Wednesday, 31 July 2013

AXIS Clinicals goes global

AXIS Clinicals goes global
v  Starts largest CRO facility in Mexico spread over 4000m2
v  100-bed facility with modern bio-analytical & reference labs

Hyderabad, Jan. 15, 2013: AXIS Clinicals Group, a leading Clinical Research Organization (CRO) announces the commencement of it’s operations at Mexico. With this facility, AXIS Clinicals Group now has three centers spread in India & overseas and can offer clinical research solutions to global clients.

This new center is the largest CRO facility in Mexico with bio-analytical and reference labs all housed in the same building that is spread over 4000 sq meters. The Mexico center is a 100-bed clinical facility that can grow to 160-beds and has over 50 employees with eight doctors all recruited from prestigious local universities. Over 300 methods have been developed on a global basis including hormonal, oncology and biotechnological products. Separate ambulatory area and sampling area with reclining reposers are also some of the key facilities at the centre.

It is the only CRO facility in Northern Mexico City with a database of 5000 healthy volunteers, thus minimizing risk of cross participation. It has received the COFEPRIS license approval in record time and has four LCMS machines in its bio-analytical division with a capacity to go up to 15 LCMS. The centre is equipped to handle phase II-IV studies and has a database of 2000 investigators. It has already been contracted for 75 studies from multinational, big pharma clientele as well as large local Mexican laboratories. It is an active member of AMETA - Mexican CRO Industry Association.

AXIS Clinicals Limited, one of India’s leading CRO is committed to serving the biopharmaceutical industry by leveraging two powerful trends impacting the world of Clinical Research - globalisation and full spectrum offering. Established in September 2004, the company has completed over 1500 clinical studies, 300 ANDA studies and received 50 product approvals from regulatory agencies. The company facilities have been accredited by DCGI (Drugs Controller General, India), NABL (National Accreditation Board for Testing and Calibration Laboratories - ISO 15189:2003) and inspected by US-FDA, UK-MHRA, Brazil-ANVISA and France AFSSAPS and conforms to ICH and CDSCO-GCP & GLP Guidelines. For further details, please visit –

Wednesday, 13 March 2013

Facts about Generic Drugs

Today, nearly 8 in 10 prescriptions filled in the United States are for generic drugs. The use of generic drugs is expected to grow over the next few years as a number of popular drugs come off patent through 2015. Here are some facts about generic drugs:  

FACT: FDA requires generic drugs to have the same quality and performance as brand name drugs.  
When a generic drug product is approved, it has met rigorous standards established by the FDA with respect to identity, strength, quality, purity, and potency. However, some variability can and does occur during manufacturing, for both brand name and generic drugs. When a drug, generic or brand name, is mass-produced, very small variations in purity, size, strength, and other parameters are permitted. FDA limits how much variability is acceptable.  
Generic drugs are required to have the same active ingredient, strength, dosage form, and route of administration as the brand name product. Generic drugs do not need to contain the same inactive ingredients as the brand name product.   
The generic drug manufacturer must prove its drug is the same as (bioequivalent) the brand name drug. For example, after the patient takes the generic drug, the amount of drug in the bloodstream is measured.  If the levels of the drug in the bloodstream are the same as the levels found when the brand name product is used, the generic drug will work the same.  
Through review of bioequivalence data, FDA ensures that the generic product performs the same as its respective brand name product. This standard applies to all generic drugs, whether immediate or controlled release.  
All generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs, and the generic products must meet the same exacting specifications as any brand name product. In fact, many generic drugs are made in the same manufacturing plants as brand name drug products. 

FACT:  Research shows that generics work just as well as brand name drugs.
A study evaluated the results of 38 published clinical trials that compared cardiovascular generic drugs to their brand name counterparts. There was no evidence that brand name heart drugs worked any better than generic heart drugs.[1]  

FACT:    FDA does not allow a 45 percent difference in the effectiveness of the generic drug product.  
FDA recently evaluated 2,070 human studies conducted between 1996 and 2007. These studies compared the absorption of brand name and generic drugs into a person’s body. These studies were submitted to FDA to support approval of generics. The average difference in absorption into the body between the generic and the brand name was 3.5 percent[2]. Some generics were absorbed slightly more, some slightly less. This amount of difference would be expected and acceptable, whether for one batch of brand name drug tested against another batch of the same brand, or for a generic tested against a brand name drug. In fact, there have been studies in which brand name drugs were compared with themselves as well as with a generic. As a rule, the difference for the generic-to-brand comparison was about the same as the brand-to-brand comparison. 
Any generic drug modeled after a single, brand name drug must perform approximately the same in the body as the brand name drug. There will always be a slight, but not medically important, level of natural variability – just as there is for one batch of brand name drug compared to the next batch of brand name product. 

FACT: When it comes to price, there is a big difference between generic and brand name drugs. On average, the cost of a generic drug is 80 to 85 percent lower than the brand name product. 
In 2010 alone, the use of FDA-approved generics saved $158 billion, an average of $3 billion every week.[3] 

FACT: Cheaper does not mean lower quality.  
Generic manufacturers are able to sell their products for lower prices because they are not required to repeat the costly clinical trials of new drugs and generally do not pay for costly advertising, marketing, and promotion. In addition, multiple generic companies are often approved to market a single product; this creates competition in the market place, often resulting in lower prices. 

FACT: FDA monitors adverse events reports for generic drugs. 
The monitoring of adverse events for all drug products, including generic drugs, is one aspect of the overall FDA effort to evaluate the safety of drugs after approval. Many times, reports of adverse events describe a known reaction to the active drug ingredient.  
Reports are monitored and investigated, when appropriate. The investigations may lead to changes in how a product (brand name and generic counterparts) is used or manufactured.   

FACT:  FDA is actively engaged in making all regulated products – including generic drugs – safer.
FDA is aware that there are reports noting that some people may experience an undesired effect when switching from brand name drug to a generic formulation or from one generic drug to another generic drug. FDA wants to understand what may cause problems with certain formulations if, in fact, they are linked to specific generic products.   
FDA is encouraging the generic industry to investigate whether, and under what circumstances, such problems occur. The Agency does not have the resources to perform independent clinical studies and lacks the regulatory authority to require industry to conduct such studies. FDA will continue to investigate these reports to ensure that it has all the facts about these treatment failures and will make recommendations to healthcare professionals and the public if the need arises.  

[1] Kesselheim et al. Clinical equivalence of generic and brand name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21)2514-2526
[2] Davit et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009;43(10):1583-97.
[3] SAVINGS An Economic Analysis of Generic Drug Usage in the U.S., GPhA, September 2011, page 1.

Tuesday, 12 March 2013

The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective

The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective

The path a drug travels from a lab to your medicine cabinet is usually long, and every drug takes a unique route. Often, a drug is developed to treat a specific disease. An important use of a drug may also be discovered by accident.

For example, Retrovir (zidovudine, also known as AZT) was first studied as an anti-cancer drug in the 1960s with disappointing results. Twenty years later, researchers discovered the drug could treat AIDS, and Food and Drug Administration approved the drug, manufactured by GlaxoSmithKline, for that purpose in 1987.

Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA. The drugs that do must undergo the agency's rigorous evaluation process, which scrutinizes everything about the drug--from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured.

Stages of Drug Development and Review

Investigational New Drug Application (IND)--The pharmaceutical industry sometimes seeks advice from the FDA prior to submission of an IND.

Sponsors--companies, research institutions, and other organizations that take responsibility for developing a drug. They must show the FDA results of preclinical testing in laboratory animals and what they propose to do for human testing. At this stage, the FDA decides whether it is reasonably safe for the company to move forward with testing the drug in humans.

Clinical Trials--Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research.

IRBs approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study's objectives, and other details. IRBs make sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.

Phase 1 studies are usually conducted in healthy volunteers. The goal here is to determine what the drug's most frequent side effects are and, often, how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80.

Phase 2 studies begin if Phase 1 studies don't reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment--usually an inactive substance (placebo), or a different drug. Safety continues to be evaluated, and short-term side effects are studied. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300.

At the end of Phase 2, the FDA and sponsors try to come to an agreement on how large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA--right before a new drug application is submitted.
Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people.

Postmarket requirement and commitment studies are required of or agreed to by a sponsor, and are conducted after the FDA has approved a product for marketing. The FDA uses postmarket requirement and commitment studies to gather additional information about a product's safety, efficacy, or optimal use.

New Drug Application (NDA)--This is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for marketing in the United States. An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured.

When an NDA comes in, the FDA has 60 days to decide whether to file it so that it can be reviewed. The FDA can refuse to file an application that is incomplete. For example, some required studies may be missing. In accordance with the Prescription Drug User Fee Act (PDUFA), the FDA's Center for Drug Evaluation and Research (CDER) expects to review and act on at least 90 percent of NDAs for standard drugs no later than 10 months after the applications are received. The review goal is six months for priority drugs. (See "The Role of User Fees8.")

"It's the clinical trials that take so long--usually several years," says Sandra Kweder, M.D., deputy director of the Office of New Drugs in the CDER. "The emphasis on speed for FDA mostly relates to review time and timelines of being able to meet with sponsors during a drug's development," she says.

Drug Review Steps Simplified

  1. Preclinical (animal) testing.
  2. An investigational new drug application (IND) outlines what the sponsor of a new drug proposes for human testing in clinical trials.
  3. Phase 1 studies (typically involve 20 to 80 people).
  4. Phase 2 studies (typically involve a few dozen to about 300 people).
  5. Phase 3 studies (typically involve several hundred to about 3,000 people).
  6. The pre-NDA period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet.
  7. Submission of an NDA is the formal step asking the FDA to consider a drug for marketing approval.
  8. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed.
  9. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor's research on the drug's safety and effectiveness.
  10. The FDA reviews information that goes on a drug's professional labeling (information on how to use the drug).
  11. The FDA inspects the facilities where the drug will be manufactured as part of the approval process.
  12. FDA reviewers will approve the application or issue a complete response letter.

Supplemental Information About the Drug Approval Process 

Reviewing Applications
Though FDA reviewers are involved with a drug's development throughout the IND stage, the official review time is the length of time it takes to review a new drug application and issue an action letter, an official statement informing a drug sponsor of the agency's decision.

Once a new drug application is filed, an FDA review team--medical doctors, chemists, statisticians, microbiologists, pharmacologists, and other experts--evaluates whether the studies the sponsor submitted show that the drug is safe and effective for its proposed use. No drug is absolutely safe; all drugs have side effects. "Safe" in this sense means that the benefits of the drug appear to outweigh the known risks.

The review team analyzes study results and looks for possible issues with the application, such as weaknesses of the study design or analyses. Reviewers determine whether they agree with the sponsor's results and conclusions, or whether they need any additional information to make a decision.
Each reviewer prepares a written evaluation containing conclusions and recommendations about the application. These evaluations are then considered by team leaders, division directors, and office directors, depending on the type of application.

Reviewers receive training that fosters consistency in drug reviews, and good review practices remain a high priority for the agency.

Sometimes, the FDA calls on advisory committees, who provide FDA with independent opinions and recommendations from outside experts on applications to market new drugs, and on FDA policies.  Whether an advisory committee is needed depends on many things.

"Some considerations would be if it's a drug that has significant questions, if it's the first in its class, or the first for a given indication," says Mark Goldberger, M.D., a former director of one of CDER's drug review offices. "Generally, FDA takes the advice of advisory committees, but not always," he says. "Their role is just that--to advise."

Accelerated Approval
Traditional approval requires that clinical benefit be shown before approval can be granted. Accelerated approval is given to some new drugs for serious and life-threatening illnesses that lack satisfactory treatments. This allows an NDA to be approved before measures of effectiveness that would usually be required for approval are available.

Instead, less traditional measures called surrogate endpoints are used to evaluate effectiveness. These are laboratory findings or signs that may not be a direct measurement of how a patient feels, functions, or survives, but are considered likely to predict benefit. For example, a surrogate endpoint could be the lowering of HIV blood levels for short periods of time with anti-retroviral drugs.

Gleevec (imatinib mesylate), an oral treatment for patients with a life-threatening form of cancer called chronic myeloid leukemia (CML), received accelerated
approval. The drug was also approved under the FDA's orphan drug program, which gives financial incentives to sponsors for manufacturing drugs that treat rare diseases. Gleevec blocks enzymes that play a role in cancer growth. The approval was based on results of three large Phase 2 studies, which showed the drug could substantially reduce the level of cancerous cells in the bone marrow and blood.

Most drugs to treat HIV have been approved under accelerated approval provisions, with the company required to continue its studies after the drug is on the market to confirm that its effects on virus levels are maintained and that it ultimately benefits the patient. Under accelerated approval rules, if studies don't
confirm the initial results, the FDA can withdraw the approval.

Because premarket review can't catch all potential problems with a drug, the FDA continues to track approved drugs for adverse events through a postmarketing surveillance program.

Bumps in the Road
If the FDA decides that the benefits of a drug outweigh the known risks, the drug will receive approval and can be marketed in the United States. But if there are problems with an NDA or if more information is necessary to make that determination, the FDA may issue a complete response letter. 
Common problems include unexpected safety issues that crop up or failure to demonstrate a drug's effectiveness. A sponsor may need to conduct additional studies--perhaps studies of more people, different types of people, or for a longer period of time.

Manufacturing issues are also among the reasons that approval may be delayed or denied. Drugs must be manufactured in accordance with standards called good manufacturing practices, and the FDA inspects manufacturing facilities before a drug can be approved. If a facility isn't ready for inspection, approval can be delayed. Any manufacturing deficiencies found need to be corrected before approval.

"Sometimes a company may make a certain amount of a drug for clinical trials. Then when they go to scale up, they may lose a supplier or end up with quality control issues that result in a product of different chemistry," says Kweder. "Sponsors have to show us that the product that's going to be marketed is the same product that they tested."

John Jenkins, M.D., director of CDER's Office of New Drugs, says, "It's often a combination of problems that prevent approval." Close communication with the FDA early on in a drug's development reduces the chance that an application will have to go through more than one cycle of review, he says. "But it's no guarantee."

The FDA outlines the justification for its decision in a complete response letter to the drug sponsor and CDER gives the sponsor a chance to meet with agency officials to discuss the deficiencies. At that point, the sponsor can ask for a hearing, correct any deficiencies and submit new information, or withdraw the application. 
The Role of User Fees

Since PDUFA was passed in 1992, more than 1,000 drugs and biologics have come to the market, including new medicines to treat cancer, AIDS, cardiovascular disease, and life-threatening infections. PDUFA has allowed the Food and Drug Administration to bring access to new drugs as fast or faster than anywhere in the world, while maintaining the same thorough review process.

Under PDUFA, drug companies agree to pay fees that boost FDA resources, and the FDA agrees to time goals for its review of new drug applications. Along with supporting increased staff, drug user fees help the FDA upgrade resources in information technology. The agency has moved toward an electronic submission and review environment, now accepting more electronic applications and archiving review documents electronically.

The goals set by PDUFA apply to the review of original new human drug and biological applications, resubmissions of original applications, and supplements to approved applications. The second phase of PDUFA, known as PDUFA II, was reauthorized in 1997 and extended the user fee program through September 2002. PDUFA III, which extended to Sept. 30, 2007, was reauthorized in June 2002.

PDUFA III allowed the FDA to spend some user fees to increase surveillance of the safety of medicines during their first two years on the market, or three years for potentially dangerous medications. It is during this initial period, when new medicines enter into wide use, that the agency is best able to identify and counter adverse side effects that did not appear during the clinical trials.

On September 27, 2007, President Bush signed into law the Food and Drug Administration Amendments Act of 2007 which includes the reauthorization and expansion of the Prescription Drug User Fee Act. The reauthorization of PDUFA will significantly broaden and upgrade the agency's drug safety program, and facilitate more efficient development of safe and effective new medications for the American public.

In addition to setting time frames for review of applications, PDUFA sets goals to improve communication and sets goals for specific kinds of meetings between the FDA and drug sponsors. It also outlines how fast the FDA must respond to requests from sponsors. Throughout a drug's development, the FDA advises sponsors on how to study certain classes of drugs, how to submit data, what kind of data are needed, and how clinical trials should be designed.

The Quality of Clinical Data
The Food and Drug Administration relies on data that sponsors submit to decide whether a drug should be approved. To protect the rights and welfare of people in clinical trials, and to verify the quality and integrity of data submitted, the FDA's Division of Scientific Investigations (DSI) conducts inspections of clinical investigators' study sites. DSI also reviews the records of institutional review boards to be sure they are fulfilling their role in patient protection.

"FDA investigators compare information that clinical investigators provided to sponsors on case report forms with information in source documents such as medical records and lab results," says Carolyn Hommel, a consumer safety officer in DSI.

DSI seeks to determine such things as whether the study was conducted according to the investigational plan, whether all adverse events were recorded, and whether the subjects met the inclusion/exclusion criteria outlined in the study protocol.

At the conclusion of each inspection, FDA investigators prepare a report summarizing any deficiencies. In cases where they observe numerous or serious deviations, such as falsification of data, DSI classifies the inspection as "official action indicated" and sends a warning letter or Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE) to the clinical investigator, specifying the deviations that were found.

The NIDPOE begins an administrative process to determine whether the clinical investigator should remain eligible to receive investigational products and conduct clinical studies.

CDER conducts about 300-400 clinical investigator inspections annually. About 3 percent are classified in this "official action indicated" category.

The FDA has established an independent Drug Safety Oversight Board (DSOB)3 to oversee the management of drug safety issues. The Board meets monthly and has representatives from three FDA Centers and five other federal government agencies. The board's responsibilities include conducting timely and comprehensive evaluations of emerging drug safety issues, and ensuring that experts--both inside and outside of the FDA--give their perspectives to the agency. The first meeting of the DSOB was held in June 2005. 

Saturday, 2 February 2013

AXIS Clinicals announces Dr. Yati Chugh as CEO

AXIS Clinicals announces Dr. Yati Chugh as CEO 

Hyderabad, Jan. 15, 2013: AXIS Clinicals Group, a leading global Clinical Research Organization (CRO) announces the appointment of Dr. Yati Chugh as the Chief Executive Officer of AXIS Clinicals Limited. Dr. Chugh assumes the responsibility for overall activities of AXIS Clinicals Group companies with presence in India, Thailand and Mexico. Under his able leadership and guidance, AXIS Clinicals team will ensure that services are offered to partners with dedication, commitment, quality and performance.

Dr. Chugh brings over two decades of experience in conducting pre-clinical, Bioequivalence / Bioavailability (BA/BE) studies and clinical research. He has extensive experience in areas of CNS, CVS, drug metabolism / pharmacokinetics and clinical pharmacology.  

“As AXIS Clinicals is one of the leading CRO’s of the country, that provides clinical studies on both male and female healthy patient population in virtually all therapeutic areas, I am looking forward to our continued leadership in delivering the AXIS Advantage of timely deliveries, accuracy and quality in accordance to global standards to our clients & partners,” Dr. Yati Chugh, CEO said. “Our fundamental focus is to provide our customers a complete clinical research portfolio under one roof that will help them achieve the competitive advantage needed in staying ahead,” he added.

Dr. Chugh holds a doctorate degree from PGIMER, Chandigarh and has published about 45 scientific papers in reputed national and international peer-reviewed journals. He has completed his Master’s and Ph.D in pharmacology from PGIMER, Chandigarh and graduated in B.Pharm from Department of Pharmaceutical Sciences, Punjab University, Chandigarh. He has about 25 patents to his credit and is a member of all the major international bodies of pharmacology and is a reviewer in major Journals of Pharmacology.

Prior to joining AXIS Clinicals, Dr. Chugh was heading Lotus Labs as Managing Director. He has been associated with several reputed biopharmaceutical companies like Wockhardt, Intas Pharmaceuticals, Torrent Pharmaceuticals Limited for over two decades.

About AXIS Clinicals

AXIS Clinicals Limited, one of India’s leading CRO is committed to serving the biopharmaceutical industry by leveraging two powerful trends impacting the world of Clinical Research - globalisation and full spectrum offering. Established in September 2004, the company has completed over 1500 clinical studies, 300 ANDA studies and received 50 product approvals from regulatory agencies. The company facilities have been accredited by DCGI (Drugs Controller General, India), NABL (National Accreditation Board for Testing and Calibration Laboratories - ISO 15189:2003) and inspected by US-FDA, UK-MHRA, Brazil-ANVISA and France AFSSAPS and conforms to ICH and CDSCO-GCP & GLP Guidelines. For further details, please visit –

For further details, contact:
Shankar Chelluri, S Paradigm Consultants, PH: +91.99490.93501