Boehringer Ingelheim's spesolimab receives US FDA approval for generalized pustular psoriasis flares in adults

Boehringer Ingelheim have announced that the U.S. Food and Drug Administration have approved spesolimab as a treatment option for generalized pustular psoriasis (GPP) flares in adults.

Spesolimab, marketed in the U.S. as SPEVIGO, is a novel, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of GPP.

The FDA’s approval of spesolimab is based on results from the pivotal EFFISAYIL 1 Phase II clinical trial. In the 12-week trial, patients experiencing a GPP flare were treated with spesolimab or placebo. Most patients at the outset of the trial had a high, or very high, density of pustules, and impaired quality of life. After one week, 54% of patients treated with spesolimab showed no visible pustules compared to placebo (6%).1

In addition to the U.S. approval, spesolimab is currently under review by several other regulatory authorities. To date, spesolimab has received Breakthrough Therapy Designation in the U.S., China and Taiwan, Priority Review in the U.S. and China, Orphan Drug Designation in the U.S., Korea, Switzerland and Australia, Rare Disease Designation and fast track in Taiwan, for the treatment of GPP flares. The European Medicines Agency validated the marketing authorization application for spesolimab in GPP in October 2021 and the submission is currently under evaluation.

FDA Ad Comm Votes Unanimously in Favor Of COMIRNATY Booster for Emergency Use in People 65+ and Certain High-risk Populations

 Pfizer (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) have announced that the U.S. Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously to recommend the FDA grant Emergency Use Authorization (EUA) for a booster dose of COMIRNATY (COVID-19 Vaccine, mRNA) in individuals 65 years of age and older and individuals at high risk of severe COVID-19. 

The committee recommended that the additional dose be administered at least six months after the two-dose series. The panel also agreed that healthcare workers and others at high risk for occupational exposure should be included in this EUA.

VRBPAC based its recommendation on the totality of scientific evidence shared by the companies, including data from their clinical program evaluating the safety, tolerability and immunogenicity of a booster dose of COMIRNATY. A booster dose of the vaccine elicited significantly higher neutralizing antibody titers against the initial SARS-CoV-2 virus (wild type), as well as the Beta and Delta variants, when compared with the levels observed after the two-dose primary series. The reactogenicity profile within seven days after the booster dose was typically mild to moderate, and the frequency of reactions was similar to or lower than after dose two. The adverse event profile was generally consistent with other clinical safety data for COMIRNATY.

Real-world surveillance data also were presented to the VRBPAC by the Israel Ministry of Health, providing further support for the public health impact of boosters. The data presented from Israel included an analysis published this week in The New England Journal of Medicine. The analysis comprised approximately 1.1 million individuals ages 60 years and older who were eligible for a booster dose of the vaccine between July 30 through August 31, 2021. No new safety signals were observed, and reported adverse events were lower than those observed after dose two. The analysis showed that a booster dose restored very high levels of protection against COVID-19 infections and severe disease in this period when Delta was the dominant strain. Individuals who received the booster dose were less likely by a factor of 11.3 (95% CI: 10.4, 12.3) to develop a confirmed infection and less likely by a factor of 19.5 (95% CI: 12.9, 29.5) to develop severe illness compared to those who were previously fully vaccinated but did not receive a booster dose.

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

Breakthrough Therapy Designation

What is a Breakthrough Therapy?

A new drug may be designated as a breakthrough therapy by the Food and Drug Administration (FDA) if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence suggests it provides a substantial improvement over existing therapies. Once the breakthrough therapy designation is requested by the drug sponsor, the FDA and sponsor work together to determine the most efficient path forward.

 

Breakthrough Designations Announced By Companies (as of October 2013):

• Kalydeco - (Vertex) - 2 cystic fibrosis designations
  • in combination with VX-809 in patients with two copies of the F508del mutation 
  • ​monotherapy for other CFTR mutations
• Ibrutinib - (J&J/Pharmacyclics) - 3 designations
  • mantle cell lymphoma
  • waldenstrom macroglobulinemia (WM)
  • chronic lymphocytic leukemia
• LDK378 - (Novartis) - ALK+ NSCLC resistant to crizotinib
• Palbociclib - (Pfizer) - treatment of post-menopausal patients with ER+, HER2- locally advanced or metastatic breast cancer
• Lambrolizumab - (Merck) - inoperable and metastatic melanoma 
• Daclatasvir*- (BMS) - interferon-free treatmemt of Hepatitis C *combination of daclatasvir with two other direct-acting antivirals, asunaprevir, an NS3 protease inhibitor and BMS-791325, an NS5B non-nucleoside polymerase inhibitor
• Daratumumab - (Janssen) - for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double refractory to a PI and IMiD
• SD101 - (Scioderm) - topical cream for the treatment of inherited Epidermolysis Bullosa (EB)
• ABT-450* - (AbbVie) - interferon-free 3-DAA treatment of Hepatitis C tested both with and without ribavirin *combination of ABT-450 with two other drugs, ABT-267, an NSA5 inhibitor, and ABT-333, a non-nucleoside polymerase inhibitor
• Obinutuzumab - (Genetech) - for the treatment of chronic lymphocytic leukemia (CLL)
• Sebelipase Alfa - (Synageva) - for the treatment of early onset lysosomal acid lipase deficiency (LAL deficiency)
• Asfotase Alfa - (Alexion Pharmaceutical) - for the treatment of patients with hypophosphatasia (HPP) whose first signs or symptoms occurred prior to 18 years of age, including perinatal-, infantile-, and juvenile-onset forms of the disease
• Serelaxin - (Novartis) - for the treatment of acute heart failure
• Drisapersen - (GlaxoSmithKline) - for the treatment of Duchenne muscular dystrophy (DMD) in ambulant and non-ambulant boys who carry dystrophin gene mutations amenable to exon 51 skipping
• BYM338 (bimagrumab) - (Novartis) - for the treatment of sporadic inclusion body myositis (sIBM)
• Sofosbuvir/ledipasvir combination - (Gilead) - for the treatment of Hepatitis C
• Firdapse (amifampridine phosphate) - (Catalyst Pharmaceutical) - for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) 
• Entinostat - (Syndax Pharmaceuticals) - in combination with exemestane for the treatment of metastatic ER-positive breast cancer in postmenopausal women who have progressed on hormonal therapy
• Arzerra (ofatumumab) - (Genmab A/S, GlaxoSmithKline) - in combination with chlorambucil for the treatment of previously untreated chronic lymphocitic leukemia (CLL) in patients for whom fludarabine-based therapy is inappropriate 
• Volasertib - (Boehringer Ingelheim) - for the treatment of previously untreated acute myeloid leukemia (AML) in patients over the age of 65
• Alectinib - (Roche) - for the treatment of non-small cell lung cancer 
• MK-5172/MK-8742 - (Merck) - for the treatment of Hepatitis C
• cPMP - (Alexion) - for the treatment of molybdenum cofactor deficiency (MoCD) type A

*As of September 30, 2013, FDA lists 92 total requests for Breakthrough designation, 27 requests granted, and 41 requests denied. FDA does not disclose information regarding specific drugs or sponsors. Currently, about one granted requests has not been publicly announced by their sponsors.

For more info:Frequently Asked Questions: Breakthrough Therapies

FY 2014 CDER BT Totals as of 10/25/13

source: FOCR

Novartis drug Ilaris® approved by FDA to treat active systemic juvenile idiopathic arthritis, a serious form of childhood arthritis

Novartis announced today that the US Food and Drug Administration (FDA) has approved Ilaris(canakinumab) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. Ilaris is the first interleukin-1 beta (IL-1 beta) inhibitor approved for SJIA and the only treatment approved specifically for SJIA that is given as a once-monthly subcutaneous injection. SJIA is a rare and disabling form of childhood arthritis characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood

This approval was based on two Phase III trials in SJIA patients, aged 2–19, showing significant improvement in the majority of Ilaris-treated patients. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15. In the open-label part of Study 2, 92 of 128 patients attempted corticosteroid tapering. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group 

Source: Novartis

New drug approved by US FDA for the treatment of COPD

The U.S. Food and Drug Administration today approved Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is also approved to reduce exacerbations of COPD in patients with a history of exacerbations. 

COPD is a serious lung disease that worsens over time. Symptoms can include chest tightness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD, according to the National Heart, Lung, and Blood Institute, and COPD is the third leading cause of death in the United States.

Breo Ellipta works by decreasing inflammation in the lungs and helping the muscles around the airways of the lungs stay relaxed to increase airflow and reduce exacerbations in patients with COPD.

“COPD is a serious disease that makes breathing difficult,” said Curtis Rosebraugh, M.D., M.P.H., director, Office of Drug Evaluation II, Center for Drug Evaluation and Research, FDA. “The availability of new long-term maintenance medications provides additional treatment options for the millions of Americans who suffer with COPD.”

Breo Ellipta is a combination of fluticasone furoate, an inhaled corticosteroid, and vilanterol, a long-acting beta2-adrenergic agonist (LABA). The safety and efficacy of Breo Ellipta were evaluated in 7,700 patients with a clinical diagnosis of COPD. Those treated showed improved lung function and reduced exacerbations compared to placebo.

The drug carries a boxed warning that LABAs increase the risk of asthma-related death. The safety and efficacy of Breo Ellipta in patients with asthma have not been established, and it is not approved for the treatment of asthma.

The FDA approved Breo Ellipta with a patient medication guide that includes instructions for use and information about the potential risks of taking the drug. Breo Ellipta should not be used as a rescue therapy to treat sudden breathing problems (acute bronchospasm) and is not recommended for people younger than 18 years.

Breo Ellipta may cause serious side effects, including increased risks of pneumonia and bone fractures. The most common side effects reported by patients using Breo Ellipta included inflammation of the nasal passage (nasopharyngitis), upper respiratory tract infection, headache, and oral candidiasis (thrush).

Breo Ellipta was developed by GlaxoSmithKline, Research Triangle Park, N.C., in collaboration with San Francisco-based Theravance.

Source: FDA

DCGI office Organizational Structure

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



 

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

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.”

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.”

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.

SALE OF BANNED DRUGS

Last week Pharmabiz reported about a series of raids conducted by the office of DCGI on pharmacy outlets in Delhi and Rajasthan for selling two of the banned drugs namely gatifloxacin and tegaserod. The officials stated to have seized huge stocks of the brands of these companies namely Lupin, Dr Reddy's, Sun Pharma, Cipla, Hetero Drugs, Torrent Pharma, Aristo Pharma, Intas and others. The inspectors of the Central Drug Standard Control Organization have conducted 135 raids in over 90 pharmacies in Delhi and Rajasthan. DCGI had banned gatifloxacin, an antibiotic and tegaserod, a chronic constipation drug for their adverse effects on last March 16. The order required the drug companies to withdraw their brands from the market with immediate effect. The decision to recall these drugs from the markets was on the basis of recommendations of the Drugs Technical Advisory Board. It is indeed surprising that these banned products continued to be sold in retail outlets even after three months of their ban. It is possible that the sales were taking place without the knowledge of the companies as most of the makers of these drugs are large and reputed companies. However, the manufacturers cannot pretend to be ignorant about such illegal sales of their products in the trade channels. Most of them have the monitoring system to track the sales of their products throughout the country.

Now, prior to the ban order of gatifloxacin and tegaserod in last March, DCGI had also banned drugs like nimesulide, cisapride, phenylpropanolamine and human placenta extracts for their adverse effects. These drugs have also been in the market for last many years and belonged again to large companies. The manufacturers, shortly after the ban, moved Madras High Court against the order and got an interim stay of the DCGI order and the case is pending in the court. CIPI, representing small drug units has, however, withdrawn its case against the ban from the Madras HC a few days ago. All these drugs have been already banned in developed nations, like the US, UK, Canada, Sweden, Denmark, Australia, New Zealand and Japan several years ago. What is being noticed in India for some time now is growing resistance from pharmaceutical companies to any withdrawal order from the regulatory authorities even if the drug is highly unsafe. One has to accept the fact that no drug is absolutely safe and all have side effects. Safety only means that the benefits of the drug outweigh the risks. Drug authorities worldwide grant marketing approval for drugs only after consideration of this principle of cost benefit. Continuation of marketing drugs with serious ADRs could be highly dangerous to the millions of patients who are taking them. Therefore, both the industry and trade have to cooperate with the regulatory authorities in withdrawing potentially harmful drugs from the market in public interest. And when the country’s most authoritative body recommends a ban on the basis of safety parameters, no pharmaceutical company has the moral ground to challenge such an action.

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.

DTAB recommendations to re-examine many FDCs likely to prolong issue further

Even as the sub-committee of the Drug Technical Advisory Board (DTAB) is meeting for two days from today, the vexed issue over Fixed Dose Combinations (FDC) is unlikely to be settled early, as being reiterated by the authorities.

The process of clearing the FDCs is going to be long-time affair as the sub-committee is scheduled to re-examine a number of FDCs already cleared by them earlier. Apart from this, the panel will also assess 64 FDCs, out of the remaining 80 FDCs to be covered, according to the agenda fixed for sessions spread on April 19 and 20.

The sub-committee will also examine six FDCs approved before 1988, as per the decision taken by it in the meeting held on October 1, 2008. They include dicyclomine+mefenamic acid+ paracetamol, dicyclomine + paracetamol + clinidium bromide, dicyclomine + paracetamol + clinidium bromide + chlordiazepoxide, mefenamic acid + dicyclomine, paracetamol + dicycloverine + mefenamic, and propranolol + Diazepam.

The meeting will re-examine a set of 22 FDCs for rationality, as per the recommendation of the meeting of DTAB. They fall in the categories of nutritionals, orthopaedics, and antihistamines. They have been already cleared by the expert panel, but the 57th meeting of the DTAB has directed re-examination of the same.

Likewise, another set of 16 FDCs will also be re-examined by the panel for rationality, as per the direction of the last DTAB meeting. These combinations are of antimicrobial with lactic acid bacillus and had been discussed by the sub-committee at its meeting on January 23 and 24.

Thus in total, the two-day meeting of the sub-committee has to clear 107 FDCs after examining the rationality. The recommendation by the DTAB for re-examination would further prolong the process of putting a final solution to the vexed issue of FDCs, though DCGI had recently claimed that the matter would be solved within one month.

Health Min denies reports of proposal to make registration of brands mandatory

The Health Ministry has categorically made it clear that there is no proposal under consideration of the Government to bring in amendment to the Drugs and Cosmetic Rules to make mandatory the registration of all brands of medicines by the manufacturers.

The clarification comes in the wake of reports that the Government was considering a proposal to make it mandatory for the drug manufacturers to register all their brands, with a view to avoid duplication of brands in the market.

“The Health Ministry has not considered any such proposal now to change the rules of the Drugs & Cosmetics Act in this regard,” a senior official of the ministry said.

Earlier reports, quoting Union Minister of State for Chemicals and Fertilizers Srikant Jena, had said the government was having such a proposal under consideration and there was need to regulate the duplication of brands to avoid confusion.

The Pharma Department is learnt to have also held discussions with some industry associations on suggesting ways to regulate brands and one of the ideas emerged was the mandatory registration. However, the administrative ministry of the D&C Act is Health and it has now ruled out such a move.

The idea of mandatory registration of brands has been under discussion for some time now, as the regulatory officials wanted to have a centralised database to streamline the process of issuing brand names. Sources said, even a direction in this regard had come from the Supreme Court a decade ago asking the regulatory authority to co-ordinate with the trade mark office, but no action could be initiated so far.

Officials held that there were many common brand names by different companies in the pharmaceutical market and consumers were getting confused. Besides, companies also have variants of existing brand that are strikingly similar to a different product with a view to cash on the popularity of the successful brand names

APDCA begins recalling of gatifloxacin, tegaserod formulations

The Andhra Pradesh Drugs Control Administration (APDCA) has initiated the process of recalling drugs that involve gatifloxacin and tegaserod formulations, following a gazette notification issued by the Ministry of Health and Family Welfare, dated March 16, 20011, banning these two drugs due to certain health risks.

The notification prohibited manufacturing, sale and distribution of these two drugs with immediate effect. The Drugs Controller General of India (DCGI) sent letters to all the state drugs controllers on March 28, 2011, asking them to ensure that the manufacturing licenses granted in the respective states for the manufacture of these drugs formulations are cancelled with immediate effect and the formulations recalled from the market on top priority. It has asked the state drugs controllers to direct the chemists and druggists in the respective states to stop the sale of these formulations with immediate effect and to return the unsold stocks to the manufacturers. The DCGI letter also states that safer alternatives of these formulations are available in the market.

It is learnt that state drugs control administration has directed all the drugs inspectors to start recalling these drugs from the market. It has also asked all the manufacturers and distributors to stop manufacturing and distribution of these drugs.

According to an APDCA official, gatifloxacin, an antibiotic, is marketed under various brand names such as Gatiflo, Gatri, Gatispan, Gatiquin, Gatigo, Biogat, Q-gat and Gatri-OZ by different companies. Gatifloxacin is also used in several eye drops available in the market. Gatifloxacin is also available as tablets and in various aqueous solutions for intravenous therapy. It is understood that the decision to ban gatifloxacin was because it posed higher health risks.

Tegaserod formulations are used for the management of irritable bowel syndrome and constipation and marketed under the brand name of Tegibs.

Pondicherry gets independent Drug Control Dept from April 1, P Rajkumar appointed DC

The first Drugs Control Department of Pondicherry came into existence on April 1 with P Rajkumar as the Drugs Controller (HoD). An official Gazette notification in this regard was made a few days ago.

The cabinet decision in respect of the formation of a separate drugs control department was taken in the cabinet meeting held on December 29, 2010, and subsequently it was approved by the governor in the first week of January this year.

It was in April last year that the health ministry of the Pondicherry government took the decision to form a separate department for drugs regulation after bifurcating the Food & Drugs Control Administration. Following it, the health minister of the state, E Valsaraj made a statement in the assembly that an independent department could help revamp and streamline the functions of the drug control administration effectively. Soon steps for the establishment of a new administration were taken and an official from pharmacy section of the FDA was appointed as the controlling authority.

The drugs controller said since his office has now got independent charge, from now on he will report directly to the health secretary. So far the department was under the control of the Director of Health Services.

Till 1989, doctors from medical services were handling the drugs control administration. After the amendment of Drugs & Cosmetics Act in 1989, the post of a controlling authority was not notified in the union territory and the charge was being handled either by the commissioner or by the additional commissioners. To fill this vacuum, in July 2010, the government made the present drugs controller as the controlling authority without mentioning the term ‘drugs controller’, but provided the statutory powers for controlling the entire department. Prior to this appointment, Rajkumar was acting as the state licensing authority.

According to him, the government has sanctioned four more posts of drug inspectors and one post of assistant drug controller. All these appointments will be made soon after the election. Currently the posts of drug inspectors are four, out of which one post in the head office is lying vacant. Two ADC offices will be functioning in Pondicherry from June and one each from Karakkal and Mahe. Proposal for an independent analytical laboratory is also under the consideration of the government.

From 1964, the food and drug control administration was functioning under one Director with separate staff and facilities using same offices in the four regions of the union territory. Even though the bifurcation has been effected already, the office of the drug control department will be functioning in the same premises of the directorate of health services, Rajkumar told Pharmabiz.