SOP-311
Biological Specimen Collection, Processing and Shipping
- Number
- SOP-311
- Category
- Study Conduct
- Edition
- Reference Edition 1.3
- Approx. pages
- 8
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] collects, labels, processes, stores and ships biological specimens for clinical trials so that each specimen reaches the laboratory identifiable, intact, within its stability window and with a documented chain of custody, and so that shipments meet US Department of Transportation (DOT) and International Air Transport Association (IATA) dangerous goods requirements.
2. Scope
This SOP applies to all protocol-required specimens (blood, serum, plasma, urine, saliva, swabs, tissue, stool, cerebrospinal fluid and others) collected at any [SITE NAME] location, during home visits by site staff, or received at the site from a local healthcare provider for processing or forwarding. It covers specimens sent to central laboratories, specialty laboratories, biorepositories and sponsor-designated vendors.
Out of scope: tests run on site with point-of-care devices or in a site laboratory (SOP-312), equipment calibration and maintenance (SOP-312), and shipment of investigational product (SOP-304). Specimens collected by sponsor-engaged home health vendors are handled per the vendor's procedures and SOP-313, with this SOP applying once the specimen is in site custody. Where the protocol, laboratory manual, sponsor or IRB requirement is stricter than this SOP, the site follows the stricter requirement.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Delegates specimen tasks to qualified, trained staff on F-302-01. Reviews laboratory results under SOP-500. Assesses specimen deviations that may affect participant safety or eligibility. |
| Site Director | Provides adequate processing space, equipment, freezer capacity and shipping supplies. Funds hazmat and dangerous goods training. |
| Quality Lead | Maintains the shipper training matrix. Reviews specimen deviations for trends and opens CAPA under SOP-703 when needed. |
| Clinical Research Coordinator (CRC) or Lead CRC | Owns specimen logistics for assigned studies: kits, requisitions, processing, storage, shipment, tracking and reconciliation of laboratory queries. Records each shipment on F-311-01. |
| Phlebotomist, nurse or other delegated collector | Collects specimens per the laboratory manual and labels them at the point of collection. |
| Trained Shipper (any staff role) | A staff member with current DOT and IATA training who prepares, packages, marks, labels and signs for dangerous goods shipments, including dry ice. |
| Regulatory Coordinator | Files laboratory manuals, laboratory certifications, shipper training certificates and specimen-related correspondence in the ISF. |
4. Definitions
| Term | Definition |
|---|---|
| Laboratory manual | The sponsor or central laboratory document specifying collection tubes, volumes, order of draw, processing, storage, labeling, requisitions and shipping for a study. |
| Kit | A sponsor- or laboratory-supplied package of collection and shipping materials for a specific visit. Kits carry an expiry date, usually set by the earliest-expiring component. |
| Chain of custody | The documented sequence of custody of a specimen from collection to receipt by the laboratory, showing who handled it, when and under what conditions. |
| Biological Substance, Category B (UN3373) | An infectious substance not in a form generally capable of causing permanent disability or life-threatening disease in otherwise healthy humans or animals when exposure occurs. Most patient specimens sent for diagnostic or investigational testing that are not exempt fall here. |
| Exempt human specimen | A human specimen for which there is minimal likelihood that pathogens are present, shipped for routine testing not related to diagnosis of an infectious disease, in packaging that meets the exempt-specimen requirements. |
| Dry ice (UN1845) | Solid carbon dioxide, a Class 9 dangerous good when shipped by air, used as a refrigerant. |
| Hazmat employee | A person who, in the course of employment, prepares hazardous materials for transport, including packaging, marking, labeling and signing shipping papers (49 CFR 171.8). |
| Specimen deviation | Any departure from the laboratory manual or protocol in collection, processing, storage or shipment (for example wrong tube, late processing, temperature excursion, lost or hemolyzed specimen). |
| Future-use or genetic specimen | A specimen collected for optional exploratory research, biobanking or genetic analysis that requires specific consent, often a separate signature or check box. |
5. Procedure
5.1 Study setup
5.1.1
Before activation (SOP-205), the Lead CRC reads the laboratory manual and confirms that the site has:
- the required equipment (refrigerated centrifuge, -20 °C or -70 °C/-80 °C freezer, refrigerator, ambient storage) with calibration and temperature monitoring under SOP-312
- dry ice supply or an alternative refrigerant if frozen shipments are required
- courier accounts or sponsor-provided airbills and pickup arrangements, including cut-off times and weekend or holiday restrictions
- staff with current shipper training (5.7) for every shipment type in the study
- processing time windows that the site can meet given the visit schedule and staffing
5.1.2
The Lead CRC creates a one-page study specimen summary (visit, tubes, processing, storage, shipping temperature and destination) from the laboratory manual. The summary is version-controlled against the laboratory manual version and re-checked when the manual is updated.
5.1.3
The Regulatory Coordinator files in the ISF the current laboratory manual, central and local laboratory certifications (CLIA, CAP or equivalent) and normal ranges, as provided by the sponsor (SOP-312 covers local laboratories).
5.1.4
The PI or Lead CRC adds specimen collection, processing and shipping to the delegation log (F-302-01) only for staff trained on the laboratory manual and, for shipping, holding current shipper training.
5.2 Kit inventory and expiry
5.2.1
The CRC checks kits on receipt against the packing list and records receipt in the sponsor's kit tracking system or the study kit inventory.
5.2.2
Kits are stored as the laboratory manual specifies (some components need refrigeration or protection from light), segregated by study.
5.2.3
The CRC checks kit expiry dates [DEFAULT: monthly and before each visit] and reorders before stock runs out, allowing for the laboratory's resupply lead time.
5.2.4
Expired kits or components are never used. The CRC removes them, labels them "EXPIRED: DO NOT USE" and disposes of them or returns them as the laboratory instructs.
5.2.5
Components are not swapped between kits or between studies unless the laboratory manual or the laboratory, in writing, permits it. Written permission is filed in the ISF.
5.3 Collection and labeling
5.3.1
Before collection, the CRC confirms:
- the participant's identity using two identifiers (for example name and date of birth, checked against the participant's study record)
- that the participant has consented to the samples being taken, including any optional samples (5.9)
- any protocol requirements such as fasting, timing relative to dosing, or time windows
- the correct visit kit and requisition
5.3.2
The collector labels each tube or container at the time of collection, in the participant's presence, with the laboratory-provided label or the information the laboratory manual requires (typically protocol number, site number, participant ID, visit, date and time of collection). Pre-labeling tubes before the participant is present is not permitted unless the laboratory manual specifies it.
5.3.3
Labels must not carry the participant's name, date of birth, medical record number or other direct identifiers unless the laboratory manual requires them and the consent form covers the disclosure.
5.3.4
The collector follows the laboratory manual for tube type, order of draw, fill volume, inversions and handling. Collection time is recorded to the minute where the protocol or processing window depends on it.
5.3.5
The collector records the collection in source: date and time, collector, specimen types, any problems (difficult draw, short fill, multiple attempts), and fasting or dosing times where required.
5.4 Processing
5.4.1
The CRC processes specimens within the time windows in the laboratory manual (for example time to centrifugation, time to freezing). The time each step starts or ends is recorded on the processing worksheet or F-311-01.
5.4.2
Centrifugation uses the speed (rpm or relative centrifugal force), time and temperature the laboratory manual specifies. Where the manual gives g-force only, the CRC uses the conversion chart for the site's centrifuge and rotor, kept with the centrifuge.
5.4.3
The CRC aliquots into the labeled tubes provided, using the volumes and number of aliquots specified, and records any short aliquot.
5.4.4
Processing is done in the designated processing area with personal protective equipment, following the site's bloodborne pathogens exposure control plan (OSHA 29 CFR 1910.1030).
5.4.5
If a processing window is missed, the CRC does not discard the specimen without instruction. The CRC records the actual times, follows the laboratory manual's instruction for late specimens or asks the laboratory, and records the outcome as a specimen deviation (5.10).
5.5 On-site storage and temperature monitoring
5.5.1
Processed specimens are stored at the temperature specified, in equipment monitored under the single temperature rule in SOP-304, section 5.4 (continuous monitoring with alarms, or a min/max thermometer read each business day on F-304-02 with the documented closed-day plan; a min/max thermometer is not continuous monitoring). Equipment and calibration follow SOP-312.
5.5.2
Specimens are stored by study and visit in labeled racks or boxes so they can be found without searching through other studies' samples.
5.5.3
Temperature alarms are routed to [ALARM CONTACTS] at all hours. On an excursion, the CRC moves specimens to backup storage, records the excursion on F-304-03, and notifies the laboratory or sponsor for instruction on specimen use. Excursions affecting specimens are also specimen deviations.
5.5.4
Batched specimens held for later shipment are listed on F-311-01 with storage location and the date they were placed in storage, and shipped within the stability or batching period the laboratory manual allows.
5.6 Requisitions and shipping preparation
5.6.1
The CRC completes the requisition (paper or electronic) for each shipment exactly as the laboratory manual specifies, including participant ID, visit, collection date and time, and any clinical information required (for example fasting status, dosing time). The requisition must not include identifiers beyond what the manual requires.
5.6.2
The CRC keeps a copy of each requisition in the participant's research record or the study's specimen file. Where requisitions are electronic, the CRC keeps the system confirmation or a printout.
5.6.3
The CRC checks the courier pickup schedule before collection and does not ship on a day when the specimen cannot reach the laboratory within its stability window (for example frozen shipments late in the week or before a holiday), unless the laboratory manual permits it.
5.7 Shipper training
5.7.1
Only staff with current training for the shipment type may prepare, package, mark, label or sign for a shipment. The Quality Lead keeps a shipper training matrix showing each person's DOT and IATA training dates and the shipment types they are trained for.
5.7.2
DOT hazmat training (49 CFR 172.704):
- A new hazmat employee, or one who changes job function, may perform hazmat functions before training only under the direct supervision of a trained employee and must complete training within 90 days.
- Recurrent training is required at least once every three years.
- The employer keeps a record of current training, covering the preceding three years, for as long as the person is employed as a hazmat employee and for 90 days afterwards.
5.7.3
The IATA Dangerous Goods Regulations require anyone preparing dangerous goods for air transport to be trained for their responsibilities (DGR Section 1.5). For UN3373 under Packing Instruction 650 the DGR requires adequate instruction rather than full dangerous goods training; dry ice shipments by air require training to the DGR. Recurrent training must be completed within 24 months of the previous training. The site applies full IATA training to every shipper (section 5.7.4).
5.7.4
Because most courier specimen shipments move by air at some point, the site trains every shipper to both DOT and IATA requirements for the shipment types they handle.
5.7.5
Training certificates are filed in each person's training record (SOP-103, F-103-01) and copies in the ISF if the sponsor asks.
5.8 Packaging, marking and shipment
5.8.1
The Trained Shipper classifies each shipment before packing:
- UN3373 Biological Substance, Category B: most clinical trial specimens that are not exempt
- Exempt human specimen: only where the laboratory manual or the shipper's professional judgment, based on known history, symptoms and local conditions, supports minimal likelihood of pathogens
- Category A (UN2814 or UN2900): not shipped by the site unless the protocol requires it and the shipper holds training for Category A; escalate to the Site Director
- dry ice (UN1845) added as refrigerant to any of the above
5.8.2
The Trained Shipper packs using the triple packaging system supplied in the kit or approved by the laboratory: leak-proof primary receptacle, leak-proof secondary packaging with enough absorbent for the full liquid volume, and rigid outer packaging. An itemized list of contents is placed between the secondary and outer packaging.
5.8.3
For UN3373, the outer package carries the UN3373 diamond mark and the words "Biological Substance, Category B" next to it, and the name and phone number of a responsible person, as the courier and IATA require.
5.8.4
For dry ice:
- dry ice is placed outside the secondary packaging, and the outer packaging permits release of carbon dioxide gas
- the package carries the Class 9 hazard label and the marking "UN1845, Dry ice" (or "Carbon dioxide, solid") with the net weight of dry ice in kilograms, plus shipper and consignee name and address
- the Trained Shipper completes any courier dangerous goods declaration or airbill section the courier requires
5.8.5
Exempt human specimens are packed in triple packaging and marked "Exempt human specimen".
5.8.6
The Trained Shipper uses only the packaging, labels and airbills supplied or approved for the study, completes the airbill, and does not reuse old markings or labels. Obsolete markings on reused boxes are covered or removed.
5.8.7
Before sealing, a second trained person checks the shipment contents against F-311-01 and the requisitions where staffing allows.
5.8.8
The CRC records each shipment on F-311-01: study, participant IDs and visits, specimen types and number of tubes, shipping temperature, dry ice weight, carrier and tracking number, date and time of pickup, shipper name, and the laboratory's receipt confirmation date.
5.9 Consent-limited specimens: future use and genetics
5.9.1
Before collecting any optional, future-use or genetic specimen, the CRC checks the participant's signed consent (main form and any optional section or separate form) and records the participant's choice in source.
5.9.2
If the participant has declined an optional specimen, the CRC does not collect it. If it was collected in error, the CRC does not ship it, records a deviation, and asks the sponsor for destruction instructions. If it has already shipped, the CRC notifies the sponsor in writing and asks for documented destruction.
5.9.3
If a participant withdraws consent for future use or genetic research, the CRC notifies the sponsor in writing within [DEFAULT: 5 business days] so the sponsor can act on the withdrawal as the consent form describes, and files the notification.
5.9.4
Genetic test results are not placed in the participant's medical record or disclosed unless the protocol and consent form provide for return of results. Results returned to a participant or their physician for clinical decision-making must come from a laboratory holding a CLIA certificate for that test (SOP-312, section 5.7). The research laboratory exception in 42 CFR 493.3(b)(2) applies only when no patient-specific results are reported.
5.10 Tracking, receipt confirmation and specimen deviations
5.10.1
The CRC tracks each shipment until the laboratory confirms receipt. If delivery is not confirmed by [DEFAULT: the next business day after expected delivery], the CRC contacts the courier and the laboratory.
5.10.2
The CRC reviews laboratory reports of specimen problems (missing, hemolyzed, thawed, unlabeled, insufficient quantity, mismatch with requisition) and laboratory data queries, and answers them within the timeline the sponsor sets.
5.10.3
Every specimen deviation is recorded and assessed under SOP-308. The PI decides whether a repeat collection is needed for safety or eligibility, and whether the participant must be re-contacted. A recollection is done only if the protocol or sponsor permits it and the participant agrees.
5.10.4
Lost specimens and shipments with significant temperature failures are reported to the sponsor within [DEFAULT: 1 business day of discovery], or the laboratory manual or sponsor time if shorter, and recorded with the courier claim or investigation outcome.
5.10.5
The Quality Lead reviews specimen deviations at least [DEFAULT: quarterly] for patterns (one collector, one courier, one study) and opens a CAPA under SOP-703 when warranted.
5.11 Records and retention
5.11.1
Specimen records are essential records: collection, processing and shipment documentation, storage conditions, and records of retained specimens at the end of the trial (ICH E6(R3) Appendix C). They are retained under SOP-402.
5.11.2
At closeout (SOP-601), the CRC reconciles all specimens collected against shipments and laboratory receipt, ships or destroys any remaining site-held specimens per sponsor written instruction, returns or disposes of unused kits, and records the outcome.
6. Related Forms and SOPs
- F-311-01 Specimen Processing and Shipment Log
- F-302-01 Delegation of Authority Log
- F-304-02 Temperature Monitoring Log
- F-304-03 Temperature Excursion Report
- F-308-01 Protocol Deviation Log
- F-103-01 Staff Training Log
- SOP-103 Staff Qualification, Training and Training Records
- SOP-205 Site Qualification, Initiation and Study Activation
- SOP-301 Informed Consent Process and Documentation
- SOP-306 Source Documentation and Data Integrity (ALCOA+)
- SOP-308 Protocol Deviations and Noncompliance
- SOP-312 Equipment Calibration and Maintenance; Local Laboratory Requirements
- SOP-313 Decentralized Trial Elements (Remote Visits, Home Health, Direct-to-Participant IP)
- SOP-402 Record Retention, Archiving and Destruction
- SOP-601 Study Closeout
- SOP-703 Corrective and Preventive Action (CAPA)
- SOP-904 Shared Staff, Cross-Site Coverage and Central Services (Model N only)
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| 49 CFR 171.8 | Definitions (hazmat employee, hazmat employer) |
| 49 CFR 172.704 | Hazmat employee training requirements (initial within 90 days, recurrent every 3 years, records) |
| 49 CFR 173.134 | Class 6, Division 6.2: definitions and exceptions (including 173.134(b) exceptions) |
| 49 CFR 173.199 | Category B infectious substances |
| 49 CFR 173.217 | Carbon dioxide, solid (dry ice) |
| IATA Dangerous Goods Regulations (current edition) | Packing Instruction 650 (UN3373), Packing Instruction 954 (UN1845), exempt specimens, training (Section 1.5) |
| 29 CFR 1910.1030 | OSHA Bloodborne Pathogens |
| ICH E6(R3) Annex 1, 2.12 | Records |
| ICH E6(R3) Appendix C | Essential Records for the Conduct of a Clinical Trial (specimen collection, processing, shipment, storage and retention records) |
| 21 CFR 312.62(b) and 812.140(a)(3) | Investigator case history records |
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