Another Look into Fakeer's Jhola : Pharma Companies warned or banned In US are ruling Indian medical scene thanks to Electoral Bonds
The Off-the-Mark Glenmark scandal :
We find a report of Reputed Glenmark Pharmaceuticals, receiving an US FDA Inspection failure report (Form 483) in Godi Media "Business standard" who actually copied from company's press release. This news report of 2022 says Glenmark had 6 Observations, never mentioning "Quality Standard Failure". If somebody isn't aware of what (Form 483) is, he might as well think, they won 6 awards.
Why am I criticising the Media, because they forgot to mention or deliberately suppressed the fact that Same US FDA inspectors gave 5 non-compliance observations for Glenmark's Goa Unit .. Instead they blabbered are Glenmark's last balance sheet, revenue increases in that financial year and market capital and what not..
What was in it? The FDA Form 483 for Goa Unit of Glenmark Pharmaceuticals? Let me show you (if I can, any accredited member of Press can too).
US FDA Report writes in their 14 page inspection report and I quote:
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:
OBSERVATION 1
Investigations of an unexplained discrepancy and a failure of a batch or any of its components to meet any of its specifications did not extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.
OBSERVATION 2
There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.
OBSERVATION 3
Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that drug products conform to appropriate standards ofidentity, strength,
quality and purity.
Procedures to ensure accurate and consistent integration of chromatographic peaks have not been established.
OBSERVATION 4
Batch production and control records do not include complete information relating to the production and control of each batch.
Procedure 19PD672 requires compression machine operators to calculate the tablet reject limits based on batch specific data from machine set-up. However, operators are using preset values without calculating the batch specific limits. If changes are made to the reject limits, these calculations are not documented in the batch record or reviewed to determine if the parameters were set correctly to reject tablets that may not meet specifications.
OBSERVATION 5
Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use and cleaning and maintenance.
These are damning indictments for any Pharma company, specially never expected out of Glenmark facility. Such Form 483 issues could lead to "Serious warning letter" followed by "cancellation of licences" or invite class action lawsuits in US, which can bankrupt a company. That's the threat to the corporate side ... but they represent serious health hazards to everyone to take medication produced in these places, be they be American or Indian or be they be of any other nationalities.
As expected, Glenmark got a Serious warning letter from US FDA.
FDA demanded strong action plans from Glenmark within 15 days and citing pretty much every single Observations in that form 483. No "Serious Warning Letter" actually lists all Form 483 issues in normal practice.
Being very long in Pharma business, Glenmark Pharmaceuticals knew that if the news of this warning is truly exposed in Indian Media, the damage it will do to its reputation in domestic Indian market will be irreparable and irreversible. Doctors may stop prescribing its drugs. So they decided to purchase Electoral Bonds worth 9.75 crore (9 one crore bonds, 7 ten lakh bonds, 5 One lakh bonds in denomination) on 11th November, 2022 about 2 weeks in advance of getting serious warning letter and gave it all to one Political party that basically controls Indian Media .
Which Party do you think I have in Mind? Of all of it went to Fakeer's jhola Or BJP.. who else controls "Godi Media"!
How did they know 2 weeks before the issue of the letter? Every Pharma insider knows that serious warning letter comes about 6 months from the issue of
How did Godi Media report these serious non-compliances found in US FDA inspection? Let me show that as well,
A 3 minute read quoting PTI full of inaccuracies, omissions and half-truths. Serious Warning letter doesn't come like that.. the process is..
Step One: Warning comes in Form 483 issued to senior most official at the facility on last day of Inspection.
In this case, US FDA observed in Form 483 and repeated in "Serious Warning Letter" and I quote
1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
A. Your investigations into rejected batches failed to extend to other batches, dosage strengths, and drug products for tablet compression machine settings.
From 2018 to 2021, you rejected 14 batches of 0.1mg and 0.2mg strength desmopressin acetate tablets for out-of-specification (OOS) results for (b)(4) and content uniformity results. You implemented additional stratified sampling and conducted engineering batches to simulate the root cause for the failures for both dosage strengths. Although you attributed the content uniformity failure to the lack of defined compression parameters for desmopressin acetate 0.1mg batch 20210776, you failed to test other batches or drug products that used the same (b)(4) process and compression equipment
Step Two: Pharma companies write back with a comprehensive plan to mitigate the non-compliance issues.
Glenmark wrote in reply to that specific issue and admitted the mistakes which was quoted in the Serious Warning as :
In your response, you acknowledged batches were rejected for the 0.1mg and 0.2mg desmopressin acetate tablets and that you did not apply the corrective actions for the compression parameters for your 0.2mg strength tablets. As a result of this inspection, you conducted a retrospective review and discovered a failing stratified sample assay result for desmopressin acetate 0.2mg tablets batch 20220121 and initiated a voluntary recall of this batch on June 10, 2022. However, your response did not adequately address your firm’s failure to investigate the assay failure and market impact at the time of its occurrence and it did not include an overall management strategy for improving all phases of your investigations.
Step Three: if FDA is either not convinced or dissatisfied with companies plan, only then FDA gives a Serious Warning Letter.
Lets continue with that single Observation 1 of Form 483, FDA demanded detailed plans as it does in cases of "Flawed Quality Control Processes" and I quote:
In response to this letter, provide the following:
A comprehensive independent assessment of the overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system to include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, corrective action and preventive action (CAPA) effectiveness, quality oversight, and written procedures. Address how your firm will ensure that all phases of investigations are appropriately conducted.
An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final quality assurance decisions, and is fully supported by executive management.
Step Four: Company now has to show that they have taken action and then FDA reevaluates that and either gives a closeout letter or inspects again.
Now Food and Drug Administration is not the only US law enforcement agency, Glenmark had problem with, Department of Justice (DoJ) included Glenmark in a price fixing investigation, in 2020... here is the DoJ Press Release.
I haven't heard any Indian Government to run an Anti-trust suit against these Drug company cartels.. Price-fixing of Medicines is rampant in India as well. Why do you think, home-made generic drugs cost so much in India.
In 2023, Glenmark admitted wrongdoing and price-fixing charges brought in by DoJ and agreed to pay $30 Million in Fine .. Another DoJ press release is the proof of that..
Besides that a fantastic report on Pharma companies and Electoral Bond purchases came out in Indian News Portal, Scroll and I quote:
Glenmark received five notices for its substandard drugs between 2022 and 2023. Four of these were issued by the Maharashtra Food and Drugs Administration, which flagged its blood pressure regulating medicine Telma as substandard, mostly failing a dissolution test.
But Did You Ever hear that Glenmark was investigated for Price-fixing in India or they recalled any batch of Medicines in Domestic market (India)?
Glenmark however recalled a lot of medicines from US, after the FDA warning..
Curious Case of Natco Pharma :
In last 5 years this company has spent 69.25 crores on Electoral Bonds and gave it all local parties TDP, BRS, Jana Sena, YSR Congress and national parties like Congress and BJP .
Basically they were looking for escape from Prosecution in US in anti-trust lawsuits..
Natco decided to use bluster and Electoral Bonds to defend itself in India about the lawsuit.
But we find they were issued an "Serious warning letter" by US FDA as well and faced lots of non-compliances in the Form 483s.
This year, NATCO received the warning letter from US FDA on 8th April. I quote the most significant parts of Warning Letter below:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Natco Pharma Limited, FEI 3004540906, at Kothur Village Rangareddy, Telangana, India, from October 9 to 18, 2023.1. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).
2. Your firm failed to thoroughly investigate any discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
Your firm’s investigations into unexplained discrepancies were inadequate. Your quality unit (QU) failed to thoroughly investigate all finished product batches and components associated with unexplained discrepancies.
These Warning letters didn't come overnight, Natco received lots of Non-compliance notices and only thing they did was to stop production at the affected facility.
This was a 27 page long Form 483 from US FDA citing 8 very damaging Non-compliances.
The non-compliances were the following:
1. Equipments and Utensils are not cleaned and maintained in proper intervals to prevent Contamination.
2. Responsibilities and Procedures of Quality control unit are either not in writing or they are not followed.
3. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed.
4. There is a failure to thoroughly review any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed. (OOS : Out Of Specification testing)
5. Separate or Defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.
6. Written records are not always made of investigations onto any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications.
7. Appropriate controls are not exercised over computers and related systems to assure that the changes in Master production and control records and other records are instituted by authorised personnel.
8. Your firm failed to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity and quality that they are purported or represented to possess.
Indian Health Ministry knew about all these as US FDA tells both Central and State agencies about their visits.. Only thing Mr. Fakeer did was to put his share of Electoral Bonds inside his Jhola. Out of 33 crore NDA parties got, 17 crore went to BJP alone ..
Don't you think this nearly 70 crore expenditure would have been better spent on improving their quality control unit?
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