Centaur Pharmaceuticals Private Ltd.
2 extracted findings · 3 model-assigned issue types
FDA source excerpt, selected passage
Your cleaning and maintenance procedures for non-dedicated (b)(4) equipment (b)(4), including your (b)(4) and (b)(4), are inadequate. Our inspection identified residues of what appeared to be different products on direct and indirect product contact surfaces, including those located inside (b)(4) systems, (b)(4) units…
Findings and supporting evidence
Model-assisted readings, not an exhaustive interpretation. Compare with the extracted source findings below.
Cleaning procedures for non-dedicated equipment were inadequate, with residues of multiple active ingredients found on surfaces, and equipment not cleaned for over 14 years.
Supporting FDA text
Source excerpt · automated text-match checkYour cleaning and maintenance procedures for non-dedicated (b)(4) equipment (b)(4), including your (b)(4) and (b)(4), are inadequate. Our inspection identified residues of what appeared to be different products on direct and indirect product contact surfaces, including those located inside (b)(4) systems, (b)(4) units (b)(4), and (b)(4). Your firm acknowledged that sections of the (b)(4), (b)(4), and (b)(4) have not been cleaned or examined for cleanliness since they were installed over 14 years ago. During the inspection, your analytical testing confirmed these residues contained multiple active ingredients. Furthermore, during the inspection, you collected residue samples at the end of placebo batches and subsequent cleaning, which also demonstrated active ingredient cross-contamination on surfaces.
The quality unit failed to ensure adequate cleaning procedures and oversight, including failure to identify visible contamination and lack of sufficient written procedures.
Supporting FDA text
Source excerpt · automated text-match checkYour quality unit (QU) failed to adequately implement the facility's quality function and ensure quality oversight. For example: A. Inadequate cleaning procedures Your procedure to clean (b)(4) lacked sufficient requirements to clean (b)(4) and (b)(4), which had not been cleaned since they were installed more than 14 years ago. Also, your procedure for visually ensuring cleanliness of equipment failed to identify visible contamination.
Investigations of extraneous peaks in stability samples were inadequate, lacking scientific justification for root cause and product quality impact.
Supporting FDA text
Source excerpt · automated text-match checkYour QU failed to adequately investigate extraneous peaks observed in long-term stability samples tested for dissolution by high-performance liquid chromatography (HPLC). Your investigation dated January 24, 2020, identified varying intensities in the peak response, and noted the peak eluted in some tablets, but not in others from the same batch. You determined the root cause to be interference from excipients used during manufacturing and concluded the peaks do not impact product quality. However, you provided no scientific explanation for this conclusion.
Findings extracted from the letter
Selected FDA passages, not the complete letter.
Source passage selected by the model
Source passage selected by the model
What FDA requested
Model-assisted summary. Consult the letter for complete requests and conditions.
- Provide a comprehensive, independent retrospective assessment of cleaning effectiveness to evaluate the scope of cross-contamination hazards, including identification of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution.
- Provide a corrective action and preventive action (CAPA) plan based on the retrospective assessment of the cleaning program, including appropriate remediations to cleaning processes and practices, timelines for completion, a detailed summary of vulnerabilities in lifecycle management of equipment cleaning, and improvements to the cleaning program including enhancements to cleaning effectiveness and ongoing verification of proper cleaning execution.
- Provide appropriate improvements to the cleaning validation program, with special emphasis on incorporating worst-case conditions, including identification and evaluation of drugs with higher toxicities, higher potencies, lower solubility in cleaning solvents, difficult-to-clean characteristics, swabbing locations for most difficult areas, and maximum hold times, and ensure use of appropriate limits that take into account recovery study results and describe steps for change management before introduction of new equipment or products.
- Provide a summary of updated standard operating procedures (SOPs) that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.
- Provide a holistic review of cleaning procedures and the associated cleaning validation strategy for all manufacturing equipment to determine whether similar deficiencies exist.
- Provide a comprehensive, independent assessment and remediation plan to ensure the quality unit (QU) is given the authority and resources to effectively function, including a determination of whether procedures are robust and appropriate, provisions for QU oversight throughout operations, a complete and final review of each batch before disposition, and oversight and approval of investigations and discharging of all other QU duties.
- Provide a comprehensive assessment of the overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures, with a detailed action plan to remediate this system, including improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality assurance oversight, and written procedures.
- Provide a detailed, independent assessment of all test methods to ensure they include specific instructions to ensure repeatability and system suitability, are supported by adequate validation (or verification for USP compendial methods) studies, are appropriate for their intended use, and determine whether test methods used in the stability program are stability-indicating, encompassing any tests conducted by the firm or its contract laboratories.
Sections and clauses cited
As cited in this historical letter, not a statement of current regulatory requirements.