As nanotechnology is being used to develop new drugs, FDA is working to ensure quality, safety, and effectiveness

By: Celia N. Cruz, Ph.D. 

Nanotechnology is a new and exciting field that offers scientists the opportunity to control matter at very small dimensions, opening many possibilities for making all kinds of new products. This technology operates on an incredibly small scale that measures things in units called nanometers. One nanometer is one billionth of a meter. It’s hard to even imagine how small that is, but here’s one way to do it: A human hair is about 100,000 nanometers wide. 

Wow, that’s small! But nanotechnology promises big things! There are already many products made using materials at the nanoscale, including new kinds of clothing, packaging materials, and light-weight, but strong, building materials. 

Why are we at FDA’s Center for Drug Evaluation and Research (CDER) writing about it? Because medical products can also be made using materials at the nanoscale. In fact some are already available, including certain sunscreens, in which the nanomaterials are used to provide UV protection while remaining transparent on the skin, and in drugs to treat cancer, including Doxil and Abraxane. Use of nanomaterials can enhance delivery of drugs to their biological target or help scientists customize them for a particular type of patient. 

Materials at the nanoscale can have different chemical, physical, or biological properties compared to their conventionally-scaled counterparts. Scientists can use these features to enhance the properties or the quality of a drug. But because such properties can affect the quality, safety, or effectiveness of a drug, FDA is studying these issues related the use of this powerful new technology in medical products. 

Recently, to help us better understand the potential impact nanotechnology could have on a drug’s quality, safety, or effectiveness, CDER’s Nanotechnology Risk Assessment Working Group (Nano Group) finalized a series of risk assessment and risk management exercises to identify potential risks associated with a drug product that contains nanomaterials. A key goal was to determine if our current regulatory processes are adequate to identify any potential risks and reduce those risks. 

Some members of the Nanotechnology Working Group in the CDER labs where characterization of gold nanoparticles is underway. Left to right, front row: Katherine Tyner, Ph.D. Office of Clinical Pharmacology; Celia N. Cruz, Ph.D. Office of New Drug Quality Assessment; middle row: Olen Stephens, Ph.D. Office of New Drug Quality Assessment: Don Henry, Office of Pharmaceutical Science; Abigail Jacobs, Ph.D. Office of New Drugs; back: Paul Brown, Ph.D. Office of New Drugs.

The CDER Nano Group consisted of a multidisciplinary team of scientists that could provide a complete evaluation of the use of nanomaterials in the types of drugs regulated in the Center. We first performed a thorough risk assessment of all stages in the lifecycle of a drug containing nanomaterials to capture any real or perceived hazards related to the nanomaterials. To complete the exercise, we evaluated the common ways a person could be exposed to nanomaterial in a drug product ― swallowing a drug, having it injected, applied to the skin, or inhaled. In addition, we evaluated unintentional and accidental exposure. 

Once all the potential risks were identified, we undertook a risk management exercise to examine the regulatory process we use to evaluate drugs. We then considered whether the identified potential risks in the first exercise could be sufficiently managed by the existing review processes we use to help protect patients from harm. 

Our risk management exercise determined that our current regulatory review processes indeed can adequately protect the public from potential risks associated with the use of nanomaterials in drug products. We also identified areas that could benefit from improvement. These areas include increased nanotechnology regulatory science research and up-to-date training of the review staff who evaluate marketing applications for drug products developed using nanomaterials. FDA does not make a categorical judgment that nanotechnology is intrinsically safe or harmful. Rather, for nanotechnology-derived and conventionally-manufactured products alike, FDA considers the characteristics of the finished product and, as applicable, its safety, effectiveness, or other product attributes. 

Historically, FDA has successfully adapted to novel technologies, and the robust review process we use will continue to capture the potential risks associated with this new technology. To share the findings of the nanotechnology risk assessment and management exercises, in January 2014, FDA will co-sponsor a workshop with the US Pharmacopeia, the International Society for Pharmaceutical Engineering, the American Association for Pharmaceutical Scientists, and the Society of Toxicology to review and share experience gained during the development and review of medical products containing nanomaterials. With these and other activities, FDA will continue to work to ensure that safe, effective drugs are available to the American public. 

Celia N. Cruz, Ph.D. is Senior Reviewer, Chemistry, Manufacturing and Controls, at FDA’s Center for Drug Evaluation and Research

“Breakthrough” Designation … Another Powerful Tool in FDA’s Toolbox for Expediting the Development and Review of Promising New Drugs for Serious Conditions

By: Janet Woodcock, M.D.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research

In fiscal year 2012, FDA approved 35 novel new drugs, also known as “new molecular entities.” Among these new products were drugs to treat patients with unmet medical needs, such as a groundbreaking treatment for a form of cystic fibrosis, the first FDA-approved human cord blood product for hematopoietic reconstitution, used to help patients with blood forming disorders, and the first drug to treat advanced basal cell carcinoma (a form of the most common skin cancer).

To enable our ongoing efforts to bring innovative drug products to the public as efficiently as possible, FDA relies heavily on several expedited development and review tools such as fast track designation, the accelerated approval pathway and priority review designation. For instance, 56 percent of the novel drugs approved by the Center for Drug Evaluation and Research in calendar year 2012 used some combination of these tools to speed promising therapies to patients with serious conditions. And any given drug may have received multiple expedited program designations. (See a brief summary of how each of these tools helps FDA shorten the development and review of promising new therapies.)

In July 2012, a provision in the new law called the Food and Drug Administration Safety and Innovation Act, or FDASIA for short, gave FDA another powerful expedited development tool, known as the “breakthrough therapy” designation. This new designation is now helping FDA assist drug developers expedite the development of new drugs with preliminary clinical evidence that indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Although the designation is not yet even a year old, FDA has received 62 requests to grant this new designation to products under development. We have been very active on this subject, meeting with companies and discussing ways to expedite the drug development process for drugs that show striking early results. We have already granted the breakthrough designation to 20 potential innovative new drugs that have shown encouraging early clinical results.

Drug developers should have a clear understanding of all of FDA’s expedited development and review tools. To help industry better understand each tool, including when the tools can be used and the features of each, we have just published an industry draft guidance titled Expedited Programs for Serious Conditions — Drugs and BiologicsAmong other important information, the draft guidance describes FDA’s policies and the threshold criteria for each expedited program, defines and discusses important concepts, including serious condition, unmet medical need, and available therapy, and provides some general considerations for products utilizing an expedited program, such as manufacturing and product quality, nonclinical considerations, and clinical inspection considerations.

The breakthrough therapy designation gives us another tool in our “toolbox” to help expedite the development and review of new drugs to treat patients with serious medical conditions and little or no treatment options. We’ll continue to use the new breakthrough therapy designation and our existing tools to help make our expedited programs even more effective.

We’ve said it before — and I believe it’s worth repeating — our decision-making on whether to approve a drug always involves an evaluation of many factors, such as the seriousness of the disease.  However, ultimately any drug approved must show that its benefits outweigh its risks and regardless of which expedited development or review program or programs are used, FDA does not compromise its safety or efficacy standards in exchange for rapid approval. Like all drugs we approve, those approved after having been designated as breakthrough therapies will meet our usual rigorous standards for safety and effectiveness.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research