The results of the inspection by the European Pharmacopoeia, FDA, discloses the information of the manufacturing facilities judged to be incompatible.
Currently, it is requested from the Ministry of health, labor and welfare.
The FDA inspected emmcure pharmaceuticals, Ltd. In February 19-20 and 2019, when a significant GMP violation was observed, the improvement plan was judged to be insufficient, and FDA issued the warning letter on August 2, 2019.
Summary
Emmcel pharmaceuticals, Ltd.
Address: plot No. P-1 & P-2, i. t.b.t. Park, phase II, M. I. D.C., hinjwadi, Pune, Maharashtra, indidia
Aseptic preparations
The contents of the WL; production, OOS, process management, packaging, and storage are not compatible with the GMP;
Main remarks;
Whether you are already shipped or not, you have failed to thoroughly inspect the disagreement or difference of unidentified or unidentified causes of the batch or its composition in order to meet conformity with the standards.
According to your aseptic mismatch investigation, the most likely root cause of both incompatibility was laboratory errors. Your survey has substantially addressed the possibility of microbial contamination during aseptic testing, but did not pay attention to potential manufacturing causes. The investigation of your sterilization incompatibility did not have enough data to support that conclusion. For example:
- Aseptic tests were performed using an airtight test system in ISO 5 lamina flow. These conditions minimize the potential occurrence of cross contamination during sterile testing, but your investigation did not address proper cross contamination that could occur in such closed test systems.
- No microbial contamination was observed in the negative controls.
- Environmental monitoring data in the ISO5 environment did not show microbial contamination during the practice of an aseptic test.
- In the survey, no aseptic deviation was identified during aseptic tests.
- In the survey, no defects in test procedures, materials, or methods used in the practice of aseptic testing were not identified.
- Potential manufacturing failure mode is not properly evaluated.
As for the latter, your investigation did not thoroughly probe the root cause of potential manufacturing. For example, organisms isolated in an incompatible test have been detected in an experimental facility in the past, but the same microorganism was detected in the production area for six months before the failure. (b) (4) lysinbacillus fusiformis USP detected on November 24, 2017 by an aseptic test of the injection, (b), (4) GM (b) (4) ml, and batch (b) (4) were detected in the filling line ((b) (4) flow area) on 1 September 2017. Similarly, Bacillus cereus was detected on 4 June 2018 from (b) (4) injection of USP (b) (4) Mg (b) (4) ml, and batch (b) (4) was detected in the vial filling chamber on December 2, 2017. The review of environmental data was insufficient because it was overdependent on the findings in the QC microbiological laboratory. You have shown the potential pollution control risk at the test facility from the data, but it has concluded that it does not deal with poor growth mode. Specifically, it is not limited to the robustness of the container sealing process.
Unable to probe the risk of container integrity integrity. Your written answer provided a table containing a retrospective review of the containment integrity test (CCIT) results, but lacks a comprehensive evaluation of contradictions, deviations, complaints, and surveys associated with the containment integrity mode of potential containers.
In particular, products have been recovered in the past due to the incompatibility of container integrity integrity in the batch of products that originally passed the cit survey. To ensure sterility of the product, the integrity of the container sealing system is important. Each batch (sublot) of each batch was judged to be incompatible, and the shipment of the remaining sub lot was judged and shipped to the United States. After discussions with the FDA, you will recognize your company's decision to recover the shipped sublots, and your decision to install the sterile test isolator. In addition, FDA agrees to further review these incompatibilities and evaluate the microbiological OOS study procedures and provide the root cause documenting and appropriate details as well as the impact studies on other lots (or sublots).
Repeat violation
FDA correspondence
Not accepting new application
Emmcure Pharmaceuticals Limited
Please refer to the FDA URL for details.
FDA news release (2018-14)
The results of the inspection by the European Pharmacopoeia, FDA, discloses the information of the manufacturing facilities judged to be incompatible.
Currently, it is requested from the Ministry of health, labor and welfare.
The FDA had inspected IDT Australia on 4 to 8 December 2017, when a significant GMP violation was observed and the improvement plan was judged to be insufficient and FDA issued the warning letter on May 23, 2018.
Summary
Manufacturer: IDT Australia
Address: 45 wadhurst drive Boronia, Victoria, 3155 Australia
AOI and pharmaceutical products
The contents of the WL; manufacturing, packaging, and storage are not compatible with GMP, the integrity of OOS, data, and lack of microbial testing.
Main remarks;
API manufacturing
- The OSS survey has not been conducted properly.
Your company was inappropriate and unconformable in the "a" batch XXX on October 23, 2015. The investigation was started on the same day, and the investigation was finished several months later on 20 March 2016.
You have identified the root cause of inappropriate (b) and (4) from March 2016 (b) and (4).
As a result of two years after the FDA survey in December 2017, when there were no more than two years of improper action, no corrective action has been made to address the underlying cause of your company.
Meanwhile, the quality department released at least (b) (4) batch finished products (b) (4) APIs
- Your quality unit cannot confirm that serious deviations are being investigated and resolved.
Your quality department decided to ship (b) and (4) batch (b) (4) on April 30, 2015, despite the detection of total aerobic microorganisms above CFU / G. The standards are (b) and (4) cfu / g or less. You have sold this batch of (b) and (4) to a company that produces sterile drugs to treat us patients (b) (4). When the company confirmed the incompatibility result on 15 April 2015, the survey of the outside (OOS) was started. Upon completion of the investigation on April 24, 2015, you have concluded that there is a possibility of contamination in the cabinet of the biohazard, despite the lack of appropriate evidence.
Drug violation
- {the test procedure is not guaranteed, unobservable, you have established a necessary quality laboratory management system, including the change management that is prepared by the appropriate organizational unit and reviewed and approved by the quality control unit, and neglected it. (21 CFR 211.160 (b))
You have reported multiple microbial inspections in the microbial (b) (4) system used in the tests of (b) and (4) as "80 CFU" if the actual number of CFU is countless. Several days after these results, a new sample was resampled and diluted and counted colonies. If the diluted sample is within the standard range, the original result is discarded. Your (b) (4) sample sampling method and assay method may result in the possibility that the results of the microorganism cover the incompatibility, and (b) (b) the system may not be suitable for (b) and (4).
- Data integrity and data concealment. You have neglected to include complete data from all tests required to ensure established standards and standards compliance. (21 CFR 211.194 (a)).
As a result of inspecting your quality test room records, it became clear that you did not report the results of incompatibility to multiple opportunities.
Analysis test
Three consecutive confirmation tests occurred during the test of batch (b) (4) in March 2016 (4) and (4). The fourth test passed and the results of this pass were reported. The data package submitted to the quality department for inspection does not include these three incompatible test results or is not included in the submitted application documents. You did not investigate the incompatibility result. At the time of the inspection, it did not notice that the analyst did not report the unsuitable result to the quality department for the inspection.
Microbiological test
The results of the samples collected on November 23, 24 November, and December 1, 2017 during the microbial inspection of your cleaning water were not reported before (b) and (4) discard plates. You said the incubator had discarded the plate because the temperature mapping results were unsuitable. A survey of failed temperature mapping results shows that the plate results are passed but the number of individual plates is not recorded.
Your quality department has not explored high performance liquid chromatography (HPLC) assay data on shipping decisions and stability of your products.
We have found that at least 100 "test" injections are being carried out by checking the electronic data of HPLC. Your analysis procedures and methods do not mention the "test" injection. The supervisor of the quality laboratory does not review these injections before submitting data packages for approval. For each injection, FDA inspectors notified the quality Laboratory Supervisor and quality department review only chromatograms created and submitted by analysts. The quality test manager and quality managers did not review these test injections because your analysts did not print the chromatographic results of "test" injection. Your procedure did not require any quality test manager or quality department to inspect the underlying electronic record or data to ensure its accuracy or completeness. Therefore, the quality department used incomplete data for batch judgment. Your quality department could not guarantee the validity of the procedure to assess the quality of drugs.
FDA correspondence
A new application is not approved until improvement is recognized in the FDA
Japanese overseas manufacturing registry
Please refer to the FDA URL for details.