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Nanobiotechnology February 2018 Viewpoints

Technology Analyst: Ivona Petrache

FDA's New Guidance for Nanomaterial-Containing Drugs for Humans

Why is this topic significant?

Recently, the FDA introduced a draft guidance for drugs that contain nanomaterials. The FDA made this move to accommodate the benefits and risks of nanotechnology in novel product developments.

Description

In December 2017, the US Food and Drug Administration (FDA) released a draft guidance for drugs—including biological products, active ingredients, delivery systems for active ingredients, and excipients—that contain nanomaterials. The guidance also covers manufacturing processes that involve nanotechnology. The draft guidance applies to drugs for humans only and not to "drugs for animals, devices, foods, or cosmetic products." According to the FDA, the new guidance complies with its final guidance documents concerning nanotechnology applications in products, including cosmetics and animal food.

Although it has not adopted a definition of the terms nanomaterial and nanotechnology, the FDA in the new guidance considers the following situations to apply to nanotechnology-based engineered materials or drug products:

  • The material or drug product has "at least one external dimension, or an internal or surface structure" approximately between 1 nanometer and 100 nanometers
  • The material or drug product exhibits physical, chemical, and biological properties that relate to the material's or product's dimensions, "even if these dimensions fall outside the nanoscale range, up to one micrometer."

Implications

The FDA's current nanomaterials regulation includes the gradual incorporation of nanomaterial-specific safety, effectiveness, and public-health-impact requirements into premarket approval. The FDA conducts this review process on a case-by-case basis. The FDA recommends the new guidance to companies that want to submit investigational and premarket applications for nanomaterial-containing drug products, as well as for postmarket submissions that may arise as a result of manufacturers' making significant changes to nanomaterial-containing drugs that the FDA has already approved.

With the new guidance, the FDA intends to improve the understanding about the intended use and application of nanomaterials in drugs. As a result, the FDA may enable the pharmaceutical industry to overcome challenges that relate to the evaluation and characterization of the potential benefits and risks of nanomaterial-containing drugs. As a result, innovation in nanomaterials-based drug technologies may progress rapidly.

Impacts/Disruptions

The FDA is the latest government agency to develop effective guidance that is in line with new technological developments. However, the FDA still has some way to go to catch up with other regulatory bodies such as the European Union in updating its regulation on nanomaterials and nanotechnology. For example, the European Union has product-specific regulations for nanomaterials. However, disagreements between government organizations in the European Union have delayed the European Union's adoption of the best and clearest terms of the definition of nanomaterials.

Adequate regulatory guidance for the use of nanomaterials in the development of drug-delivery systems is an important part of the move to make nanomedicine technologies available to patients; more drugs' reaching the market may improve the treatment quality for patients in the long term. In addition, such guidance could result in higher-quality R&D initiatives in nanomedicine technologies that can pass the initial stage of development.

Scale of Impact

  • Low
  • Medium
  • High
The scale of impact for this topic is: Medium to High

Time of Impact

  • Now
  • 5 Years
  • 10 Years
  • 15 Years
The time of impact for this topic is: Now

Opportunities in the following industry areas:

Pharmaceuticals, nanomedicine

Relevant to the following Explorer Technology Areas:

CRISPR-Cas9: Not-So-Safe Therapy?

Why is this topic significant?

The CRISPR-Cas9 system has given a huge boost to gene-editing therapies, making potential applications of gene editing more viable. However, humans' preexisting adaptive immunity to Cas9 homologs means that CRISPR-Cas9-based treatments may not work correctly or at all.

Description

Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9) is an efficient DNA-cutting enzyme that is part of the CRISPR-Cas9 gene-editing system—a bacterial-immune-system-derived tool that scientists use to make permanent alterations to the DNA of living cells. In January 2018, scientists at Stanford University published research describing the identification of preexisting adaptive immune responses in humans to the homologs of Cas9 proteins. The researchers claim that 79% of the blood donors in their study possessed antibodies against a Staphylococcus-aureus-derived Cas9 homolog, and 65% of the blood donors possessed antibodies against a Streptococcus-pyogenes-derived Cas9 homolog. The presence of anti-Cas9 antibodies may not only weaken the efficiency of the CRISPR-Cas9 editing system to treat disease but also induce toxicity in humans. The researchers tested the blood of 22 newborn babies and 12 adults. The results appear in bioRvix, a free online archive for unpublished preprints (not yet peer reviewed).

Implications

The Stanford researchers' results are worrying because the most widely used Cas9 proteins derive from Staphylococcus aureus and Streptococcus pyogenes bacteria. Usually, these bacteria can cause infections in humans at high frequencies. As a result, humans have built an immune response to fight against the bacteria. If patients who already have antibodies to fight Staphylococcus aureus and Streptococcus pyogenes receive CRISPR-Cas9-based treatments, their immune systems are likely to fight the "snipping" protein of the CRISPR system.

Nevertheless, since scientists developed the CRISPR-Cas9 gene-editing system in 2012, new CRISPR systems have continued to emerge; between 2012 and 2017, more than 5,000 published papers mention the CRISPR system. For example, scientists discovered other DNA-targeting Cas enzymes such as CasY and CasX (both discovered by researchers at the University of California, Berkeley) and cpf1 (discovered by researchers at the Broad Institute) and RNA-targeting Cas enzymes such as C2c2 (discovered by a team of researchers led by Harvard University; see the July 2016 Viewpoints).

Impacts/Disruptions

Currently, developments in CRISPR-based therapies are a hot topic because of the recent increase in the number of CRISPR-based treatments that entered, or will enter in the near future, human clinical trials (see the December 2017/January 2018 Viewpoints). However, the market for CRISPR-based therapies is at an early stage of maturity. Substantially more research on the effectiveness of the CRISPR system in living cells is necessary to understand how to use the technology efficiently and safely in humans. Additionally, researchers need to establish the best method of applying CRISPR-based therapies to humans. New CRISPR-Cas systems and ex vivo strategies to apply gene editing may also enable researchers to develop safer and more efficient CRISPR-based therapies. The CRISPR-Cas system may continue to be a tool for scientists to produce novel, improved gene-editing systems. However, some companies' (such as Editas Medicine's and CRISPR Therapeutics's) stock may lose value in the short term.

Scale of Impact

  • Low
  • Medium
  • High
The scale of impact for this topic is: High

Time of Impact

  • Now
  • 5 Years
  • 10 Years
  • 15 Years
The time of impact for this topic is: Now to 5 Years

Opportunities in the following industry areas:

Pharmaceuticals, health care

Relevant to the following Explorer Technology Areas: