Failed to conduct adequate investigations into these significant deviations prior to making batch disposition decisions

This is continuous to previous post about FDA observations 1,2 of 4.

3.      Failure to ensure all production deviations are reported and evaluated, and that critical deviations are investigated and conclusions are recorded.

Our investigator’s review of your 2014 and 2015 annual product quality reviews (APQR) revealed that your firm had eight critical process parameter failures related to time limits for (b)(4) or (b)(4) operations under (b)(4) conditions for (b)(4) USP API. 

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For example, batch (b)(4), Deviation Report D/PR/052/14 under Operation (b)(4) specifies that (b)(4) should be attained within (b)(4). However, the actual (b)(4) time was more than (b)(4). Furthermore, you failed to conduct adequate investigations into these significant deviations prior to making batch disposition decisions.

In your Critical process parameters in manufacturing process of (b)(4) document, signed on February 19, 2016, you stated, “Under (b)(4) condition, (b)(4) degrades to give the (b)(4) material and (b)(4). The (b)(4) material and (b)(4) will react with (b)(4) to generate the (b)(4) impurity.” Failure to meet time limits for (b)(4) or (b)(4) operations could lead to inconsistent strength and purity.

Your response is inadequate. Although you attribute these failures to mechanical breakdowns and operator delays, your response lacks a comprehensive assessment of how these critical deviations affected your API quality.

In response to this letter, provide:

·         Test results of all batches that may have been compromised by (b)(4) impurities

·         Evaluation of product impact when critical parameters exceeded established limits

·         Data to support the root cause analysis in your March 9, 2016 response

·         List of improvements in your quality system to ensure that

o   all deviations are reported to the quality unit before batch release

o   all investigations are properly performed

o   the quality unit conducts robust APQR and effective internal audits

4.    Failure to ensure that test procedures are scientifically sound and appropriate to ensure that your API conform to established standards of quality and/or purity.

During a review of your customer complaints, our investigator found a September 13, 2014, complaint concerning a batch of (b)(4) ((b)(4)) that failed water content. The specification range of (b)(4) water content was (b)(4)% to (b)(4)%. Although your firm measured (b)(4)% water content during the release of the batch, the complainant measured (b)(4)% water content.

Your retrospective analysis concluded that your firm’s laboratory reported lower water content results than your customer’s laboratory obtained for all (b)(4) batches of (b)(4) you supplied to the customer. Significantly, our inspection revealed that you had not validated your method for measuring water content.

According to your response, you have completed method validation for water content. However, your response is inadequate because it does not detail your investigation into the released API batches tested using non-validated method.

In response to this letter, provide:

·         Retrospective review or retesting of all batches of (b)(4) that remain within retest period or expiry

·         A review of all test methods to ensure they are validated

Click Here for FDA Warning Letter

Also read Observation 1: Cleaning of equipment's and how to write regulatory response 

Also read about Effective CAPA SYSTEM

Author: Mahender Nagaraju

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GMP News, GMP guidelines, GMP Violations, GMP warnings, GMP Trends. A Public Health Global News Portal. (This story has not been edited by GMP Violations staff and is auto-generated from a syndicated feed.) Disclaimer: The Logos/Images & content posted here are belongs to respective to Authority / owners of firm. The Article posted under public health importance news.