www.law360.com/.../fda-stings-gilead-for-manufacturing-violati...May 3, 2013 - Gilead Sciences Inc. disclosed Thursday that U.S. Food and Drug ... The FDA issued a so-called Form 483 in response to the issues.
FDA has released form 483 issued to Gilead Sciences, Inc. Summary is given below:
- The accuracy, sensitivity, specificity, and reproducibility of test methods have not been established.
- Test methods have not been validated to support release and stability testing of drug substances (DS) and drug products (DP). There is no assurance that the data generated from these test methods are reliable.
- Test methods have not been adequately validated to support release and stability testing of clinical, registration, process validation batches of Elvitegravir drug product. There is no assurance the data generated from these test methods are reliable.
- Test methods for the clinical and primary stability batches are not the same as the proposed commercial test methods because the analytical techniques and parameters are different between the methods. Bridging study to establish method comparability for test methods was not conducted.
- Suitability of USP compendial methods for testing of drug product and drug substance was not verified.
- Stribild test method for "Identification, Assay, and Degradation Product Content may not be suitable for accurately determining related impurities, the unidentified impurities.
- Unqualified instruments were used for analysis of stability samples.
- There is no documentation or traceability to lot numbers, manufacture dates, re-test dates, weights and balance used to prepare the excipients in the placebo mixtures for determining the accuracy in the validation of drug products.
- Several discrepancies were observed between the printout of certain data and the data record during method verification.
- Certain results of method verification are missing form laboratory records.
- Certain results of stability testing are missing form laboratory records.
- Bulk hold studies for final powder blends, core tablets and film-coated tablets were not validated with representative samples. Additional study data to justify the use of these sampling plans in the bulk hold studies were not provided.
- The cleaning methods for instruments are not validated. Carry-over and artifact peaks were observed in the chromatograms of the blank solutions attributed to residual active ingredient(s) that were left over from previous analyses.
- All laboratory worksheets (QC forms), logbooks and chromatography instrument usage logs used to record raw data for sample analyses and instrument calibrations and usages are not issued and controlled by your Quality Assurance unit to assure the reliability and integrity of the data
Posted 31st May 2013 by Uday Shetty
Labels: FDA 483
Gilead is latest drugmaker in FDA's sights
Published on 13/08/10 at 08:00am
A manufacturing and distribution facility operated by US biotech Gilead Sciences is at risk of receiving a warning letter from the FDA unless management can bring it back up to scratch.The plant in San Dimas, California, underwent a routine inspection by the US regulator in January and February 2010 which resulted in a number of deficiencies being recorded via a Form 483 (a notice of inspectional observations).
The issues uncovered by the inspectors included problems with the maintenance of aseptic processing conditions in the manufacturing suite for Gilead's antifungal product AmBisome (liposomal amphotericin B), as well as environmental maintenance issues in the site's warehousing facility.
In addition to AmBisome which brought in $155 million of the firm's total sales of $3.6 billion in the first six months of 2010, the San Dimas site also makes Gilead's cystic fibrosis treatment Cayston (aztreonam for inhalation) and provides filling and finishing of the firm's Macugen (pegaptanib sodium injection) for age-related macular degeneration, a leading cause of blindness.
The manufacturing problems do not appear to affect any of Gilead's HIV treatments Truvada, Atripla and Viread, which account for the bulk of its sales and are packaged at the San Dimas facility. ....
The True Epidemic Approaching: Mass Tamiflu Poisoning
Who distributes Tamiflu and how is it manufactured?
Oseltamivir is manufactured of llicium floridanum, or Chinese Star Anise, an herb indigenous to southeast Asia. During a 10 step process which takes a year to complete and involves some fairly precarious high explosive work, Shikimic acid is extracted from the plant and serves as the active ingredient in Tamiflu. It is refined into oral capsules as well as a spray for inhalation, and an injectable delivery system is presently being tested.
In a slightly off topic note, a warning was initiated by the FDA back in 2003 to avoid Star Anise teas, which were being marketed increasingly in the wake of the initial flu pandemic fears, due to an outbreak of illnesses including serious neurological effects such as seizures, vomiting, jitteriness and rapid eye movement. It was believed to be caused due to a contamination of Japanese Star Anise, a similar species of tree which is a known poison.
Oseltamivir itself was invented by Gilead Sciences Inc. in 1996, and due to lackluster sales the commercial and manufacturing rights were quickly sold to Roche of Switzerland - named top corporate criminal of the 90's by the Multinational Monitor - in exchange for annual royalties. Four years ago a dispute was settled in which Gilead charged Roche with failing to adequately promote and produce the drug as well as contamination issues and invoked a contract clause to demand the return of all commercial and manufacturing rights, which was settled by a payment of retroactive royalties as well as the creation of a body to promote globalized production of generic Tamiflu - somewhat coicidently in stride with a renewed burst of fear mongering in the media provoking a massive stockpiling of the drug. In the time since, amidst fears of global pandemic, stockpiling has gone global with countries everywhere scrambling to purchase the drug, which sells for upwards of 100$ a dose - with the increased demand leading to Roche outsourcing much of the production process - setting the stage for windfall profits.
What are the side effects of Tamiflu?
"Adverse drug reactions include: nausea, vomiting, diarrhea, abdominal pain, and headache - rarer reactions include hepatitis and liver disorder, rash, severe allergic reactions, and Stephen-Johnson Syndrome (often fatal detachment of skin)... other ADRs reported in post-marketing surveillance including: toxic epidermal necrolysis (skin falling off), irregular heartbeat, seizure, confusion, abnormal behavior, inability to walk, convulsion, loss of consciousness, hallucination, aggravation of diabetes, and haemorrhagic colitis (digestive disorders)." -From Wikipedia and FDA reports