PMI Petition - Cont.

As a general matter, the FDA is involved in preclinical research as well as all three Phases of clinical research. The FDA should seek comment on which, if any, of these activities should be exempt from regulation for Precision Medicine Initiatives. Commenters should also be encouraged to translate their recommendations into tangible costs and benefits to be compared to those emanating from the status quo regulatory scheme.

C. Conditional Approvals

The FDA could choose an approach for PMIs that involves surveillance only, with conditional approval after clinical trials (provided that no deaths or significant adverse results were reported in the trials).

Such an approach would rely on the fact that Title 21 does not give the FDA to regulate the practice of personalized medicine, which rests with the states and medical professional associations.

The use of conditional approvals would impose significant reporting obligations on PMIs to provide comprehensive information to personal medical providers and it would also put extensive reporting obligations on the sponsors to track performance in commerce. After a certain amount of time such as two years had passed, the conditional approval could become final, if warranted by the real-world performance as certified by personal medical providers.

D. A New Market-Based Process

The FDA should seek comment on regulations designed to improve private capital formation for research and development of Precision Medicine Initiatives targeted to small populations without compromising consumer safety.

One such approach is as follows:

i) The FDA’s role in preclinical research would be limited to surveillance.

ii) Each pre-approved, qualified professional research organization filing a Phase I PMI drug application would receive a provisional license from the FDA within 60 days from the time it provided the details of its trial and put a corresponding deposit into an escrow account.

Likewise, applications for Phase II and Phase III trials would also be subject to a 60 day review cycle and would require additional funds to be deposited into an escrow account, the amount of which would be subject to the size of the trials. A sample deposit schedule follows:

Phase I – $25,000 per trial participant

Phase II – $10,000 per trial participant

Phase III – $5,000 per trial participant

The above schedule would produce escrowed deposits as follows: 

                     Number of          Incremental                     Cumulative

                     Participants           Deposits                           Deposits

Phase I                20 – 40        $0.5M – $1M                 $0.5M – $1M

Phase II           100 – 200           $1M – $2M                  $1.5M -$3M

Phase III      1000 – 3000        $5M – $15M               $6.5M – $18M

The FDA could reduce the above deposits for special considerations. Alternatively, the deposit schedule could vary according to the size of the target audience.

iii) An industry organization would be required to provide regular reports to the FDA for purposes of PMI oversight (along with the reports provided by individual research organizations with the results of each phase of its trial). This industry organization would have the authority and responsibility to audit individual trial results and to maintain a secure whistle blower system.  A reward would be paid to whistle blowers whose efforts led to the successful prosecution of fraud by a licensee.

iv) The FDA would have the authority and obligation to stop the sale of any new drug, procedure or device that it believed was unfit for human application.  If a company were found to be in violation of the FDA’s guidelines, the company would lose its license and forfeit its escrowed funds.

v) Research organizations would be required to maintain and submit relevant health statistics on patients for two years from commercial launch.  Sixty days after such filings, the FDA would issue a commercial license (if warranted by the real-world experience) and the escrowed funds would be returned.

Likewise, if the research organization voluntarily abandoned its program during development, the deposit would also be refunded.

Such an approach would place the risk, pace and costs of both pre-clinical research and clinical trials principally under the control of qualified research organizations.  The effect would be greater funding opportunities for the private sector to pursue promising research opportunities.

In addition, this approach would put the proper incentives and penalties in place to forestall the introduction of unsafe products to the public.

The FDA should request commenters to attempt to quantify the costs and benefits to consumers of such a market-based approach compared to applying the status quo regulatory approach to Precision Medicine Initiatives.

VI. Statement of Legal Grounds

This Petition is being filed pursuant to Title 21 of the Code of Federal Regulations, Sections 10.30 and 10.33.

The FDA has the power to issue an Advance Notice of Proposed Rulemaking subject to the Administrative Procedures Act and the broad discretion afforded to it by Title 21.

Since 1906, Congress has passed over 200 laws creating a framework to empower the FDA to act on behalf of the public’s health and well-being.

These laws do not provide an explicit formula for drug safety analysis or thresholds of efficacy. Rather the FDA must balance the risks and benefits in determining whether to approve a drug according to the regulations that it implements. 

By the same token, the FDA cannot take away an individual’s rights under the 5th Amendment of the United States Constitution to receive state-of-the-art medical care. In this regard, the Courts have identified the relevant factors to consider for such taking, including the economic impact of the regulation, the degree to which the regulation interferes with investor-backed expectations, and the character of the government action. All of these factors are at play in the context of the President’s Precision Medicine Initiatives and the associated FDA’s regulations.

VII. Conclusion

President Obama kicked off the Precision Medicine Initiative with the promise of revolutionizing how we treat disease and improve the health of people in this country.

Unfortunately, as presently constituted, it appears that the FDA’s drug approval procedures will have the unintended effect of preventing most Precision Medicine Initiatives from legally entering interstate commerce. 

Accordingly, the FDA should issue an Advance Notice of Proposed Rulemaking seeking comment on the impact of applying the FDA’s current drug approval procedures to Precision Medicine Initiations as well as soliciting thoughtful analysis of the alternative procedures.

VIII. Environmental Impact

The action requested is subject to a categorical exclusion and therefore does not require the preparation of an environmental assessment.

IX. Economic Impact

No statement of economic impact of the requested action has been requested at this time.

X. Certification

The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner that are unfavorable to the petition.

Respectfully submitted,


Steven A. Zecola