In February, FDA posted four Form 483s and one untitled letter to compounding/outsourcing facilities. Also posted were three Form 483s to firms in India: Aurobindo, Lupin Limited, and Dr. Reddy’s. We cover these below.
And, we reviewed the FDAzilla Store to see which 483s were most-purchased and trending during February.
483s Posted
Aurobindo Unit VII
The inspection late last year at Aurobindo’s Unit VII (Telangana, India) was determined to be OAI, and the FDA recently sent a letter to that effect to the company. The firm manufactures solid oral dosage forms.
The 7-day inspection with three investigators ended September 27, 2019. The 14-page Form 483 includes 7 observations that included some serious data integrity deficiencies, failures in complaint management/investigation, and failures in the management of OOS events.
In particular, with OOS events, the percent of OOS results that were invalidated, obviously without adequate scientific justification, ranged from 43% for process validation to 100% for 72 samples in finished product stability testing. In addition to inappropriate invalidation of OOS results, FDA provided examples of problematic hypothesis testing in OOS investigation.
In a review of the audit trail in the electronic document management system, investigators identified batch records that were not provided in the list they requested from the firm. Further, more than 100 batch records were identified in an uncontrolled excel spreadsheet that the firm said they used for a variety of reasons including “the server was down.” This appears to represent a set of double bookkeeping at the firm.
In evaluating the audit trail from the Tiamo software application used to auto titrators, frequent events of “Determination stopped”, “Determination reprocessed”, “Determination interrupted” and “Determination error” appeared for test runs between operate April 2018 and September 2019. I would certainly look for additional enforcement action in the near future.
Lupin Limited
Lupin Limited (Andhra Pradesh, India) received a form 483 at the close of a 5-day inspection on January 17, 2020. The site manufactures APIs. The observations were written in a manner I’ve not seen commonly used. There is the frequent use of “should” in the general statement prior to the observation examples, an uncommon approach.
Observations include but are not limited to:
- The firm failed to identify critical process parameters prior to ‘validating’ the manufacturing process.
- Investigations were not conducted for discrepancies that happened during the manufacture of exhibit batches.
- Receiving and storage of reference standards were deficient. The QC lab released the secondary reference standard prior to performing appropriate analysis.
- Raw material sampling was deficient. The top, middle, and bottom of the raw material containers were not sampled.
- Control of changes to batch records was the responsibility of the Production department and not QA document control. As such, there is no assurance that QA reviewed and approved all changes.
Dr. Reddy’s Laboratories Limited, CTO Unit VI
Dr. Reddy’s Laboratories Limited, CTO Unit VI (Andhra Pradesh, India) received an 8-page form 483 including 5 observations at the close of an 8-day inspection conducted by two investigators ending January 28, 2020. This site manufactures APIs.
Observations from the most recent inspection include but are not limited to:
- Process validation is not adequate based on the continued and recurring OOS results for residual solvents that were not adequately investigated.
- OOS investigations did not identify the root cause. A variety of analyses were cited including, for example, assay, impurity, and residual solvent. Unknown peaks in residual solvents were not investigated. These examples were well redacted.
- Cleaning is not adequately validated. The examples were well redacted, but it appears that perhaps the firm was not manufacturing the product in question when the cleaning validation was conducted. It’s not clear. What is clear is that the firm could not provide the raw data for the surface calculations for each piece of equipment. The head of QA admitted there is no raw data for that calculation. Thus, there is no evidence that cleaning validation swab samples were actually analyzed. The head of QA also admitted no raw data calculations exist for any equipment cleaning validation efforts. Swab sampling locations are not scientifically justified. The firm also demonstrated unknown peaks to be present in the analysis of [redacted] API.
- The Quality Unit did not have adequate control over documentation. Documentation of OOS events was destroyed or missing pages. Method transfer documentation did not include test conclusions and test results.
483s to Compounding/Outsourcing Facilities
ABC Pharmacy, Inc.
ABC Pharmacy, Inc. (Encino, CA) received a form 483 issued at the close of inspection on Dec 20, 2019.
Hawaii Health Systems Corporation
Hawaii Health Systems Corporation (Kealakekua, HI) received a form 483 at the close of inspection on December 13, 2019.
Johns Pharmacy Inc.
Johns Pharmacy Inc. (Sullivan, IL) received an untitled letter on December 9, 2019, based on the form 483 issued at an inspection ending Feb 22, 2019.
New Era Pharmacy LLC
New Era Pharmacy LLC (Portland, OR) received a form 483 issued at the close of inspection on November 27, 2019.
SCA Pharmaceuticals, LLC
SCA Pharmaceuticals, LLC (Windsor, CT) received a form 483 issued at the close of inspection on November 19, 2019.
[NOTE: With a 483 Observation Report, you can quickly determine if there’s a citation trend you should be aware of. Learn more here!]