Drug row sets Pakistan scientists against ministries

Hepatitis B is transmitted through blood and infected bodily fluids

Efforts to produce a cheap local version of a hepatitis B drug have ground to a halt in Pakistan amidst a row between a leading scientist and senior officials from two government ministries.

Officials claim to have evidence that scientists involved in the drug's production have cut corners in carrying out trials, abused resources and misused research funds.

But two of the scientists said they feel they are being deliberately prevented from launching the drug, interferon, because it could undermine the lucrative contracts for supplying it currently held by international pharmaceutical companies.

Viral hepatitis B is endemic in Pakistan, with an estimated seven million people infected,according to research published by the Pakistan Journal of Medical Sciences in 2009.   

The government's claims relate to scientists at the Centre for Applied Molecular Biology (CAMB) in Lahore. The ministry of science and technology commissioned an audit of the centre, carried out by a committee of officials and external auditors, according to sources.

The ministry referred the findings to the Federal Investigation Agency this month (8 December) which will decide whether to proceed with charges. In the meantime, the centre's accounts have been frozen.

Meanwhile, officials in the ministry of health said they are refusing to approve use of interferon produced by CAMB because of alleged irregularities in the clinical trials.

And, in a separate development, an independent petitioner, Batish Mahmood Tipu, filed a petition in the High Court this month (13 December) which has led to the court issuing notices to both ministries.

The notices require them to explain before the court why they are not allowing the use of locally produced interferon that, according to the petitioner, costs 70 Pakistan rupees (around 82 US cents) per injection, compared with the imported version, which costs around US$11.

CAMB trains molecular biologists and specialises in recombinant DNA technology. The centre has a good record of achievements related to Bt (Bacillus thuringiensis) rice, Bt cotton and Bt pesticide formulations. It has obtained more than ten patents. 

The centre received regular funding from the ministry of science and technology for the interferon project and, from 2004 onwards, it also received financial support from Pakistan's Higher Education Commission (HEC).

CAMB also received prize money of US$100,000, in 2008, from the Islamic Development Bank for its outstanding contribution to molecular biology.

Clinical trials criticised

Sheikh Riazuddin, one of five scientists targeted by the government's investigation, was director of CAMB from its establishment in 1985 until June 2009.

Riazuddin was working on a project entitled 'Local Production of Interferon', headed by Javed Akram, a professor at Jinnah Hospital, Lahore, which began in 2000.

According to Riazuddin phase III clinical trials of the local version of the drug were conducted at Jinnah Hospital, a teaching hospital of the Allama Iqbal Medical College, Lahore, and it was ready for final approval in December 2008.

By January 2009, CAMB had patented the drug and produced 100,000 vials of it — which have still not been used.

Sources from the ministry of health said they have not approved the drug because of the omission of two key stages normally conducted in clinical trials: phase I (laboratory testing of the drug) and phase II (safety testing on humans).

But Riazuddin said these stages are not necessary in the case of a 'biosimilar' drug — an exact copy of a drug for which these trials have already been conducted. 

Rauf Khalid, drug registration controller of the ministry of health, toldSciDev.Net: "The approval of hepatitis interferon for commercial release can only be granted when CAMB completes all the requirements, including tests, and shows the capability of its production facilities".   

The ministry of science and technology's audit committee, whose findings have not been made public, has, according to sources, found among other alleged irregularities that Riazuddin had been using CAMB facilities, such as transport and phone, even after he had left the organisation.

The committee has also said it can find no satisfactory answer about where the bulk of the prize money from the IDB has gone.

Khalid Siddiqui, joint secretary of the ministry of science and technology, said: "Irregularities have taken place at CAMB for the last many years and all the findings by our committee have formally been sent to the Federal Investigation Agency for verification.

"We respect them [the CAMB scientists] as researchers but any irregularities identified by the fact-finding committee have to be dealt with according to law." 

Allegations have 'no substance'

Riazuddin confirmed to SciDev.Net that he has been contacted by the [FIA] which informed him that it had received a case against him involving corruption, to the tune of millions of rupees, and misuse of authority — charges he denies.

"There is no substance in the allegations," he said.

He agreed that, even after leaving CAMB, he continued to direct the team and spent most of his time at CAMB.

"I did that not for my sake but to see my brainchild become a reality. I assumed if I do not look after the research I started, that might vanish, rendering many years' effort futile."

Riazuddin and Akram claimed that there have been government moves to try to block the development and production of their drug.

"Some sections in the ministry of science and technology and in the health ministry are playing into the hands of multinational companies who do not want a local launch of this medicine as Pakistan is importing hepatitis drugs worth Rs 4 billion (around US$47 million) annually from those multi-nationals," Riazuddin said.

"This all is to force us into saying goodbye to the local production of interferon," Akram told SciDev.Net. 

"At every step, from release of funds to the approval stages, we faced bureaucratic hurdles so much so that we felt that they do not want local production of hepatitis interferon," Akram added.

Anwar Nasim, patron of the Pakistan Biotechnology Information Centre (PABIC), told SciDev.Net: "It is not shocking to know about corruption allegations in research when the menace of corruption is all around us. An external investigation by the FIA would soon help us know who was in the wrong — the ministry or the researchers".