US FDA has issued a guidance on Environmental Assessment (EA) of drugs with estrogenic, androgenic or thyroid activity. It is intended to help sponsors of such drugs determine whether they should submit EAs for drug applications and certain supplements.

The drugs include estrogenic, androgenic, or thyroid hormones. Now the drugs that are not based on these hormones but that have the potential to interact with E, A, or T hormone pathways like for instance aromatase inhibitors, which block a key enzyme from converting androgens into estrogens.

Kaushik Desai, general secretary, Indian Pharmaceutical Association said that this guidance is most appropriate keeping the current and future needs of development under this category. “We see the regulation to achieve the patient-centric objective of the US FDA,” he said.

The National Environmental Policy Act of 1969 (NEPA) requires all Federal agencies to assess the environmental impact of their actions. To comply with NEPA, the USFDA considers the environmental impacts of its actions as an integral part of its regulatory process. The 21 CFR part 25 specify that EAs must be submitted as part of certain NDAs, abbreviated new drug applications (ANDAs), biologic license applications (BLAs), supplements to such applications, and investigational new drug applications (INDs). Failure to submit either an EA or a claim of categorical exclusion is sufficient grounds for FDA to refuse to file or approve an application under 21 CFR 25.15(a), 314.101(d)(4), and 601.2(a) and (c).

Categorical exclusions for actions related to human drugs and biologics are listed at 21 CFR 25.31. The guidance focuses on the categorical exclusion for actions on NDAs and NDA supplements that would increase the use of an active moiety.

Consistent with these regulations, when the sponsor of an NDA or NDA supplement submits a claim of categorical exclusion under 21 CFR 25.31(b), FDA considers whether extraordinary circumstances exist under 21 CFR 25.21. If extraordinary circumstances exist, FDA will require the sponsor to submit an EA. If FDA needs more information to determine whether extraordinary circumstances exist, the regulator may ask the sponsor to submit additional information concerning the potential environmental effects of approval of the sponsor’s application or supplement.

Drugs with endocrine-related activity and specifically, drugs with E, A, or T activity, have the potential to cause developmental or reproductive effects in the aquatic environment at concentrations below 1 ppb. For this FDA has, on a case-by-case basis, requested additional information from sponsors to help it determine whether extraordinary circumstances exist.

Accordingly, this guidance is intended to clarify that sponsors of drugs with potential E, A, or T activity should consult with the Agency early in product development concerning the information. The FDA may need to determine whether an EA will be required or whether a claim of categorical exclusion will be acceptable.

The guidance noted that certain classes of FDA actions are subject to categorical exclusion and do not require the preparation of an EA. This is because it does not affect the quality of the human environment as per 21 CFR 25.15(c), 40 CFR 1508.4.