Second Letter to FDA Requesting Response to Citizens Petition to Withdraw Approval for Pregnancy Drug 17-OHPC ("Makena") Pending Fetal Germline Impact Assessment

Note: Sometimes I need to pinch my arm to remind myself that it's 2017. You know, it's easy to forget! Because so much of our world is lost in a time warp. Take, for example, the FDA, which seems to be completely — and I mean completely — oblivious to the fact (1) that fetuses have germ cells, and (2) that fetal germ cells are tissues of interest for pharmaceutical toxicology. Basic high school biology stuff. Oh, people of the United States, I weep for all of you, and for all our successive generations. —JE

Escher Fund for Autism

Division of Dockets Management
Food and Drug Administration
Department of Health and Human Services
5630 Fishers Lane, rm. 1061
Rockville, MD 20852

February 8, 2017

Re: Docket Number FDA-2015-P-0876—Re Citizen Petition to Withdraw Approval for 17α-Hydroxyprogesterone Caproate (“17-OHPC,” Including Brand “Makena”) as a Drug Used in Pregnancy, Pending Fetal Germline Impact Assessment

To the Commissioner of the Food and Drug Administration:

The FDA received the undersigned’s above-referenced petition on March 19, 2015. Nearly two years later, the agency has taken no action on the petition, which seeks immediate action to withdraw approval for the pregnancy drug 17-OHPC, pending fetal germline impact assessment. The synthetic compound at issue is an endocrine disrupting chemical (“EDC”) widely administered to pregnant women, exposing simultaneously their fetuses and those fetuses’ early germ cells to that chemical and/or its metabolites, as the chemicals easily pass the placenta and enter fetal tissues, including gonadal tissues. EDCs are documented to interfere with healthy germ cell development.

By sitting on the petition, the FDA is acting in reckless disregard for the gametic health of countless exposed offspring, and risking the developmental integrity of their offspring, and in so doing, continuing its indefensible and outdated policy of ignoring outright the pharmaceutical risks to vulnerable fetal germline. The petitioner asks that the FDA act expeditiously to grant the petition.

• There is little question that germ cells are direct targets of endocrine disruptors from the very early stages of fetal gonad formation. Epigenetic pathways are crucial for germline development and EDCs can interfere with epigenetic mechanisms, including DNA methylation, histone modifications, changes of chromatin structure and microRNA expression, resulting in the transmission of deranged genetic information to the following generation.

• In genes subject to fine dosage control such as imprinted genes, for example, geno-affective exposures such as EDCs may easily cause small molecular glitches with catastrophic, life-long neurodevelopmental consequences.

• In June 2015, the world’s most esteemed hormone biologists, the Endocrine Society, issued a public statement that EDCs must be assessed for fetal germline impacts. Petitioner is not presenting a “fringe” or novel question, but rather a fundamentally critical issue for drug toxicology and generational public health.

• The drug at issue has only a most minimal impact on preterm birth, and patients can receive natural progesterone analogues instead of 17-OHPC where preterm birth is a consideration, while the drug is undergoing safety review.

• As an alternative to removing the drug from the market, the FDA can require the vendors of this drug to warn all consumers of the possibility for germline damage to their babies, and to their eventual grandchildren.

• In the event that adequate safety assessments reveal no adverse molecular effects on fetal germline, the vendors of 17-OHPC may resume marketing and selling the drug.

It is tragedy that the FDA, which is commissioned with the duty to assess damaging effects of pregnancy drugs, seems to possess neither the ability nor interest to contemplate the manifest, unequivocal drug vulnerabilities of fetal germline, even to intentional, high-dose persistent EDC exposures such as 17-OHPC. Given the potential germline consequences of the drug as outlined in the petition, the petitioner implores the agency to act responsibly and grant the petition without further delay.

The petitioner wishes again to thank FDA staff for its consideration.

Very truly yours,

Jill Escher
Escher Fund for Autism