Central Drugs Administration in India

 Rejecting the proposal of the Ministry of Health and Family Welfare to set up a Central Drugs Authority, to check malpractices in drug manufacturing, a Parliamentary panel has, instead, recommended creation of a professionally-managed Central Drugs Administration under the amended Drugs and Cosmetics Act.

In its 79th report on the Drugs and Cosmetics (Amendment) Bill, 2013, the Parliamentary Standing Committee on Health and Family Welfare has said that there was a need for effective discharge of enforcement activities, which requires a strong, professionally-managed administration that can take action against unscrupulous manufacturing companies.

The panel pointed out that neither the Mashelkar Committee report nor the Committee on Health and Family Welfare had recommended constitution of a Central Drugs Authority as proposed in the Bill, but had instead recommended strengthening of the existing Drugs Regulatory body (Central Drugs Standard Control Organisation).

"The proposed Central Drugs Authority is studded with bureaucratic heads of seven central ministries and four secretary and additional secretary/joint secretary-level bureaucrats as ex-officio members with the Health Secretary as its chairperson. Its composition is unprecedented as no other regulatory body in the country or outside has such a composition and it is not acceptable to the Committee," it said.

The Committee said that the central drugs administration should be headed by a chief drug controller general of India of the rank of secretary/special secretary who possesses the requisite technical and professional expertise for the role.

The panel also said that the chief controller general should be selected by a committee headed by the Cabinet Secretary with the review of the functioning of CDA to be done by a panel of independent experts under the Act.

There should be three separate sections dealing with clinical trials, cosmetics and medical technologies, the 

panel noted.

The panel also raised the issue of the flooding of markets with food supplements making claims of possessing medicinal properties and pointed out that the current drug regulating authorities had no control over them.

"The Committee recommends that if any such food supplement claims to have medicinal properties (and) effectiveness in curing disease, they should also be brought under the purview of the proposed Central Drugs Administration for the purpose of their import, sale and distribution," it said.

As regards compensation for injury or death due to clinical trial, the committee has recommended that Principal Investigator appointed by the Chief Drug Controller of India (as recommended by Committee) and the Ethics Committee should be given responsibility for determining the cause of injury or death. The Chief Drug Controller of India should act as Appellate Authority for both, the ``subject’’ and the ``sponsor’’.

The Chief Drug Controller should refer such appeals to the Serious Adverse Event Panel of experts, which will give the final decision, the committee said.

-The Hindu

Pondicherry accounts for highest number of FDCs approved without prior permission from DCGI

Pondicherry, which has been recently in the news regarding violation of 122E Drug & Cosmetic Rules, was found to have approved the highest number of fixed dose combinations without the prior approval of the Drug Controller General of India (DCGI) in the past.

According to the information gathered by the Union Health Ministry, of the total 23 such cases of approvals to FDCs, Pondicherry has reported as many as 8 cases. The Centre had fixed October 1, 2012 as the cut-off date for implementing the rule to get prior permission by the state authorities from the DCGI for approving FDCs.

After Pondicherry, Uttarakhand was found to have sanctioned five FDCs while Maharashtra, Madhya Pradesh and Himachal Pradesh reported two each cases. Goa, Tamil Nadu, Haryana and Union Territory of Daman and Diu sanctioned one FDC each. Out of these, 11 were approved during 2011 and the rest during 2012, as per the information.

“As many as 23 cases of new FDCs , considered as new drugs, were also found to be licenced by State Licensing Authorities (SLAs) without approval of the DCGI . In all such cases, the office of DCG (I) took up the matter with respective SLAs for necessary action,” according to official sources.

“The State Drug Controllers have been requested in the Drugs Consultative Committee meeting to ensure that new drugs and FDCs are not permitted without approval from the office of DCG (I) and the drugs prohibited by the Central Government are withdrawn from the market with immediate effect. States have also been advised to strengthen their infrastructure for better enforcement and develop vigilance mechanism over the drugs moving in the market,” sources added.

On October 1, 2012, the Central Government issued statutory directions under Section 33 P of the Drugs and Cosmetics Act, 1940 to all State/UT Governments to instruct their respective drug licensing authorities to abide by the provisions prescribed under the Drugs and Cosmetics Rules for grant of manufacturing licenses for the drugs falling under the definition of the term “new drug” and not to grant licenses for manufacture for sale or for distribution or for export of such new drugs, except in accordance with the procedure laid down under the said rules without prior approval of the DCG (I).

Recently, the health secretary to the government of Pondicherry had issued show-cause notices to 20 pharmaceutical manufacturing companies operating in region for violation of provision of 122E of the Drugs & Cosmetics Rules following a probe by the Government on the alleged nexus between a former official and a section of the manufacturers.

Source: Pharmabiz

Videorecording of consent for clinical trials mandatory

 The Union Health Ministry has made audio-visual recording of the informed consent of each subject mandatory in a clinical trial. This is in addition to obtaining his/her written consent.

This decision comes in the wake of the Supreme Court pulling up the Ministry for lack of transparency in clinical trials.In its October 21, 2013, order on a writ petition filed by an NGO, the Swasthya Adhikar Manch, Indore, the court said with respect to five global clinical trials, which was approved by the Drugs Controller-General of India (DCGI) office from January 1, 2013, to August 31, 2013, an appropriate provision should be made or administrative direction issued, ensuring that audio-visual recording of the informed consent process was done and the documentation preserved, adhering to confidentiality principles.

In his order, DCGI G.N. Singh said all sponsors/investigators/institutes/organisations and other stakeholders involved in clinical trials should adhere to this requirement with immediate effect.

Reacting to this, the Indian Society for Clinical Research — an association of professionals involved in clinical trials — said lack of guidance and direction on operational and logistical issues of managing the audio-visual recording process like the kind of equipment to be used, and where and how information should be stored could leave room for ambiguity and inconsistencies in execution.

More clarity was required on how confidentiality of patients should be protected and maintained in an ‘audio-visual’ context and what processes needed to be followed in instances where, for religious and socio-cultural reasons, patients might not want to be videographed, the association said. 

Source: The Hindu

Indian Pharmacist Revolution Yatra

The Indian Pharmacist Revolution Yatra has reached Andhra Pradesh and has raised various issues pertaining to pharmacy profession and demanded amendments in various aspects of Pharmacy Act in the country. The main aim of the yatra is to create awareness about the role of pharmacists among the people across the country. The yatra reached Hyderabad on October 20, 2013.

According to Convenor of the yatra, Amitav Joyprakash Choudhury, the main objective of this country wide yatra is to create awareness among the people of this country about the role of pharmacist in healthcare sector. Today the pharmacists have a major role to play in the community pharmacy, manufacturing of pharmaceuticals and research.

The Udyog Development Foundation which began the yatra on January 04, 2013 at Jantar Mantar in New Delhi has planned to tour entire country from Kashmir to Kanyakurmari. As part of this yatra, the Foundation is raising various issues concerning the pharmacy professionals and seeking amendments to Food Safety & Standards Act 2011, Drug and Cosmetics Rules - 1945 (rule 64, 65, 71 and 76, Pharmacy Act-1948, NIPER Act (National Institute of Pharmaceutical Education and Research) and demanded formation of a separate Ministry of Pharmaceuticals, and formation Indian Pharmaceutical Services in the country.

The Indian Pharmacist Revolution has also demanded employment generation for pharmacists in NRHM/Primary Health Centre (PHC), Community Health Centre (CHC), Head Quarters Hospitals and teaching Hospitals. It has also demanded formation of Central Register of pharmacist done by Pharmacy Council of India (PCI).

Till date the foundation has already completed its tour visiting almost all the Northern and Northeaster states. Starting from Jammu & Kashmir in the North, the members of Udyog development foundation have travelled to Punjab, Himachal, Uttarakhand, Uttarapradesh, Haryana, Rajasthan, Gujarat, Bihar, Jharkhand, Chhatisgarh, Odisha, WestBengal, Sikkim, Tripura, Mizoram, Manipur, Nagaland, Arunchal Pradesh, Assam, Madhya Pradesh and now it has begun its tour in the south beginning with Andhra Pradesh.

With this country wide yatra, the foundation is aiming to spread the message of professional ethics and responsibility of the pharmacists towards the society and strengthen the unity among the Pharma professionals. “Today, there are lakhs of pharma professionals spread across the country holding  professional degrees such as D. Pharm, B. Pharm, M. Pharm, M.S. Pharm, Pharm D, Ph.D. and working in different organizations. Many more are freshly graduated every year, but still there is lack of proper awareness about the profession among the common people. Our aim is to highlight the national and state issues relevant to the pharmacy profession and create awareness among the common public,” says Amitav Joyproakash Choudhury.

Steve Eaton jailed in pre-clinical trial data scam

Steven Eaton, a former employee of Aptuit was found guilty at Edinburgh Sheriff’s Court in March following a prosecution under the Good Laboratory Practice Regulations 1999, was today sentenced to three months in prison for altering pre-clinical trial data designed to support applications to perform clinical trials. - The first time the Medicines and Healthcare Products Regulatory Agency (MHRA) has successfully used these regulations to bring a prosecution.

The case came about when Aptuit informed the MHRA that they had identified serious irregularities in pre-clinical data generated to support human clinical trials and the registration of new medicines.

The irregularities involved changing or providing false analytical data that would be used to determine the concentration of medicine that could be given to clinical trial subjects used to assess the safety and efficacy of a new medicine.

The MHRA launched an investigation to identify the number of studies affected and the impact the data irregularities would have on the interpretation of important safety data. The investigation concluded that Mr Eaton had selectively reported analytical data over a number of years, dating back to 2003. During this period he selectively reported data which was used to assess whether analytical methods were working properly or to assess the concentration of the drug in blood. The data manipulation ensured an experiment was deemed successful when in fact it had failed.

The actions led to the review of many hundreds of safety studies assessing the impact of the data manipulation and to ensure that the compromised data was not used in future submissions to relevant authorities without their knowledge.

The development of a number of new medicines were significantly delayed and considerable cost to the study sponsors was incurred as a result of the delay due to the fraudulent activities of Eaton.

Following a full assessment by the MHRA’s inspection team and assessors it was concluded that the data integrity issues did not invalidate the results of the clinical trials that were affected.

Clinical Trials in India plummet after stringent norms - Article from The Hindu

Clinical trials of drugs in India have seen a drastic fall this year after toughened norms were introduced following Supreme Court directives.

 

Not only have the number of trial approvals in the country reduced, there has also been a significant

reduction in the number of sponsoring pharma firms applying for such approvals.

 

Official Health Ministry data shows that until January 31 this year, only six trials had been approved. Even these pertained to older applications where the Drug Controller General of India had asked the applying firms to make some amendments.

 

Sources say until April, only around 12 approvals have been granted by the DCGI for trials of drugs in India. Pending applications for trials as of today are just 70.

This is in sharp contrast to the past when the number of Global Clinical Trials (GCTs) approved for conduct in India was in hundreds

 

Though in 2008 the DCGI had granted just 65 approvals for trials, the number in 2009 rose sharply to 391. The trend continued with a whopping 500 GCTs being allowed in 2010 and 325 in 2011 followed by 262 approvals in 2012.

 

Admitting that there has been a drastic fall in fresh applications for conduct of global clinical trials of drugs in the country, DCGI GN Singh told PTI, “The safety and well being of Indian subjects participating in clinical trials is the foremost in our minds.

 

“This is why the Government has tightened the norms putting the onus of safety of participants on firms conducting the trials. It is for the first time that such norms have been put in place.”

As many as 2,262 people died in these trials during the past five years, leading to a public outcry and Supreme Court intervention for stricter norms for holding drug trials. The apex court had rapped the Health Ministry for allowing Indians to be used as “guinea pigs” in the conduct of drug trials.

 

Also before the new rules were put in place, the average compensation awarded per death was a meagre Rs 2.2 lakh as per Health Ministry data.

 

The Government recently notified new rules for the conduct of drug trials in India, making it mandatory for investigators and sponsors to address issues of serious adverse events such as death of subjects involved in trials and fixing a formula for grant of adequate compensation in such cases.

Pharma firms, the sources say, have been discouraged to apply for new trials due to recent stringent norms which the Government has notified as a precondition for grant of approvals.

 

The new rules which came into force this year, for the first time, propose a formula for minimum compensation to be paid by the sponsoring firm in case of serious adverse events such as death or injury of the trial participant.

 

New rules also require the setting up of independent ethics committees under medical institutes to monitor ongoing drug trials.

 

These committees must now be registered with the DCGI prior before the conduct of clinical drug trials.

 

In the older system, pharma company hosting the trial could set up its own committee and have its own investigators for inquiring into serious adverse events.

 

Currently pegged at USD 500 million, India’s clinical research market was projected to more than double and cross USD one billion mark by 2016 driven by a large and easy-to-access population with much lower cost than in the developed world.

 

Source: The Hindu

DCGI office Organizational Structure

Here is the Organizational Structure of the Drugs Controller General of India office.



 

98 New Drug Inspectors to be recruited in Tamilnadu

As part of strengthening the department of drugs control for better enforcement of drug acts, the government of Tamil Nadu has decided to fill up vacancies of 98 drug inspectors against a sanctioned strength of 146 posts.

The state public service commission has called for applications from graduates in pharmacy for written test and interview and the process will be completed by June this year, it is learnt.

Along with the recruitment of new drug inspectors, the government will also fill up 23 vacancies of junior analysts in the state drug testing laboratory, for that too, the PSC has invited applications. Graduates with B Pharm or B Sc qualifications can apply for the posts.

The last time recruitment of drug inspectors in the department was taken place in January 2010, when 23 vacancies were filled up. It was after a period of ten years that appointments were held, still vacancies were existing. At present the Tamil Nadu drugs control department has only 48 drug inspectors for inspection and sample collections in the hospital pharmacies, retail and wholesale shops and manufacturing companies covering 32 revenue districts.

Currently, due to shortage of staff, the workload on the drug inspectors is quite heavy affecting the work efficiency. As per rules one inspector has to inspect 50 retail outlets and an equal number of wholesale stores in a month and should collect seven samples for testing. In most of the months the routine work cannot be completely fulfilled with the limited staff. Since the majority of drug inspectors are females and working in villages, they cannot fulfill the target always.

As far as the drug testing laboratory is concerned, due to lack of technical staff and analysts the test reports are always delayed. So the drug inspectors are collecting samples of long expiry drugs. If short expiry samples are taken and found in the lab test as ‘not of standard quality’, the department will not get sufficient time to hold investigation and further action. So, all the drug inspectors are collecting long expiry samples, sources from the traders’ community maintained.

To solve all these problems, the present drug controller has submitted a project, including new recruitment, to the government which later approved it. The drug inspectors complain that inadequacy of conveyance facility is becoming a major challenge to their work.

Source: Pharmabiz

FDA Guidance Documents Update

The US FDA have released the following guidance documents recently.


1. Guidance for Sponsors, Investigators, and Institutional Review Boards: Questions and Answers on Informed Consent Elements,21 CFR § 50.25(c) (Small Entity Compliance Guide)

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf

2. Guidance for IRBs,Clinical Investigators,and Sponsors: IRB Continuing Review After Clinical Investigation Approval

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294558.pdf

3. Guidance for Industry and FDA Staff: FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND, Frequently Asked Questions

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294729.pdf

4. Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers, Final Guidance

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM295372.pdf

Plea to address span of control issues in new drug policy

The Indian Pharmaceutical Alliance (IPA) has a few issues relating to the ‘span of control' in the draft National Pharmaceutical Policy (NPP) 2011.

IPA Secretary General D. G. Shah said the draft policy stated that the ‘span of control' was likely to go up to 60 per cent. The prices of almost half the ‘essential medicines' will be reduced by 5-80 per cent and the other half by 5 per cent.

The IPA estimates that domestic price reductions alone will result in about Rs 3,000 crore loss in sales to the domestic industry where the players have contributed 95 per cent of increase in gross fixed assets and 77 per cent of R&D expenditure in the industry in the last 15 years.

However, IMS Health data show that the ‘span of control' can effectively be as high as 75 per cent — more than four times the current ‘span of control' and more than twice the ‘span of control' as per the National List of Essential Medicines (NLEM), 2011.

It will, in effect, bring an additional 1,154 drugs and 6,441 formulations under price control as against the Drug Price Control Order (DPCO), 1995, of 38 drugs and 800 formulations with an 18 per cent ‘span of control'. “The proposed additions will enlarge the scope of price regulation by over eight times the current volume to about 68,000 packs, making the task unwieldy and ineffective. ,'' said Mr. Shah.

With an enlarged ‘span of control', the domestic manufacturers can shift investment outside India as they have facilities all over the globe. “Importantly,'' according to Mr. Shah, “large domestic companies, which contribute around 81 per cent of total pharma exports, earn an average 50 per cent of their revenues from exports. The price reductions in the country will have an impact on export price realisation also as all importing countries check domestic prices.''

The IPA has suggested that to ensure a sustainable supply of essential medicines, the policy should stay with the NLEM 2011 list, which covers 348 drugs and 654 formulations with a ‘span of control' of 30 per cent.

In a bid to balance consumer interest and the pharmaceutical industry's growth, the government is considering plans to increase its procurement of essential medicines by 7-8 times from the domestic industry for supply to the weaker sections of the society.

The IPA Secretary General felt the success of such a programme would hinge on the industry being able to produce huge volumes and also its ability to absorb the costs of supplying the enhanced volumes at heavily discounted rates.

Source: The Hindu

Lok Sabha takes up Transplantation of Human Organs Bill for discussion

The clearance of the much-awaited Transplantation of Human Organs (Amendment) Bill during this ongoing session of Parliament is almost certain now as the Bill has already been taken up in Lok Sabha for discussion.

The Bill, which is an amendment to the Transplantation of Human Organs Act, 1994, seeking to make the organs transplantation more transparent and patient friendly, and also for imposing stringent penalties on persons and hospitals violating the provisions of the Act, was taken up for discussion in Lok Sabha by Union health minister Ghulam Nabi Azad on August 11.

In fact, the Bill was introduced in Lok Sabha way back on December 18, 2009 and it was referred to the Parliamentary standing committee attached to the Union health ministry for its scrutiny. After examining the Bill in detail, the standing committee laid the report on the Table of Lok Sabha on 4 August, 2010. For the tentative list of transaction of business for the ongoing session of Parliament, which started on August 1, the Bill was listed for 'consideration and passing'.

Since the Lok Sabha has already taken up the Bill for discussion, it is now certain that it may get the final Parliament nod. Once the Bill is passed in Parliament, it will be sent to the President for her consent. Once the President signs the Bill, it becomes an Act of Parliament and will come into effect in the country.

The government took the initiative to amend the law, which was originally framed around 16 years back, as there were repeated reports about a thriving human organ trade in the country and the consequential exploitation of economically weaker sections of the society. There was an increasing perception among the common people that while the Act has not been effective in curbing commercial transactions in organ transplant, it has thwarted genuine cases due to the complicated and long drawn process involving organ donation.

As the voice against the Act became louder, the central government held a national consultation on the need to have an effective regulation of organ transplantation in the country. State governments and various sections of civil society were also consulted during the process. Ultimately, a proposal to comprehensively amend the Transplantation of Human Organs Act, 1994, was submitted to the Union cabinet for its consideration.

HURDLES IN CDA FORMATION

The move to establish a centralized system of drug administration in the country by forming Central Drug Authority is being revived by the Union health ministry now after the proposal got shelved a few years ago. The plan was strongly opposed by the state governments and industry bodies from the very beginning. The health ministry had been wanting to centralize licensing for manufacture, sale, export and distribution of drugs in pursuance of the recommendations of the Mashelkar Committee. And the Drugs & Cosmetics (Amendment) Bill 2007 was drafted to set up the CDA. The Bill was introduced in the Rajya Sabha on August 21, 2007 and was thereafter referred to the Parliamentary Standing Committee of ministry of health. The Standing Committee had then submitted its recommendations to the government dropping the proposal for CDA and instead recommended setting up of a 'central drug administration' as an independent body with headquarters in Delhi and its zonal and sub-zonal offices at state-levels and by strengthening, modernising and restructuring the CDSCO. The health ministry seems to have taken expert opinion on the matter once again and the move now to set up CDA is on the basis of this new thinking.

Formation of CDA was contemplated by the government considering the fast pace of growth of Indian pharmaceutical industry over the years. Need for centralizing the drug control administration was felt on account of the urgency in bringing some uniformity in enforcement of various drug rules. Some of the key provisions of the D&C Act such as Schedule K, Schedule M, Schedule Y, etc. have been already amended and elaborated over the years considering the growth needs of this sector. As per the current system of drug administration, enforcement of all amended rules under the D&C Act is with the state health departments. But, most of the states have not been successful in implementing these amended regulations so far. This, in effect, has been making a mockery of the Act and rules in the pharmaceutical sector. Licensing of products has been one area where there was a lot of confusion prevailed in the country until 2008. A new drug is approved for marketing by CDSCO but issuing licences for its manufacture used to be done by various state drug administrations. Although states and Union territories are having drug control departments, most of them do not have officials with sufficient competence to evaluate an application before a manufacturing license is issued. The issues like these were under discussion by the office of the DCGI for some time but not in a comprehensive manner. All the state governments are still not in support of formation of CDA as that could take away a lot of powers from them. Now, without the support of the state governments and industry, it will be difficult for the health ministry to implement CDA even if the bill gets passed. Therefore, the health ministry needs to take the concurrence of most state governments and the industry again considering the sensitive features of the new system.

Indian Govt. invites application for the post of DCGI

A day after the Madras High Court granting three-month extension to Dr Surinder Singh as the Drug Controller General of India (DCGI), the Health Ministry has stepped up the moves to find a replacement to Dr Singh within the period stipulated by the Court.

The advertisement by the Ministry hit the main newspapers today, inviting application for the post of Drug controller (India). The Ministry had already issued advertisement on June 14, with the same purpose.

The post will be filled by deputation (including short-term contract) from officers under the Central, State Governments, recognised research institutions, public sector undertakings, semi-government, autonomous and statutory organisations, according to the advertisement.

Sources in the ministry said, the government had decided to go for new DCGI many months back and the extension was an interim option till the new person was inducted. The files in this regard had been moved in time, even before the case came up in the courts, sources claimed.

While vacating the interim stay and allowing Dr Singh to continue for three months, the High Court had asked the Union Government to expedite the process of recruiting a new person for the post of DCGI within three months, as it specifically ordered that Dr Singh cannot continue beyond the said period.

The Additional Solicitor General of India Mohan Parasaran, appearing for the Government, had also given assurance in this regard to the Court. The Government on June 8, 2011 extended the appointment of Dr Singh till March 31, 2012, as his tenure was to expire on June 21. However, the public interest litigation was filed against this order and the Court passed an interim stay, before pronouncing the final order other day.

As per the advertisement, the applicant should be a “graduate degree in Pharmacy or Pharmaceutical chemistry or in Medicine with specialization in clinical Pharmacology or Microbiology from a recognized University established in India be law; postgraduate degree in Pharmacy/ Pharmaceutical chemistry/ Biochemistry/Chemistry/Microbiology/ Pharmacology from a recognized University or equivalent; and 15 years experience in manufacture or testing of drugs in a concern of repute or enforcement of the provisions of the Drugs and Cosmetics Act, 1940 and Rules.”

US FDA releases reports on pilot programmes on increasing international regulatory collaboration

The US Food and Drug Administration (FDA), together with its European and Australian counterparts, released two reports detailing the results of pilot programmes focused on increasing international regulatory collaboration among the agencies so that drug quality and safety can be enhanced globally.

The report on the Good Clinical Practice (GCP) initiative details the success of information-sharing and collaboration on inspections relating to clinical trials. Under the GCP pilot programme, the FDA and the European Medicines Agency (EMA) exchanged more than 250 documents relating to 54 different drug products and, in conjunction with the GCP inspectors of the EU member states, organized 13 collaborative inspections of clinical trials. This lays the foundation for a more efficient use of limited resources, improved inspectional coverage, and better understanding of each agency’s inspection procedures. It demonstrates how the agencies can work together to improve human subject protection and better ensure the integrity of data submitted as the basis for drug approvals.

The report on the Active Pharmaceutical Ingredients initiative details the success of information-sharing among the FDA, Australia’s Therapeutic Goods Administration and for Europe, the EMA, France, Germany, Ireland, Italy, the United Kingdom and European Directorate for the Quality of Medicines & Healthcare (EDQM). Over the course of the 24 month pilot phase, the participants shared their surveillance lists and found 97 sites common to all three regions, resulting in the exchange of nearly 100 inspection reports and in nine collaborative inspections.

The FDA used these reports to inform decisions, such as whether to postpone or expedite its own inspection. The FDA also prohibited imports into the US of a firm’s products based on the negative findings from a European inspection. The information-sharing and collaborative inspections were important milestones in establishing a sense of mutual trust and common purpose among the drug regulatory agencies involved.

“It is imperative that FDA work closely with its counterparts in order to ensure the safety and quality of products and the integrity of clinical trials. We cannot do it alone,” said Deborah M Autor, FDA deputy commissioner for Global Regulatory Operations and Policy. “We are grateful to our European and Australian colleagues for their willingness to partner with us in these pilot programs. The pilots are important stepping stones toward further global regulatory collaboration.”

These pilot programmes are part of the FDA’s global strategy to ensure the safety and quality of imported products. The new strategy builds on efforts that are currently underway at the FDA. The agency increased the number of foreign drug manufacturing inspections by 27 per cent between 2007 and 2009 and has opened several international offices in key locations such as China and India. The FDA has been an active contributor in the effort to harmonize certain aspects of drug regulation via the International Conference on Harmonization, and the agency recently joined the Pharmaceutical Inspection Cooperation/Scheme, an organization of drug manufacturing inspectorates from 39 countries.

In June, the FDA unveiled a new strategy to meet the challenges posed by rapidly rising imports of FDA-regulated products and a complex global supply chain in a report called the “Pathway to Global Product Safety and Quality.” The FDA report calls for the agency to transform the way it conducts business, to build upon its ongoing collaborations with its regulatory partners around the world, and to act globally in order to promote and protect the health of US consumers. In the report, the FDA says that it will partner with its counterparts worldwide to create global coalitions of regulators focused on ensuring and improving global product safety and quality. FDA looks forward to working with its counterparts on this important effort.

The FDA, an agency within the US Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Pharma companies that used Cetero Research come under FDA Scanner

The FDA have notified pharmaceutical companies that bioanalytical studies conducted by Cetero Research between April 2005 and June 2010 in support of marketing applications may need to be repeated or confirmed. Cetero is a contract research organization (CRO) that performs bioequivalence and pharmacokinetic testing for a number of pharmaceutical companies.

The FDA is asking drug sponsors to identify those tests conducted by Cetero during the designated time frame that were used to support New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs). Drug sponsors will need to determine whether any of the testing performed by Cetero should be re-done.

Also, the FDA will send letters to drug sponsors with pending applications, requesting that they either repeat the bioequivalence testing done by Cetero or retest drug samples using a different test laboratory or contractor.

It is unlikely that these concerns relating to data integrity affect the overall safety and efficacy of drugs already on the market and, at this time, there is no evidence of problems with the safety, quality, purity or potency of drugs already approved. However, as a precautionary measure the FDA is asking drug sponsors to review the testing in question conducted by Cetero to make sure that data are completely reliable.

FDA is taking this action as a result of two inspections of Cetero’s bioanalytical facility in Houston, Texas conducted in 2010, as well as the company’s own investigation and third party audit. The inspections and audit identified significant instances of misconduct and violations of federal regulations, including falsification of documents and manipulation of samples.

The pattern of misconduct was serious enough to raise concerns about the integrity of the data Cetero generated during the five-year time frame. FDA concurs with the assessment of Cetero’s independent auditor who stated, “This misconduct appears to be significant enough to cast doubt on the data generated…If the foundation of the laboratory is corrupt, then the data generated will be also.” As noted in a letter FDA sent to the company, Cetero also failed to conduct an adequate internal investigation to determine the extent and impact of the violations and failed to take sufficient measures to assure data integrity within the 5 year time frame.

As noted in the July 26 letter sent to Cetero, “FDA has reached this conclusion for three reasons:

(1) the widespread falsification of dates and times in laboratory records for subject sample extractions

(2) the apparent manipulation of equilibration or ‘prep’ run samples to meet pre-determined acceptance criteria

(3) lack of documentation regarding ‘prep’ runs that prevented you from conducting an adequate internal investigation to determine the extent and impact of these violations.”

Dr. Surinder Singh to continue as DCGI Until October

Much to the relief of many, the Madras High Court have granted a three month extenstion to Dr. Surinder Singh to continue as the Drugs Control General of India (DCGI) for three more months until October 31, 2011.

Earlier, the Government of India had on June 8, 2011 extended the appointment of Dr Surinder Singh as DCGI until 31. 3. 2012. The DCGI’s deputation tenure was to expire on June 21, this year.

A public interest litigation (WP 15607/2011) against the appointment of DCGI and the extension was filed by T K Ramalingasamy, a former regulatory officer of the Tamil Nadu Drugs Control Department. Advocate P T Asha from Sarvbhouman Associates, appeared on behalf of the petitioner. She quoted the reference of a government order (GO) passed by the central government that the period of deputation of a government servant should not exceed beyond five years. She said Dr Singh has already completed five years on deputation.

Additional Solicitor General of India, Mohan Parasaran, who appeared on behalf of the Government assured the court that Government would speed up the process of recruiting a new DCGI.

Chaos in Clinical Research

The recent irregularities reported in conducting of clinical trials by Axis Clinicals, a Hyderabad based CRO, in Andhra Pradesh has once again brought to focus the questionable ways in which clinical trials are being done in India by the pharmaceutical companies and their agents. The report said that the CRO conducted bio-equivalence studies for an anti cancer drug on poor women early this year without securing their informed consent. The episode came to light only last month when some women belonging to this group complained of severe body ache, joint and chest pain and extreme weakness after taking the drug. A few of them even had difficulty in walking. The office of the DCGI raided the premises of the CRO after report came in the media and suspended its license. Axis also will be disallowed from conducting all bio-availability and bio-equivalence studies at their centre for some time now. Investigation carried out by the DCGI officials found irregularities in procedures such as recruitments of subjects and in taking their informed consents. The DCGI also found that the ethics committee at the centre was not functioning independently as required under the existing ICMR guidelines. Many such violations by CROs while conducting clinical trials in India were reported in the recent past and actions were taken against the offenders. But, these offences keep occurring in various parts of the country and very few of them get reported in the media.

After the action taken against the Hyderabad CRO, the office of the DCGI decided to audit all CROs in the country to ensure that the bio-availability and bio-equivalence studies are performed strictly in accordance with the regulatory provisions and prescribed guidelines. The DCGI office has already completed auditing of CROs in Andhra Pradesh and Mumbai. The basic problem with the clinical research in the country is that the sector is not at all effectively regulated. The health ministry has been working for last ten years to put in place a set of comprehensive rules to regulate clinical research with huge flow of contract research jobs into the country. But that has not happened yet. Ethics Committees at most of the trial sites are not active with no monitoring of the trials. What the country has a set of guidelines after amendment of the Schedule Y of Drugs & Cosmetics Act and it is not yet notified. That is what emboldens the MNCs and CROs to conduct trials as they do it now. Now in the case of CROs, a set of draft rules for their mandatory registration was issued by the DCGI some time in July 2009 after it was approved by the Drug Technical Advisory Board. But the registration process is still not in place. The move to make registration mandatory for CROs was taken after finding a spate of irregularities in conducting trials in the past. In short, the slow decision making process in the health ministry is the prime reason for the whole chaos in clinical research front. The matter has to be taken up by the health minister seriously and urgently if this critical sector of the pharmaceutical industry has to function with some order.

Source: Pharmabiz

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 20-23 June 2011

Positive opinions for new medicines adopted

The Committee adopted positive opinions recommending the granting of marketing authorisations for the following new medicines:

Buccolam (midazolam), from ViroPharma SPRL, intended for the treatment of prolonged, acute, convulsive seizures in paediatric patients from the age of 3 months to 18 years. The review for Buccolam began on 22 September 2010 with an active review time of 210 days. This is the first CHMP recommendation for a paediatric-use marketing authorisation (PUMA).Eurartesim (dihydroartemisinin/piperaquine phosphate), from Sigma-tau Industrie Farmaceutiche Riunite S.p.A., intended for the treatment of uncomplicated Plasmodium falciparum malaria. The review for Eurartesim began on 22 July 2009 with an active review time of 210 days. This is the first CHMP recommendation for an anti-malaria medicine.

Trajenta (linagliptin), from Boehringer Ingelheim International GmbH, intended for the treatment of type 2 diabetes mellitus to improve glycaemic control in adults. The review for Trajenta began on 21 July 2010 with an active review time of 210 days.

Votubia (everolimus), an orphan medicine from Novartis Europharm Ltd, intended for the treatment of patients aged 3 years and older with subependymal giant-cell astrocytoma (SEGA) associated with tuberous sclerosis complex. The review of Votubia began on 18 August 2010 with an active time of 210 days.
The CHMP recommended the granting of a conditional marketing authorisation for Votubia, which means that further evidence on the medicinal product is awaited. In the case of Votubia this relates to the submission of the final results from pivotal phase III study and the long-term follow-up on the efficacy and safety in SEGA patients. The European Medicines Agency will review new information within one year and update the product information as necessary.

Negative opinions for new medicines adopted

The Committee adopted negative opinions recommending that marketing authorisations should not be granted for the following orphan medicines:

Bronchitol (mannitol), from Pharmaxis Pharmaceuticals Ltd, intended for the treatment of adult patients with cystic fibrosis.
Luveniq (voclosporin), from Lux Biosciences GmbH, intended for the treatment of chronic non-infectious uveitis.

DCGI withdraws approval given to Axis Clinicals for BE studies after probe confirms allegations

The Drugs Controller General of India (DCGI) has suspended the clearance given to Hyderabad-based Axis Clinicals for conducting bio-availability and bio-equivalence studies at their centres in Miyapur 'in public interest', in the wake of the recent controversies for allegedly using women in Piduguralla as trial subjects.

“The Drugs Controller General (India)’s South Zone Office, Chennai and Sub-zonal office, Hyderabad has conducted investigations in the matter of recent reports about certain irregularities in conduct of clinical study by Axis Clinicals Ltd., Hyderabad in violation of the norms specified in Schedule Y of the Drugs and Cosmetics Rules. The investigations have revealed various irregularities in conduct of the above said studies with respect to subject recruitment process, informed consent process, independence of the Ethics Committee and its review and decision making process. The investigations were conducted on 20th and 21st June 2011 at the bio-equivalence study centre of Axis Clinicals Ltd. situated at Serlingampally, Miyapur, Hyderabad,” according to official statement here.

The Drugs Controller General (India) has therefore suspended the approval of the said firm for conducting all bio-availability and bio-equivalence studies at their centres in Miyapur, Hyderabad in public interest, it said.

The office of the DCG(I) has further decided to investigate the working of all bio-availbility and bio-equivalence study centres in Andhra Pradesh within a period of two months to ensure that such studies are performed strictly in accordance with the applicable regulatory provisions and prescribed guidelines.

“Axis Clinicals Ltd., Hyderabad had conducted bio-equivalence studies on Exemestane tablets in its Serlingampally, Miyapur, Hyderabad centre during the period 27th January 2011 to 15th February 2011. It was alleged that the firm had conducted study by administering the anti-cancer drug to the poor women in Piduguralla town of Andhra Pradesh without securing their informed consent,” the statement added.

Fixed Dose Combination (FDC) issue - will there be an end to it ?

A lasting solution to the vexed Fixed Dose Combination (FDC) issue, which has been evading a solution for almost four years, does not appear to be on the cards as the expert panel, headed by DCGI, is adamant that the industry should come out with clinical trial details on each of the FDC products, even those products which were in the market for decades together.Industry sources said that the expert panel, which consisted of doctors from renowned hospitals, was not ready to even consider the drugs which were in the market for several years. Though the industry also took the help of several renowned doctors, that too specialists in each area, the panel simply refused to consider the pleas of these doctors and insisted on clinical trials for each of the FDC products, sources said.

After a long gap of more than one year, the expert panel on FDC held its meeting on April 19 and 20 this year to take a call on most of the remaining FDC drugs. In fact, the industry was optimistic on finding a lasting solution to the vexed issue during the two-day meeting, especially in the wake of DCGI Dr Surinder Singh's public announcement on January 7 this year in Mumbai that the long pending FDC issue would be resolved within one month. On that day, the DCGI was addressing the captains of Indian pharma industry on the occasion of the 49th annual day celebrations of the Indian Drug Manufacturers Association (IDMA) in Mumbai.But the insistence of the DCGI-headed expert panel on clinical trial for all the products has belied such a hope.Taking strong exception to the adamant attitude of the panel, industry sources said that if the DCGI wanted clinical trials for every product, the entire exercise of holding periodic meetings between the industry and the expert panel is a waste of time for one and all. “The industry has roped in several renowned doctors to present their case in the meetings. But, their views were not heeded by the panel,” the industry regretted. In fact, the industry is annoyed with the DCGI over his indifferent attitude in handling the entire FDC issue. There is resentment among the industry over the inordinate delay on the part of the DCGI in sending the list of FDCs, which have been accepted as 'good and rational' by the expert panel, to the State Licensing Authorities (SLAs) as the SLAs are directing the companies to approach DCGI office in Delhi for getting the license renewal of drugs which have been in the market for as long as 10 to 15 years. The expert panel on FDC had so far cleared more than 200 of the total 294 controversial combination drugs as 'good'. But, the DCGI is yet to officially communicate the same to the SLAs in writing, leaving the industry to approach the DCGI office for licenses.