Contents

4.5 - SAMPLING: PREPARATION, HANDLING, SHIPPING

4.5.1 - Objective

The preparation, handling, and shipping of samples is your responsibility, and must be carried out in a manner which assures the sample's integrity and supports testimony that the sample examined was the same sample you collected from the shipment you documented.

As few persons as possible should handle the sample to reduce the likelihood of compromising sample integrity. See the Laboratory Procedures Manual (LPM), Chapter 4, 4.1 for information about relinquishing samples.

4.5.2 - IDENTIFYING MARKS

4.5.2.1 - Subsamples

Identify a representative number of subsamples (subs) with the sample number (including prefix, if appropriate), collection date and your handwritten initials. If individual sub identity must be maintained, assign and mark each sub with a separate Arabic numeral. In some comprehensive inspections or investigations it may be important to correlate the manufacturing control code with the sub number.

When a variety of articles are included under one sample number, fully identify each sub and describe them on the C/R. Factory exhibits should be fully identified and, where appropriate, correlated with inspectional observations, manufacturing procedures, and/or routes of contamination. See IOM 4.2.5.6 for using the FDA 484 - Receipt for Samples as a memo to accompany C/R to describe subs collected.

When multiple subs are taken from cases, bales, boxes, etc. in the lot, Arabic numerals and letters in combination may be used for identification. For example: if two cans are taken from each case in the lot, the cans may be marked as subs 1a, 1b, 2a, 2b, etc. to identify the subs as coming from case #1, case #2, etc. If the second can or container taken from each case is the 702(b) [21 U.S.C. 372(b)] portion, it is desirable that all duplicate portions be sealed separately from the FDA portion. This fact should be so noted on the cases and C/R.

If multiple subsamples are to be collected, it may be advantageous to place identifying information such as sub number, sample number, and collection date on peel-off labels, tape, etc. in advance of sampling to save valuable time. Your initials must be in your own handwriting.

4.5.2.2 - Borrowed Samples

Although most samples are purchased, some may be borrowed, non-destructively examined, and returned to the owner. These samples must be handled carefully to avoid defacing or damaging the product.

Identify borrowed samples so the identification can be removed with no damage to the product, i.e. a sticker label that can be peeled off.

4.5.2.3 - Identification Techniques

Mark a representative number of subsamples with the sample number, collection date and your written initials. Similarly identify any outer packaging, labels or circulars. If more than one person is involved in collecting the sample, the person preparing and signing the C/R initials the subs. Reinsert circulars removed from packages. See IOM 4.2.9.2 for procedures on identifying lots from which sampled.

Transparent tape such as Scotch Magic Transparent tape accepts ball point ink and may be used on glossy items such as glass, plastic, tin, etc. Glass, such as bottles, vials and ampoules, may be identified by using a very fine pointed felt or nylon marking pen and covering the identification with transparent tape for protection.

Do not use tape on very small containers such as ampoules, which must be snapped or broken to remove the contents for analysis. Tape wrapped around the container may interfere with assay.

Do not use permanent type markers when identifying subs in absorbent containers if the ink may penetrate into the product thus contaminating the sample.

Diamond or carbide tipped stylus pencils may be used to mark tin, glass, etc. Do not use diamond or carbide tipped stylus to mark products in glass under pressure (i.e., carbonated beverages).

4.5.2.4 - Photographs

Unless they are part of a DOC Sample, photographs are exhibits, to an EIR, report of investigation, or complaint. They are not samples. Photos taken during inspections and investigations are not described on a C/R, but are submitted as exhibits with the EIR. Photographs related to DOC Samples, i.e., labeling, records, product, etc. are identified with the sample number, collection date, and handwritten initials on the border or backside. See IOM 5.3.4.2.1 Attach the photos to the printed FACTS Collection Record. See IOM 4.4.10.5.

In describing photographs, do not mark the face of the print. Narrative descriptions may be placed on the mounting paper next to the print or, if explanatory graphics are required, use a plastic overlay. See IOM 5.3.4.2.3 for negative identification and submission procedures.

4.5.2.5 - Records - Accompanying Literature and Exhibits

Identify all copies of sample records, accompanying literature, and attached documents with the sample number (including prefix, if applicable), collection date and your handwritten initials as described in IOM 4.5.2.1. If an attached document is more than one page in length, it must be numbered or attached in a manner that will always allow further reviewers to determine if any pages are missing.

4.5.3 - SAMPLE HANDLING

All samples must be handled, packaged, and shipped to prevent compromising the identity or integrity of the sample. Samples must be packed with shock absorbing materials to protect against breakage of containers or damage to Official Seals. Frozen samples must remain frozen; perishable products may be frozen, if freezing doesn't interfere with the planned analysis, products requiring refrigeration (e.g., fresh crabmeat for bacteriological analysis) should be shipped in ice. Use your experience and knowledge (and that of your supervisor, if necessary) to determine the most appropriate packing and shipping method.

4.5.3.1 - Fumigation

See IOM 1.5.3.1 for safety precautions.

General - As soon as possible, freeze any sample containing, or suspected to contain live insects, as long as freezing will not change or damage the product or break the container. If freezing is inappropriate to maintaining the integrity of the sample, fumigation may be carried out using air tight containers (such as a mason-type jar with inner ring, or a polypropylene container with air tight lid), with sufficient fumigant to kill the insect infestation. Contact your servicing laboratory for alternative fumigants.

Moth crystals, containing paradichlorobenzene (PDB), is an alternative fumigant. Do not use mothballs or moth flakes containing naphtha or naphthalene. Do not use moth crystals in or near plastics, particularly Styrofoam/ polystyrenes as crazing or melting may occur. Other alternative fumigants include: liquid household ammonia or ethyl acetate, either of which can be used to dampen a cotton ball and placed in an appropriate container; or cut small portions of commercial pesticide strips.

4.5.3.1.1 - Fumigation Safety Precautions

Follow safety precautions when fumigating samples. Contact your local servicing laboratory or MSDS for the appropriate protective gear and handling of fumigants.
Guidance is as follows:

1. Carry all alcohols, fumigants, and other hazardous liquids in approved safety containers.
2. When fumigants or preservatives are used, limit your exposure to these chemicals. Minimize transfer and exposure time. Avoid getting chemicals on hands or clothing. DO NOT MIX CHEMICALS.
3. Insure DOT guidelines are followed when mailing or shipping samples containing fumigant or preservative. Exceptions for small quantities are listed in 49 CFR 173.4. If the samples are sent via Federal Express, the International Air Transport Association (IATA) dangerous goods regulations must be met. (Call 1-800-238-5355, extension 922-1666 for specific instructions for shipment.)
4. The sample identification data on your packaging, the FDA-525 and C/R, must always identify the fumigant and method of fumigation, and/or preservative used.
5. Material Safety Data Sheets (MSDS) for each chemical fumigant or preservative used must be available at each duty site and enclosed with the shipped sample. Read and follow all instructions and precautions listed on the MSDS.

4.5.3.1.2 - Procedures for fumigation

Place a small amount of fumigant, in an airtight container. Separate the fumigant from the sample with a piece of paper, paper napkin, or unscented facial tissue. Put specimen or product into container and seal tightly. Do not re-open container unless absolutely necessary. If possible, use a glass container with a lined screw lid. A mason-type jar with inner ring is also acceptable.

4.5.3.1.3 - Exceptions to Fumigation

When submitting samples or exhibits to show live infestation, do not fumigate. Consult with your supervisor or your servicing laboratory PRIOR to sending or bringing a live infestation into the laboratory to permit preparation for proper handling and storage. Do not fumigate sample when submitting samples for pesticide residue analysis.

4.5.3.1.4 - Preservation Liquids

Insects may be killed and preserved in 70% ethyl alcohol or a 1:1 mixture of 70% ethyl alcohol and glycerin (may be labeled glycerol). These chemicals can be obtained from your servicing laboratory. Do not collect rodents or animal tissues unless specifically instructed. Insure all vials or bottles of preservation liquids are tightly sealed to avoid leakage. Identification labels may be placed in containers, but must be written in India ink or 2H pencil only. Keep all preservation liquids away from excessive heat or open flame.

Identify preservative used on FDA 525, C/R, and on sample container. Enclose a copy of the MSDS with the shipped sample. Follow DOT and IATA guidelines when shipping or mailing samples with preservatives as stated under fumigants.

4.5.3.2 - Labeling

Samples collected for label review only should be officially sealed in clear plastic bags. This will permit cursory review and, if necessary, photocopying of the container label and reduce the need to break the seal each time the label is examined.

4.5.3.3 - Samples for Pathological Examination

Tissue samples are not routinely collected for microscopic or pathological examination. Authorization must be obtained from the appropriate Center before collecting samples of this material.

When assigned to collect tissue samples, unless directed otherwise by the program, the assignment, or your supervisor, cut the tissue into 1/4 inch pieces and preserve in 10% buffered formalin, or in other suitable preservatives as directed. Do not freeze the sample since frozen tissue is not suitable for pathological studies.

4.5.3.4 - Small Sample Items

Samples in small vials, bottles, boxes and similar type containers may be placed inside the FDA 525 envelope after identification. When the envelope is used as the sample package, place the official seal across the glued flap and the blank face of the form.

If the sample container (vial, bottle, etc.) is officially sealed, it may be placed in the same FDA 525 together with copies of the assignment.

4.5.3.5 - Frozen Samples

Containers - Pre-chill sterile containers before collecting frozen samples. Transfer liquids in glass to expandable containers before freezing. If the liquid must be frozen in glass, leave sufficient headspace to allow expansion. If freezer facilities are not available or if the sample is to be shipped, pack with dry ice in insulated cartons.

Dry ice and insulated cartons may be obtained from ice cream or dry ice dealers, and economical polystyrene (Styrofoam) containers are available at most variety stores. However, while Styrofoam containers have excellent insulating qualities, they will not withstand shipping abuse unless protected by sturdy outer cartons.

Note: If your district desires the return of Styrofoam freezer chests or ice packs used in shipping samples, note this fact on the C/R and FDA 525.

Dry Ice - Caution: Dry ice is potentially dangerous and requires caution in handling and shipping. Do not handle with unprotected hands; transport in your car without adequate ventilation; or place inside tightly closed metal, glass, plastic, or similar type containers that do not breathe. If it is necessary to use this type container, adequately vent to prevent pressure build up.

Note: If a sample is to be analyzed for ammonia contamination, it must not be shipped frozen in dry ice. Use other methods of freezing, if frozen shipment is necessary.

4.5.3.5.1 - Shipping Frozen Samples

If using a U.S. Government Bill of Lading, it is important to give a full and accurate description of the sample for rate purposes. If more than one commodity is in the shipment, describe and enter each separately.

In all packages where dry ice is used, distribute the dry ice equally on all sides of the sample package using pieces as large as possible. Be sure the container is insulated on all six sides and tape all edges securely to assist in insulating the carton. Do not place dry ice inside officially sealed packages.

Freezing by dry ice is not effective for more than forty-eight hours. For overnight shipments, use at least one pound of dry ice per pound of sample. Increase the amount for longer hauls or unusually warm weather. (Note: When samples are in plastic type containers, the dry ice must be wrapped in paper to prevent direct contact with the plastic. The extreme cold generated by the dry ice may cause plastic to become brittle and rupture.)

Shipments made via FedEx Corporation, Priority I, Purolator, Airborne or by other fast air express carriers, will be delivered to consignees early the next business day. Tests have shown the following amounts of dry ice will be adequate when this method is used:

For samples already in frozen state: five to ten pounds of dry ice depending on sample size is normally sufficient. For samples requiring only to be refrigerated: A minimum of ten pounds of dry ice is sufficient.

Note: The dry ice may freeze the edges of the product, so if it is imperative no part of the sample becomes frozen, use coolants other than dry ice. Mark the FDA 525 that dry ice was used.

See IOM 4.5.5.8.6 when shipping sample packages containing hazardous or toxic items, including dry ice, by air.

4.5.3.5.2 - Control

To prove the shipment did not thaw in transit, place a jar or leak proof plastic bag of chipped ice in the shipment adjacent to the sample package, but not within the officially sealed package.

4.5.3.6 - Refrigerated (Not Frozen) Samples

Maintain refrigerated (not frozen) samples in a refrigerator at 4.4^oC (40^oF) or below. Use either wet ice or some type of "Ice Pak", "Liquid Ice", "Sno-Gel", "Kool-It", or similar products to maintain the required temperature range.

Place Ice Paks, etc., in sealed plastic bags to protect samples from possible contamination should the container break, the ice melt, or the refrigerant penetrate the sample. Use Styrofoam insulated shipping cartons for shipping samples to the laboratory.

4.5.3.6.1 - Control

If it is necessary to show the sample temperature did not go above the desired or specified temperature, you can use one of several methods, such as including a pre-chilled, shaken down, maximum reading thermometer or commercially available indicators. Take care to place the thermometer outside of the sealed sample package and attempt to place in an area anticipated to be likely to reach the highest temperature. Describe the method used on your C/R.

4.5.4 - OFFICIAL SEALS

Domestic samples, regardless of type, shall be sealed with form FDA 415a, Official Seal, or, in some situations with the FDA "metal Seal". See IOM 4.5.4.6 for use of metal seals. See also IOM 4.1.4.2.

Note: With the approval of your supervisor and laboratory, it is not necessary to affix an official seal to a sample that will be in the sample collector's continuous personal custody until it is submitted personally to an analyst. This procedure should be reserved for emergencies and high priority situations. The sample should be submitted the same day it is collected with the subs properly identified. The C/R must state you personally delivered the sample to "Analyst ______"or other appropriate staff member.

Make every effort to prepare and submit your samples on the date collected so the C/R, sub identification, and the final official seal bear the same date, and thus enhance sample integrity. However, if you cannot finish the sample preparation on the same day collected, you must explain in the C/R Collection Remarks field what steps you took to protect the integrity of the sample, e.g., officially sealed and locked in supply cabinet, locked in safe, etc.

Never place more than one sample in the same officially sealed package.

4.5.4.1 - Preparation

Inscribe FDA 415a, official seal, with the district office name, sample number (with the appropriate prefix), the date applied, your signature, printed name and title. See IOM Exhibit 4-17. The seal must bear only one signature. If more than one person is involved in collecting the sample, the person preparing and signing the collection record must sign the seal.

4.5.4.2 - Application

Seal the sample package so that it cannot be opened at any point without evidence of tampering. If the surface of the sample container is of such construction or condition that the FDA-415a, official seal, will not adhere (e.g., waxed carton, frosted over, sweating, etc.), wrap or place sample in a container to which the official seal will hold. See IOM 4.5.4.6.

When using the self-adhering seals, the surface on which the seal is to be placed must be clean and dry. The seal must be rubbed when affixed to generate heat and help it bond.

4.5.4.3 - Sealing Method

There are many acceptable methods of officially sealing samples. Because of the wide variety of shapes and sizes of samples, and the ingenuity you may have to apply to package and packaging situations, explicit methodology will not be detailed here. Your supervisor, your on-the-job training, and your developing experience will familiarize you with the most effective methods.

4.5.4.4 - Protecting the Official Seal

Protect the sealed surface by wrapping the package securely with heavy wrapping paper for mailing or shipment.  If your officially sealed package is not further wrapped for shipping and the tape(s) and official seal are thus exposed, you must protect the Official Seal from damage during shipment by:

1. Covering the official seal with a sheet of heavy wrapping paper or heavy clear plastic (e.g. from a document protector) of sufficient size to cover the surface of the official seal.
2. Tape the protective paper or heavy clear plastic securely around the edges so it cannot come loose and expose the official seal. Do not paste or glue the paper or plastic to the face of the official seal since this will obliterate the official seal when removed.
3. When you protect the official seal by heavy paper, write "FDA Seal Underneath", or similar wording across the protective paper. This alerts the receiving custodian the official seal is underneath, and to take care when removing the protective paper. If you cover and protect the seal with heavy clear plastic, the sample custodian will be able to copy the necessary information off the seal without removing the protective cover.  

4.5.4.5 - Broken Official Seals and "Temporary Seals"

Reseal the sample whenever you break the official seal. Each seal used on the sample will be submitted with the records associated with the collection record, properly initialed and dated, to provide a continuous history.

There is only one class of seal: an "official seal". Anytime a sample is sealed with the FDA 415a, or with the FDA Metal Seal, the item is "officially sealed". An officially sealed sample must sometimes be reopened to prepare it for submission to the laboratory, or for some other legitimate reason. In that situation, the original seal must show the date it was broken. When the sample is ready to be resealed the new seal must show the date it is applied. This procedure must be followed each time the official seal on a sample is broken. Each seal will show the history of the date it was applied and broken. See instructions in Exhibit 4-17. Indicate in the collection remarks field of the FACTS C/R the fact that the seal was broken and reapplied and attach the broken seal to the printed FACTS C/R. This provides an unbroken, documented chain of custody.

4.5.4.6 - Metal Seals

Where it is impossible to use the paper official seal, the numbered self-locking "U.S. Food and Drug" metal seal may be used. This seal is effective for use on wooden crates, drums, baskets, etc., where the FDA 415a cannot be used. Record the number of the metal seal used on the CR. See IOM 4.3.4.3 for instructions on the use of the metal seal to reseal railroad cars or conveyances. When a supply of these seals are needed by your district, contact the Division of Field Investigations (DFI) (HFC-130) at 301-827-5653.

4.5.4.7 - Sealing Non-Sample Items

Although the primary purpose of the official seal is for sealing samples, there are times when the official seal may be used to officially seal items other than samples. The FDA metal seal is often used to seal rail cars or vehicles as indicated in IOM 4.3.4.3.

When directed by your supervisor, you may use an official seal to seal questionable or suspicious bioresearch records encountered during an inspection or investigation to prevent tampering or to preserve their integrity. As explained in the applicable compliance program, the procedure must have the approval of the bioresearch monitoring staff (HFC-230) prior to implementation.

4.5.5 - SAMPLE SHIPMENT

When you cannot personally deliver a sample to the examining laboratory, ship it by the most economical means commensurate with the need for rapid handling. See IOM 4.5.5.2 and 4.5.5.6 for special information on shipments to FDA Headquarters' laboratories.

FDA collects a wide variety of samples, many of which are unstable, toxic or hazardous material, e.g., etiological agents, radiation products, chemical, hard swells, etc. Use safety precautions in handling and shipping commensurate with the hazard. See IOM 4.5.5.8.7.

4.5.5.1 - Sample Package Identification

Form FDA 525 - Place the FDA 525, sample package identification, near the official seal. For small containers or surfaces that will not accommodate the FDA 525, you can tie it to the sample package by using twine through the eyelet. Do not affix the FDA 525 on the outside of the shipping carton or under the official seal. Enclose a copy of the assignment document in the FDA 525 envelope and provide the following information on the FDA 525:

1. District or Headquarters' laboratory to which the sample is directed, City, State, and unit symbol (e.g., SRL, HFD-400, HFS-300, etc.).
2. Date.
3. Your district and symbol.
4. Sample Number.
5. Name of dealer.
6. Product Identification.
7. Address of dealer.
8. Enter the reason for collection. (Copy from C/R.) Provide reference to any sampling assignment.
9. Provide information as to the analysis to be made.
10. Enter any pertinent remarks. Note if your district desires the return of any freezer chests, ice packs, or maximum/minimum thermometers used.
11. Provide any special storage instructions. Mark appropriate block and enter suggested refrigeration temperature if necessary. Elaborate in Remarks if necessary.
12. Print your name.

See IOM 4.5.3.4 and the reverse side of the FDA 525 when using the FDA 525 as a sample package. See IOM 4.5.5.3.6 for information to include with the FDA 525 for medical device samples.

Outer Wrapper - Always place the words, "SAMPLE NO. ________" followed by the actual FACTS or OASIS sample number(s)(with appropriate prefix) on the outside of the package near the address label. This alerts the receiving mail room that the package contains a sample and must go to the sample custodian.

4.5.5.2 - Routing of Samples

In general, samples will be submitted to your district's designated servicing laboratory, except as directed by the Compliance Program Guidance Manual, assignment or your supervisor. The following provides general guidance for sample submission.

1. Vitamin and Nutritional Labeling - Submit to FDA, Science Branch (HFR-SE680), 60 Eighth St. N.E., Atlanta, GA 30309.
2. Radiopharmaceuticals for Sterility - Submit samples to WEAC.
3. Tissue Residues - Submit to the Denver District Tissue Residue Lab.

A complete, current listing of designated servicing laboratories can be found in the current ORA Field Workplan as Appendix III. This appendix is comprised of a table designating the servicing laboratories for each collecting district and for each compliance program or subpart.

4.5.5.3 - Samples to Administration Laboratories

When shipping samples to headquarters or other special laboratories follow the procedures for each laboratory.