Accelerated approval

Accelerated approval of drugp is offered by die FDA as a means to make promising products for life-direatening diseases available on die market, based on preliminary evidence before formal demonstration of patient benefit. 

For drugs approved under accelerated approval regulations on the basis of a surrogate endpoint or an endpoint other than survival or irreversible morbidity, FDA may require a Phase IV study to confirm the drug s efficacy. Failure to show efficacy may result in withdrawal of approval. 

When some pharmaceutical products are approved, the FDA will ask the manufacturer to commit to postmarketing phase IV studies. These studies are mandatory for accelerated approval of products to treat serious and life-threatening illnesses ("fast-track" products) and deferred pediatric studies where safe use in children needs to be clarified. Other studies may be requested by the FDA before or after granting marketing approval if the FDA concludes that additional information is important to the prescribing and use of the product. 

FDA is able to rely on less well-established surrogates for accelerated approval of drugs that provide meaningful benefits over existing therapies for serious or life-threatening illnesses, such as AIDS, rare carcinomas, or breaking infectious diseases. In these cases, the... 

The mechanism by which the cytotoxic agents were approved is of inferest. Many were approved on fhe basis of response rafe as a surrogafe for survival (e.g., via the accelerated approval path). - Of nofe is the development of fhe cytotoxic agents, capecitabine received initial accelerated approval on the basis of fhe surrogafe endpoint of response rate in patients with refractory breast cancer. This was later followed up with a randomized Phase 111 trial of docetaxel wifh or withouf capecifabine in patienfs with refractory breast cancer with this trial demonstrating an improvement in survival for the combination of docetaxel + capecitabine vs. docetaxel alone. ... 

The DNA-interactive agent oxaliplatin had a slightly different trial design leading to accelerated approval and that was used as a comparator (oxaliplatin and fluorouracil + leucovorin vs. fluorouracil + leucovorinj. The approval was on the basis of response rate but additional studies clearly demonstrated that oxaliplatin improved survival and indeed in an adjuvant setting led to a significant increase in disease-free survival (78.2% disease-free survival at 3 years vs. 72.99%, p = 0.002). ... 

Campath was given accelerated approval on the basis of response rate. The pivotal trial was a study in 93 pahents who had been previously treated with an alkylating agent and whose disease had progressed on treatment with fludarabine. The FDA requested a follow-up sfudy for full approval of Campafh by randomizing patients between Campath and chlorambucil (Leukeran) as front-line therapy This trial is ongoing. Thus, Campath has had a convenhonal development approach. 

Cleevec was the first of the tyrosine kinase inhibitors approved via an accelerated approval for patients with CML (accelerated, chronic, and blast crisis phases). This approval was based on three Phase II trials. ° i... 

Dagher, R. et al.. Accelerated approval of oncology products a decade of experience, /. Natl. 

Gleevec was approved by the FDA under the accelerated approval regulations for the treatment of CML. 

The CTDs were implemented in July 2003. They are format-based documents for submission to the regulatory authorities the country-specific process of review, for example, via the IND and NDA of the United States or the Centralized Procedure of the EMEA, is not affected. The harmonized CTDs help to reduce cost and accelerate approval time. Figure 7.1 shows the CTD structure five modules with Module 1 for regional administrative information specihc to each country. Module 2 on summary of quality, nonclinical and clinical. Module 3 on quality. Module 4 on nonclinical study reports, and Module 5 on clinical study reports. 

Food and Drug Administration. Accelerated Approvals, FDA, 21 CFR Parts 314.500 and 601.4. 

Despite the efforts of the ICH, the regulatory requirements in the different regions are still quite different. For instance, only the USA has the possibility for accelerated approval of drugs to treat life threatening or severely debilitating illnesses (so-called Subpart E drugs). 

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. 

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. 

Accelerated drug approval program Mechanism to accelerate approval of products designed to treat life-threatening or seriously debilitating diseases based on modified criteria for marketing approval for example, the use of surrogate end points. 

While the benefits of FDA s fast track approval and accelerated approval procedures are described in Chapter 1, it should be noted that a company seeking to use this option must also expedite its preparation for preapproval inspection and GMP compliance. Because FDA signoflf of the manufacturing facility will likely be required for NDA approval and such signoflf is to be accelerated, a firm must recognize that expedited compliance is necessary for this expedited review and have its own manufacturing house in order. 

Accelerated Approval—This is a program that the FDA developed to make new drug products available for life-threatening diseases when they appear to provide a benefit over available therapy (which could mean that there was no existing effective treatment). This guidance provides additional information http //www.fda.gov/cder/guidance/5645fnl.htm. 

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