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ORA Laboratory Manual Volume III Section 2

Document Number:

III-02

Revision #: 02

Revision Date:

06/06/2019

Title: 

Chain of Custody – Sample Handling Page 1 of 21

For the most current and official copy, check QMiS.

Sections in This Document

1. Introduction................................................................................................................................. 2

1.1. Sample Documentation ................................................................................................... 2

1.2. Definitions ........................................................................................................................ 3

2. Protection and Storage of Samples in the Laboratory............................................................... 5

2.1. Physical Security of FDA/ORS Laboratory Facilities ...................................................... 5

2.1.1. Controlled Areas................................................................................................ 5

2.2. Security of Samples and Controlled Substances in the Laboratory ............................... 6

2.2.1. Analyst Storage of Samples.............................................................................. 6

2.2.2. Temporary Sealing of Samples......................................................................... 6

2.2.3. Import Samples ................................................................................................. 7

2.2.4. Controlled Substances (Schedule I and II drugs)............................................. 7

2.3. Environmental Storage Conditions for Samples ............................................................. 7

3. Custodial Receipt and Storage of Samples ............................................................................... 8

4. Receiving Samples from Custodial Storage and Opening the Sample Package ..................... 9

4.1. Receiving Samples from Custodial Storage ................................................................... 9

4.2. Opening the Sample Package......................................................................................... 9

4.2.1. Breaking Official Seals .................................................................................... 10

4.2.2. Opening the Package and Inspecting the Sample ......................................... 10

5. Intra/Inter Laboratory Splitting and Transferring of Samples .................................................. 11

5.1. Splitting and Transferring Samples within the Laboratory ............................................ 11

5.2. Recording the Sample Transfer on the Analytical Worksheet...................................... 11

5.3. Recording Sample Transfer through FACTS................................................................ 11

5.4. Splitting and Transferring Samples between FDA/ORS Laboratories or External (NonORS) Entities................................................................................................................. 12

5.4.1. Recording the Sample Transfer on the Analytical Worksheet ....................... 12

5.4.2. Recording Sample Transfer through FACTS.................................................. 12

6. Reserve Samples..................................................................................................................... 12

6.1. Sealing the Reserve Samples....................................................................................... 13

6.2. Documenting the Reserve Samples.............................................................................. 13

7. Returning Samples to Custodial Storage................................................................................. 14

7.1. Returning Samples to the Sample Custodian............................................................... 14

7.2. Returning Samples to Storage Areas not Controlled by the Sample Custodian.......... 14
FOOD AND DRUG ADMINISTRATION

OFFICE OF REGULATORY AFFAIRS

ORA Laboratory Manual Volume III Section 2

Document Number:

III-02

Revision #: 02

Revision Date:

06/06/2019

Title: 

Chain of Custody – Sample Handling Page 2 of 21

For the most current and official copy, check QMiS.

8. Shipping Samples from the Laboratory.................................................................................... 15

8.1. Shipping the Entire Sample........................................................................................... 15

8.1.1. Sample is Stored in the Custodial Storage Area............................................ 15

8.1.2. Sample is in the Custody of the Analyst......................................................... 15

8.2. Shipping a Portion of the Sample.................................................................................. 16

8.2.1. Samples Stored in the Custodial Storage Area.............................................. 16

8.2.2. Samples in the Custody of the Analyst........................................................... 17

8.3. Documenting the Sample Shipment.............................................................................. 18

9. Disposition of Samples............................................................................................................. 18

9.1. Sample Destruction ....................................................................................................... 18

9.2. In-House Disposition of Reserve Samples ................................................................... 19

10. References ............................................................................................................................... 19

11. Document History..................................................................................................................... 19

12. Change History......................................................................................................................... 20

13. Attachments.............................................................................................................................. 21

1. Introduction

The FDA national procedures for sample management are found in ORA 

Laboratory Manual, Volume II, ORA.LAB.5.8 Sample Management. This 

document provides additional sample chain of custody work instructions for 

such operations as laboratory receipt of sample, storage, protection, opening 

the sample package, handling split samples, shipment of samples, and 

disposition. 

Field Accomplishments Compliance Tracking System (FACTS) centralizes the 

data gathered by Office of Regulatory Affairs (ORA) into one nation-wide 

system. FACTS is therefore recognized as the Food and Drug 

Administration’s (FDA) automated system for field assignments, firm 

information, compliance actions, time reporting, and sample tracking.

Basic FACTS training is provided by staff during the analyst’s training period.

1.1. Sample Documentation

A. Laboratory receipt of samples is documented in FACTS. The method of 

documenting the laboratory receipt of samples is dependent on the 

following:

1. sample has been entered into FACTS for sample analysis prior to 

arriving at the laboratory;
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ORA Laboratory Manual Volume III Section 2

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2. availability of the FACTS system.

3. sample has not been entered into FACTS for sample analysis prior 

to arriving at the laboratory, or 

4. sample has been entered into FACTS for storage only.

B. When sample not entered into the FACTS application prior to arriving at 

the laboratory: 

1. the sample accountability procedures cannot be performed (e.g. 

laboratory receipt, sample transfer) in the system. 

2. Sample analysis can proceed only with management approval and 

special circumstances (e.g. when the nature of the sample dictates 

that withholding such analysis will seriously affect the product 

causing microbial growth, deterioration or contamination, or 

immediate results are needed due to an emergency situation).

In this case, the laboratory will utilize its Computer Contingency Plan 

in order to document the sample receipt operations.

1.2. Definitions

A. Analyst - The term “Analyst” applies to all professional and 

paraprofessional positions associated with the analytical operation of 

the laboratory.

B. Analytical package - The Analytical package consists of the Analytical 

Worksheet and other documents directly related to the sample (e.g. 

collection report, memorandum of analysis).

C. Controlled areas – Controlled areas are designated areas that contain 

information or material requiring additional protective measures and 

strict access controls. These areas may store pharmaceuticals, alcohol, 

samples, or be a document/computer room. Only authorized personnel 

are allowed in controlled areas.

D. Controlled drugs and substances (Schedule I and II) – Controlled 

drugs and substances (scheduled I and II) are designated by the 

Controlled Substance Act as amended to 21 Code of Federal 

Regulations (CFR) 1308.11-12, current revision.

E. FACTS – FACTS is the FDA acronym for the Field Accomplishments 

and Compliance Tracking System.

F. Laboratory supervision – Laboratory supervision includes managerial 

positions from the First-Line Supervisor to the Laboratory Director.
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ORA Laboratory Manual Volume III Section 2

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G. Official Sample (21 CFR 2.10) - An official sample is one taken from a 

lot for which Federal jurisdiction has been established. If violative, the 

official sample provides a basis for an administrative or legal action. 

Official samples generally consist of “goods,” or a physical portion of the 

lot sampled, but not always. Official samples are further classified 

according to the manner in which they are collected, how Federal 

jurisdiction is established, and their intended use or purpose.

H. Sample accountability - The term “sample accountability” includes 

requirements for proof of sample receipt, storage, transfer of sample or 

sample portions between individuals, analysis, disposition authorization 

and destruction. Records covering these transactions are part of the 

regulatory file. A permanent FACTS record achieves uniform 

accountability for samples in the FDA/ORS laboratory system. See ORA 

Laboratory Manual, Volume II, ORA.LAB.5.8 Sample Management.

I. Sample custodian – The person(s) granted the role of Sample 

Custodian within FACTS are responsible for receiving all samples into 

the laboratory, both physically and electronically in FACTS, from the 

collector. This person(s) assures the samples are stored under the 

appropriate environmental conditions until the sample is transferred to 

the assigned analyst. The Sample Custodian also ensures proper 

disposition of all samples and records the disposition in FACTS, 

whether or not the sample is analyzed.

J. Samples – Samples are identified as all items, both domestic and 

import, collected and identified as Official Samples. Import samples 

need not be sealed, unless Division Policy dictates, as long as the 

integrity of the sample is maintained, (See Investigations Operations 

Manual, Official Samples, and Section 10 References)

K. 702(b) Portion - In accordance with the provisions of Section 702(b) of 

the FD&C Act, a portion of an official domestic sample collected directly 

from the manufacturer or if requested under other circumstances, is to 

be available for examination or analysis by any person named on the 

label of the article, or the owner thereof, or his attorney or agent. The 

two exceptions to this regulation are Medical Devices and Import 

Samples. Medical devices are not specifically referenced in 21 CFR 

2.10(b) and samples being imported or offered for entry into the United 

States are exempt under 21 CFR 2.10(b)(4).

The sample, no matter what the content, may be involved in a court 

proceeding, and therefore must be preserved by the best means 

possible. Preservation must be effective until any legal or regulatory 

actions are completed. 
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ORA Laboratory Manual Volume III Section 2

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2. Protection and Storage of Samples in the Laboratory

2.1. Physical Security of FDA/ORS Laboratory Facilities

The General Services Administration (GSA) has established government-wide 

minimum physical security standards for federal facilities. Due to the 

differences found in federal facilities, (e.g. size of the facility, number of 

employees, use and mission of the agencies) there are five security levels 

based on minimum standards for each security level. The categories range 

from Level I (e.g. a leased space with ten or fewer employees) to level V (e.g. 

a large building with many employees and a critical national security mission 

as found in the Pentagon).

The FDA Physical Security Staff (HFA-204) maintains a database for all FDA 

facilities, their assigned security level, and the physical security standards 

associated with each security level.

The FDA Staff Manual Guide f:2280.2, Physical Security in Field Activities, 

provides additional instructions for physical security in FDA field offices. This 

includes: building security; protection of official samples; visitor control; 

document security; controlled substances (Schedule I and II); alcohol (95% 

and absolute). The Guide also provides security instructions for some other 

laboratory items such as platinum dishes United States Pharmacopoeia (USP) 

reference standards, National Institutes of Standards Technology (NIST) test 

weights, and syringes (1 mL to 20 mL).

2.1.1. Controlled Areas

The following areas are designated as controlled areas within the laboratory 

and need additional protective measures to ensure the integrity of the security 

interest involved:

A. Drug vault/storage area;

B. Solvent storage area;

C. Alcohol storage area;

D. Sample storage area;

E. Radioactive Material Area;

F. Infectious Materials Room;

G. Sterility Testing Room;

H. PCR Room;

I. Document room;

J. Computer room; and
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ORA Laboratory Manual Volume III Section 2

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K. Mail room

For these controlled areas, the following additional protective measures are 

provided:

A. Access is limited to only those who need access in the performance of 

their official duties. 

B. Entrances are secured at all times or monitored by an authorized 

employee or security guard.

C. Doors are equipped with high security locks or card readers with alarm 

contacts. High security locks are keyed “separately” from the building 

master key system. Card readers are keyed “alike.”

D. Controlled areas are cleaned only during normal working hours and 

under the supervision of an authorized employee or security guard.

E. Locks or their combinations are changed if the key or combination has 

been compromised, if the area has been discovered unsecured or 

unattended, or when an employee no longer needs access due to 

transfer, termination, retirement.

2.2. Security of Samples and Controlled Substances in the Laboratory

The Sample Custodian is responsible for the initial and final stages of sample 

storage. 

Samples are secured in a storage area where additional security measures 

can be effectively implemented in accordance with Section 2.1.1 Controlled 

Areas.

2.2.1. Analyst Storage of Samples 

The analyst is responsible for the integrity, security, and proper handling of the 

sample while it is in his or her possession. All portions of the sample in the 

analyst’s possession are kept in a secured laboratory area (e.g., analyst’s 

lockable cabinet) when not under the analyst’s control. 

2.2.2. Temporary Sealing of Samples

When secured storage is not possible, a temporary seal is used to 

demonstrate that sample integrity was maintained. The temporary seal is an 

Official Seal (FDA-415a) used for securing a sample for a short period. When 

the temporary seal is broken, the seal is initialed and dated. 

The temporary seal and the following information is submitted with the 

worksheet:

A. The fact a temporary seal was used,
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ORA Laboratory Manual Volume III Section 2

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B. How the temporary seal was used, and

C. The quoted temporary seal.

2.2.3. Import Samples

Import Samples are Official Samples and require the same integrity as 

domestic Official Samples. Import Samples need not be sealed, unless 

Division Policy dictates, as long as the integrity of the sample is maintained. 

(See Investigations Operations Manual, Official Samples)

2.2.4. Controlled Substances (Schedule I and II drugs)

Controlled substances are secured in a drug storage vault/area where 

additional security measures can be effectively implemented in accordance 

with Section 2.1.1 Controlled Areas. After issuance, additional security controls 

(e.g. sample storage, inventory) are implemented.

2.3. Environmental Storage Conditions for Samples

When a Sample Custodian or analyst receives a sample for analysis, he or she 

assures that the product is provided proper environmental storage. Samples 

are stored at frozen, refrigerated, or ambient temperatures, depending on the 

type of sample and the analysis that is being conducted.

Environmental storage conditions are in accordance with those instructions:

A. Received with the sample, 

B. Described in the FACTS record for the sample, or

C. Instructed by the Laboratory Supervisor or Analyst.

Samples are maintained at the following temperatures:

A. Frozen samples are maintained at -28 to -18°C

B. Refrigerated samples are maintained at 2 to 8 °C; and

C. Ambient samples should be protected from heat and moisture.

Brief temperature fluctuations outside specified ranges are acceptable as long 

as sample integrity is maintained. Various temperature measurement devices 

(e.g. calibrated thermometers, thermocouples interfaced with computer 

systems and temperature recorders) may be used to monitor temperature 

control. All sample storage temperature information is recorded at a minimum 

daily and in accordance with the laboratory’s local Standard Operating 

Procedures (SOP) or work instructions. See ORA Laboratory Manual, Volume 

II, ORA.LAB 5.3 Facilities and Environmental Conditions for general laboratory 

requirements.
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ORA Laboratory Manual Volume III Section 2

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3. Custodial Receipt and Storage of Samples

Samples are delivered to the ORS laboratory receiving area, (e.g. shipping 

company, state personnel, and other private courier). 

Any chain of custody form (e.g. from the Office of Criminal Investigations) 

received with the sample follows the sample records throughout the laboratory.

It is the responsibility of the person receiving physical custody of the sample to 

initiate the original record of sample receipt. The Sample Custodian receives 

the majority of samples delivered to the laboratory. Occasionally, an analyst or 

supervisor may receive a sample into the laboratory. 

Only those designated with the FACTS sample custodial role may 

electronically receive and sign for the laboratory receipt of the sample within 

FACTS. If the sample is received in the laboratory by someone who does not 

possess the role of Sample Custodian, the receipt of the sample must be 

recorded.

If FACTS is unavailable (e.g. computer server is down) at the time of 

laboratory receipt of the sample, the laboratory uses its Computer Contingency 

Plan in order to record sample receipt and handling operations.

All samples should be kept in their original shipping container until ready to be 

entered into FACTS by the Sample Custodian. Frozen samples should be 

priority to avoid thawing. 

Sample packages are inspected during laboratory receipt processing to assure 

the following:

A. Physical condition is satisfactory,

B. Official seal (if present) is intact, and

C. Identification on the sample package matches that described in the 

accompanying records and/or in the FACTS “Collection Report” record. 

Immediate action is taken to record and reconcile any discernible 

abnormalities and/or discrepancies such as the following:

A. Conflicting sample numbers,

B. Broken seals, 

C. Breakage, and

D. Leakage or thawing. 

Abnormalities and/or discrepancies are recorded according to SOP-000285 

Sample Feedback Report Process using the Sample Feedback Report (SFR) 
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located in QMiS. The sample may be placed on hold pending resolution of the 

issue. 

The Sample Custodian (or designee) completes laboratory receipt and 

custodial storage of the sample by recording the relevant information in the 

FACTS “Lab Receipt of Sample” record. 

If FACTS is unavailable, (e.g. computer server is down) at the time of the 

sample receipt, the laboratory uses its Computer Contingency Plan to 

document the sample receipt operations.

Stored samples are provided the physical security measures as described in 

the Section 2.1.1 Controlled Areas and Section 2.3 Environmental Storage 

Conditions for Samples.

4. Receiving Samples from Custodial Storage and Opening the Sample Package

4.1. Receiving Samples from Custodial Storage

When needed for laboratory use, the Analyst obtains a stored sample from the 

Sample Custodian, and the transfer/change of custody of the sample is 

documented using FACTS or LIMS. This transfer is also recorded on the 

worksheet.

The analyst verifies that the physical sample received matches that described 

in the Sample Packages section of the FACTS “Lab Receipt of Sample” 

record. Any observed discrepancies (e.g., package number, condition, seal 

inscription, seal condition) are recorded on the analytical worksheet and the 

Sample Feedback Report.

The analyst verifies that the physical sample received matches that described 

in the FACTS “Sample Transfer” record. Any discrepancies (e.g., quantity, unit, 

split number) between the sample and that described in the FACTS “Sample 

Transfer” record are immediately reported to the Sample Custodian. 

Discrepancies are reconciled and, if needed, the FACTS record is corrected. 

If FACTS is unavailable, (e.g. computer server is down) at the time of the 

sample transfer, the laboratory uses its Computer Contingency Plan to 

document the sample transfer operations.

4.2. Opening the Sample Package

After receiving custody of a sample, the analyst performs the following 

functions:

A. Breaks the Official Seal (if present); and

B. Opens the package and inspects the sample. 
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4.2.1. Breaking Official Seals

Once the sample is packaged for transport to its designated laboratory, it is 

sealed so that it cannot be opened at any point without evidence of tampering.

Form FDA-415a is the Official Seal for samples. A numbered self-locking “US 

Food and Drug” metal seal may be used where a paper seal is not possible or 

practical. This seal is effective for use on metal drums and baskets where the 

FDA-415a cannot be used. 

The Investigations Operations Manual (IOM) Chapter 4, Subchapter 4.5.4 

Official Seals, discusses the following:

A. Application of official seals,

B. Sealing methods,

C. Protecting the official seals,

D. Broken official seals and temporary seals, and

E. Metal seals. 

The seal is broken, when possible, across the section showing the sample 

number, date, and signature of the Collector. The analyst who broke the seal 

initials and dates it in ink in the designated area at one end of the paper seal. 

It is acceptable to break the paper seal in another location, if necessary. See 

IOM Exhibit 4-17. When breaking a metal seal, a sharp metal tool is used to 

scratch initials and date on the seal.

Generally, original seals are not to be removed from the sample package. If 

removed, the broken seal is submitted with the Analyst Worksheet as an 

attachment and noted on the Analyst Worksheet in block 11, Reserve Sample. 

The entire seal, with all fields easily visible, is attached to mounting paper and 

identified with the attachment number, sample number, date, and initials in the 

upper right corner. See ORA Laboratory Manual, Volume III, Section 3, 

Recording of Results Analyst Worksheet.

4.2.2. Opening the Package and Inspecting the Sample

After breaking the Official Seal (if present) and opening the package, the 

analyst removes and inspects the sample. 

The analyst records any discernible abnormalities, discrepancies, and 

problems on the analytical worksheet and a Sample Feedback Report form. 

The problems may include:

A. Discrepancies between the sample received from the sample described 

in the FACTS “Collection Report” or any other record,
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B. Broken paper seals without initials or date in the designated area,

C. Damaged sample or sample package,

D. Records failing to describe type of analysis requested, and

E. Sample inappropriate for sample analysis requested.

5. Intra/Inter Laboratory Splitting and Transferring of Samples

5.1. Splitting and Transferring Samples within the Laboratory

A split/transfer of a sample occurs when a sample requires an additional 

analysis by another analyst or laboratory. If the sample will be analyzed in its 

entirety at the designated servicing laboratory, an intra-laboratory transfer or 

split is performed in FACTS. 

If the original analysis is complete, the entire sample may be 

transferred/change custodianship to the next analyst for the additional 

analysis. If the original analysis is not complete, the sample may be split into 

smaller portions. Of these smaller portions, one portion will be analyzed by the 

original analyst and the “split” portion will be transferred to the next analyst 

who will perform the additional analysis.

5.2. Recording the Sample Transfer on the Analytical Worksheet

To ensure sample integrity, information regarding delivery and receipt of 

samples or sample portions is recorded on a new analyst worksheet as 

follows:

A. Sample description and amount delivered (Blocks 7 and 8);

B. Sample identification (Block 2);

C. Date (Block 4); 

D. Name of analyst(s) involved in the sample exchange (Block 5), and;

E. Brief explanation of the reason for transfer (on 431 or 431a).

5.3. Recording Sample Transfer through FACTS

The FACTS “Sample Transfer” and “In-House Split” operations document 

intra-laboratory sample transfers and splits. The “In-House Split” is initiated by 

the original Analyst. Each portion of the “split” is given its own unique 

alphanumeric identification that becomes part of the sample number. The “InHouse Split” allows each analyst to independently return the reserve portion to 

the Sample Custodian or dispose of it appropriately. These individual 

transactions are documented in FACTS.
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5.4. Splitting and Transferring Samples between FDA/ORS Laboratories or 

External (Non-ORS) Entities

If additional analysis of a sample will be performed at a facility other than the 

designated servicing laboratory, an interlaboratory split and transfer is 

performed in FACTS.

A sample that needs an additional analysis performed by a second FDA/ORS 

laboratory or external entity (e.g. non-ORS contract laboratory for specialized 

testing, return of a claimant’s sample) may be split into smaller portions and 

shipped.

For samples that are split between FDA/ORS laboratories, each examining 

laboratory handles and describes its portion of the sample as an original 

analysis. The original servicing laboratory retains an intact 702(b) portion, 

when required. The receiving laboratory is informed of the amount retained as 

the 702(b) portion.

5.4.1. Recording the Sample Transfer on the Analytical Worksheet

Documentation on the analyst worksheet includes the following:

A. Description of sample and amount delivered,

B. How it was prepared for delivery, 

C. How it was identified and sealed,

D. Brief explanation as to why the sample was sent, 

E. To whom the sample was sent and, 

F. Date of shipment.

5.4.2. Recording Sample Transfer through FACTS 

The FACTS “Sample Transfer” documents the transfer between the original 

servicing laboratory and another ORS facility or an external entity. This screen 

is also used to document a sample “Split” between the original servicing 

laboratory and either another section of the same lab, another ORS facility, or 

an external entity. The “Split” will add a unique alphanumeric identification 

after the sample number for each sample portion that is split or transferred 

within the laboratory. 

6. Reserve Samples 

At the conclusion of the analysis, the analyst annotates the status of the 

reserve sample on the worksheet and prepares the reserve sample for storage 

or shipment.
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The samples are returned to the Sample Custodians. Exceptions include the 

following circumstances:

A. Analyst has received permission in advance from laboratory supervision 

to effect immediate In-House Disposition of the sample (see 2.9 

Disposition of Samples),

B. Entire sample has been consumed during analysis, or,

C. Reserve sample needs special environmental storage or handling 

conditions not found in the sample storeroom.

The reserve sample consists of any remaining intact sample, sample 

composite(s), 702(b) claimant’s portion, and exhibits associated with an 

Official Sample (e.g. Investigator/Inspector filth exhibits, Analyst filth analysis 

plates, and microbiological isolates). Section 702(b) of the FD&C Act requires 

‘...upon request, provide a part of such official sample for examination or 

analysis by any person named on the label of the article, or the owner thereof, 

or his attorney or agent....’ A domestic sample collected directly from a 

manufacturer may not be used in its entirety, as an analyst is not authorized to 

use a 702(b) claimant’s portion.

Each portion of the reserve sample should remain in its original container, if 

possible, and, if appropriate, officially sealed using FDA-415a. The sample is 

then returned to the Sample Custodian for storage until the sample is 

dispositioned. If a seal is placed on the reserve sample, the seal is quoted on 

the Analyst Worksheet, FDA 431, Reserve Sample.

6.1. Sealing the Reserve Samples

The reserve portion of a sample is officially sealed using FDA-415a prior to 

being returned to the Sample Custodian. The seal is affixed so that it actually 

seals the sample package and the sample package cannot be opened without 

any evidence of tampering. More than one seal may be needed. The original 

broken seal is not to be defaced or hidden when resealing a sample. All seals 

must be visible to provide a chain of custody. The Investigator’s seal on the 

sample, the Analyst’s information on the broken seal and the Analyst’s seal(s) 

on the sample should all be visible for the sample to be introduced as a court 

exhibit.

6.2. Documenting the Reserve Samples

For accountability purposes, a clear description of the reserve sample, 

including the 702(b) claimant’s portion (if present), is documented on the 

analyst worksheet. The amount of reserve sample remaining is compatible 

with the amount received and the amount used in the analysis; any 

discrepancies are explained on the analyst worksheet.
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If no physical sample or exhibits remains: 

A. Analyst records “NONE” or “NO RESERVE” on the Analyst Worksheet 

or electronic form block 11, Reserve Sample, and, if applicable, 

documents the sample disposition in the FACTS.

B. If a sample is received with an official seal and no reserve portion 

remains, the analyst must include the broken official seal in the 

worksheet package or electronic form.

Conditions where no reserve sample remains are usually confined to no action 

indicated (NAI) import and NAI perishable samples where the supervisor has 

concurred in immediate destruction. 

If the entire FDA portion of the sample has been used in the analysis, an 

analyst may be instructed by a supervisor to return the empty container(s) 

under an official seal to the Sample Custodian for possible use in court.

7. Returning Samples to Custodial Storage

The laboratory reserve sample is kept until all legal or other action requiring 

the sample is closed. The reserve sample consists of any remaining intact 

sample, sample composite(s), exhibits and the 702(b) claimant’s portion, if 

applicable. 

Upon completion of the analysis, the Analyst returns any remaining sample 

reserve to the Sample Custodian for storage, unless the reserve needs 

storage conditions not under the control of the Sample Custodian. (e.g. 

storage in the laboratory).

7.1. Returning Samples to the Sample Custodian

For those samples returned to the Sample Custodian, the sample custodian 

and the analyst document the transfer of the sample in FACTS. 

The Sample Custodian verifies that the physical sample received matches that 

described in the FACTS “Sample Transfer” record. Any discrepancies (e.g. 

quantity, unit) between the physical sample and the sample description in the 

“Sample Transfer” record are immediately reported to the analyst. 

Discrepancies are reconciled and, if needed, the FACTS record is corrected. 

The Sample Custodian updates the sample storage location in the FACTS 

“Sample Transfer” record. 

7.2. Returning Samples to Storage Areas not Controlled by the Sample 

Custodian

Special storage may call for all or a portion of the sample or exhibits to be 

stored in areas not controlled by the Sample Custodian (e.g. the laboratory). If 

the reserve sample is not returned to the Sample Custodian, the following 
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ORA Laboratory Manual Volume III Section 2

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Revision #: 02

Revision Date:

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documentation is recorded on the Analyst Worksheet or electronic form, Block 

11, Reserve Sample:

A. Location and environmental conditions where the reserve is stored;

B. An explanation why the sample was not returned to the Sample 

Custodian for storage; and,

C. Amount of sample stored.

8. Shipping Samples from the Laboratory

Samples or portions thereof are shipped from the FDA/ORS laboratory facility 

by various means (e.g. shipping companies, or FDA personnel). All shipment 

information is documented by the Sample Custodian or their designee in 

FACTS.

The individual circumstance will dictate whether the entire sample or only a 

portion of the sample is shipped. The Sample Custodian is generally 

responsible for shipment of samples to other facilities. He or she assures that 

the sample is packaged in a manner that maintains its integrity. If the Sample 

Custodian is uncertain how a sample should be packaged for shipment, a 

supervisor or analyst is consulted.

When a 702(b) portion of a sample is to be shipped to a claimant, an FDA 

portion shipped to another laboratory, or a complaint sample is returned to the 

consumer, the Sample Custodian proceeds only with electronic or written 

authorization from laboratory management.

8.1. Shipping the Entire Sample

Preparation and shipment of the entire sample depends upon whether the 

sample:

A. Is stored in the sample storage area under the custody of a Sample 

Custodian; or

B. Is in the custody of an analyst.

8.1.1. Sample is Stored in the Custodial Storage Area

If the sample to be shipped is in the sample storage area, the Sample 

Custodian retrieves the sample from the storage area, packs the sample for 

shipment, and ships the sample following the laboratory’s local shipping 

process for samples. 

8.1.2. Sample is in the Custody of the Analyst

If the sample to be shipped is in the custody of the analyst, the analyst 

prepares the sample for shipment. 
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Revision Date:

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The analyst returns the sample to be shipped to the Sample Custodian 

following the procedure described in Section 7 Returning Samples to Custodial 

Storage.

The Sample Custodian packs the sample for shipment, and ships the sample 

following the laboratory’s local process for shipping samples. The Sample 

Custodian ships the sample in accordance with carrier and federal regulations, 

i.e., dangerous goods, infectious substances, hazardous materials. Trained 

personnel ship dangerous goods, infectious substances and hazardous 

materials.

8.2. Shipping a Portion of the Sample

For the preparation and shipping of a portion of the sample to a claimant or 

another laboratory, an analyst prepares the portion for shipment. Preparation 

and shipment of the portion depends upon whether the sample:

A. Is stored in the sample storage area under the custody of a Sample 

Custodian, or,

B. Is in the custody of the analyst.

8.2.1. Samples Stored in the Custodial Storage Area

Samples that are stored in the sample storage area are obtained by the 

analyst from custodial storage following procedures described in Section 4

Receiving Samples from Custodial Storage and Opening the Sample Package. 

If the sample had previously been analyzed by the laboratory, the analyst 

whose name appears on the seals(s) of the Reserve Sample (if applicable) 

obtains the sample, prepares, and seals the portion for shipment.

After receiving custody of the sample, the analyst breaks the official seal and 

opens the sample package following the procedure described in Section 4 

Receiving Samples from Custodial Storage and Opening the Sample Package. 

The analyst splits the sample into portion(s) and documents the split by 

following the procedure described in Section 5 Intra/Inter Laboratory Splitting 

and Transferring of Samples. Additionally, the analyst documents the process 

of breaking seals, preparing samples, and describing the reserve sample on a 

new Analyst Worksheet. The worksheet is processed through normal channels 

to become an addition to the original worksheet. 

The analyst prepares the portion(s) for shipment. The analyst returns the 

portion of the sample to be shipped to the Sample Custodian following the 

procedure described in Section 7 Returning Samples to Custodial Storage. 

The Sample Custodian packs the sample portion for shipment, and ships the 

portion in accordance with federal regulations. The Sample Custodian 
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ORA Laboratory Manual Volume III Section 2

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documents shipment of the sample following the procedures described in 

Section 8.3 Documenting Sample Shipment.

8.2.2. Samples in the Custody of the Analyst 

The analyst splits the sample into portions following the procedure described in 

Section 5 Intra/Inter Laboratory Splitting and Transferring of Samples.

If the sample being prepared for shipment is in process, the analyst states the 

following on the Analyst Worksheet or web application:

A. Sample description, sample provided, and amount;

B. How it was prepared for delivery;

C. Sample identification (description of seal, if appropriate);

D. Brief explanation as to why the sample was sent;

E. To whom the sample was sent; and, 

F. Date of shipment.

If the sample being prepared for shipment is a reserve sample that has not 

been returned to the Sample Custodian due to special storage requirements 

(refer to Section 7 Returning Samples to Custodial Storage), a new Analyst 

Worksheet record is initiated to document the following:

A. The process of breaking seals (if applicable),

B. Preparing the sample portions,

C. Sample description and amount provided,

D. To whom the sample was sent,

E. How the sample was sent for delivery,

F. Short explanation why the sample portion was sent, and

G. Description of the reserve sample.

The worksheet is processed through normal channels to become an addition 

to the original worksheet or record. 

The analyst prepares the portions for shipment. The analyst returns the now 

split portions of the reserve sample to the Sample Custodian following the 

procedure described in Section 7 Returning Samples to Custodial Storage.

The Sample Custodian packs the sample portion identified for shipment and 

ships the portion in accordance with carrier and federal regulations, i.e., 

dangerous goods, infectious substances, hazardous substances. The Sample 
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Custodian documents shipment of the sample following the procedures 

described in Section 8.3 Documenting Sample Shipment.

8.3. Documenting the Sample Shipment

The Sample Custodian (or designee) documents the shipment of samples or 

sample portions by entering the information into FACTS or LIMS. 

9. Disposition of Samples

Once all legal action requiring the sample is concluded, the Sample Custodian 

receives notification for disposition of the sample. Sample disposition 

notification is initiated through FACTS. Additional sample disposition 

notification may be provided through written authorization from the laboratory 

supervision. Upon receipt of the sample disposition notification, the sample is 

removed from its place of storage and destroyed within thirty (30) days.

The Sample Custodian or other personnel as directed by the laboratory 

management perform sample destruction. When any portion or the entire 

reserve sample is stored in a location other than the custodial storage area, 

the analyst may be assigned to destroy the sample.

In some instances, samples may be placed under a litigation hold, 

preservation order, or a hold order. This requires all routine disposition 

processes to be halted and the samples to be preserved until final notification. 

Please note that all litigation holds, preservation orders, or general hold orders 

also apply to any isolates that may have been derived from the regulatory 

samples. All isolates associated with the regulatory sample placed on hold 

must be preserved along with the sample until final notification is issued and 

the hold order is withdrawn.

9.1. Sample Destruction 

Sample destruction entails destroying and denaturing the entire reserve 

sample to the point the material is rendered unusable. The manner of 

destruction will depend on the individual sample and/or results of lab analysis. 

Destruction processes that minimally impact the environment are considered. 

Methods such as incineration, de-characterization, chemical destruction, 

landfill disposal, and autoclaving can be used. Immediate sample containers 

are empty when placed in a waste receptacle. Sample destruction is 

conducted in accordance with the laboratory hazardous waste management 

plan, applicable biosafety guidelines, and general safety precautions.

Designated Supervisor must witness destruction of all controlled drugs 

following Drug Enforcement Agency (DEA) regulations. The person assigned 

to perform the sample disposition must contact the laboratory management if 

there is any question regarding the method of destruction.
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ORA Laboratory Manual Volume III Section 2

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Revision #: 02

Revision Date:

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Title: 

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Destruction or other authorized disposition is the last step in accountability for 

the physical sample. FACTS or LIMS documents sample destruction; only the 

Sample Custodian, or those designated with this role within FACTS or LIMS, 

may complete and document the disposition of the sample. 

9.2. In-House Disposition of Reserve Samples

In certain instances, the Analyst may destroy the Reserve Sample prior to 

receiving official notification authorizing sample disposition. Conditions where 

no Reserve Sample remains are usually confined to NAI import and NAI 

perishable samples where the laboratory supervisor has concurred with 

destruction. The Analyst documents the In-House destruction in FACTS.

With the approval of the Laboratory or Compliance Branch Director, the 

Reserve Sample may be used for FDA purposes rather than destroyed (e.g., 

research, working standard, exhibit). In these instances, sample numbers are 

removed or obliterated to avoid potential confusion with samples that are inprogress.

10. References

A. U.S. Food & Drug Administration, Office of Regulatory Affairs, 

Investigations operations manual or the website address

B. SOP-000285 Sample Feedback Report Process

C. ORA Laboratory Manual, Volume II, ORA.LAB 5.3 Facilities and 

Environmental Conditions

D. ORA Laboratory Manual, Volume II, ORA.LAB 5.8 Sample Management

11. Document History

Revision

#

Status*

(D, I, R) Date Author Name and Title Approving Official Name and Title

1.3 R 02-02-10 LMEB LMEB

1.4 R 07-20-10 LMEB LMEB

1.5 R 09-14-10 LMEB LMEB

1.6 R 01-11-11 LMEB LMEB

1.7 R 02-06-12 LMEB LMEB
FOOD AND DRUG ADMINISTRATION

OFFICE OF REGULATORY AFFAIRS

ORA Laboratory Manual Volume III Section 2

Document Number:

III-02

Revision #: 02

Revision Date:

06/06/2019

Title: 

Chain of Custody – Sample Handling Page 20 of 21

For the most current and official copy, check QMiS.

1.8 R 01-29-13 LMEB LMEB

1.9 R 05-02-14 LMEB LMEB

02 R 06/06/2019 LMEB LMEB

* - D: Draft, I: Initial, R: Revision

12. Change History

Revision 

# Change

1.3

Contents – updated

Footer - web link updated

Minor revisions made to following sections – 2.1; 2.1.1, 2.1.2, 2.2.3, 2.3, 2.4.2.1, 

2.4.2.2, 2.5.2, 2.5.1.1, 2.5.1.2, 2.5.2, 2.6, 2.6.1, 2.6.2, 2.7.2, 2.8, 2.8.1, 2.8.1.1, 

2.8.1.2, 2.8.2, 2.8.2.1, 2.8.2.2, 2.9, 2.9.2, 2.10

1.4

2.5.1 – changed “interlaboratory” to “intralaboratory”; moved last sentence of 

paragraph 1 to 2.5.2

2.5.1.2 – changed “interlaboratory” to “intralaboratory”

2.5.2 – deleted second paragraph; moved last paragraph up 

2.5.2.1 and 2.5.2.2 – section titles added

1.5 2.5.1.1 – corrected identification on analyst worksheet

1.6

2.1.2 – IOM reference changed to Chapter 4

2.2.2.4 – IOM reference changed to Chapter 4

2.4.2.1 – IOM reference changed to Chpater 4

2.10 – updated second reference

1.7

2.2 - Title changed

2.2.2.4 – updated IOM reference

2.4.2.1 – added Subchapter 4.5.4; corrected IOM Exhibit to 4-17

2.5.2 – revised second line in second paragraph

2.8.1.2 – removed “standard Operating Procedure” in third paragraph; revised last 

sentence in last paragraph

2.8.2 – changed “subdivision” to “portion”

2.8.2.2 – revised first sentence in last paragraph

1.8 Header – Division of Field Science changed to Office of Regulatory Science

2.10 – removed Division of Investigations and Division of Field Science
FOOD AND DRUG ADMINISTRATION

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ORA Laboratory Manual Volume III Section 2

Document Number:

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Revision #: 02

Revision Date:

06/06/2019

Title: 

Chain of Custody – Sample Handling Page 21 of 21

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Revision 

# Change

1.9

Throughout document – sample custodian changed to Sample Custodian

2.1 – revised section to include reference to LIMS

2.1.1 – added “or LIMS” to section

2.1.2 – added LIMS definition and “orLIMS” to other definitions as applicable

2.2.3 – added “or LIMS’ to second bullet of second paragraph

2.3. added “or LIMS” to section

2.4.1 – added “change of custody” to first paragraph & “or LIMS” to section

2.5.1 – added “or LIMS” to first paragraph & “change of custodianship” to second 

parag.

2.5.1.2 – added “or LIMS”

2.5.2 - added “or LIMS”

2.5.2.2 - added “or LIMS”

2.6.2 – added “or electronic form” to first & second bullet and “or LIMS” to first bullet

2.7.1 - added “or LIMS”

2.7.2 – added “or electronic form”

2.8 - added “or LIMS”

2.8.2.2 – added “or web application” to 2nd paragraph and “or LIMS record” to 3rd & 4th

paragraph

2.8.3 - added “or LIMS”

2.9.1 - added “or LIMS”

2.9.2 – added “or LIMS record” to first paragraph

2.10 – added FACTS Manual and LIMS User’s Manual

02

Reformatted; updated vocabulary throughout for clarity

- added use of Computer Contingency Plan

– updated frozen sample temperature range

- added use of SFRs

- added instructions for samples under litigation hold

- reviewed and revised as needed against ISO 17025:2017 and AOAC requirements

- section numbers changed as a result of formatting; section references corrected

13. Attachments

None