FDA Data KNOCKS OUT BOTTLE OF LIES

After reading the book “Bottle of lies”, I wrote the first blog “The American Jugaad” in which it was shown with examples how Katherine Eban’s logic and thinking of relating the frauds in Indian Generic companies to Indian Culture was flawed. This blog can be read here.

In the second blog “ The Real lie in Bottle of lies” with data from FDA database I gave comparison of the figures for OVI, VAI and NAI for Indian and US companies. This comparison did not reveal a huge difference. If Katherine Eban’s conclusion that most Indian Industry is fraud is true then there should have been a significant difference in these numbers for the Indian and US companies. The comparison clearly showed that the difference does not substantiate Eban’s conclusions. I left it to the wisdom of the readers to decide for themselves what is the reality and what is a lie. This blog can be read here.

I had interesting comments on the second blog challenging my logic and thinking about this comparison. Excerpts from these comments are given below:

Michael de la Torre -Chief Executive Officer at Govzilla

“FDA inspections can be ineffective and misleading Katherine Eban outlines these reasons very clearly in her book 1) the FDA is not designed to combat systematic institutional fraud, like the case of Rambaxy 2) FDA inspectors have vastly different skillsets (i.e. the FDA has too few inspectors with the skillset and hutzpah of Peter Baker) and 3) the FDA is crippled by political pressure to keep cheap drugs on the market, so it defangs its observations (which causes them to downgrade very serious inspections to VAI when they should be OAI”

Katherine Eban

“Thank you for spelling this out so clearly, Michael de la Torre. As my reporting for #BottleofLies shows, over 6 years (2012-2018), the US FDA downgraded over 110 inspections at Indian plants, from Official Action Indicated (OAI) to Voluntary Action Indicated (VAI). In the same time period, the FDA downgraded only one U.S. plant. Why? Concerns over drug shortage, bureaucratic apathy and delays, and a revolving door between FDA/Industry all played a role.”  

Dinesh Thakur

Comment 1 ( I had missed adding this part of the commnet on my earlier post by Dinesh in this post. I am adding it now as both the comments will give the reader Dinesh's complete position on the issue)

Reading the comments on this thread with great interest. One question came to my mind, which hopefully will draw some parallels to the origin of this post.

I wonder if it is a reflection of the legal justice system (where wrongdoers are held to account) or the wrongdoing of these companies which paid “several million $ in compensation” that underlies this statistic? If the US was not a country of laws, would it absolve these wrongdoers in any manner because when compared with another country for example, Australia, the prosecution statistics were lower by 60%, hypothetically speaking? Or if we flip this argument upside down, should the absence of such convictions in India for example (where I have documented several cases where despite rock-solid evidence, those manufacturing and distributing substandard drugs are let off with but a slap on their wrist) mean that all Indian companies make poor quality product?

Statistics without context can be very misleading... it is the context that provides the background on how to interpret the data.

Commnet 2

What I am trying to say is that this comparison is silly IMHO. We have to read the metrics for OAI in the US in the context of how inspections are conducted in the US. Likewise, we have to read the metrics for OAII in India in the context of how inspections are conducted by the US FDA in India. They are not the same; how the FDA executes inspections in the US is not even close to what it does in India. So let us not draw any meaningful conclusions based not his comparison. My two cents....

Was FDA downgrade due to Concerns over drug shortage, bureaucratic apathy,delays, and a revolving door between FDA/Industry? Did political pressure play really a role? Is my comparison really silly?

The FDA has a procedure “FMD 86: Establishment Inspection Report Conclusions and Decisions”. The decision to classify an Inspection is with the District Office / Compliance Branch. The policy further clarifies that a VAI classification is applied when “Objectionable conditions were found and documented but the District and/or Center is not prepared to take or recommend any of the regulatory (advisory, administrative, or judicial) actions since the objectionable conditions do not meet the threshold for regulatory action. The district may use an Untitled Letter, Regulatory Meeting or other communication with responsible individuals to inform the establishment of findings that should be corrected. The district may request a written response from the establishment, but this is not necessary. Any corrective action is left to the establishment to take voluntarily.

Why can’t the downgrades of the inspections be because the objectionable conditions did not meet the threshold for regulatory action?

Katherine Eban & Michael de la Torre - Is there any irrefutable evidence to prove otherwise? Or is it a personal opinion of certain people?

I now quote a Para from the book about the inspections carried by Peter Baker.

“Already, Peter Baker’s razor-sharp inspections had halted imports and contributed to drug shortages rippling across the country. His findings had placed a question mark over generic drug companies operating overseas. They had also slowed drug approvals. That, in turn, jeopardized FDA funding, which was based in part on how many drug applications the agency approved. Baker’s proposal—to train the FDA’s investigators to look harder and find more violations—threatened even more disruptions. Consequently, some in the agency began to target a different problem: Peter Baker himself."

“ Now if I were to say that “the overenthusiastic approach of Peter Baker was to deliberately target the Indian companies, halt the imports to financially cripple them at the instance of the MNC companies and a US conspiracy to harm India” would be as preposterous as the comments made by Katherine Eban, Michael de la Torre and Dinesh Thakur above.

Yes Ranbaxy was a company wide fraud. As I said in my first blog the main culprits went scot-free. The Incidents, which happened in other companies quoted in the book, is something, which can not be accepted and should be condemned.

However Katherine Eban, Michael de la Torre and Dinesh Thakur should realize is that the Indian Industry has changed in the last 10 years. The Indian Industry when Dinesh Thakur worked in 2004 and the Industry now is vastly different.

FDA inspections in the last 4 years or so happen as in the US without announcements. The frequency of inspections of Indian plants though slightly less is still significant. From the figures given in the report issued by The Office of Pharmaceutical Quality (OPQ) on Quality of Pharmaceuticals it can be concluded that there are currently 314 Indian plants registered with the FDA. Corresponding number of US plants are 1021. The number of reports issued for Indian companies over the period 2015 to 2019 is 773 and that for US companies it is 3699. If you calculate the ratio of number of inspections per registered plant is 2.28 for Indian companies and 3.62 for US companies.

The Office of Pharmaceutical Quality monitors the quality of CDER-regulated drugs legally marketed in the U.S. This is an objective assessment using quality indicator based on available FDA drug product-specific and manufacturing site- specific data. The data used are

• Recalls;
• Product Quality Defect Reports-Field Alert Reports MedWatch Reports Consumer Complaints Biotechnology Product Deviation Reports;
• Drug Shortages and
• Application Stats-Submissions Refuse-to-Receive Refuse-to-File Approvals, Complete Responses.

FDA uses a site inspection score, on a scale of 1 to 10, as a measure of a site’s compliance to Current Good Manufacturing Practice (CGMP) regulations based on the classification of FDA Drug Quality Inspections -Following Compliance Program 7356.002 – Drug Manufacturing Inspections (PAC 56002 series)-conducted over the last 10 years. i.e., FY2009 to FY2018. An algorithm determines this score (from 1-10) and assigns more weight to more recent inspectional outcomes. Of course FDA uses this report for comparison purposes to look for trends and target resources.

In short, a higher inspection score represents better compliance with respect to CGMPs. The score for US companies was 7.7 and that for companies in India it was 7.0. This comparison demonstrates that Indian companies are not way behind US companies as far as cGMP compliance is concerned. The report itself states, “For instance, the score for ANDA sites in Europe (8.2) is higher than that of ANDA sites in India (7.0). These scores indicate an acceptable level of compliance to CGMPs on average.”

When President Trump tweeted that he is banning Huawei due to security reasons, very few believed him that the reason was US security. Judge for yourself what Katherine Eban says is a Reality of Indian Industry?