Drugs

The U.S. Food and Drug Administration (FDA) will resume a pilot program that will lead to unannounced onsite inspections in India and China. FDA intends to start the inspections in early 2022.

Elizabeth Miller, in FDA’s Office of Regulatory Affairs (ORA), announced the forthcoming inspections during a virtual conference hosted by the Food and Drug Law Institute on December 9, 2021.

Read on to learn about FDA’s inspection pilot program and other inspection plans.

FDA’s Inspection Pilot Program

On July 13, 2020, the House Appropriations Committee released a report that, among other things, addressed the growth of oversees drug manufacturing facilities, stating that FDA’s inspections practices have not kept pace with global industry growth. The report also noted the disparity between U.S. and non-U.S. inspections.

The Committee referenced FDA’s 2014 pilot program in India, which implemented unannounced inspections. The report directed FDA to restart the pilot, which it had discontinued in 2015. The Committee also directed FDA to create an additional pilot in China.

Other Inspection News

Along with the pilot programs in India and China, FDA has adjusted inspections procedures to address an inspection backlog. FDA fell behind on inspections due to delays occurring during the COVID-19 pandemic.

Though travel restrictions have delayed certain oversees prioritized inspections, FDA plans to resume these inspections starting February 2022. Prioritized inspections, typically announced, are for products used to treat serious diseases or condition or for products related to a serious adverse event or foodborne illness outbreak.

FDA also plans to continue using a hybrid approach to conducting inspections. During the pandemic, FDA requested facilities send reports prior to onsite inspections. Miller informed the conference that this hybrid model will likely become commonplace.

The U.S. Food and Drug Administration (FDA) has released details regarding new annual reporting requirements that the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) set forth for drug registrants. On March 27, 2020, the CARES Act amended a section of the Federal Food, Drug, and Cosmetic Act (FD&C Act) to require registered drug establishments to report the amounts of each of their listed drug distributed in the United States.

The guidance, Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the Federal Food, Drug, and Cosmetic Act; Draft Guidance for Industry, applies to FDA-registered establishments that distribute drug products such as OTC drugs, medical gases, homeopathic products and animal drug products. FDA states that the purpose of this new annual reporting requirement is to help FDA identify, prevent, and mitigate possible drug shortages.

How do you properly submit reports? Registrar Corp can help file these reports on your behalf as part of our U.S. Agent and Registrant Contact service. Keep reading to learn more about this new requirement.

Reporting on Various Drug Types

Finished Dosage Forms
Packaging is a significant factor when accounting for drug quantities in a finished dosage form product. For example, you must report a bottle that contains a certain number of tablets by the amount of bottles distributed, not by the individual tablet count. Multi-level packages are identified by the National Drug Code (NDC) of the outermost layer, such as the outer case, and also by the amount of containers released.

If your report includes kits, identify those products by the outer most packaging. Include both the amount of the outer most packaging, such as number of cases, and the inner most packaging, such as numbers of bottles within the cases.

APIs
If your establishment has listed an Active Pharmaceutical Ingredient (API) with FDA, you should report the total amount of the API according to the unit container reported in the drug listing, such as the number of cylinders that contain the API. You should also report the amount of unit containers released for drugs that include an API with other ingredients and are not in a finished dosage form product.

Private Label Drug Products
Registrants distributing drugs commercially under the trade name or label of a private label distributor must include the distributor’s labeler code and the NDC associated with the code. The report you submit for data pertaining to private label distributors should be separate from data you submit for other distributors.

Biological Products
There is a proposed order for certain categories of biological products that, if finalized, would exempt such products from CARES Act reporting requirement. FDA states it does not intend to take action against registrants with products that fall under this category until the effective date of the proposal’s finalization or withdrawal.

Submitting Accurate, Timely Reports

Companies should submit their annual report for drugs distributed in 2020 by February 15, 2022 and their report for drugs distributed in 2021 by May 16, 2022. All future reports are due annually by February 15 of the following year.

Establishments should report the actual amounts of the drugs released during the reporting period and not the theoretical yield based on available amounts. The reported amounts should include recalled or returned products. If you listed a drug during the calendar year but did not distribute the drug, FDA still requires you to submit a report specifying that you released zero amount of the drug.

If your drug establishment is located outside of the U.S., you should list the amount of drugs released for U.S. distribution. If you don’t know this information, report on the total amount of drugs released globally.

On September 20, 2021, the U.S. Food and Drug Administration (FDA) released an initial batch of final administrative orders for Over-The-Counter (OTC) drug monographs, the first to emerge from the OTC Monograph Reform. FDA established the reform on March 7, 2020, under the Coronavirus Aid, Relief, and Economic Security (CARES) Act.

FDA released the first final administrative orders for the following:

• Nighttime Sleep-Aid Drug Products for OTC Human Use
• Antiflatulent Drug Products for OTC Human Use
• Topical Otic Drug Products for OTC Human Use
• Corn and Callus Remover Drug Products for OTC Human Use

FDA has continued to release several more final administrative orders since the initial batch, which the portal reflects. Recent additions include a final order for Sunscreen Drug Products for Over-the-Counter Human Use.

The Sunscreen Drug Product Final Order

FDA had regulated Sunscreen products under enforcement discretion for more than 20 years, maintaining a stay on a 1999 final monograph. FDA had previously established several proposed rules for Sunscreen products that would lift the stay. In 2011, FDA published a final rule that codified the labeling of OTC sunscreen drug products, including dramatic changes to the content of the Drug Facts panel. In 2019, FDA issued a tentative final monograph in the form of a proposed rule that deemed all of the active ingredients non GRASE with the exception of titanium dioxide and zinc oxide, and included changes to the labeling requirements.

FDA has released the deemed final order for Sunscreen Drug Products for Over-the-Counter Human Use. At the same time, FDA issued a proposed order to amend the final order that included significant changes, mimicking much of what had been in the 2019 tentative final monograph. FDA is currently taking public comments on the proposed order.

Notable comparisons and contrasts between the final order and the most recent proposed order include:

• The final order maintains the same GRASE active ingredients that  were covered under the original 1999 final monograph. Titanium dioxide and zinc oxide remain classified as generally recognized as safe and effective (GRASE) for use in sunscreens at concentrations of up to 25 percent, per the proposal. However, the proposed order would exclude several other ingredients from GRASE, citing insufficient data.
• A maximum labeled Sun Protection Factor (“SPF”) value of 60+ and limits on the maximum formulated SPF value of the product.
• Powder as a dosage form is included in the final order but deemed not GRASE in the proposed order.

How FDA is Handling OTC Monographs Moving Forward

FDA has stated it will release the remaining orders in phased batches. The Agency will also post all orders on its new web portal, OTC Monographs@FDA. FDA has stated that, as final administrative orders add, remove or change conditions for an existing OTC monograph, the portal will reflect such changes. Final administrative orders will not be announced on the Federal Register, which was common practice for publishing proposed and final rules prior to OTC Monograph reform.

Before the OTC Monograph Reform, the Administrative Procedure Act determined the process for establishing, revising, and amending a monograph. If FDA determined that a drug was generally recognized as safe and effective (GRASE) for a therapeutic category, FDA would place the drug in a proposed rulemaking stage, and the final monograph was tentative. Rulemaking is a lengthy process that requires a proposal, periods of public comment, and finalization.

The OTC Monograph Reform replaced the extensive rulemaking stage for monographs with a more streamlined administrative order process. This process indicates that a drug that meets certain requirements is GRASE, not a new drug, and not subject to certain requirements. Administrative orders may apply to drugs that, among other things, meet specified requirements for conformity to current tentative or final monographs and represent the most recently issued version of the drug’s conditions of use.