Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 9
tamination of product by adventitious and
non-adventitious agents during manufacturing.
For Module 1, the administrative information
section of the CTD, the final guidance sets require-
ments for labeling autologous vs. allogeneic mate-
rials. For any manufacturing change amendments
made to the IND, FDA has asked for a "reviewer's
guide," essentially, a document with Microsoft
Word's "track changes" enabled. The regulators
have also asked that developers give them 30 days
to review any changes before releasing a new lot of
clinical trial materials.
Experts note that there were few changes to draft
guidance for the testing of retroviral vector-based
gene therapy products, except that a new section
was added discouraging the use of replication-
competent retrovirus testing for vectors produced
using a vector producer cell working cell bank, and
revising recommendations on test assays (7,8,9).
Similarly, final guidance for long-term patient
follow-up remained similar to draft guidance, ex-
cept that a footnote was added to clarify conditions
to which the final guidance will not apply (e.g.,
vaccines for infectious diseases or bacteriophage
products) (7,10).
Experts note few changes from FDA's draft to
its final guidance for gene therapies developed to
treat retinal disorders (7, 11). In moving from draft
to final guidance for rare diseases in general (12),
they note changes to the CMC section, to bring
the document in line with the final CMC guid-
ance (5,7), as well as the inclusion of more informa-
tion on biomarkers. The final guidance for gene
therapies designed to treat hemophilia includes
revisions to recommendations on specific clinical
efficacy endpoints, and recommendations for en-
hanced pediatric studies and more frequent com-
munication with the agency (7, 13).
Gene and cell therapy development shows no
signs of slowing, and, quoting FDA projections,
McKinsey analysts expect to see from 10 to 20
cell and gene therapy approvals per year over the
next five years, using platforms including adeno-
associated virus and lentivirus, but also anti-sense
oligonucleotides and ribonucleic acid interference
(14). These new guidance documents should help
clarify expectations, thereby improving commu-
nication between regulators and developers, and
speeding the overall commercialization of more
gene and cell therapies.
References
1 . FDA, "FDA Continues Strong Support of Innovation in Develop-
ment of Gene Therapies," Press Release, fda.gov, Jan. 28, 2020.
2. K. Hacker, "FDA Gene Therapy Guidances: The Latest Updates Ex-
plained," Clarkstonconsulting.com, February 17, 2020.
3. FDA, "Cellular and Gene Therapy Guidances," fda.gov, Feb. 14,
2020.
4. E. Bender, "Regulating the Gene-Therapy Revolution," nature.com,
December 12, 2018.
5. FDA, Interpreting the Sameness of Gene Therapy Products Under
the Orphan Drug Regulations, Draft Guidance (CBER, January
2020).
6. FDA, CMC information for Human Gene Therapy Investigational
New Drug Applications, Final Guidance (CBER, January 2020).
7. K. Auchincloss, "An Analysis of FDA's Recently Issued Gene Ther-
apy Guidances," cellandgene.com, Feb. 20, 2020.
8. Ropes & Gray Regulatory Practice, "FDA Issues Gene Therapy
Guidances," ropesgray.com, February 3, 2020.
9. FDA, Testing of Retroviral Vector-Based Human Gene Therapy
Products and Replication-Competent Retrovirus Drug Manufactur-
ing and Patient Follow-Up, Final Guidance (CBER, January 2020).
10. FDA, Long-Term Follow-up After Administration of Human Gene
Therapy Products, Final Guidance (CBER, January 2020).
11. FDA, Human Gene Therapies for Retinal Disorders, Final Guidance
(CBER, January 2020).
12. FDA, Human Gene Therapies for Rare Diseases, Final Guidance
(CBER, January 2020).
13. FDA, Human Gene Therapies for Hemophilia, Final Guidance
(CBER, January 2020).
14. E. Capra et al., "Gene Therapy Coming of Age: Opportunities and
Challenges to Getting Ahead," mckinsey.com, October 2019.
PT
Gene and cell therapy
development shows no signs
of slowing.
