FDA issues guidance on pre-market approval applications

July 28, 2008

Four different types of action by the FDA can affect the agency’s review time for pre-market approval applications (PMA).

All four actions stop the review clock, or the period of time allowed for FDA review. In recently updated guidance, FDA and Industry Actions on Premarket Approval Applications (PMAs): Effect on FDA Review Clock and Goals, the FDA explained what the actions are and what is needed to resolve problems and restart the review. The actions include:

  • Approvable orders, which require the applicant to resolve deficiencies in a PMA.
  • Major deficiency letters, which require the applicant to supply significant information that is missing from the application.
  • Not approvable letters, for items the FDA believes cannot be approved, which keep the application on hold while the applicant is given the opportunity to respond. The agency generally issues these only after sending a major deficiency letter and giving the applicant a chance to respond.
  • Denial letters, which the agency issues when the review is complete.

The guidance also discusses the review cycle and performance goals the FDA has for processing both expedited and non-expedited PMAs and supplements. Finally, the guidance addresses the various actions applicants can take after submitting an application, including:

  • Making unsolicited major amendments that introduce substantial new data
  • Making solicited major amendments in response to an FDA request in a deficiency letter or not approvable letter
  • Clarifying already submitted data with minor amendments
  • Withdrawing the application

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FDA Rule and Companion Guidance Make Early Stage Clinical Drug Development Safe and Efficient

July 28, 2008

The U.S. Food and Drug Administration today issued a final regulation that makes early phase 1 clinical drug development safe and efficient by enabling a phased approach to complying with current good manufacturing practice (CGMP) statutes and FDA investigational requirements.

To facilitate this new approach, the regulation exempts most phase 1 investigational drugs from the requirements in 21 CFR part 211 — FDA will continue to exercise oversight of the manufacture of these drugs under FDA’s general statutory CGMP authority and through review of investigational new drug (IND) applications.

A companion guidance recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, as well as testing, stability, packaging, labeling, distribution, and recordkeeping.

“With this action, we are tailoring the CGMP requirements to make them appropriate to the earliest stages of drug development. This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection,” said U.S. Health and Human Services Deputy Secretary Tevi Troy.

When FDA originally issued CGMP regulations for drug and biological products (21 CFR parts 210 and 211), the agency stated that the regulations applied to all types of pharmaceutical production, but explained in the preamble to the regulations that FDA was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials. The reason for this is that certain requirements in part 211 are directed at the commercial manufacture of products — such as repackaging and relabeling of drug products, rotation of stock, and maintaining separate facilities for manufacturing and packaging.  These types of requirements may be inappropriate to the manufacture of investigational drugs used in phase 1 clinical trials, many of which are carried out in small-scale, academic environments, typically involving fewer than 80 subjects.

“The new rule and guidance are intended to assure that manufacturers meet high standards for the safety of phase 1 drugs and biologics while removing unnecessary barriers that can slow the development of these potentially life-saving products,” said Rachel Behrman, M.D., associate commissioner for clinical programs and director of FDA’s Office of Critical Path Programs.

The guidance, CGMP for Phase 1 Investigational Drugs, describes an approach manufacturers can use to implement manufacturing controls that are appropriate for the phase 1 clinical trial stage of development. The approach described in this guidance reflects the fact that some manufacturing controls and the extent of manufacturing controls needed to achieve appropriate product quality differ among the various phases of clinical trials.

Manufacturers will continue to submit detailed information about relevant aspects of the manufacturing process as part of the IND application. The FDA may inspect the manufacturing operation, suspend a clinical trial by placing it on “clinical hold,” or terminate the IND if there is evidence of inadequate quality control procedures that would compromise the safety of an investigational product.

To find the Guidance for Industry, CGMP for Phase 1, Investigational Drugs, visit: http://www.fda.gov/cder/guidance/GMP%20Phase1IND61608.pdf

To find Current Good Manufacturing Practice and Investigational New Drugs Intended for Use in Clinical Trials/Final rule:  http://www.fda.gov/OHRMS/DOCKETS/98fr/oc07114.pdf


First arrest in Ahmedabad blasts case

July 28, 2008

An activist of the banned militant outfit — Ahle Hadeez — was today (July 27) arrested in connection with the serial blasts in Ahmedabad, which was on the edge with a live bomb in the city being defused and another three found in Surat city as the death toll rose to 49. The arrested activist, identified as Abdul Halim and wanted in connection with 2002 post-Godhra riots, was picked up by the police from the communally sensitive Dani Limda area in the walled city. Meanwhile, in New Delhi, Home Minister Shivraj Patil chaired a high-level meeting to review the situation in the country and assured all possible help to the Gujarat government.


Ahmedabad after Bangalore: Glaring lapses

July 28, 2008
An audacious attack in Ahmedabad, barely a day after serial blasts in India’s IT capital Bangalore, leads us to several obvious questions.

Is India now a sitting duck for terrorists? What is causing these men to attack India at will and get away with it?

Also, what about the role of intelligence agencies and the network formed to be in the know of any such attacks?

How could Ahmedabad be targeted hours after Bangalore?

What lessons have we learnt from similar attacks in the past and why have there been no conclusive breakthroughs?

There are more questions than answers.

Let us take a look at the first intelligence lapse that occurred. The Gujarat blasts took place within hours of nationwide alert after Bangalore blasts.

How could 16 bomb blasts take place in Ahmedabad when the entire country was on high alert?

In Ahmedabad, most bombs were placed on cycles and went off within a short time span like in Bangalore, Jaipur, Uttar Pradesh and Malegaon.

The second lapse was that the groups of serial bombers could not be traced.

It takes several people to carry out a serial blast, so how come they can’t be traced? And even those who provide them logistical support like houses, phones and transport could not be traced.

Modi and Gujarat are prime targets of the terror since the 2002 riots. How could intelligence agencies not even get a whiff of such an elaborate network? This was the third lapse on the part of the intelligence.

For the last three years, terrorists have been making minimal use of telecommunication devices before and after each strike, making it difficult for security agencies to track them.

Had there been a strong human intelligence network or local policing, things would have been easier. And this constitutes the fourth lapse.

And People like A S Dullat, former secretary of RAW and director of Intelligence Bureau, who have spent their entire life tracking terror, feel something is definitely wrong.

“It is very evident that there is an intelligence failure. I think there is a need to do a threat assessment of metros. For instance, leaders and state governments should take terror more seriously and not just depend on what is given to them,” said Dullat.

Under pressure, this is exactly what the Centre intends to do. Home Minister Shivraj Patil will meet chief ministers of all states, hoping to push through police modernisation and reforms. The Intelligence Bureau too will be upgraded.

Police reforms would in no doubt help but the big question is whether states would agree and more importantly how long will it take?