, accelerated and long-term stability studies at the same time so that all required data can be obtained when filing the submission.
    Q3 (iii): What should I do if one of the three acceleration trials shows significant changes?
    A3 (iii): If one or more batches of acceleration data exhibit significant changes or any one attribute failure, the applicant should submit each batch of intermediate condition data. In addition, a failed analysis (such as discussing observed failures) should be submitted, and it is recommended that all three batches of intermediate condition data be submitted.
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    . Q4:(OGD),/ANDA?
    A4: Yes. You can design according to the ich industry guide Q1D "New API and New Formulation Stability Test Classification and Orthogonal Design" and the requirements of its sample table.
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    . Q5(i): If the filing complies with the 10-month review requirements of the Counterfeit Drug Payment Act (GDUFA), which includes six months of accelerated and long-term stability test data, and no patent obstruction seditu or administrative protection, will it be approved for a 24-month validity period?
    Q5 (ii): Do You need to submit 12 months of long-term stability update data during the audit?
    A5 (i,ii): The FDA will give a protection period, according to the ICH Q1E evaluation requirements, if the submitted data meets the requirements, the data is evaluated in accordance with THE requirements of ICH Q1E, the validity period is twice the length of long-term stability test data at the time of approval (up to 24 months). See the decision tree in ICH Q1E (Annex A). ANDA should update the long-term stability test data for 12 months.
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    . Q6: If there are only two batches of finished product synth batch, is it sufficient to support THE ANDA single-dose form stability test requirements?
    A6: According to the FDA stability guidelines, applicants should submit 3 batches of pilot batches or 2 batches plus batch of pilot batch to enlarge the batch. This requirement applies to all dosage forms. If the volume size does not match ICH, the applicant should submit a valid reason. See Section C, Article 20 question sings more about disclaimers.
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    . Q7: How should the proposed duration be calculated? Is the six-month acceleration equivalent to a 24-month long-term trial?
    A7: ICH Q1E principle scant the duration of protection. Three batches of ANDA declaration batch (i.e. 6 months) stability data, acceleration data in line with all criteria (no significant change severance according to ICH Q1A (R2), 12 months of long-term stability data no change, no statistical evaluation is required. If the advance request contains an appropriate stability commitment, the protection period can be extended to 24 months.
    if there is a significant change in acceleration data, ICH Q1E Annex A provides a detailed description of when intermediate condition data is recommended.
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    . Q8: Can 6 months acceleration data and 24 weeks of data equally? Because 12 weeks of data with 3 months of data is already waiting.
    A8: No, the FDA is based on the monthly time in the ICH stability guidelines, not the week.
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    . Q9: If a patent is about to expire and there is no approved ANDA, can we submit three-month stability test data and commit to supplement it when the data is available for six months?
    A9: No. The ICH stability guidelines must be observed regardless of patent status.
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    . Q10: If the ANDA declaration batch is a large number of three batches, do you need to store it until it is destroyed?
    A10:, and ANDA shall declare batch sample storage time at least 1 year after ANDA approval, and preparation samples for bioequivalent research should comply with 21 CFR 320.38 and 21 CFR 320.63. In addition, the contents of the industry guidelines regarding the handling and retention of BA and BE test samples are helpful for the processing of BA and BE reserved samples. For more discussion on the number of samples (for preservation control), see 21 CFR 211.170 (a) and (b) to retain the samples.
    B. Drug Master File Drug Master File

    . Q1: Please explain the impact of the Stability Test Guide on DMF holders
    Q1(i): Do you need to provide months of long-term and accelerated data when conducting a DMF integrity assessment? What should be provided for integrity assessments in the DMF stability section?
    A1(i) :D MFs should include stability protocols, commitments, and stability studies data before integrity assessments can be achieved. Initial data and new additions to a point in time data and long-term research data are sufficient. If the DMF does not meet the requirements of A1 (ii) as described below at the time of submission of the integrity assessment, dMF holders should update the latest DMF stability data in preparation for a comprehensive scientific examination.
    Q1 (ii): Is the stability data used to support API retesting three batches (filled in dMF) as required by cGMP? How many months will it take to put large amounts of long-term and accelerated data in a few months' time?
    A1 (ii): Yes, official stability test data that meets the requirements of ICH Q1A (R2) should be available in at least three main batches, and the API filled in the DMF should produce the smallest pilot batch. These batches should also comply with CGMPs. The FDA Stability Guidelines recommend six months of acceleration and six months of long-term data when submitting a pilot batch for comprehensive scientific inspection by dMF. For the new long-term data added in the three batches, if the data for the retest test ingress are valid, they should be submitted as supplements.
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    . Q2: Can DMF declarations be accepted based on the stability data of the batch of production batch?
    A2: Yes. According to ICH Q1A (R2), Part II, A, 8, Stability Commitment (2.1.8), if the declaration document is in the GMP conditions of three large production batches, with 6 months of acceleration and long-term stability test data, covering the recommended retest period, is acceptable.
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    . Q3: Should the three batches of batch production records be included in the submitted DMF?
    A3: 1 representative batch production record is sufficient
    . C. Drug Product Manufacturing and Packaging
    Pharmaceutical Production and Packaging

    Q1: Should bulk solutions be packed into different sub-assembling volumes as different batch numbers?
    A1: According to ICHQ1A (R2), bulk batch of finished products should represent different batches of bulk solutions. The distribution of a batch number bulk solution to different sub-assembled volumes does not constitute batch.
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    . Q2: Can you explain what the packaging suggestions are for the declaration of the packaging form of blowing bottle/filling/sealing?
    A2: The packaging form of blowing/filling/sealing is still a regular type of packaging, usually in outer packaging or carton packaging. All three batches should be packed. Ich Q1A (R2) explains that outer packaging is useful. (See Part II, B, 4, Pharmaceutical Packaging (2.2.4))
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    Q3: Should all three batches be stored in a complete package?
    A3: Yes. Three batches of products need to be packaged in the form of the application for listing. This problem is described in Q1A (R2) (see Part II, B, 4, Pharmaceutical Packaging (2.2.4).).
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    . Q4: What is the attitude of the regulatory authorities towards the use of different batches of API and/or packaging materials? How many batches of API can be used in pharmaceutical production to support ANDA?
    A4: No different batches of packaging materials are required unless the packaging material may affect the performance and/or shipping of the drug. At least 2 batches of raw materials should be used to prepare 3 batches of basic batches of pharmaceutical production.
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    . Q5: Do small quantities of products have to be packaged in commercial equipment, or can they be packaged with research and development equipment or hand-packed?
    A5: Small batches should be packaged with commercial equipment. The packaging system used should be the same or similar to the target storage and commercially available packaging. It is not recommended to use research equipment or manually package small quantities. See ICH Q1A (R2) Part II, B, 3 batch selection (2.2.3) and definition of terms for inner packaging.
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    . Q6: What are the suggestions for external packaging?
    A6: We recommend compliance with the requirements of ICH Q1A (R2) Part II, B,4 Pharmaceutical Packaging Sealing System (2.2.4).
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    . Q7: What are the recommendations for stability testing of slow-release products?
    A7: According to the requirements of the three batches of ICHQ1A (R2), the applicant shall provide three batches of data on all dosage forms (including the relief of preparations). The ICH stability guidelines do not distinguish between dosage forms.
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    . Q8: What recommendations are there for oral solutions, eye drops, oral and eye suspensions, transdermal patches, ointments, wipes, remodeling granules and injections?
    A8: We recommend submitting three non-continuous batches, 6 months acceleration and long-term stability data for any dosage form. See other questions and related answers to other dosage forms in this document. (e.g. Q7)
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    Q9: Are the three batches declared required to submit 6 months stability test data, or as long as one batch has 6 months, the other two batches can only have 3 months of data?
    A9: According to the ICH stability test guidelines, it is recommended that all declared batches submit 6 months (accelerated) stability test data.
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    . Q10: Do the batch records filled out by three batches of production be included in the ANDA declaration?
    A10: Yes
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    Q11: Does all relevant CMC batch information with the three stability test batches need to be included in the declaration material?
    A11: Yes. If.
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