Company Name：Alkem Laboratories ( India )

Defect description：

A During the inspection, we observed two (2) different QC lab analyst demonstrate the ability to change calculation function in the excel spreadsheet used for finished product testing for the following:

(1) On 22 March 2018, we observed your QC Analyst use an uncontrolled excel spreadsheet to calculate the Average, Standard Deviation, and %RSD values for (b)(4) Tablets, Batch #(b)(4) product release testing. The use of this spreadsheet is not mentioned in any written procedure when conducting (b)(4) Product Release Testing. In addition, this excel spreadsheet is not saved or printed. Therefore, the QC Reviewer is unable to verify these calculations are correct and the correct formula was used.

(2) On 23 March 2018, we observed the QC Reviewer use an uncontrolled excel spreadsheet to verify the potency of (b)(4) working standard during the Analytical Worksheet review for (b)(4) Tablets, Batch #(b)(4). The use of this spreadsheet is not mentioned in any written procedure when conducting Analytical Report reviews.

B. On 19 March 2018, we observed your QC Manager’s use an excel spreadsheet to track quality functions, such as stability samples. This document is not maintained through document control and there is no protection from dat manipulation, overwriting, erasing of data, or audit trails.

C. On 19 March 2018, during the inspection, we observed two (2) (b)(4) employees use an uncontrolled spreadsheet to calculate due dates used during the manufacturing and packaging of drug products.

(1) For example, but not limited to, the (b)(4) stage is to be completed within (b)(4) initiating the compressed tablet stage. However, the dates used to calculate these timeframes has not been validated. In addition, this spreadsheet was no password protected.

Company Name：Alkem Laboratories ( India )

Defect description：

In addition, your firm failed to maintain and retain logbooks that are not obsolete or outdated. For example, once completed your firm destroys logbooks from the following areas: (b)(4) block warehouse, Housekeeping (b)(4)-Block QC, (b)(4)-Block QA,(b)(4)-Block Manufacturing, (b)(4)-Block, QC, Warehouse, and Production-(b)(4)Block.

As recent as 2018, the destruction of logbook examples include, but are not limited to: Notification Record for Invalid Data, Line Clearance Checklist, Preventive Maintenance, Instrument Logbooks, training records, cleaning check lists.

Company Name: Hunan Norchem Pharmaceutical Co., Ltd ( China )

Defect description：

Failure to prepare and use production and control records for each intermediate and API batch.

Your Quality Unit failed to retain and locate 20 of (b)(4) of your (b)(4) base batch records, including but not limited to records for batches (b)(4) and (b)(4).In your response, you stated the batch records “are not missing” and are “archived properly.” Your response is inadequate because you did not provide evidence, such as copies of the executed batch records.

Additionally, your Quality Assurance department approved batch record 0220151203 and batch record0220151204 despite the inaccuracy of the weight of raw materials added. In your response, you stated the operator “did not follow the procedure” and did not recognize this as a deviation. You also stated personnel had “inadequate awareness of deviations.” It is your responsibility to ensure the accuracy and completeness of your batch records in order to establish that your manufacturing process was followed and is reproducible.

Company Name：Daito Kasei Kogyo Co., LTD., Okayama Factory ( Japan )

Defect description：

Failure to completely report test results on certificates of analysis.

During the inspection, were viewed certificates of analysis (COA) for batches of (b)(4) API that you manufactured and released between June 2011 and February 2016. Your quality control unit signed these COA, which indicated that all required tests had been conducted on these batches. However, you told our investigator during the inspection that you signed these COA without having conducted all the tests for which you reported results on these COA. For example, your COA reported the results of identity and impurities tests that you never conducted.

You falsified the COA you issued to your customers. Regulators and customers rely on COA for accurate information about the quality and sourcing of drugs and their components. Falsifying information about the quality of your drugs on COA compromises supply chain accountability and traceability, and may put consumers at risk.

Company Name: Cosmecca Korea Co., Ltd. ( Korea )

Defect description：

Your firm’s quality control unit failed to review and approve all drug product production and control records to determine compliance with all established, approved written procedures before a batch is released or distributed (21 CFR 211.192).

Your OTC sunscreen drug product, (b)(4), contains (b)(4) active ingredients: (b)(4).Your batch records for lot (b)(4)of this product included concentration values for these active ingredients that did not match the data found in your instruments. You used the inaccurate data reported in your batch records to calculate potency results that were within specification, and you relied on these inaccurate results to release your product. However, when we used the instrument data instead of the results in your batch records to perform the same calculations, we found that the lot was out-of-specification (OOS)(super potent) for (b)(4) active ingredients. Your quality unit did not identify this discrepancy prior to releasing this lot.

Company Name: Cosmecca Korea Co., Ltd. ( Korea )

Defect description：

Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

Laboratory equipment used to generate analytical data for release purposes lacked restricted access. For example, analysts shared usernames and passwords, and all users had administrator rights that permitted them to delete or modify files in high-performance liquid chromatography and gas chromatography equipment. You had no mechanism to facilitate traceability of the individuals who changed, adjusted, or modified data generated by computerized systems.

Company Name: Alchymars ICM SM Private Limited ( India )

Defect description：

Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure your API complies with established specifications and standards.

Our investigator found that your firm was falsifying laboratory data. For example, the number of colony-forming units (CFU) found on (b)(4) plates for (b)(4)water point-of-use tests differed substantially from the number recorded on your (b)(4) water report. For multiple points of use, your analyst reported far fewer CFU than observed on the plate by our investigator. In addition, while you reported absence of growth on a selective media plate used to detect objectionable microorganisms, our investigator observed growth on this plate. This is concerning because you use(b)(4) water to manufacture products, such as (b)(4) API, that are intended for use in sterile injectable dosage forms.

Company Name: Zhejiang Ludao technology co., LTD. ( China )

Defect description：

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

Your firm lacks basic laboratory controls to prevent changes to paper and electronic records for your over-the-counter (OTC) drug products. You were not able to provide analytical test data for three batches of (b)(4) spray and one batch of (b)(4). We found that you created certificates of analysis (COA) for these four batches before they were manufactured and tested.

When questioned, your firm acknowledged falsifying the analytical test results on the COA you used to support release and distribution of (b)(4) spray and (b)(4) drug products to the United States.

In addition, we found three electronic data files in the electronic recycle bin of the stand-alone HPLC system you used to test finished drug product (b)(4) spray. Because this instrument lacks back-up and audit trail capabilities, we could not determine how frequently test data obtained prior to “official” batch testing was discarded. You were unable to explain why these electronic files were deleted.

cGMP-related data must be retained by a laboratory to enable appropriate assessments and decisions by the quality unit regarding batch disposition and to demonstrate ongoing control.