FDA describes detailed CAPA Procedure in Warning Letter

An FDA Warning Letter is a formal communication from the US Food and Drug Administration (FDA) notifying a company or individual of regulatory violations. These typically describe observations made during an inspection and list violations found (referencing the specific sections of the FD&C Act, the Code of Federal Regulations (CFR), and other applicable laws as appropriate). In addition, specific measures are listed that the recipient must take to remedy the violations. It does not go into great detail, especially not with regard to instructions on the desired procedure.

In a Warning Letter issued to Sun Pharmaceutical Industries Limited (India) at the beginning of July, this is now different. It describes in great detail what the FDA considers to be appropriate CAPA measures in a specific case.

What happened?
The company was criticised for not adequately cleaning and maintaining the equipment used to manufacture drug products. According to the company's response, a defective valve was the cause of the observed liquid build-up. This was discovered in the course of investigating the cause following the inspector's observation. Affected batches were recalled, but this was not enough for the FDA, which now lists very specifically what to expect:

A comprehensive, independent retrospective evaluation of the effectiveness of cleaning measures, including consideration of production equipment that may have been improperly cleaned.
A corrective and preventive action plan (CAPA) based on the retrospective assessment of the cleaning programme, including appropriate corrective actions for cleaning procedures and practices and a timeline for completion.
A detailed summary of weaknesses in the process for the life cycle management of equipment cleaning.
Identification of improvement actions to the cleaning programme, cleaning effectiveness and improved ongoing verification of proper performance.
Among other things, the CAPA plan should ensure that potential problems with equipment are recognised immediately so that, for example, repairs are carried out effectively. The plan should also ensure that appropriate action is taken across the organisation's network.
The CAPA plan must comprehensively address any gaps identified by an external consultant when assessing the maintenance programme.
The review of the effectiveness of the CAPA measures must include at least the following:

Evaluation of improvements to cleaning and maintenance procedures, including determining the specific frequency and locations to be cleaned at all relevant facilities
Adequacy of maintenance and repair history analysis
Assessment of all major production facilities for other sources of cross-contamination
Adequacy of improvements to the method of analysis to identify residual carryover
Adequacy of investigations of other unknown (unidentified) peaks
Assessment of whether the scope of the investigation and the associated CAPA were sufficient
However, the FDA was also not satisfied with the measures taken in the investigation of OOS results: "Your investigations of out-of-specification (OOS) results were inadequate because they lacked scientific rationale for root cause determinations."

Comments

Post a Comment

Popular posts from this blog

FDA Warning Letter Missing Ongoing Stability Studies for APIs

Company Antaria Pty. Ltd, Australia Synopsis  1.Inadequate Investigation  2. Own Analytal Methods used but proved to equivalent to USP methods 3.Annual Stability missed 1.Failure to adequately investigate and document out-of-specification results and implement appropriate corrective actions . Your firm manufactures API (b)(4) USP, labeled in part to be the active ingredient used in (b)(4). You failed to adequately investigate out-of-specification (OOS) test results. Specifically, your firm lacked adequate investigations and corrective actions for numerous OOS results obtained during laboratory testing of your API, including assay and loss on ignition (LOI) testing. The root causes were not clearly defined nor adequately documented, and lots with OOS results were released by your quality unit (QU). In your response, you state that staff turnover and insufficient staff training attributes to the lack of competency in good laboratory practices . Additionally, you state that you will rev
Read more

Understand ICH Q7

What is meant by ‘quality unit(s) independent from production The intent of the term ‘independent’ is to prevent any conflict of interest and ensure unbiased decision-making regarding quality-related decisions in the organization structure. The person in the quality unit who is responsible for final decision-making (e.g., batch release decision) should not have responsibilities for production activities [ICH Q7, 2.13]. Does ICH Q7 expect that the quality unit performs API release testing While the quality unit has responsibility for the release of the API, which includes oversight of the testing and results, ICH Q7 does not prescribe specifically who performs testing. ‘Quality control’ in the ICH Q7 Glossary [ICH Q7, 20] refers to the activities, not the organisational structure. For examples of quality responsibility related to testing and release, refer to [ICH Q7, 2.13, 2.22, and 11.12]. Appropriate laboratory controls should be followed [ICH Q7, 11.10, 16.10] regardless of who
Read more