FDA Unveils 6 New Draft Guidances on Gene Therapy

Regulatory NewsRegulatory News | 11 July 2018 |  By 

As first announced in January, the US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) on Wednesday offered a swath of new draft guidance documents on human gene therapies – offering a look at what it expects from an industry that’s beginning to take off.

The six guidance documents focus on developing hemophilia, rare disease and retinal disorder gene therapies, and include one on chemistry, manufacturing and control (CMC) information, one on long term follow-up observational studies collecting data on adverse events and one on the testing of retroviral vector-based therapies.

Last December, FDA approved a new gene therapy, priced at $850,000, from Spark Therapeutics for the treatment of children and adult patients with an inherited form of vision loss that may result in blindness. And back in 2016, FDA began to see the number of gene and cell therapy applications spike. 

Last November, FDA also announced its policy framework for regenerative medicine, including a draft guidance that describes the expedited programs, such as the breakthrough therapy designation, and the regenerative medicine advanced therapy (RMAT)  designation, that may be available to sponsors of these therapies. Companies have already weighed in on such guidance.

(Links to guidance documents are in headers below).


The 15-page draft guidance provides recommendations on the clinical trial design and related development of coagulation factor VIII (hemophilia A) and IX (hemophilia B) activity assays, including how to address discrepancies in factor VIII and factor IX activity assays.

The draft guidance also includes recommendations regarding preclinical and clinical considerations to support development of hemophilia gene therapies (GTs), as well as information on expedited programs and communication with FDA.

Rare Disease

This 14-page draft guidance provides recommendations on developing a GT product intended to treat a rare disease in adult and/or pediatric patients. The guidance relates to the manufacturing, preclinical, and clinical trial design issues for all phases of the clinical development program.

“Such information is intended to assist sponsors in designing clinical development programs for such products, where there may be limited study population size and potential feasibility and safety issues as well as issues relating to the interpretability of bioactivity/efficacy outcomes that may be unique to rare diseases or to the nature of the GT product itself,” FDA said.

Retinal Disorders

This 13-page draft guidance provides recommendations to stakeholders developing GTs for retinal disorders affecting adult and pediatric patients. The focus pertains to issues specific to GT products for retinal disorders and provides recommendations related to product development, preclinical testing and clinical trial design.


This 54-page draft guidance provides sponsors of a GT investigational new drug application (IND) with recommendations regarding CMC information required to assure product safety, identity, quality, purity and strength (including potency) of the investigational product.

The draft applies to GTs and to combination products that contain a human gene therapy in combination with a drug or device.

“The field of gene therapy has progressed rapidly since FDA issued the April 2008 guidance. Therefore, FDA is updating the guidance to provide current FDA recommendations regarding the CMC content of a gene therapy IND,” FDA said.

When finalized, the draft is intended to supersede the document entitled “Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs),” from April 2008.

Long Term Follow-Up

This 36-page draft guidance provides sponsors with recommendations regarding the design of protocols for long term follow-up observational studies for the collection of data on delayed adverse events following the administration of a GT.

When finalized, the draft is intended to supersede the document entitled "Guidance for Industry: Gene Therapy Clinical Trials--Observing Participants for Delayed Adverse Events" from November 2006. This draft, when finalized, is also intended to supplement the guidance discussed below.

Testing of Retroviral Vector-Based Human Gene Therapies

This 16-page draft provides sponsors of retroviral vector-based human GTs with recommendations regarding the testing for replication competent retrovirus (RCR) during the manufacture of retroviral vector-based products, and during follow-up monitoring of patients who have received retroviral vector-based products.

“Recommendations include the identification and amount of material to be tested, and general testing methods,” FDA said. “In addition, recommendations are provided on monitoring patients for evidence of retroviral infection after administration of retroviral vector-based gene therapy products.”

When finalized, the draft is intended to supersede the document entitled “Guidance for Industry: Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors,” from November 2006.

The draft guidance, when finalized, is also intended to supplement the long term follow-up and CMC guidance documents discussed above.


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