Statutory Requirements for new drug approval in 2016:

  1. Substantial evidence of effectiveness for treatment of the proposed indication.
  2. Benefits for proposed population outweigh risks
  3. Manufacturing that ensures product identity, strength, quality (purity)
  4. Evidence-based drug labeling that adequately guides providers and patients to use the drug safely and effectively


Substantial Evidence of Effectiveness will continue to be a requirement, and demonstration of substantial evidence of effectiveness requires studies designed well enough and quoting 21CFR 314.50 and 21CFR 314.126: “to distinguish the effect of a drug from other influences, such as random phenomenology, spontaneous change, the placebo effect, or biased observation”  The Usual approval standard is two adequate and well-controlled studies


To A Degree, Flexibility Is Part of FDA Regulation Paradigm (21 CFR 314 (APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG)

  1. Regulations allow for flexibility and judgment in applying the standards, and the FDA has a solid record of appropriately applying regulatory flexibility.


“While the statutory standards apply to all drugs… the many kinds of drugs… and wide range of uses for those drugs demand flexibility in applying the standards.

Thus FDA is required to exercise its scientific judgment to determine the kind and quantity of data and information an applicant is required to provide for a particular drug to meet the statutory standards.” (21 CFR 314.105 Approval of an Application)


medical devices and expert scientist


How Much Evidence Is Enough to Obtain FDA Approval?

FDA may consider “data from one adequate and well‐controlled clinical investigation and confirmatory evidence” to constitute substantial evidence

(FDA Modernization Act (FDAMA))  However, flexibility in FDA regulations does not mean marketing approval prior to demonstration of substantial evidence of effectiveness.

Still unclear? Speak to a Medical Saftey Officer and FDA Regulations Expert.


Four Programs Exist to Expedite Drug Development for Certain Types of New Drug Applications (Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics, May 2015)


  1. Fast Track Designation FDAMA /FDASIA 2012
  2. Breakthrough Therapy Designation FD&C Act/FDASIA 2012
  3. Priority Review PDUFA 1992
  4. Accelerated Approval 21CFR314 subpart H, 601 subpart E/FDASIA 2012

These four programs have been utilized as follows over the past year: (October 2015 – 03 October 2016)


    • 17 Approvals for Rare Disease Indications (10 for were for oncology indications)
    • 7 BLAs and 10 NDAs
    • 8 Designated as Breakthrough Therapy
    • 2 Received a Rare Pediatric Disease Priority Review Voucher
    • 6 Received Accelerated Approval  (4 of those 6 were for oncology Indications)
    • 1 Employed a novel End Point
    • 12 Approved with fewer than 2 Adequate and Well Controlled Trials


Two pathways exist for FDA Drug Approval

  • Accelerated approval
  • Traditional approval


Accelerated approval is not about faster review – it is a regulatory pathway to speed availability of drugs for serious unmet need by using an appropriate, more readily measured, surrogate or intermediate clinical endpoint when a lengthy trial would be needed to measure direct clinical benefit of a drug


In accelerated approval, the candidate drug must provide a meaningful advantage over available therapies to treat a serious condition, generally irreversible morbidity or mortality.


  • Relies on a more readily measured surrogate or intermediate clinical endpoint
  • A post-approval confirmatory study to further define clinical benefit is generally required


Clinical vs. Surrogate Endpoints

  1. Clinical endpoint: characteristic or variable that directly measures a therapeutic effect – how a patient feels, functions, or survives
  2. Surrogate endpoint for accelerated approval: marker thought reasonably likely to predict clinical benefit; not itself a measure of benefit

Need more information? Get a free consultation with a Clinical Trial Expert who can help with trials, testimonies, depositions, and any other questions.