An open letter to K L Sharma

Posted by on Jan 24, 2017 in Blog | 4 comments

Shri K L Sharma, Joint Secretary (H), Ministry of Health and Family Welfare

Dear Shri Sharma,

If you recall, I met you in May 2015 after the PMO forwarded my letter to them to you for your consideration. During our meeting, you assured me that the government is taking steps to correct the systemic issues that plague the CDSCO and our regulatory process for approving medicines sold to 1.2 billion Indian citizens.

I am not sure if you have read about the recent observations made by a foreign regulator, US FDA upon inspection of a manufacturing facility of a large manufacturer of Active Pharmaceutical Ingredients located in Telangana. The observations made by the foreign inspectors thoroughly document behavior of the employees of this company which is consistent with inspection findings of almost every other large pharmaceutical manufacturer in India. CCTV records prove that the company destroyed and altered manufacturing records just prior to the inspection.

While we wait for the government to overhaul the Drugs and Cosmetics Act as you indicated to me, how do we ensure that the medicines already in the market today comply to the standards of basic quality to our citizens? I am sure you will agree that there isnt a valid reason to destroy records if everything was done by the book as many of these companies claim they do when manufacturing product for our consumption. Where Sir, is the rule of law that holds the people who indulge in such outrageous behaviour accountable to the people of this country? Isn’t destruction of records a criminal felony? If companies are so emboldened to do this for records for products sold in the US, which I am sure you will agree has a much more stringent quality expectation of their drug supply compared to what we accept in India, what do you think they are doing with the records for products they make for our patients? Do they even document what they do to manufacture products for our consumption? Does anyone care?

The CDSCO and its leadership has lost all credibility among its peers. No one takes what it says seriously anymore. Changing its name to Indian Drugs Administration does nothing to change the culture and the level of competence in our regulator. Creating a long checklist consolidating every observation made by a foreign regulator about our manufacturing facilities does not inspire confidence in our ability to understand what quality means and how to enforce standards in our manufacturing facilities. And issuing notifications to prescribers and consumers to follow label information does nothing to address the underlying problem of substandard drugs; as we have seen in the recent case of drug resistant antibiotics.

It is high time Sir, that the government did something to actually effect a meaningful change in the drug supply for the country. I realize passing legislation is not easy, and I do not envy your job. However, holding people accountable also has to be a part of the equation. When will we learn that cutting corners especially with medicine plays with lives of our citizens? Only when you hold people who do this publicly accountable. I just hope that the credibility that we, the people, have in the government to protect our drug supply doesn’t go the way of CDSCO.

Dinesh Thakur





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Will we ever learn?

Posted by on Nov 25, 2016 in Blog | 1 comment

There is news today that the US FDA made observations about Sun Pharma’s facility at Mohali that are very similar to what led to the import alert for products manufactured at this facility back in 2013. The Economic Times and Live Mint both report of what inspectors from the US FDA found about data integrity violations at this facility. Upon closer inspection, these observations are no different from what foreign regulators have been finding and documenting in various actions on the veracity of the data that Indian pharmaceutical companies use  to secure market authorization in their respective countries. A cursory search will list many such examples from both manufacturing and clinical facilities in India.

In parallel, it was reported in the Economic Times that the national drug regulator, CDSCO has inspected approximately 200 manufacturing facilities that supply medicines to the Indian market and found that none of them to be compliant with the Indian version of cGMP (Schedule M). It is a different discussion altogether whether Schedule M is consistent with cGMP, but for the sake of today’s discussion, let us assume that it is. By their own admission, 100% of manufacturing facilities that supply life saving medicine to the India patients do not comply with the standard that the country’s regulator expects them to.

In the past, the standard response from the industry association representing pharmaceutical companies was that somehow western interests were out to defame and destroy the Indian pharmaceutical industry. Clearly, the country’s drug regulator finds substance independent of what foreign drug regulators have consistently found when it comes to compliance with standards for manufacturing medicines. I wonder what the next argument from the industry association will now be?

The larger question to ask is why is it that after three years of not being able to export product to the largest and most lucrative market in the world, the country’s largest pharmaceutical company once again finds itself in the same place it did earlier? Were the army of consultants who professed to “train” its employees not effective? Was the hundreds of millions of dollars of investment which was touted to upgrade its facilities to make it compliant with US standards not enough? Why is it that time again, we come back to the same question?

The answer is not hiring external consultants who charge exorbitant fees  or building shiny new manufacturing facilities to impress the regulators. I spoke about this very topic recently at the Rx360 Annual Conference in Washington DC and here is my take on it.

As to the question of what the DCGI will ever do with its own findings about the 200 odd manufacturing facilities it found not to be compliant with its own standards, I am not holding my breath. Unless the regulation changes, and people are held accountable for making and selling substandard medicines, nothing will change. I had documented cases where despite proving guilt, the legal justice system in the country lets such people go with nothing more than a slap on the wrist. If the highest court in the land thought that was an academic issue, what more is there to say?



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Differences in approach to regulation: why leadership and science matters

Posted by on Jun 28, 2016 in Blog | 3 comments

In my past blogs, I have documented how the CDSCO and the Drugs Consultative Committee (DCC) have taken decisions that adversely affect public health and give the industry a free pass even in cases where there is clear evidence of the industry breaking the law. Leadership and integrity of the national health regulator is an important factor in how it responds to advancing science. When members of the industry intentionally produce and sell substandard drugs in the country, it is the responsibility of the national health regulator to prosecute them to the fullest extent of the law.

A recent example of the difference in approach between the national regulators of India and US was how the US FDA responded to the complexity of drug formulations and the rules governing bioequivalence. A few weeks ago, the US regulator released 38 new and revised guidance documents that address the challenges of how to assess therapeutic equivalency of generic drugs. Each document also contains information on what analytes should be measured, what dissolution test methods should be used and sampling times.

Issues with existing guidelines for conducting bioequivalence studies was first pointed out to the FDA by People’s pharmacy. They provided conclusive patient outcome data to the regulator about generic Wellbutrin which made the US FDA reconsider its guidelines for establishing therapeutic equivalence of generic drugs. The arguments supporting revision of existing guidelines were explained in this peer-reviewed paper. With mounting evidence, the US regulator initiated a process of reevaluating its approach to therapeutic equivalency of generic drugs and the result is a completely new approach. Earlier this year, the US FDA provided product-specific recommendations for 31 different active pharmaceutical ingredients (APIs) linked to new generic drugs and revised recommendations for 11 APIs. Included in the latest release are guidelines for Everolimus (Novartis’ blockbuster cancer and transplant treatment) and Viekria Pak (Abbvie’s Hepatitis C blockbuster). These drugs were approved in 2009 and 2014 respectively and have no generic equivalents in the market today. This shows that the agency is thinking ahead in providing guidance to the industry which may be working on development generic therapeutic equivalents for these drugs after they go off patent.

Compare this action to how the DCC issued guidelines to undermine therapeutic efficacy of generic drugs sold in India by giving the pharmaceutical industry a free pass when it comes to prosecuting manufacturers of substandard drugs. While the CDSCO guidelines for establishing bioequivalence mirror those that were followed by the US FDA until very recently, the DCC in its 47th meeting held in July 2014 proposed that bioequivalence studies for generic drugs be deemed optional for products sold in India under the guise that infrastructure to conduct those studies doesn’t exist in the country. We all know how many CROs exist in the country, so this argument is blatantly false. What is more ridiculous is that in the same breath, the DCC recommended that bioequivalence studies be conducted for the product made for export. This action clearly undermines the law of the land, the Drugs & Cosmetics Act. Actions such as these go the root cause of the dysfunction within the CDSCO and its function; this is a direct influence of the industry lobby exercising its influence over policy making at the expense of national health.

This is the reason why, in addition to a new set of laws governing manufacture and distribution of drugs, India needs a fundamental change in leadership of the national regulator. As the Parliament Standing Committee said, leadership at the CDSCO is beholden more to the industry’s agenda and interests than the public health of the citizens of India. Unless we bring people with unimpeachable integrity to lead this organization, new laws and regulations will have limited effect on its function.

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