In September, there was one notable Form 483 issued by the FDA to Ipca Laboratories that cites serious deficiencies with the Quality Unit. We look into the details below. We also provide the 59-page response from AveXis regarding the 483 issued to the firm in August.
And finally, we reviewed the FDAzilla Store to see which 483s were most-purchased and trending during September.
[NOTE: Are you interested in learning more about observations with specific industry keywords? Get your FREE 483 Observation Report and you can quickly determine who has been hit with the same observations. Learn more here!]
Source – GMP Regulatory Intelligence Newsletter by Barbara W. Unger
DRUG FIRM: Ipca Laboratories
FDA posted a 10-page form 483 to Ipca Laboratories (Silvasa, India) issued at the close of inspection August 23, 2019. The firm is identified as a finished drug manufacturer.
The 483 identifies that “Your Quality Unit has not been effective in carrying out its duties of ensuring that drug products are manufactured in accordance with current good manufacturing practices…demonstrated by a cascade of failure [emphasis added] in your Quality Unit responsibilities related to controls on issuance of GMP forms, review of laboratory testing data, conducting investigations and conducting activities per written instructions.” And it proceeds from that point.
I would not be surprised to see a warning letter in a few months. The form 483 is worth reading for the specific details it provides on the failures in Quality Systems and Quality Unit performance. Failures in their Quality Unit and problems with data integrity are the focus of the observations. Particularly painful is the section where FDA “teaches” the Quality Unit how to use their laboratory instrument software to identify potentially problematic activities and practices.
Observations include but are not limited to:
- The sporadic appearance of unknown peaks in GC analysis were not investigated. At least one peak was 15% of total peak area. The analysis for residual solvents was specifically identified. FDA states that the firm “…did not integrate, identify, document, trend, calculate and investigate the root cause…” for the presence of these unknown peaks.
- The firm used the “inhibit integration” functionality to select peaks of interest and avoid integration of unknown peaks.
- The Quality Unit did not adequately review OOS and OOT investigations, electronic data, and routine testing worksheets.
- The firm received a warning letter on January 29, 2016 that addressed practices at three sites in India. All three sites currently retain OAI status as a result of that inspection according to the FDA database. The firm conducted an electronic data assessment in response to a violation identified in the warning letter. The investigators demonstrated where the firm failed to identify all shortcomings in their data, 2.5 pages worth. The Quality Unit seemed to be unaware of the capability of the CDS software.
- OOS and OOT results were invalidated without identifying the root cause of the original data failures. They provide a list of examples of inappropriate behaviors.
- The Quality Unit did not ensure that investigations and change controls were closed in a reasonable timeframe. CAPAs from 2017 and 2018 remained open for between 258 and 770 days.
- The Quality Unit permits the [apparently uncontrolled and undocumented] destruction of draft and interim laboratory investigation reports. Shredders are located in the QA office area. Further, a variety of GMP documents are located on QC computers and are not under the control of the Quality Unit.
- Raw data generated by equipment software in tablet compression operations are stored, without restriction, in a location where all production operators have access to the raw data.
DRUG FIRM: AveXis
AveXis’ 59-page response to the recent form 483 (August 2019) issued at the close of inspection is provided here. The 483 identified data manipulation. (Note: read more about the Zolgensma data manipulation here.)
COMPOUNDING/OUTSOURCING: Fagron Compounding Services LLC
Fagron Compounding Services LLC (Wichita, KS) received an 8-page form 483 issued at the close of inspection on June 9, 2019.
COMPOUNDING/OUTSOURCING: First Royal Care Co. LLC
First Royal Care Co. LLC (Irvine, CA) received a form 483 at the close of inspection on June 14, 2019.
COMPOUNDING/OUTSOURCING: Anderson Compounding Pharmacy
Anderson Compounding Pharmacy (Bristol, TN) received a form 483 issued at the close of inspection on April 5, 2019.
COMPOUNDING/OUTSOURCING: Hieber’s Pharmacy
Hieber’s Pharmacy (Pittsburgh, PA) received a form 483 at the close of inspection on July 17, 2019
COMPOUNDING/OUTSOURCING: Shertech Pharmacy
Shertech Pharmacy (Easley, SC) received a form 483 at the close of inspection on July 2, 2019
FDAzilla Store’s Most Popular 483s
Most Purchased Individual 483s
Most Purchased 483s by Site (not specific 483)
ABCO Labs Fairfield
Alps Pharmaceuticals Industrial Hida
AmbioPharm Beech Island
Amgen Manufacturing Juncos
Downing Labs Dallas
GlaxoSmithKline Biologicals Dresden
Immunomedics Morris Plains
Patheon Italia S.p.A. Monza
Smithfield Bioscience Cincinnati
Torrent Pharmaceuticals Levittown
[NOTE: With a 483 Observation Report, you can quickly determine if there’s a citation trend you should be aware of. Learn more here!]
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