Posted on 30th April 2009 by gjohnson in Uncategorized
Chanzghou SPL, contaminated heparin, FDA recall heparin, heparin adverse reactions, heparin attorney, heparin lawyer
A different wrongdoer, but so many similar complaints to what the FDA found wrong with Baxter/SPL’s production of Heparin. Here is the second part of the FDA warning letter to Qingdao Jiulong Biopharmaceuticals Co. Ltd. Like Chanzghou SPL, insufficient quality review was pervasive.
2. Failure to conduct and document regular product quality reviews for the drugs produced that would include at a minimum, a review of your critical in-process controls and test results; review of all batches that failed to meet the established specifications; and investigation of process deviations and complaints to ensure your product remains within specifications and that corrective actions have been implemented.
In a letter sent to your attention on September 29, 2008, we informed you that your written response to the FDA-483 of August 13, 2008 was found deficient and lacked specific information related to the responsibilities of your quality control unit. In your letter of November 07, 2008, you acknowledge our concerns regarding the failure to perform product quality reviews by committing to perform Annual Product Reviews. You indicate that most of the product review activities were documented as part of your annual internal auditing reports. However, during the inspection, the investigators noted that your annual internal reviews involved only completing a check box document. This product quality review is inadequate in that it lacks adequate content or information, such as explanation of all deviations from established procedures and outcome of
investigations of critical deviations.
Although in your response of November 7, 2008 you include a new SOP specifying that “Annually, QA shall perform annual quality review on all products manufactured, distributed and marketed by the Company,” the corrective action implemented is inadequate. We are concerned that you have only committed to conduct an “annual product review for product lots produced during 2008.” As you are aware, 19 lots of heparin sodium manufactured at your facility during 2007 and shipped to the U.S. were found contaminated with OSCS.
Please include in your response a copy of complete product quality review reports covering the manufacturing of heparin sodium for all lots that remain within expiration. Include the following:
- A review of all critical in-process controls and critical test results.
• A review of all batches that failed to meet established specifications.
• A review of all critical deviations or non-conformances and related investigations.
• A review of any changes carried out to the process or analytical methods.
• A review of the stability monitoring program.
• A review of all quality-related returns, complaints (formal or informal from all customers) and complaints.
• A review of adequacy of corrective actions implemented (also include the conclusions).
OSCS again. Is there a common thread here?
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
Posted on 22nd April 2009 by gjohnson in Uncategorized
heparin, heparin attorney, heparin lawyer, Qingdao Jiulong Biopharmaceuticals, qui, Shanghai No. 1 Biochemical Pharmaceutical
The problem of bad Chinese Heparin, and even OSCS, has continued into 2009. Yesterday we outlined the problems the FDA cited with Qingdao Jiulong Biopharmaceuticals Co. Ltd. manufacture. Here is the first part of the FDA warning letter to Qingdao.
WARNING LETTER
WL NO. 320-09-02
April 14, 2009
VIA FEDERAL EXPRESS
Ms. Wang Weiru
President
Qingdao Jiulong Biopharmaceuticals Co. Ltd.
Jiulong Industrial Garden,
Jiaoshou City
Qingdao, People’s Republic of China (PRC) 266319
Dear Ms. Weiru:
This is regarding an inspection of your pharmaceutical manufacturing facility, Qingdao Jiulong Biopharmaceutical Co., Ltd. (QJBC) located at Jiulong Industrial Garden Jiaoz, Qingdao, Shangdon Providence 266319, People’s Republic of China, conducted by Investigator Carl Lee and Compliance Officer Zi-Qiang Gu, Ph.D., during the period of July 28 to August 1, 2008. The inspection and other information revealed significant deviations from U.S. current good manufacturing practices (CGMP) requirements in the manufacture of drugs.
Deviations were listed on an Inspectional Observations Form (FDA-483) issued to you at the close of the inspection. These and other CGMP deviations cause your heparin sodium to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C; Act) [21 U.S.C. 351(a)(2)(B)]. Section 501(a)(2)(B) of the Act requires that all drugs, as defined in the Act, be manufactured, processed, packed, and held according to CGMP.
We have reviewed your August 13, 2008 written response to the FDA-483 observations and subsequent response of November 7, 2008 to our Request for Additional Information Letter of September 29, 2008. We note that you assert that some corrections have been completed or will soon be implemented. However, your response does not adequately address some of the deficiencies. Our review of the information revealed the following CGMP violations:
1. Your firm’s quality unit fails to have the appropriate system and procedures to provide confidence that the drugs manufactured at your facility meet the intended specifications for identity, strength, quality and purity.
In April 2008, FDA learned that 19 lots of heparin sodium were contaminated with Over-Sulfated Chondroitin Sulfate (OSCS), and these lots were later determined to have been manufactured at your facility. Although this heparin sodium did not ultimately reach U.S. patients, your firm has not demonstrated that it has conducted an investigation of these contaminated lots, identified the source of this contamination, and taken appropriate corrective actions to ensure the quality of heparin sodium produced at this site. There is no assurance that your quality unit has systems in place to prevent manufacture and distribution of heparin sodium that has been contaminated with OSCS or other hazardous contaminants. These lots were supplied to Shanghai No. 1 Biochemical Pharmaceutical Co., Ltd. (Shanghai) over an extended period, spanning 2007 and 2008, for distribution under their name.
We are concerned that your firm lacked adequate systems to ensure the safety of raw materials used in your manufacturing, particularly to prevent the substitution of an unsafe substance (OSCS) in place of heparin sodium. It is essential that strict controls over your suppliers be established to prevent any such supply chain breach.
Your firm also failed to ensure that manufacturing and testing procedures apparently transferred to your facility provided for acceptable drug identity, strength, quality, and purity. It is critical for a firm to assess the impact of a change in manufacturing facility, including determining how production and control practices and conditions at the new facility may affect the identity, strength, quality, and purity of a drug.
During the August 2008 inspection, our investigators learned that your current manufacturing process for Heparin Sodium USP was apparently transferred in 2005 from Qingdao Kangyuan, which you assert is a related business entity, to your site and that Qingdao Kangyuan no longer manufactures heparin sodium. However, no information regarding the procedures, protocols and reports related to this technology transfer were available for review. Only estimated dates of when Qingdao Kangyuan ceased manufacturing heparin sodium and when your firm initiated production were provided.
In our next blog, we will continue with the warnings given to Qingdao with respect to its failure to conduct regular product quality reviews.
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
Posted on 21st April 2009 by gjohnson in Uncategorized
FDA recall heparin, heparin attorney, heparin lawyer, Qingdao Jiulong Biopharmaceuticals, Shanghai No. 1 Biochemical Pharmaceutical
The FDA on April 14 issued a warning letter to two Chinese companies for shipping Heparin after the FDA closed Chinese imports of the drug- Qingdao Jiulong Biopharmaceuticals Co. Ltd. and Shanghai No. 1 Biochemical & Pharmaceutical Co. Ltd. The Warning letter to Qingdao Jiulong Biopharmaceuticals Co. Ltd. (Qingdao) highlights similar problems in production as were found in the Inspection of Chanzghou SPL, discussed recently on this blog. Those problems included:
- 1. Qingdao’s quality unit failed to have the appropriate system and procedures to provide confidence that the drugs manufactured at the facility met the intended specifications for identity, strength, quality and purity.
- 2. Qingdao failed to conduct and document regular product quality reviews for the drugs produced that would include at a minimum, a review of critical in-process controls and test results; review of all batches that failed to meet the established specifications; and investigation of process deviations and complaints to ensure the product remains within specifications and that corrective actions had been implemented.
- 3. Qingdao failed to investigate specific discrepancies related to the lots of impure drugs supplied to its customers. The FDA learned that heparin sodium lots manufactured at Qingdao’s facility were determined to be contaminated with OSCS. At the time of the inspection, no investigation had been conducted into this repeated and unacceptable contamination.
We will look at each specific issue on these warning letters in our subsequent blogs. However, that these problems are now occurring at other Chinese suppliers shows how perilous it was for Baxter to import Heparin from a place so seemingly incapable of controlling quality, purity and standards.
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
Posted on 7th April 2009 by gjohnson in Uncategorized
Baxter recall of heparin, contaminated heparin, FDA censure of Changzhou SPL Company, heparin attorney, Heparin deaths, heparin lawyer
Yesterday we ended our series of the four serious problems that the FDA found with the Changzhou SPL plant in China with the statement that Baxter’s failure to control what SPL was doing in China was outrageous. Today, I discovered this quote on Baxter’s website,
http://www.baxter.com/about_baxter/news_room/news_releases/2009/03_05_09_world_kidney_day.htmlBaxter International Inc. (NYSE:BAX) develops, manufactures and markets products that save and sustain the lives of people living with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.
If Baxter’s mission is to apply a unique combination of expertise, how could they have delegated the critical steps in making an intravenous pharmaceutical to a company who didn’t have anyone on site who understood what he was doing? Poor quality control of the manufacture of Heparin API at Changzhou SPL, meant poor quality control of Baxter Heparin. If the stuff which Heparin is made from isn’t pure, the Heparin can’t be.
Baxter claims they inspected Changzhou SPL but how could such inspection done within six months of the FDA inspection, not have uncovered such blatant systemic problems? That failed inspection may have been responsible for thousands of deaths. Isn’t it time for justice for those casualties?
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
Posted on 6th April 2009 by gjohnson in Uncategorized
Baxter recall of heparin, Chinese toxic imports, FDA censure of Changzhou SPL Company, FDA recall heparin, heparin and punitive damages, heparin attorney, heparin lawyer, heparin recall
Today we discuss what has to be the most staggering aspect of the manufacturing situation at the Changzhou SPL plant in China, Baxter’s source of the API which made up the contaminated Heparin: No one with specialized knowledge of Heparin, was working for SPL in China.
These quotes are taken from the April 29, 2008 hearings before the House Subcommittee on Oversight and Investigations hearings, see:
The Heparin Disaster: Chinese Counterfeits and American FailuresFor more, click here:
http://energycommerce.house.gov/cmte_mtgs/110-oi-hrg.042908.Heparin.shtmlRegina Brown of the FDA was questioned in those hearings by U.S. Representative, Jan Schakowsky:
Question by Schakowsky: There was no person with special knowledge of Heparin at the firm to guide decisions made by the quality unit. So Ms. Brown, I would assume that if a plant was making Heparin API, it would want to have a person with “special knowledge” of that product, in case deviations from any manufacturing process were observed, wouldn’t you agree?
Answer by Brown: They had a quality unit there, which consisted of four people, they were trying to track what was going on with the firm. The person with the special knowledge I mentioned, because when I arrived, management was aware that there were Baxter recalls, and that there were adverse drug events and deaths in the United States. It was middle of February, the general manager of the firm, Mr. Wong, was the one who described the process to me and how he thought that impure materials were removed from the crude heparin to make it into the heparin API and he said he wasn’t a heparin expert. And so, he was really the person who gave me my fullest extent of knowledge during the inspection.
Q: So, neither he nor the others had any special knowledge, he had the most knowledge?
A: I believe so, yes.
Unbelievable. SPL is manufacturing a drug that is going to be put in to the veins of our sickest people and they don’t have anyone on site with specialized knowledge as to how to make Heparin? How could Baxter have allowed this? Any superficial investigation would have determined that Changzhou SPL didn’t know what it was doing. Such a breakdown in the process of making an intravenous pharmaceutical is outrageous and is an institutional catastrophe.
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
Posted on 2nd April 2009 by gjohnson in Uncategorized
Baxter recall of heparin, Chanzghou SPL, FDA, heparin, heparin attorney, heparin lawyer
Today we discuss additional problems with the equipment used at the Changzhou SPL plant in China when that plant was inspected by Regina Brown of the FDA.
Again, these quotes are from the April 29, 2008, House Subcommittee on Oversight and Investigations hearings, see: The Heparin Disaster: Chinese Counterfeits and American Failures
For more, click here:
http://energycommerce.house.gov/cmte_mtgs/110-oi-hrg.042908.Heparin.shtmlBrown was questioned in those hearings by U.S. Representative, Jan Schakowsky:
Answer by Brown: Another piece of equipment that was the centrifuges that they used to get rid of the waste protein. They used two of them. They had one that would be in use and they would clean the sludge out of the other one, while, to find out how long they should run the one that was going, that would last 30 minutes, without getting to full. And that was a very unusual manufacturing step. It wasn’t described in the procedures for how to use the centrifuges. So you had to actually be at the plant to try and figure out what they were doing.
Normally you see one centrifuge and you run your material thru it and separate the solid from the liquid.
A third piece of equipment that was outstanding to me was their lyophilizer, it was, they didn’t have the software that would provide for the person running it, for the perimeters, that he put in it.
Q by Rep. Schakowsky: What is that?
A: The lyophilizer is a big freeze dryer.
Put in trays of liquids and they turn into solids after days, sometime. You freeze the liquid and you warm it up slowly, they are under vacuum. So it turns into a solid material. So and for this lyophilize there were no records of the actual perimeters that were punched into the screen at the front of it. But there was no screen at the front of it. No way to tell what temperature they actually used to dry the material.
Q: So this is clearly substandard or not up to par, or what should be?
A: Yeah, the settings weren’t there.
Q: Why couldn’t Baxter’s audit have found these things, do you think?
A: I don’t know. I walk thru facilities as part of my inspection. I don’t know if they do that.
What is so disturbing about this revelation is that this was not a matter of simple neglect, made worse by a long standing practice of poor oversight. This was a flawed process from its inception. This process does not even contemplate a scientific process to assure that the API is pure.
Attorney Gordon JohnsonChair Traumatic Brain Injury Litigation Group, American Association of Justice
g@gordonjohnson.com :: 800-992-9447 :: Attorney Gordon S. Johnson, Jr.
http://subtlebraininjury.com :: http://brainanatomyguide.com :: http://car-accident-rain.com :: http://tbilaw.com
http://waiting.com :: http://vestibulardisorder.com :: http://youtube.com/profile?user=braininjuryattorney
