WARNING LETTER Indoco Remedies Limited MARCS-CMS 575313 — JULY 16, 2019

1.  Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).

Compression machine process control values were not adequately reported in your batch production records during the manufacture of (b)(4) mg tablets intended for the U.S. market. Your quality unit used these deficient records to release batches of this drug product.

While multiple batch records of (b)(4) mg tablet included handwritten values routinely within process parameters, the values recorded by the programmable logic controller (PLC) of your compression machine were frequently outside your established process parameters. For example, (b)(4) mg batch (b)(4) had compression force values handwritten (b)(4) in the batch record ranging from (b)(4) (your limit was (b)(4)).

However, the PLC data recorded individual values ranging from (b)(4) for the same time period. In addition to compression force values, handwritten values for filling depth and automatic weight control (AWC) did not accurately reflect the values within the PLC data...

3.  Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).

On several occasions, you conducted a new analysis after obtaining an initial OOS test result. These analyses included water content tests on a Karl Fischer instrument and an assay test on an auto titrator instrument. We reviewed the electronic data on these instruments and found OOS testing results which were not reported in the analytical records. Only passing results were ultimately included in the data presented for batch review and disposition decisions.

Additionally, your laboratory failed to maintain basic raw laboratory data (e.g., original raw data sheets, original chromatograms, instrument usage logs, original weight printouts) in many instances.