In November, FDA posted three notable Form 483s to sites of Aurobindo, one of which is a substantial 37 pages. Zydus Cadila received a 23-page, 14-observation Form 483 based on an inspection performed by FDA investigators Thomas Arista and Justin Boyd.
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483s Issued
DRUG FIRM: Aurobindo Pharma Ltd Unit 8
Aurobindo Pharma Ltd Unit 8 (Telangana, India) received a form 483 at the close of inspection on October 25, 2019. The firm manufactures APIs.
Observations include but are not limited to the following:
- Cleaning validation is not adequate because it appears that not all equipment was considered during the validation. Also, the cleaning logbook was not maintained, so details of cleaning could not be verified.
- Investigations were not complete or fully documented, particularly for OOS events.
- Procedures are not established to determine when a reprocessed lot will be placed upon stability.
- Electronic batch processing data for equipment is not maintained.
DRUG FIRM: Aurobindo Pharma Ltd Unit 5
Aurobindo Pharma Ltd Unit 5 (Telangana, India) received a form 483 at the close of inspection on October 28, 2019. The firm manufactures both sterile and non-sterile bulk drugs.
Observations include but are not limited to:
- There is no scientific basis for invalidating OOS results.
- Personnel activities during product filling do not fully protect drug substance. Personnel equipment, such as goggles, used in aseptic processing areas are not adequate to completely cover skin.
- Process validation does not always include identification of parameters that should be monitored to ensure reproducible processing.
DRUG FIRM: Aurobindo Pharma Ltd Unit 4
Aurobindo is having a very bad quarter. This is the fourth 483 from inspections since the end of September 2019 that has been made available.
This one, issued at the end of an inspection on November 13, 2019 is substantial at 37 pages. This inspection addressed Unit IV in Telangana, India for sterile drug manufacture. The inspection was conducted by five investigators including, Thomas Arista and Dipesh Shah, and lasted eight days. The 483 is heavily redacted but it’s worth reading. Here is an abbreviated approach to the 37 pages.
Observations include but are not limited to:
- Observation #1 takes approximately 6 ½ pages and addresses aseptic technique as well as failures in how media fill simulations were conducted.
- The EM sampling plan does not represent worst-case locations.
- Equipment used to ensure adequate environmental control is not adequately maintained. This observation addresses a commitment made in response to an inspection in December 2018. There are 12 pages of heavily redacted examples.
- Test methods, particularly for sterility testing, were not followed.
- A Field Alert was not submitted for a customer complaint as it should have been within 3 days.
- At least 10 complaints for lack of effect were received and not adequately investigated. During the inspection, FDA noted that there seemed to be a trend that might implicate the API supplier for the product in question. The supplier was not named.
- The computer system that identifies facility type alarms does not record the data from the event causing the alarm. The observation lists a collection of BMS type alarm events. Thus, investigation of what might have caused the alarm event is severely limited.
- Laboratory analysts do not need to be trained on the tests they perform. Quality control checks are not conducted frequently enough to ensure that tests are being run correctly.
- QC lab worksheet documentation is not adequate. When multiple analysts contribute to an analysis only a single analyst is identified and only a single analyst signs the worksheet.
DRUG FIRM: Cadila Healthcare Limited
Zydus Cadila (Moraiya, India) received a 23-page, 14-observation form 483 issued in May 2019 at the end of the recent inspection. The firm received a warning letter on October 29, 2019. The FDA investigators included Thomas Arista and Justin Boyd. The site manufactures sterile parenteral products.
Observations include but were not limited to:
- Non-dedicated equipment that was labeled as ‘clean’ had visible residues.
- Personnel aseptic practices were poor.
- Not all media fill vials are subject to incubation.
- Smoke studies did not demonstrate laminar airflow.
- Adverse EM Personnel trends and other EM trends have not been the subject of effective corrective actions.
- As-built diagrams for HVAC are not available at the company. It’s not clear that HVAC systems are adequate for aseptic processing areas.
- SCADA data are not subject to backup.
- Investigations into failures in periodic requalification aren’t accurate.
- Tablet variability has not been assessed between batches and within batches.
- Responsibilities of the Quality Unit are not fully followed.
- Laboratory methods are not adequate; for example, extraneous peaks are not considered in raw materials received from vendors.
Compounding/Outsourcing Facilities
Athenex Pharma Solutions, LLC
Athenex Pharma Solutions, LLC (Clarence, NY) received a form 483 issued at the close of an inspection on August 29, 2019.
BSO LLC
BSO LLC (Lakewood, CO) received a form 483 at the close of inspection on September 20, 2019.
D&D Pharma LLC
D&D Pharma LLC (Noblesville, IN) received a form 483 at the close of inspection on July 17, 2019.
Downing Labs, LLC
Downing Labs, LLC (Dallas, TX) received a form 483 at the close of inspection on November 19, 2018.
InfuScience Inc
InfuScience Inc (Chantilly, VA) received a form 483 issued at the close of inspection on July 30, 2019.
Innoveix Pharmaceuticals
Innoveix Pharmaceuticals (Addison, TX) received a form 483 at the close of inspection on September 12, 2019.
Isorx, Corp.
Isorx, Corp. (Richmond, CA) received a form 483 based on the outcome of an inspection ending September 18, 2019.
Maimonides Medical Center-Pharmacy
Maimonides Medical Center-Pharmacy (Brooklyn, NY) received a form 483 at the close of inspection on July 29, 2019.
Medi-Fare Drug & Home Health Center Inc
Medi-Fare Drug & Home Health Center Inc (Blacksburg, SC) received an untitled letter on March 18, 2019.
Medoz Pharmacy of Pilk, Inc.
Medoz Pharmacy of Pilk, Inc. (Davenport, FL) received a form 483 at the close of inspection ending August 9, 2019.
Pacifica Pharmacy
Pacifica Pharmacy (Torrance, CA) received a form 483 issued at the close of inspection on September 9, 2019.
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[NOTE: With a 483 Observation Report, you can quickly determine if there’s a citation trend you should be aware of. Learn more here!]