In my previous post, I explained how unscientific and dysfunctional the sampling process is that is used by both State and Central Drug Inspectors to establish the quality of commercially available medicines in India. Lack of training, consistency of implementation and underfunded budgets bais even conscientious drug inspectors like the ones in Tamil Nadu toward relatively low priced medicines, e.g., antibiotics, anti-acids, steroids, anti-inflammatory drug (NSAID), cough syrups and pain killers. The unfortunate consequence is that expensive drugs such as those used in cancer treatment are seldom tested for quality.

In this blog, I will try and explain how the process works once the analyst in a government laboratory establishes that a sample drawn by the inspector is Not of Standard Quality (NSQ). Under the D&C Act, once the analyst informs the drug inspector that the sample is NSQ, the inspector is required to initiate an investigation to establish the reason for poor quality.

In order to examine and understand the manner in which investigations are conducted, we tried procuring copies of criminal complaints filed by drug inspectors under the Drugs & Cosmetics Act after completion of their respective investigations. These complaints are the starting point for criminal prosecution under the Indian criminal justice system. For the purposes of our research, we targeted three states: Maharashtra, Andhra Pradesh and Tamil Nadu. As always, it was not easy procuring such information under the RTI Act.

Let me begin with Andhra Pradesh (AP) first. We applied for a list of criminal prosecutions initiated by drug inspectors of the Andhra Pradesh Drug Control Administration which were still pending trial in various criminal courts across the state. From this list, we picked cases with different factual circumstances. Three of these cases are explained below. RTI responses that we receicved are accessible by clicking on the respective headings for each of the cases.

(i) Drug Inspector, State of AP v. Quest Laboratories Pvt. Ltd. & its Managing Director before the Court of the Judicial First Class Magistrate at Vizianagaram: In this case, the Drug Inspector visited Central Drug Stores at APMSIDC (AP Medical Services and Infrastructure Development Corporation) located in the cantonment area of Vizianagaram and drew samples of Tinidazole tablets IP 300 mg, Batch No. 02, Mfg. date: 11/09, Exp date: 10/11 manufactured by Quest Laboratories Pvt. Ltd. which is located at Indore in Madhya Pradesh. Tinidazole is an anti-parasitic drug used to treat a variety of amoebic and parasitic infections.

These samples were drawn by the drug inspector on January 2, 2010 and sent to the Drugs Control Laboratory, Hyderabad for testing. The test report declaring the sample to be NSQ was sent back to the drug inspector only on July 21, 2011; it took 19 months for the lab to complete its analysis. It is safe to assume that the entire batch of this product had already been consumed by patients by the time it was declared NSQ! The government laboratory found that the drug had failed disintegration test. Disintegration test is conducted to establish the time it takes for a tablet to completely disintegrate in a chosen medium. If a tablet fails a disintegration test, it means that the tablet has been manufactured incorrectly, for example it could be compressed with inadequate strength. The failure of a tablet to disintegrate properly will affect the way it dissolves in the stomach and its bioavailability. This has a direct impact on the therapeutic efficacy. In the worst case, failure of a disintegration test makes it equivalent to eating chalk. In serious cases of infection, the failure of a drug like tinidazole can possibly result in the death of a patient.

The drug inspector served a copy of the report from the government lab under Section 24(2) on the pharmacist the same day that he received it along with a notice under Section 18A requiring the pharmacist to disclose the name of the manufacturer and the source of the drugs. This notice is important in order to establish the custody of the supply chain from the manufacturer to the pharmacist. A week later, on July 28, 2011 the pharmacist responded to the drug inspector that a batch of 100,000 tablets had been procured from the manufacturer on 10/12/2009.

On the basis of this information, the drug inspector wrote to Quest Laboratories (A1- Accused No.1) on July 20, 2011 with a copy of the test report and a sealed portion of the sample that was drawn from the pharmacy informing the company that it was required to furnish the following details: drug license, list of approved products, constitution particulars, batch manufacturing records and distribution particulars. The company never replied to the notice. A reminder notice was sent on September 8, 2011 and another notice was sent on October 25, 2011 and yet another notice on May 11, 2012. The company apparently didn’t think it was necessary to respond to any of these notices.

After failing to receive responses to all 4 notices, the drug inspector proceeded to file a criminal complaint on June 7, 2012 before the Court of the Judicial Magistrate First Class at Vizianagaram accusing Quest Laboratories and its Managing Director of manufacturing and selling NSQ drug under Section 27(d), failure to furnish information and maintain records as required under Sections 18B, 24, 22(1)(cca), 22(3),28A of the Drugs & Cosmetics Act, 1940.

The time between drawing the sample of the drug (January 2, 2010) and filing of the criminal complaint (June 7, 2012) was therefore 30 months. The time elapsed between the receipt of the test report (July 21, 2011) and filing of the criminal complaint (June 7, 2012) was almost a year. Since this case was listed as pending in the list provided us in the middle of last year, it means that the prosecution has dragged on for more than 3 years – a very long time, for a simple case of a NSQ drug.

Delays apart, also appalling, is the manner in which the investigation was conducted. For example, if an accused isn’t responding to notices, international prosecution standards are that the drug inspector investigating the case should ideally enter the premises of the accused and seize the records and documents required for the criminal investigation. We saw this happen with Ranbaxy when the US Marshals conducted a raid on its offices in Princeton, NJ in February 2007. In the present case, the drug inspector most likely did not have the jurisdiction to exercise such powers because Section 22 of the D&C Act is quite clear that a drug inspector can exercise Search and Seizure provisions only within the local area for which he has been appointed (AP). In such a case, there is nothing preventing the drug inspector from writing to his counterparts in either the CDSCO or in the state drug regulator in Madhya Pradesh (MP) where the drug was manufactured to seek their co-operation. At the very least, one would expect that the licensing authority in MP be informed of the sub-standard medicine detected in AP. The complaint is silent on whether any such attempt was made. By filing a criminal complaint without seeking the batch manufacturing records or testing the stored reference samples, the entire prosecution is weakened. In any criminal prosecution, the guilt of the accused has to be proved beyond reasonable doubt and the criminal complaint filed with the Magistrate should be based on a watertight investigation.

We aren’t aware of the current status of this case.

(ii) Drug Inspector, State of A.P. v. Sri Lakshmi Agencies & its Proprietor before the Court of 2^nd Addl. Judicial Magistrate, First Class, Bhimavaram District: We specifically selected this case because the prosecution list showed the manufacturer to be a Chinese company by the name M/s Quzhou Werong Pharmaceuticals and Chemicals Co. Ltd.

The copy of the criminal complaint provided to us narrated the following facts: On May 5, 2011, the Drug Inspector of the Bhimavaram District conducted a raid on the Pharmacy Sri Lakshmi Agencies and discovered that the shop was stocking for sale certain drugs, etc. without the required licences under the Drugs & Cosmetic Act, 1940. Such raids are a fairly common practice in India. During the course of the raid, the Drug Inspector also picked up some “powders” as a sample for analysis and dispatched them to the Drugs Control Laboratory (DCL), Vijayawada on May 22, 2011. A few days after the raid, on May 13, 2011 the proprietor of the shop was served notice under the provisions of Section 18-A ad Section 22(1)(cca) of the D&C Act, 1940 directing him to disclose the source of purchase in order to establish the chain of custody of the drug. In the meanwhile, the Drug Inspector procured certain details of the shop from the Commercial Tax Officer and discovered that the shop in question had actually been registered for fish and prawn medicines and had a turnover of Rs. 41 lakhs over 5 years.

A couple of weeks later on June 9, 2011, the proprietor replied that he was unable to produce the purchase bills of the drugs. The containers seized by the Drug Inspector however mentioned that the importer of the drug was Medipharma Drug House in Mumbai. On September 23, 2011, the Drug Inspector issued notice to this importer requiring them to produce the photocopy of the import license and sales particulars. The letters was returned as undelivered.

On October 18, 2011, the DCL sent back the test reports stating that the samples seized, now disclosed to be Oxytetracycline, were not compliant with the standard laid down in the BP. Oxytetracycline is a broad-spectrum antibiotic, in addition to human use, it is also used on animals. Indiscriminate use of substandard quality of this drug is a key factor in development of drug-resistant pathogens in India. The reports were served on the accused and on the same day a fresh letter was addressed to the importer Medipharma Drug House requiring it to produce the import license and sales details latest by December 1, 2011. The importer replied this time claiming that they neither imported the products in question nor sold it to the accused and that the seized products did not belong to them. The drug inspector took the claim at face value and prosecuted only the firm found to be selling the drug in question.

Although the investigation in this case moved forward relatively quickly, the investigation was hardly satisfactory. Ideally, the drug inspector should have contacted the CDSCO to cross-check Medipharma’s claims because imports are regulated only by the CDSCO in India. If this procedure had been followed, CDSCO would have been able to corroborate Medipharma’s import licences and verify whether any drugs had been imported from Quzhou Werong Pharmaceuticals and Chemicals Co. Ltd. Unfortunately, none of these procedures seems to have been followed.

(iii) Drug Inspector, State of A.P. v. Sri Venkata Ramana Medical and Fancy Stores & Ors before the Court of the 2^nd Addl. Judicial First Class Magistrate, Machilipatnam: In this case, the Drug Inspector on February 23, 2010 picked up samples of Glucored forte tablets, manufactured by Sun Pharmaceuticals in Jammu & Kashmir (J&K) and samples of Primolut N manufactured by Zydus Healthcare in Sikkim from the shop of accused no. 1 located in Machilipatnam district. Both samples failed quality control tests. The pharmacist had failed to maintain receipts as required under the law to demonstrate the chain of custody of the supply. Unlike the other cases, the drug inspectors investigating this case, travelled to J&K and Sikkim respectively and contacted their counterparts in those states before meeting the manufacturers themselves. Both Sun Pharmaceuticals and Zydus denied that the drugs in questions had been manufactured by them. The reasons provided by Sun aren’t very clear from the complaint. Zydus claimed that the packaging of the seized samples was different from the control samples for the batch in question. The drug inspector seems to accept this explanation and files the complaint only against the pharmacist and some of the other persons from whom he has claimed to have sourced the tablets.

While this case saw much better inter-agency co-ordination, the failure of the drug inspector to explain in detail his reasons for accepting the explanation given by both Sun Pharma and Zydus that neither of the drugs were manufactured by them is disappointing. Faced with a charge that they were manufacturing sub-standard drugs, the safest defence for a pharmaceutical company is to deny any responsibility. Unfortunately, there is no national systems for us to verify the veracity of these claims. In an ideal outcome, the drug inspector should carefully examine such claims and provide a scientific reasoning for either accepting or discounting such claims in the criminal complaint rather than take the easy way out by prosecuting only the pharmacist.

It is a valid question to ask why we do not see adverse events from such NSQ drugs. The sad reality is that as a country, we do not have a national system of surveillance. The easy way out for practicing physicians is to change the manufacturer if they observe either lack of effect or worse, adverse events from the medicine that they prescribed. The very same products sold in the US market produce more frequent adverse events compared to what are reported in India; do you ever wonder why? If you discount for the quality of manufacturing for products sold in India, one should expect to see a higher frequency of adverse events. Clearly we don’t. It tells us something about the prevailing culture within our practicing medical fraternity and the lack of a consistent national reporting system that holds healthcare professionals accountable.

As we can see from these three cases, drug inspectors are not trained adequately to conduct investigations and frame charges against wrongdoers. Perfuntory investigations such as these engender a culture of complicity between the inspectorate and the very companies they are expected to regulate. This is a major deficiency in the current system.

We invested a great deal of time and effort in procuring these reports from the respective state health authorities to factually establish the dysfunction that engenders poor quality, substandard medicine in India. In the next blog, I will analyze more cases, from other states to show you how the process works across states. Unfortunately, the Supreme Court thought this was an academic exercise and denied us an opportunity to present our case. If what we present here doesn’t demonstrate that the dysfunction we document affects the health of over a a billion people in India, I don’t know what else does.