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

FDA Voice interviews Paul C. Howard, Ph.D, on Nanotechnology

FDA Voice: Thank you for taking time to discuss the exciting field of Nanotechnology with us.  We’ve heard so much about Nanotechnology – what is it exactly and why has it been tagged as the second industrial revolution?

Paul C. Howard, Ph.D., Dr. Howard:  Thank you for the opportunity. It’s been tagged as the “second industrial revolution,” because of its ability and promise to create new materials with new properties.  Decreasing larger-size materials down to sizes in the nano domain may change the properties of these materials. This could have enormous benefits in many arenas. That’s why there is considerable worldwide investment and research for product performance improvement, usefulness, and marketability using nanotechnology.

Nanotechnology is the science of manipulating materials on a scale so small that they can’t be seen with a regular microscope. The technology could have a broad range of applications, such as increasing the effectiveness of a particular drug, improving the packaging of food, or altering the look and feel of a cosmetic.

Nanotechnology could also be used in medicines designed for the detection, treatment, and prevention of disease; food production and preservation; water decontamination and purification; environmental remediation; lighter and stronger materials for construction and transportation; and energy resources such as solar cells and fuel-efficiency additives, just to name a few.

FDA Voice: Is Nanotechnology considered a new field?

Dr. Howard:  Nanomaterials are not new. They have been around as a result of natural and man-made processes for a long time; however, the ability to see and the ability to manipulate matter at the nanoscale are relatively new.

Nanotechnology draws from several science fields like physics, material science, supra-molecular and polymer chemistry, interface and colloidal science, as well as from the chemical, mechanical, biological, and electrical engineering fields.

FDA Voice: If nanotechnology-sized particles are so tiny, how can you actually see them?

Dr. Howard: The best light microscopes you can look through with the human eye get close to seeing materials on the nano scale.  However, to best view nanomaterials, electron microscopes are needed.

Typically, “transmission” electron microscopes – either like an X-ray, where the electrons go through the material – or “scanning” electron microscopes – which bounce electrons off the surface of the object to give stunning three-dimensional images, are used.

Another type of microscope is the atomic force microscope. Fundamentally, it is a bit like an old phonograph, with an arm with a tiny tip on the end (stylus) and it “feels” along the surface.  When it encounters a nanomaterial, or larger, it deflects, giving a measure of its height.

At the National Center for Toxicological Research (NCTR) and the adjacent FDA Office of Regulatory Affairs laboratory, we use all three types of microscopes to image the smallest nanomaterials.

FDA Voice: How does  nanotechnology impact FDA research?

Dr. Howard: Nanotechnology can be used in FDA-regulated products and we are aware that materials that exist in the nanoscale may have unique properties, and thus may warrant examination.

FDA participates in research programs with collaborating federal agencies to understand the behavior of nanomaterials in biological systems, especially any risk of short- or long-term toxicity.  FDA also collaborates with the National Nanotechnology Initiative (NNI), which serves as the central point of communication, cooperation, and collaboration for all Federal agencies engaged in nanotechnology research.

FDA Voice: Finally, please tell us about the Nanotechnology Core Facility at FDA’s National Center for Toxicological Research.

Dr. Howard: FDA is investing in an FDA-wide nanotechnology regulatory science program that further enhances FDA’s scientific capabilities, including Laboratory Core Facilities, to support regulatory science.

FDA’s Nanocore facilities are located in Maryland and at FDA’s Jefferson Laboratories just south of Little Rock, Arkansas. The Arkansas Nanocore facility is a joint effort between FDA’s NCTR and Office of Regulatory Affairs’ Arkansas Regional Laboratory. Both facilities are co-located on the Jefferson Laboratories campus.

Nanocore has been designed to support research scientists by providing the equipment and knowledge to characterize nanomaterials. Nanocore also anticipates the needs of scientists by being involved in developing methods to detect nanomaterials in biological samples following the use of nanomaterials in biology experiments.

Characterization is very important in any science endeavor, especially research where you are trying to understand the relationship between an object and its good or bad properties when it is in a biological system.

For example, characterization for nanomaterials includes the average size, the aggregation (where they stick together to form a larger mass), shape, chemical composition and purity, surface area, chemistry properties on the surface, chemical/electrical charge on the surface, and stability.  A good description of these is at Characterization Matters,  Nanocore experts work with scientists who need to understand nanomaterial behavior or toxicity and support the work of other scientists who investigate the safety of nanomaterials that may be used in FDA-regulated products. We also characterize the nanomaterials before, during, and after biology or toxicology experiments. Since the equipment and expertise are centralized into this core facility, FDA Nanocore operations also serve as a training resource for FDA regulatory scientists in nanomaterial characterization and detection methods.

Anyone interested in more on nanotechnology can find a wealth of information on FDA’s website, the U.S. National Nanotechnology Initiative (NNI), and the National Science Foundation.

Paul C. Howard, Ph.D., is the Director of the Office of Scientific Coordination and Director of the Nanotechnology Core Facility at FDA’s National Center for Toxicological Research near Jefferson, Arkansas.