GLG News by Council Members in the U.S. who are Familiar with Regulations Pertaining to Andrx Corporation's Form 483

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

Risk/Benefit is the Answer, Even More Now

December 22, 2008

Analysis of:Tysabri - Multiple Sclerosis patient with progressive multifocal leukoencephalopathy has died | www.msrc.co.uk

1. In general, the more pharmacologically potent a therapy, the more the possibllity that adverse experiences will be seen. 2. Risk/Beneift is a critical consideration, even for products intented for serious or life-threatening disease. It is incumbent upon both the FDA and the physician community to realistically assess preclnical and clinical data during the review and approval process. 3. Patients must be fully and competently informed of the risks and benefits of such therapies and have the right to decide for themselves whether or not to participate in clinical trials and therapeutic treatment with marketed products. 4. No therapeutic regimen is risk-free and society needs to understand and embrace this fact.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

A Complex Personal and Societal Issue

July 17, 2008

Analysis of:Costly Cancer Drug Offers Hope, but Also a Dilemma | www.nytimes.com

The issues associated with expensive therapeutics are multifaceted and involve personal, professional and societal components. Value related to medical treatment is uniquely assessed by each individual with respect to his/her financial burden, overall lifestyle and quality of life, societal role, and belief structure. Society itself is beset with contrary stakeholders in the insurance, governmental, medical and belief-centered establishments. This article is important in that it lays out some fundamental questions that wealthy countries face with respect to cost vs. benefit for new therapies in an environment relatively little constrained by cost-containment in the medical arena.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

A Word to the Wise...

July 8, 2008

Analysis of:Drug Makers Say FDA Safety Focus Is Slowing New-Medicine Pipeline | online.wsj.com

1. Sponsors need to be "squeaky clean" with respect to their assessment of signals of toxicity in drug develpment programs. 2. This assessment should be made at the preclinical and early clinical stages of the process, irrespective of political and financial considerations. 3. The per cent of failures in Phase 2 and 3 will be higher unless programs are honestly and thoroughly assessed according to the above. Even so, there will likely be more failures in late-stage programs as clinical data are generated. The FDA will spend more time and effort on safety assessment to avoid large populations being exposed in the marketing environment to new drugs.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

Just a Matter of Time

April 1, 2008

Analysis of:The Drug Scare That Exposed a World of Hurt | www.nytimes.com

Overseas manufacturing controls for both APIs and finished drug products will need to be improved and the FDA will closely monitor compliance in an increased fashion. Drug regulation itself is not likely to change, but more inspections and more thorough review of DMFs and information submitted in support of late-stage INDs and NDAs/BLAs will occur. The FDA has been lax in assuring that the veritable explosion of outsourcing of raw material and API manufacture to third-world and emerging nations has been closely monitored for compliance with purity, potency and other requirements.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

But What Does it Mean for The Patient in the Real Clinical Arena?

November 13, 2007

Analysis of:NicOx' Naproxcinod ABPM Data Presented At American Heart Association | www.medicalnewstoday.com

1. The results are intriguing, but the clinical relevance for the large number of patients who could be exposed in the real-life clinical situation is uncertain. 2. The hypotheses for thsi program early-on seem to be supported by the phase 3 data to date, i.e., the nitro-comopounds may have actions that are different than their parent compounds. 3. It will be inteesting to see across finished studies what the actual effects on blood pressure may be.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

The Start of an Exciting, But Long Road

November 13, 2007

Analysis of:SNTA: Patients Treated in Ph III Trial of Elesclomol for Metastatic Melanoma | www.therapeuticsdaily.com

1. Metastatic melanoma in Stage IV is difficutl to treat. 2. Previous interventions have proven almost worthless 3. The succesful SPA agreement is an important regulatory step for the program. 4. Data will take years to develop, validate, and translate into an approved product.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

What this means for the present course and future of the program.

October 24, 2007

Analysis of:FDA Removes Partial Hold on TELCYTA Clinical Development | www.prnewswire.com

This announcement indicates that clinical development can now proceed under the IND for all outstanding and recently submitted protocols. It does not mean that the initial reason for clinical hold has been fully satisfied throughout the rest of the clinical development program. That will be dtermined by the data emergent results from the clinical tirals and any ongoing or planned preclinical studies. Likely there was a safety issue, either clinicaly or nonclinical that caused the hold. Future work may be needed to assure that the program can proceed to substantial evidence trials.

Evan SiegelAdjunct Professor THE UNIVERSITY OF QUEENSLAND

Lessons for Product Profile Creation

October 24, 2007

Analysis of:Pfizer Abandons Exubera, Posts 77% Earnings Decline | online.wsj.com

The user-friendly and health care provider comfort aspects of an product with otherwise proven safety and efficacy must be considered when deciding how, when, and in what manner to develop f drug product. Despite the desirability of a non-injectibel insulin, the inhaled route of administration and acceptability of the formulation must be carefully examined in the real-world, and not just clinical trial, environments. This firm, despite its long history and expertise, missed the boat.