In the next series of blog posts, I will try and explain how the current regulatory structure encourages the manufacture and distribution of substandard medicine in India. These are the arguments we had hoped to make to the highest court in the land through my PILs, unfortunately, we were denied the opportunity to do so.
In manufacturing, quality of a drug is measured by the product being free from defects, deficiencies and variations. This is achieved by a strict commitment to standards in order to achieve uniformity of the product across every batch manufactured. This is the principle that most health regulators across the world work on when ensuring drug quality. Unfortunately, in India, the starting point for enforcement of quality standards under the Drugs & Cosmetics Act, 1940 is to verify compliance by drawing samples of a drug from the marketplace and testing the product to establish compliance. Samples of commercial product drawn by these drug inspectors are sent to government laboratories for testing by government analysts, against standards prescribed in either the Indian Pharmacopeia(IP) or any of the other Pharmacopeias such as the United States Pharmacopiea (USP) or British Pharmacopiea (BP). If the sample passes the quality check the matter ends; but if a sample fails the quality check, the government analyst informs the drug inspector that the sample is Not of Standard Quality (NSQ). It is up to the discretion of the drug inspector then whether to further investigate and prosecute such cases.
There are two specific issues with this approach. First, by the time it takes an inspector to establish that a particular batch of drug is NSQ, it would have been consumed by millions of patients. Second, such a system of enforcement is inherently dependent upon the size of the sample drawn from the market. Batch-to-batch variability, which is a key aspect of pharmaceutical manufacturing resulting in sub-standard drugs is rarely detected with this approach. Compliance with cGMP, on the other hand, ensures that quality is built into the manufacturing process, rather than being an after-thought. Indian regulators rarely audit manufacturing plants for cGMP compliance because they are not required to. Establishing quality of drugs in India is retrospective and this is partially the reason why foreign regulators discover problems with manufacturing processes than our own. In a country that has literally no systems of surveillance, retrospectively testing for quality is a recepie for unscrupulous companies to flood the market with substandard drugs.
Why does this matter? Think about the simplest of the drugs, antibiotics. If the drug is substandard, meaning it contains less than the required active ingredient, or doesn’t dissolve in the stomach as quickly as is it should, or doesn’t get absorbed in the blood stream as intended, the concentration of the drug needed to kill the pathogen that is responsible for the infection doesn’t materialize. This leads to the pathogens become resistant to drugs, which is what we see in India. Multi-drug resistant Tuberculosis is a direct consequence of this. This is one of the reasons why we wanted the Supreme Court to hear our petition; the current regulatory structure needs to be fundamentally overhauled in order to make it more responsive to public health in India.
Without a fundamental change to our approach, the process of drawing samples from the market place becomes all the more important. It is also necessary that the guidelines for sampling are based on a robust statistical model which covers a wide cross-section of the market. A failure to have well thought out sampling guidelines will skew the entire system of drug enforcement because the sampling guidelines are the starting point of the enforcement framework under the D&C.
In order to determine whether the drug inspectors at the State Regulators and Central Regulator CDSCO were following a well-designed statistical model to draw samples from the market, we filed a series of RTI Applications with the CDSCO and a number of state level drug regulators, asking them the two following questions:
- As per Section 23 of the Drugs & Cosmetics Act, 1940 a Drug Inspector is required to tender a fair price for any sample of Drug or Cosmetic picked up for the purpose of testing. In this regard the PIO is requested to provide the applicant with details of the amount sanctioned per inspector over the last 5 years, per year, for the purpose of purchasing samples under Section 23 of the Drugs & Cosmetics Act, 1940.
- While purchasing samples under Section 23, is a Drug Inspector required to follow any guidelines regarding the different types of drugs that are required to be drawn from the market for testing. Please provide the applicant with a copy of any such guidelines.
The first question was important because drug inspectors are required under law to tender a fair price for any drug sample that is purchased from a pharmacist. If an adequate budget isn’t sanctioned to them, it would directly affect the type of drugs that can be drawn from the market. As we all know, oncology drugs, injectables etc are often more expensive than over-the-counter drugs. The second question aimed at understanding what procurement guidelines were followed by each drug inspector for the purpose of drawing samples from the market; whether these sampling guidelines were based on a scientific statistical model. The replies that we received on both counts demonstrated the degree of dysfunction within regulators on this relatively simple issue.
The CDSCO HQ declined to answer the RTIs, preferring instead to divert the applications to its zonal offices. This is a tactic frequently adopted by the CDSCO HQ while dealing with RTI applications. We received responses from three zonal offices: the East Zone (EZ), the West Zone (WZ) and the South Zone (SZ). All three zones claimed that there was no specific budget sanctioned for the purpose of drawing samples from the market and that money was generally drawn from the ‘office expenses’ head of the budget. None of them gave us a specific reply on the amount of money that they spent on drawing samples – such accounts should be readily available with the accounts officers. Given the critical role of sampling in ensuring quality drugs, it is quite surprising that the CDSCO hasn’t budgeted specifically for this task. One wonders why?
With regard to the second question, EZ and WZ did not even bother to provide a reply. The SZ provided a reply to the second question pointing out to the “Guidance Document for Functions and Responsibilities of Zonal, Sub-Zonal and Port Offices of CDSCO”. Page 15 of this document states that each drug inspector should collect at least 5 samples every month for testing from Government dispensaries, hospitals, CGHS dispensaries, rural outlets and from manufacturing premises. The document also makes mention of deputation of drug samplers to specifically carry out this function and that each sampler is required to purchase at least 20 samples per month from the fast moving and generic products. Not a single one of these zones referred to a circular from the DCGI’s office on 20.07.2010 which laid down different criteria: “5 samples from Government dispensaries, hospitals, rural outlets and from manufacturing premises during inspection.” And “At least 5 survey samples of drugs per month shall be collected from manufacturing premises as part of the inspection procedure. This may also include raw material samples from the stores of the manufacturers.” Even this circular (which we found buried in a parliamentary report) does not require a scientific statistical model which would ensure testing of a cross-section of the drugs available in the market.
Of the State Governments who replied to us, we received a range of diverse answers. The regulator in Uttarakhand transferred our RTI applications to various drug inspectors within that state, none of whom actually provided us with details of either the amount they spent on sampling or the guidelines that drug inspectors follow to draw samples. Their replies were mostly evasive. Similarly, the regulator from Gujarat simply stated that no particular amount was sanctioned for sampling but failed to disclose the actual amount spent. It also stated that no guidelines were followed on how to draw samples. The Drug Controller from Karnataka provided some guidelines in Kannada, which we haven’t yet translated. Regarding the amount spent on drawing samples, the authority merely provided a copy of their entire budget outlay for the last 5 years without telling us exactly how much they had spent specifically on purchasing drugs for testing. Our application with the Maharashtra FDA was transferred from their HQ to the Office of the Joint Commissioner whose office promptly replied claiming that they had none of the information and that their HQ would provide the information. The only states which did provide us with some useful information were, Kerala and Tamil Nadu.
The reply from Kerala provides a district-wise breakup of the amount spent on drawing samples. The highest amount drawn by an Assistant Drug Controller (ADC) in any district was Rs. 1,13,800 by the ADC (Kollam) in 2013-014 and the lowest amount for an ADC was Rs. 12,500 by the ADC (Ernakulam) in 2013-14. A separate breakup is provided for Drug Inspectors (DI), with the highest amount being Rs. 48,657 in 2012-13 by the DI of KTM zone, while the lowest was Rs. 1,700 by the DI of WD zone in 2014-15. The high variance in the funds being spent in different zones by different officials could be due to many reasons such as population size etc.
On the issue of guidelines, Kerala informed us that there were no guidelines that it followed while drawing samples.
The reply from Tamil Nadu was by far the most detailed and extensive. The HQ of the Tamil Nadu Food Safety & Drug Administration (TNFSDA) transferred our RTI application across to the public information officers in all zones across the states. Tamil Nadu is perhaps the only state where money is specifically budgeted for the purpose of drawing samples. Most of the individual zones provided a list of the amount that they had spent on sampling drugs. For example Zone III in Chennai city spent an average of Rs. 40,000 every year on drawing samples while Zone II spent Rs. 93,000 in 2014-15 and Rs. 60,000 last year. The Virudhnagar Zone started off with spending only Rs. 12,000 in 2011-12 before its spending increased to Rs. 50,000 in 2014-15, 2015-16. Other zones like Vellore spent close to Rs. 40,000 last year while the Thanjavur zone spent Rs. 1,74,754 last year on drawing samples from the market. One of the lower spending zones was the Thiruvallur zone which spent only Rs. 16,000 in 2014-15 before hiking spending to Rs. 30,000 for 2015-16.
Tamil Nadu as a whole appears to be spending a significant amount of money on drawing samples for testing. Although, it is a still an open question whether the amounts sanctioned are adequate to purchase more expensive medication which can cost thousands of rupees per vial or capsule.
On the issue of guidelines, we received widely inconsistent answers from the different zones within Tamil Nadu. While some zones claimed that there were no guidelines, other zones like Coimbatore did provide us with a copy of guidelines issued on 8.1.2003 by the Director of the state authority. These guidelines basically require each drug inspector to draw 7 samples from the market with at least 3 samples being drawn from government hospitals. The guidelines also state that sampling should be planned well in advance, judicious and drawn from all categories of drug administered on the human body. Since many drug inspectors replied that there were no guidelines, they clearly don’t even know that they exist. In any event, these are far from adequate. Drug inspectors need to be given much better and consistent instructions to ensure that a wide cross-section of drugs are covered in each market to ensure quality of drugs available to Indian public.
If this doesn’t demonstrate regulatory incompetence, I don’t know what else does. Since the sampling process is itself so bereft of method or science, it follows that the rest of the enforcement mechanism is built on a faulty foundation. We spent so much time and effort in collecting and analyzing this information that it is truly a disappointment not to be able to make our case. This is not an academic exercise, as you can see from the data, this affects the health of a billion people living in India.