Inspections, Compliance, Enforcement, and Criminal Investigations
SUBCHAPTER 4.1 - GENERAL
4.1 - GENERAL
4.1.1 - AUTHORITY
220.127.116.11 - Examinations and Investigations
18.104.22.168 - Notice of Inspection
22.214.171.124 - Receipt for Sample
126.96.36.199 - Report of Analysis
4.1.2 - VALID SAMPLE
4.1.3 - RESPONSIBILITY
4.1.4 - OFFICIAL SAMPLES (21 CFR 2.10)
188.8.131.52 - Definition - Official Sample
184.108.40.206 - Documentary Samples
220.127.116.11 - In-Transit Samples
18.104.22.168 - 301(k) Samples
22.214.171.124 - Induced Sample
126.96.36.199 - Undercover Buy
188.8.131.52 - Post Seizure (P.S.) Sample
184.108.40.206 - Domestic Import Sample
220.127.116.11 - Import Sample
18.104.22.168 - Additional Sample
22.214.171.124 - Reconditioning Sample
126.96.36.199 - Audit/Certification Sample
188.8.131.52 - Mail Entry Sample
4.1.5 - FOOD STANDARDS SAMPLE
4.1.6 - INVESTIGATIONAL SAMPLES
184.108.40.206 - Non-Regulatory Sample
Collecting samples is a critical part of FDA's regulatory activities. FD&C Act, Section 702(a) [21 U.S.C. 372 (a)] gives FDA authority to conduct investigations and collect samples. A Notice of Inspection is not always required for sample collections. If during a sample collection, you begin to conduct an inspection (examining storage conditions, reviewing records for compliance with laws and regulations, etc.), issue an FDA 482 and continue your activities. See IOM 5.1.1 and 5.2.2.
While inspections and investigations may precede sample collection, a sample must ultimately be obtained for a case to proceed, under the law. Proper sample collection is the keystone of effective enforcement action.
- Carriers - Issue an FDA 482 - Notice of Inspection to the driver or agent when it is necessary to inspect vehicles. See IOM 220.127.116.11.
- Manufacturers, etc. – Issue an FDA 482 - Notice of Inspection when samples are collected from lots in possession of a manufacturer, processor, packer or repacker, whether or not regulatory action is intended toward the articles, the dealer, the manufacturer or the shipper.
Section 704(c) of the FD&C Act [21 U.S.C. 374 (c)] requires issuing a receipt describing any samples obtained during the course of an inspection. The receipt is to be issued to the owner, operator, or agent in charge, upon completion of the inspection and prior to leaving the premises. See IOM 5.2.4 for special situations. See IOM 18.104.22.168 for instructions on completing the form.
Section 704(d) of the FD&C Act [21 U.S.C. 374 (d)] requires FDA furnish a report of analysis on any sample of food (including animal food and feed, medicated and non-medicated), collected during an inspection of an establishment where such food is "*** manufactured, processed, or packed ***," if the sample is examined for compliance with Section 402(a)(3) of the FD&C Act [21 U.S.C. 342 (a)(3)]. The servicing laboratory is responsible for furnishing the report of analysis. See FMD 147.
A valid sample is the starting point and keystone for most administrative and legal actions. As evidence, the sample must support the government's charge there is a violation of the law. Also, it must conform to the rules on admissibility of evidence. A properly collected and prepared sample provides:
- A portion of the lot of goods for laboratory analysis and reserve, a 702(b) of the FD&C Act [21 U.S.C. 374 (b)] reserve portion if appropriate, and/or an exhibit demonstrating the violation represented by the lot.
- A report of your observations of the lot.
- Labels and labeling, or copies of such, which "accompany" the goods.
- Documentary evidence of federal jurisdiction over the lot, information about individuals responsible for the violation, where the violation was committed, and similar data.
- Signed statements from persons who may be called upon as witnesses, if there is a subsequent court action.
Collect every sample as if you will be required to testify in court about everything you did concerning each and every event surrounding the sample collection. Mistakes or deficiencies, however trivial they may seem, can fatally damage the government's case. Be objective, accurate, and thorough.
4.1.4 - OFFICIAL SAMPLES (21 CFR 2.10)
A sample of a food, drug, or cosmetic is an "Official Sample" if records [see IOM 4.4.7] or other evidence obtained shows the lot from which the sample was collected was:
- Introduced or delivered for introduction in interstate commerce, or
- Was in or was received in interstate commerce, or
- Was manufactured in a territory or the District of Columbia.
A sample of a device, a counterfeit drug, or any object associated with drug counterfeiting, no matter where it is collected, is also an "Official Sample". The statute permits proceeding against these articles, when violative, at any time. See Sections 304(a)(2) of the FD&C Act [21 U.S.C. 334 (a)(2)].
Import Samples are Official Samples and require the same integrity as domestic Official Samples. They must be identified with sample number, collection date and collector's handwritten initials. Interstate documentation is not required; see CPG manual section 110.200 and 110.600. Import Samples need not be sealed, unless District policy dictates, as long as the integrity of the sample is maintained.
Normally, 702(b) of the FD&C Act [21 U.S.C. 374 (b)] portions (hereby referred to as either 702(b) portion or 702(b) reserve portion) are not collected for routine Import Samples. However, in situations where a dispute arises or a potential for regulatory action exists, the 702(b) portions should be collected and the sample sealed as described in IOM 4.5.4.
An Official Sample is one taken from a lot for which Federal jurisdiction can be established. If violative, the Official Sample provides a basis for administrative or legal action. Official Samples generally, but not always, consist of a physical portion of the lot sampled. To be useful, an Official Sample must be:
- Accompanied by records establishing Federal jurisdiction, and identifying the persons having knowledge of the lot's movement and custody of the records. (Evidence of Interstate movement is not required for medical device samples, but, according to policy, is to be obtained when a seizure, injunction, prosecution or civil penalty is contemplated). See IOM 4.4.7.
- Representative of the lot from which collected.
- If a physical sample, large enough to permit proper laboratory examination and provide a 702(b) reserve portion when necessary.
- Handled, identified, and sealed in such a manner as to maintain its integrity as evidence, with a clear record of its chain of custody.
In a "Documentary" (or "DOC") sample, no actual physical sample of the product is taken. Other elements of an official sample described in 4.1.4 and 22.214.171.124 are required -- see special official sealing instructions below. This official sample consists of the article's labels (or label tracings, photocopies, or photos), accompanying labeling (leaflets, brochures, promotional materials, including Internet websites, etc.) and documentation of interstate movement (freight bills, bills of lading, affidavits, etc. See IOM 4.4.7) Photos of the product, drawings, sketches or schematics, production records, diagrams, invoices or similar items may also be part of the sample. See IOM Exhibits 4-1 and 4-2. As a rule, no FDA 484, receipt for samples is issued during collection of a DOC Sample. See subparagraph 126.96.36.199 for physical evidence exception.
A DOC sample is collected when an actual physical sample is not practical (e.g., very large, expensive, complex, permanently installed devices), in instances where the article is no longer available, or when there is little need for laboratory examination. A single piece of life support equipment for example, which must remain in emergency service until a replacement is available, may be sampled in this manner.
Another instance where a DOC sample might be collected involves a shipment of product recommended for seizure based on misbranding charges. During availability check, the lot sampled is found to have been distributed; however, a new shipment, identically labeled, is on hand. In this instance, the new shipment may be sampled on a DOC basis since another physical sample and examination is not required. Regulatory action may proceed on the basis of the earlier examination. Thus, only labeling, transportation records, the appropriate dealer affidavits, and an inventory of product on hand need be obtained.
A variation of this procedure involves collecting one or more units and removing (stripping) the original labels/labeling from the product container. It is frequently easier and quicker to collect relatively inexpensive units to field strip than it is to photocopy or photograph all accompanying labels. The sample is handled in exactly the same manner as any other DOC sample, once original labeling has been removed and the remainder of the sample destroyed. A prominent explanation on the C/R alerts reviewers that the original units collected were destroyed after the original labeling was removed. This procedure is not appropriate where complete, intact, labeled units are desired for exhibit purposes, even though there is no intention of analyzing the units obtained.
A documentary sample collected to document GMP deviations, should contain copies of records obtained that document the deviations encountered. You should explain what is being documented in the remarks section of the documents obtained screen in FACTS. Fully describe any record collected as part of the DOC sample and where possible indicate the page of the document that demonstrates the deviation.
When photos are taken as part of DOC samples, the rolls of exposed film should - unless developed by the Investigator - be sent to established commercial film dealers or color processors for developing. Report the identity of the film processor on the FDA 525. Also see IOM 5.3.4.
See IOM 188.8.131.52 for guidance on identifying records associated with a DOC sample. Do not officially seal these records, but list them on the C/R. If any photos are taken as part of the DOC sample, the negatives or electronic media, if any, must be officially sealed per IOM 184.108.40.206 or IOM 220.127.116.11. See IOM Exhibits 4-1 and 4-2 for examples of DOC samples. Attach the documents, photos and negatives along with any other records associated with the sample to the printed FACTS Collection Record. See IOM 18.104.22.168.
In-Transit samples are those collected from lots held on loading/receiving docks of steamships, truck lines, or other common carriers, or being transported in vehicles. The lot is considered to be in-transit if it meets any of the following characteristics:
- A Bill of Lading (B/L) or other order to ship a lot interstate has been issued.
- The owner/shipper or agent acknowledges, preferably by signed affidavit, he has ordered the lot to be shipped interstate.
- The owner or operator of the common carrier acknowledges, preferably by signed affidavit, he has an order from the shipper to move the lot interstate.
Section 301(k) of the FD&C Act [21 U.S.C. 331 (k)] describes prohibited acts, which can result in one or more separate legal procedures. A sample collected from a lot of food, drug, device or cosmetic which became adulterated or misbranded while held for sale, whether or not the first sale, after shipment in interstate commerce is often referred to as a "301(k) Sample". The term "301(k) Sample" is misleading, but widely used within FDA to describe certain samples collected from lots which become violative after shipment in interstate commerce.
Since some act took place which resulted in the adulteration or misbranding of a previously nonviolative product after shipment in interstate commerce, the "301(k)" documentation is incomplete without identifying the act, establishing when and how it occurred, and the person(s) responsible for causing the violation. This feature, more than any other, distinguishes a "301(k) Sample" from the other Official Samples. When you report the sample collection, the responsible party will always be the dealer. See IOM Exhibits 4-1 and 4-7, "301(k) affidavit".
For example, to document insect adulteration of a finished product, caused by a live insect population in the processing areas of a food manufacturer such as a bakery, you must document receipt of clean raw material and subsequent adulteration caused by the firm's handling or processing of the raw material. Therefore, you would need to show there was an insect infestation at the firm that either did, or may have contaminated the finished product. You would need to collect a sample of the clean incoming flour, and subsamples at points in the system to demonstrate where insect infestations exist in the system. In situations where sampling may disturb static points in the system, which may result in a higher level of adulteration of the finished product than normal, you should sample in reverse.
301(k) samples can also be used to document adulteration (including noncompliance with GMPs) or misbranding of other regulated commodities, including drugs and biologics. If possible, when collecting a 301(k) sample covering a drug product, you should attempt to document 'adulteration' or 'misbranding' of the active ingredient by the firm's actions. In the case of a biologic (for example, whole blood), which has not moved in interstate commerce, document the interstate receipt of the bag, and the firm's subsequent 'adulteration' or 'misbranding' of the anti-coagulant (considered a drug) in the blood bag.
An induced sample is an Official Sample ordered or obtained by agency response to some type of advertisement or promotional activity. The sample is procured by mail, telephone, or other means without disclosing any association of the requester or the transaction with FDA. See IOM 22.214.171.124 for additional information.
An "undercover buy" is an Official Sample, similar to and obtained in much the same manner as an "induced sample". In an "undercover buy", however, the solicitation is made in person, usually under an alias. Pre-arranged explanations or cover stories are necessary to dispel any suspicions about the requester that may surface in face-to-face discussions. "Undercover buys" are frequently used in investigating complaints of illegal activity where the information cannot be substantiated or refuted through more conventional means.
A lot under seizure is in the custody of the U. S. Marshal. If either the claimant or the government desires a sample from the seized lot, for any reason, it may be collected only by court order. In most cases, the order will specify how the sample is to be collected, and may provide for each party to collect samples. If the order was obtained by the claimant, permit the claimant's representative to determine how his/her sample collection is made. If the method of collection is improper, make constructive suggestions, but do not argue. Report exactly how the sample was drawn. Unless the claimant objects, mark subdivisions collected with "P.S.", your initials and date. "P.S." Samples are Official Samples.
Do not pay for Post Seizure Samples or any samples collected of a lot reconditioned under a Consent Decree. See IOM 126.96.36.199.
To record information on FDA's total coverage of imported products, an additional classification of samples, "Domestic Import" or "DI" was devised. These are Official Samples of foreign products, which have passed through customs and are in domestic commerce. The FDA may have previously taken a sample of the product while in import status, or the product may have been permitted entry without being sampled. If sampled while still in import status, the samples collected are import samples, and not "DI" Samples. However, once the product leaves import status and enters domestic commerce, any sample collected is considered an Official "Domestic Import" (DI) Sample. Note: When collecting DI Samples, especially if a violation is suspected, attempt to determine the port of entry and importer of record. Report this information on the CR. Include the name of the Country of Origin of the product and the Country Code if known.
A sample is classed as Domestic Import (DI), if any of the following situations apply:
- The label declares the product to be from a foreign country.
- The label bears the word, "Imported".
- Records obtained or reviewed reveal the product originated in a foreign country.
- It is known that the product is not grown or produced in the US; it is packed as a single item with few or no other ingredients added, and it is not manipulated in any major manner, which changes the product or its composition. For example, "Olive Oil" imported in bulk and merely repacked with no added ingredients and no manipulation would be a "DI" sample, while pepper which is processed, ground and packed after entry would not. However, retail packages of ground pepper processed and packaged in a foreign country would be "DI" Samples.
- Samples of imported raw materials, which are collected before further processing or mixed with other ingredients.
DI samples are significantly different from other official samples in another important respect. Unlike domestic products, where considerable information is readily available on manufacturing and distribution channels, it is frequently difficult to identify the responsible parties for products of foreign origin once they enter domestic commerce. The most practical way is to establish a paper trail of records going back as far as possible in the distribution chain to the actual entry.
Identifying "DI" Samples - When identifying the physical samples, related documents and filling out the seals of Domestic Import samples, preface the sample number with the prefix "DI" in the same manner that other sample type prefixes are used (such as, "DOC", "FS" (See IOM 4.1.5), "PS", etc.)
Import samples are physical sample collections of products, which originate from another country, collected while the goods are in import status. Import status ends when Customs has cleared an entry for the shipment. See IOM 188.8.131.52, and chapter 6.
This is a physical sample collected from a previously sampled lot of either a domestic or imported product.
- Additional Import Samples - The sample collected must have the same sample number as the original sample collected.
- Additional Domestic Sample - The sample collected may have another sample number, but it must be flagged as an "ADD" Sample and the original sample number referenced in the "Related Sample" block on the Collection Record.
Reconditioning Samples - These are taken from lots reconditioned under a Decree or other agreement to bring the lots into compliance with the law. The sample is taken to determine if reconditioning was satisfactorily performed. These samples should be submitted as Official Samples.
A sample collected to verify analytical results provided by a certificate of analysis or private laboratory analysis that purports to show a product complies with the FD&C Act and/or regulations. This sample type will usually be used with an import sample. See IOM 184.108.40.206.
A mail entry sample is a sample of an imported product that enters the U.S. through the U.S. Mail. See IOM 220.127.116.11.
Food Standards (FS) samples are collected to provide information on which to base Food Standards. Sample integrity is maintained in the same manner as Official Samples.
Note: Samples of standardized foods are not FS Samples.
These samples, referred to as "INV Samples", need not be collected from lots in interstate commerce or under federal jurisdiction. They are generally collected to document observations, support regulatory actions or provide other information. They may be used as evidence in court, and they must be sealed and their integrity and chain of custody protected. Examples of INV Samples are:
- Factory Food Samples - Raw materials, in-process and unpackaged finished products to demonstrate manufacturing conditions. See IOM 18.104.22.168.3
- Exhibits - Filth exhibits and other articles taken for exhibit purposes during inspections to demonstrate manufacturing or storage conditions, employee practices, and the like. Typically filth exhibits submitted as part of an INV sample are not tied to any specific lot of product, but are meant to illustrate the conditions at a firm. An example of an INV filth sample would be rodent excreta pellets, apparent nesting or other rodent gnawed material, and other evidence of rodent activity collected from the perimeter and at multiple locations throughout a manufacturing facility or warehouse in order to document widespread rodent infestation. See IOM 22.214.171.124.7
- Environmental Samples See IOM 126.96.36.199.1
- Certain Complaint Samples - Injury and illness investigation samples from certain complaints where there is no Federal jurisdiction, or where the alleged violation offers no basis for subsequent regulatory action. Complaint samples from lots for which Federal jurisdiction is clear should be submitted as Official Samples.
When identifying the sample/sub samples and docu¬ments related to the sample, and filling out seals, preface the sample number with "INV" in the same manner as other sample prefix types are used (e.g. "DOC", "DI").
Samples collected and analyzed by FDA for other federal, state, or local agencies of products over which the FDA has no jurisdiction.