The scope of the regulatory responsibilities of the U.S. Food and Drug Administration is vast. Their mission is to protect the public health and they employ 16,914 civilians and 1,148 military, totaling 18,062. They are extremely “siloed” and slow to gain consensus on policy among their various internal groups.

Their enforcement on the drug manufacturing sector stems from CFR 210 & 211, et seq., which constitutes “Current Good Manufacturing Practices,” abbreviated cGMP. The verbiage of those regulations has changed little since the 1970s, but the FDA’s “current thinking” about what the regulations mean seems to change daily at times. The only industry avenue open to help comprehend the FDA’s “current thinking,” is to read the language of enforcement actions or to study Draft Guidance or Final Guidance documents, which are rarely published and are released only after months or years of internal debate.

One sure way to draw fire within the Agency as an employee of the FDA is to have anyone at any inspected facility quote you as saying, “Yes, that would be an acceptable remedy.” All responses to enforcement actions are guesswork and are more art than science, yet an entity’s responses are the critical pivot points for regulatory success.

Are All FDA Interactions Initiated With an Inspection?

FDA interactions usually start with inspection, although they should start with FDA-entity conferences regarding Basis-of-Design and User Requirement Specifications. The Office of Regulatory Affairs (ORA) is in charge of drug inspections. Inspections typically last several days to 6 weeks, typically involving 1 to 4 FDA personnel.

When an entity undergoes an inspection, the lead inspector keeps a careful record of every material observation or event that is observed and this is called, the “Establishment Inspection Report” or “EIR.” At the end of the inspection, the inspection team, guided by their superiors at the District or Center level, determine whether an FDA Form-483 is issued.

An entirely uneventful inspection will be categorized as “No Action Indicated” or “NAI” and this is the goal. If they inspection has resulted in any meaningful Observations, then a Form-483 is presented to the entity at the “closeout meeting.” The 483 cites all the Observations from the inspection that MAY represent a violation of federal regulation. All the entity knows is that the inspection was NOT deemed to be NAI, but FDA has sometimes taken up to 18 months to decide whether the Observations were egregious (“Official Action Indicated” or “OAI”) or were mild enough to be addressed by the entity’s corrective action plan. (“Voluntary Action Indicated” or “VAI”)

If FDA’s decision is VAI, their internal responsibility is to send the compounding entity an FMD-145 Letter within 14 days. The FMD-145 includes a copy of the EIR (the lead inspector’s detailed notes) or informs the entity they have the right to read their EIR if they make the request.

Alternatively, if FDA’s decision is OAI, the inspectional findings are potentially evidence in a legal proceeding, therefore FDA is not required to share the EIR with entity. Instead, the entity learns that FDA has categorized the inspection as OAI only when it receives a Warning Letter (“WL”) or an Untitled Letter.

Every WL has the boilerplate language stating: “The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

What Actions Are Required After An FDA Inspection?

You should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.

From the FDA –
“Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of any violations, as well as copies of related documentation. If you believe that your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.”

These are intimidating words, but if an entity remains focused on creating a corrective action plan and remains in close contact with the assigned compliance officer, there is a high likelihood of achieving a “Warning Letter Closeout Letter” or “WLCL,” which restores the entity to what might be thought of as “in good standing.”

The other end of the spectrum is to ignore, dispute, argue, or contest a WL, which may result in a “Permanent Consent Decree,” that basically puts the entity out of the business of producing drug products.

If you or your facility have received an FDA form 483 or a WL, you will require expert guidance as to how best to respond to the FDA and how to quickly and efficiently address the observations identified within the 483. Please contact us online now, or call us at (877) 503-7687 to discuss your situation and how we can help guide you in this highly complex and regulated industry. Our inhouse experts have decades of direct hands-on experience in the fields of drug compounding and manufacturing.