Beginning in the first half of the 20th century, particularly with the advent of the Food and Drug Administration and the Drug Enforcement Administration, the federal government began to take an increasing role in regulating pharmacies.
Until the 1930s, pharmacies were subject to very little government oversight. Beginning in the first half of the 20th century, particularly with the advent of the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA), the federal government began to take an increasing role in regulating pharmacies. There are several reasons for this change, including the New England Compounding Center tragedy.
The end result is that the FDA is more aggressively looking at compounding pharmacies. While the FDA, generally, has no jurisdiction over pharmacies, the FDA takes the position that it has jurisdiction over pharmacies that cross the line from “being a pharmacy” to “being a manufacturer.” If the FDA believes that a pharmacy has crossed this line, then it will conduct an inspection.
FDA Inspection: Overview
The Federal Food, Drug, and Cosmetic Act (“Act”) allows FDA investigators to inspect facilities in which drugs are manufactured. FDA inspections are usually unannounced. Communications with FDA investigators require the utmost professionalism. Do not create an adversarial environment; it is counterproductive. The degree of the pharmacy’s cooperation will be reflected in the investigator’s Establishment Inspectional Report (“EIR”).
A pharmacy Inspection Leader should be assigned to deal with the inspector. This leader should be aware of the pharmacy’s policies, operations, and record-keeping. The leader should accompany the investigator throughout the inspection.
The investigator should be made aware at the outset that there is a pharmacy policy for working with the FDA. An investigator will more readily accept a denial based on established policy than a refusal based on an “instant policy” created on the spot.
The Act deems a drug to be adulterated if “it has been manufactured … in any … establishment and the owner of such … establishment … denies … an inspection.” If the pharmacy refuses inspection, the FDA’s recourse will be to obtain a search warrant allowing it entry onto the premises. There is no legal basis for refusing an inspection.
The investigator will want to examine “manufacturing” records to see if the pharmacy is complying with current good manufacturing practices (“cGMPs”) for drugs. It is not. The issue is not cGMP compliance; it is whether the pharmacy is a “pharmacy” or a “manufacturer.” The pharmacy should politely try to persuade the investigator to focus on this point, and not on cGMP compliance.
Special attention should be paid to records that contain proprietary information. These documents should be marked “CONFIDENTIAL - TRADE SECRET,” and this fact should specifically be called to the attention of the investigator.
The pharmacy will have patient records. The pharmacy can reasonably ask that the investigator not seek to copy records that contain patient identifiers. Alternatively, the pharmacy may tell the investigator that the pharmacy wishes to delete patient identities from copied documents.
Information to Which the FDA Is Not Entitled
The FDA does not have authority to obtain financial information, sales data, pricing data, research data, personnel data, and marketing plans.
Copying of Documents
If the FDA inspector asks to copy records, the pharmacy should make the copies for the investigator. Always make a duplicate set of copies for the pharmacy’s own records.
Do not let the investigator have free access to the photocopying machine. Someone should be present with the investigator at all times. Have someone perform the copying for the investigator. Nor should the pharmacy let the investigator have unrestricted access to the files -- provide only those documents that are specifically requested.
If the FDA collects samples of products, the pharmacy should take the following steps:
Photographs — Samples
The FDA Investigations Operations Manual says, “photographs are one of the most effective and useful forms of evidence.” The best pharmacy policy is “NO CAMERAS ARE ALLOWED IN THE FACILITY.” A sign stating this policy should be posted at the reception desk.
Signing Official Documents
The FDA has no authority to compel the pharmacy to sign anything. Signing a document does not benefit the pharmacy in any way. The better approach is to have pharmacy officials refuse to sign or to even give an oral “OK” that a statement is correct.
Establish an Inspections File
During the inspection, the pharmacy should create a separate file. This file will include the notes taken during the inspection by pharmacy employees, the forms filled out regarding the inspection, duplicates of the records copied by the investigator, the FDA-482 Notice of Inspection, the FDA-483 Notice of Observations, the FDA-484 Receipt of Samples, the pharmacy’s analytical results for samples tested, and any subsequent correspondence with the FDA.
FDA-483 (List of Observations) Response
At the inspection’s end, the investigator will have an exit interview with management to detail the findings of the inspection and to obtain the pharmacy’s comments. If an FDA-483 is issued, the investigator will request a response. It would be advisable to review each point for clarification with the investigator, but make no comments regarding follow-up action. The pharmacy should not sign the FDA-483.
During the exit interview, do not reject observations out-of-hand, become defensive, or be unwilling to listen; on the other hand, make commitments sparingly. The pharmacy should submit a response letter to the FDA-483. The main purpose of the response letter is to persuade the FDA not to issue a Warning Letter. The FDA’s current policy is to issue Warning Letters within a few weeks of the completion of the inspection. A Warning Letter will state that the pharmacy has violated the law in some respect; this letter is made publicly available.
Each observation in the FDA-483 will be separately numbered. The response letter should address each point individually. Give a detailed reason for any disagreement with the findings. When responding to a valid point, concisely explain how the pharmacy will modify its conduct or what changes will be made. Do not admit that there was an error; rather, just describe the new procedures. Give a target date for corrective actions to be implemented.
Letter Response to FDA Form 483
The response letter to the FDA-483 can include some or all of the following language:
FDA Warning Letter to Pharmacy
Notwithstanding the response letter, the FDA may send a “Warning Letter” to the pharmacy that includes some or all of the following language:
Reply to FDA Warning Letter
The reply letter by the pharmacy to the Warning Letter should say something like the following:
Jeffrey S. Baird, Esq. is Chairman of the Health Care Group at Brown & Fortunato, P.C., a law firm based in Amarillo, Texas. He represents pharmacies, home medical equipment companies, and other health care providers throughout the United States. Mr. Baird is Board Certified in Health Law by the Texas Board of Legal Specialization. He can be reached at (806) 345-6320 or firstname.lastname@example.org.