The World Health Organisation (WHO)'s recent decision to review the prequalification given to some of the drugs manufactured by Ranbaxy and Cipla after the procedures adopted by the contract research organizations involved in the bioequivalence studies were found far from satisfactory has proved to be a warning signal for Indian CROs as a whole.

While the two cases are prompting some of the CROs to tighten their systems, others are strengthening their documentation procedures. The way the sponsors (Ranbaxy and Cipla) handled the post-WHO directive crisis by squarely passing on the entire blame over the CROs has also come under heavy criticism.

According to leading Indian CROs, the incidents have caused lot of embarrassment for the clinical research organizations in general. They feel that the companies should not have been allowed to absolve from all their responsibilities as clinical research is always a joint programme of the sponsor and the CRO where the CRO is doing what it has been asked to do by the sponsor. The companies also have the responsibility to monitor the programme and ensure quality compliance at every stage, they say. Responding to pharmabiz queries, CROs in cities like Delhi, Mumbai, Hyderabad and Bangalore all voiced the need for strengthening the internal systems for better performance.

"In a CRO where 200 to 300 employees are actively associated, there needs to be very effective internal regulation. We have to maintain ethics and take more responsibility for what we are doing. Our duty is to train our people on ethics more than anything else. One or two employees may have opted for shortcuts thereby causing bad name for the whole company. I don't think the top managements of either of the CROs involved in the cases are to be blamed for the problem. My only suggestion is that everyone should be very careful in following GLP, GCP practices," Sudhir Pai, managing director, Lotus Labs, Bangalore opines.

According to a top brass of a CRO, "The CRO managements should be able to convince the pharmaceutical companies that undue pressure on time can have its negative impact on quality. Indian CROs should be very clear about their long-term goals. Quality should be maintained at any cost, even if it means losing a bit of business. One should realize that even minor mistakes can result in major changes in final outcome," he explained.

While there was no difference of opinion with regard to the importance of ethics in clinical research, CROs differed in their opinion on the role of pharmaceutical companies. Most of them felt that the pharmaceutical companies should stop pressurizing the CRO to complete the work ahead of time.

"There are several instances where companies are asking us to prepare the report in record time. The time constraint comes when the companies depend too much on their volume of business. But they should also remember that by demanding too much, they are ignoring the possible adverse effect on the quality of the study," CROs say.

Another major complaint many of the top executives of CROs shared was the price factor. They feel that Indian pharmaceutical companies are yet to fully realize the importance of clinical research. "It is high time Indian pharmaceutical companies realized that quality comes with a price. They have been paying peanuts for clinical trials all these years. How can they expect international standards by paying so low," they ask.

Interestingly, one of the pharmaceutical companies figured in the recent WHO controversy is learnt to have contracted the bioequivalence study to the CRO without disclosing the latter the purpose of the study. According to CROs, the result might have been different if the CRO concerned had known that the report for meant for WHO submission. "One should realize that both Indian drug companies and Indian CROs are in an evolving stage. The standards and specifications are also evolving. A report prepared as per today's specifications may not meet the quality standards of tomorrow. It is the same with various regulatory authorities also. The data we need to furnish Indian drug regulatory authorities may not be the same that needed to be submitted to US FDA. The pharmaceutical companies should notify the CROs the intended purpose of the study and should also be prepared to pay a price for conducting it as per international norms and standards," CROs say.

In the opinion of Brijesh Regal, managing director, Apothecaries, New Delhi, "A CRO by itself is not an entity. It does what it has been asked to do by the sponsor. As per international guidelines, the sponsor has a major responsibility in undertaking the clinical trial." He felt that the CROs should realize the need for continous review of their systems.

Optimistic among the CROs felt that the issue cannot be generalized as these are not even CRO specific, but are just study specific issues. "What should be noted here is that the WHO has not blacklisted any particular CRO. Even when they have disapproved a particular study of a CRO, other studies of the same CRO have been approved. This clearly indicates the study specific nature of the issue. Disapproval of studies is a routine matter in developed countries. What happened here is that it has been blown out of proportion," they feel.

In the words of Dr Satish Bhattia, president, WellQuest, Mumbai, the CROs who are not prepared for long-term relationship with sponsors are going to be in trouble. "It is not correct to think that the job of a CRO ends with the generation of the data. The CRO has to be ready for audits at any stage. Your system, training, staff, calibration, data management, all should be perfect. Entire documents should be preserved," he stated.

The alleged involvement of multinational companies in tarnishing the image of Indian CROs / drug firms was another doubt expressed by few of the executives. Pointing out that the "CROs involved in both the cases were fairly good ones," they feel that the whole issue needs to be looked at in a different angle.

Whatever be the case, the pharmaceutical companies, both Indian majors as well as multinationals, are known to have tightened their pre-audits before choosing an Indian CRO to do their clinical studies.