1. Purpose
This appendix is the single place that says who does what when the library runs in a network (Model N). It lists the major activities in each SOP and assigns each one to the Network Office, to the member site, or to both. SOPs and Network notes point here instead of naming the actor for each network variant. A single site (Model S) does not use this appendix.
2. How to use this matrix
The Network Quality Lead completes the matrix once for the network, with the Network Regulatory Lead, the Network Contracts and Finance Lead, the Network Clinical Operations Lead and at least one PI from a member site. Each member site then confirms the rows that affect it.
Steps:
- Read the default for your variant: N-Integrated (one legal entity owns all sites) or N-Affiliated (separate legal entities under a network or affiliation agreement). A member site that is a separate legal entity uses the N-Affiliated column for the rows named in section 3.
- Accept the default or write a different assignment in the Site's choice column. Write C, S or C/S. For C/S, state the split in a few words (for example "C drafts, S approves").
- Do not change any row marked Yes in the Must stay at site? column so that the duty leaves the site. You may add central support to those rows (for example the Network Office prepares a form for the PI to sign), but the site person named in the SOP still performs and signs the duty.
- Record the adopted matrix, its version and its effective date on F-900-02 Network Operating Model and Appendix B Adoption Record. The Network Quality Lead and each member site's Site Director sign F-900-02.
- Where a member site needs a different assignment from the network choice, record it as a local addendum on F-900-01 Local Addendum to a Network SOP and list it on F-900-02.
- Review the matrix at least [DEFAULT: annually], when a site joins or leaves the network (SOP-901), when the network agreement changes, and when a CAPA or audit finding shows that an assignment does not work.
Codes:
| Code | Meaning |
|---|
| C | Network Office performs the activity and keeps the record, unless the Activity text says the site keeps it |
| S | Member site performs the activity and keeps the record |
| C/S | Shared. The Activity text states which part the Network Office does and which part the site does |
| Yes (Must stay at site?) | The duty belongs to the investigator or to the site's legal entity by regulation or by the nature of the work. The reason is given. The Network Office may support but may not take the duty over |
| No (Must stay at site?) | The network may assign the activity either way, within the network agreement |
3. Rules that apply to every row
Investigator duties never move to the Network Office. The investigator of record at each site keeps the duties in 21 CFR 312.60 to 312.69 (drugs and biologics), 21 CFR 812.100 to 812.150 (devices) and ICH E6(R3) Annex 1, section 2. These include personal supervision of the study, informed consent, eligibility decisions, medical care and safety assessment, control of investigational product, delegation, accurate records and reports, and permitting inspection. The Network Office may prepare documents, run systems, provide trained staff and give advice. The PI still decides, signs and supervises. The Network Medical Director, where the network has one, does not replace any PI's duties.
N-Integrated defaults need the same legal entity. N-Integrated defaults apply only where the member site and the network entity are the same legal entity. A separate subsidiary, or a professional corporation under a management services arrangement, follows the N-Affiliated rows for PHI, direction of staff, contract signature, records custody and payments unless counsel confirms otherwise (SOP-900, 5.2.1).
N-Affiliated defaults are limited by the network agreement. In N-Affiliated, each member site is a separate legal entity. The Network Office can perform an activity for a site only as the network or affiliation agreement allows. It cannot direct the site's employees except as the agreement allows, cannot sign for the site's legal entity without written authority, and cannot receive the site's PHI except under a business associate agreement, a data use agreement, participant authorization or another basis recorded on F-905-01 Cross-Entity Data Flow Register. Where the agreement is silent, the site default applies (S) until the agreement is amended.
Legal-entity duties stay with the entity. Some duties attach to the legal entity or to a licensed location, not to a person: HIPAA covered entity duties (45 CFR 164.530), CLIA certificates by testing location (42 CFR 493.35(b), 493.55(b)), DEA registration by registrant and location (21 CFR 1301.12), state facility and pharmacy licenses, employment and tax reporting. In N-Integrated these duties sit with the owning entity and may be run centrally, but a certificate or registration still covers only its own location, and separate subsidiaries remain separate entities unless counsel confirms otherwise (for HIPAA, an affiliated covered entity designation under 45 CFR 164.105(b)). In N-Affiliated they stay with each site entity.
Financial flows between entities. In N-Affiliated, payments between the Network Office and member sites for study allocation, referrals or services are set in the network agreement at fair market value for services actually performed, and are reviewed by counsel against the federal anti-kickback statute (42 U.S.C. 1320a-7b(b)) and state law. No row in this matrix authorizes a payment for referrals.
Records. Where a row is C, the Network Office keeps the record and the site keeps whatever the SOP says must be in the Investigator Site File (ISF). Essential records for a study stay available to the site's PI for the full retention period (21 CFR 312.62(c), 812.140(d)).
4. 100 series: governance and quality system
SOP-100 Writing, Approving and Controlling SOPs
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-100-01 | Own the SOP system: master index, numbering, version control and review schedule for network SOPs | 5.2, 5.7 | C | C/S: Network Quality Lead keeps the network index; each site keeps its own index of the versions it has adopted and its local addenda (F-100-03) | No | |
| B-100-02 | Draft, review and approve network SOPs and forms. Network approval: Author, Network Quality Lead, Network Executive, and the Network Medical Director or a named PI where 5.4.1 applies. Site adoption: Site Director and Site Quality Lead record adoption and training readiness on F-100-01 | 5.3, 5.4, 5.11.3, 5.11.4 | C, with site adoption signatures | C/S: Network Office approves the network version; each member entity adopts it on F-100-01, since the Network Office cannot bind it otherwise | No. In N-Affiliated each legal entity adopts its own SOPs | |
| B-100-03 | Write and approve local addenda for state law or site practice (F-900-01) | 5.11.2, 5.11.3; SOP-900 5.5 | C/S: Site Quality Lead drafts; Network Quality Lead checks against SOP-900 5.5.2 and signs; site approvers in SOP-100 5.11.3 sign, including the PI where 5.4.1 applies | C/S: Site Quality Lead drafts; Network Quality Lead checks against SOP-900 5.5.2 and signs; site approvers in SOP-100 5.11.3 sign, including the PI where 5.4.1 applies | Yes for PI approval where the addendum affects investigator duties, safety, consent, IP or data integrity | |
| B-100-04 | Publish effective versions at one controlled location and withdraw superseded versions | 5.6, 5.8 | C | C/S: Network Office publishes the network set; site withdraws superseded copies at its points of use | No | |
| B-100-05 | Train staff before the effective date and record on F-100-02 | 5.5, 5.11.5 | C/S: Network Training Lead sets curricula and runs network sessions; site records completion and confirms local addenda training | S, with network training material offered | No | |
| B-100-06 | Record and assess SOP deviations; trend them across sites | 5.9 | C/S: site reports and assesses; Network Quality Lead trends across sites | C/S: same split, with site data shared as the agreement allows | No | |
| B-100-07 | Keep one Appendix A State Law Worksheet per state where any member site operates or sees participants remotely | 5.10.2; SOP-400 5.7 | C/S: Network Quality Lead prepares with counsel; each site in that state confirms and adds local IRB points | C/S: same split; each site entity confirms the answers it relies on with its own counsel | No | |
| B-100-08 | Approve planned deviations from a network SOP at a member site; report unplanned deviations to the Network Quality Lead | 5.11.6 | C/S: Site Quality Lead approves; Network Quality Lead also approves where this row is set to C/S | C/S: same split | No | |
| B-100-09 | Control site-only SOPs for activities the network library does not cover and send the list to the Network Quality Lead | 5.11.7 | S | S | No | |
SOP-101 Roles and Responsibilities of the Principal Investigator
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-101-01 | Review protocol, IB and site capacity and decide to accept the study, including a study the Network Office allocates. Allocation does not commit the PI; the workload check counts the PI's studies at every member site | 5.1 | S | S | Yes: investigator duty (21 CFR 312.60; ICH E6(R3) Annex 1, 2.1 and 2.2) | |
| B-101-02 | Sign Form FDA 1572, device investigator agreement and protocol signature page | 5.2 | S | S | Yes: signed personally by the investigator (21 CFR 312.53(c), 812.43(c)) | |
| B-101-03 | Prepare 1572, investigator agreement and CV packet for the PI to check and sign | 5.2 | C/S: Network Regulatory Lead prepares; PI checks and signs | C/S: same split if the agreement includes regulatory services | No for preparation; signature stays with the PI | |
| B-101-04 | Personal conduct and supervision of the study, team meetings and oversight of delegated work | 5.4, 5.6 | S | S | Yes: investigator duty (21 CFR 312.60, 812.100; ICH E6(R3) Annex 1, 2.3) | |
| B-101-05 | Arrange PI coverage and a covering investigator during absence | 5.13 | C/S: PI names the covering investigator; Network Clinical Operations Lead may supply one from another site, who is first listed as a Sub-I for the study at this site (SOP-302 5.5.2) and added to its delegation log | S, unless the agreement provides shared investigators | Yes: covering investigator must be listed and delegated for this site (21 CFR 312.53(c); ICH E6(R3) Annex 1, 2.3) | |
| B-101-06 | Physician advice and oversight across PIs (Network Medical Director, optional) | 5.4 | C | C, advisory only | No. Never replaces the PI's duties (21 CFR 312.60) | |
| B-101-07 | Replace a PI who leaves: Network Office may propose a replacement, including one from another member site; sponsor and IRB approval and a new 1572 are still needed | 5.13.5 | C/S: Site Director tells the Network Clinical Operations Lead; Network Office proposes; Site Director and Regulatory Coordinator complete 5.13.5 | S, with Network Office proposals as the agreement allows | Yes: new investigator signs the 1572 (21 CFR 312.53(c)) | |
SOP-102 Site Organization, Roles and Staff Responsibilities
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-102-01 | Keep the organization chart and role assignments (F-102-01), including network roles that serve the site | 5.1 | C/S: Network Office keeps the network chart; site keeps F-102-01 for its location and lists the network roles it relies on | S, with network roles listed by name | No | |
| B-102-02 | Write standard role descriptions | 5.2 | C | C/S: Network Office supplies templates; site employer issues role descriptions to its own staff | No | |
| B-102-03 | Check combined roles and independence limits | 5.3 | C/S: site records; Network Quality Lead approves controls, and may supply an independent reviewer from another site | S | No | |
| B-102-04 | Onboard and offboard staff (F-102-02), including keys, codes and system access | 5.5, 5.7 | C/S: Network Office runs HR, license checks and central system accounts; site handles local access, keys and study handover | S. Network Office handles only accounts in network systems | No in N-Integrated. In N-Affiliated the employer does it | |
| B-102-05 | Manage contractors, agency and per diem staff | 5.8 | C | S, unless contracted through the Network Office | No | |
SOP-103 Staff Qualification, Training and Training Records
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-103-01 | Set role-based curricula | 5.1 | C | C/S: Network Training Lead sets the network curriculum; site adds local and state items | No | |
| B-103-02 | Open and maintain qualification files (F-103-02), license tracking and debarment and exclusion screening | 5.2 | C | S, with central screening offered as a service | No | |
| B-103-03 | Deliver GCP, human subjects protection, SOP and system training | 5.3 to 5.5, 5.8 | C/S: Network Office delivers and records network courses; site delivers local addenda training | C/S: same split if the agreement includes training | No | |
| B-103-04 | Protocol training before delegation | 5.6 | S | S | Yes: the PI confirms each person is informed of the protocol before delegating (21 CFR 312.53(c)(1)(vi)(g)); protocol training before delegation (ICH E6(R3) Annex 1, 2.3.2) | |
| B-103-05 | Shipping (DOT and IATA) training and records | 5.7 | C/S: Network Office provides the course; site keeps the employer's record | S | Yes: the employer of the hazmat employee keeps the training record (49 CFR 172.704(d)) | |
| B-103-06 | Competency checks for high-risk tasks | 5.9 | S, with network assessors allowed | S | No | |
| B-103-07 | Report overdue training and expiring credentials | 5.11 | C | C/S: site reports to its Site Director; Network Office receives a summary as the agreement allows | No | |
SOP-104 Conflict of Interest and Financial Disclosure
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-104-01 | Collect sponsor financial disclosure from each investigator and send it to the sponsor | 5.1, 5.2 | C/S: investigator completes; Network Regulatory Lead checks and sends | C/S: same split if the agreement includes regulatory services | Yes for the disclosure itself: the investigator provides it (21 CFR 312.64(d), 812.110(d)) | |
| B-104-02 | Collect and review staff and owner COI disclosures (F-104-01), including Model N questions on interests in the Network Office, its parent or investors, or other member sites, and compensation tied to study allocation | 5.4, 5.5 | C | S, with the Network Office reviewing network-level interests | No | |
| B-104-03 | Disclose and manage institutional interests of the network, its owners and investors | 5.7 | C | C/S: each entity discloses its own interests; the Network Office discloses interests of the network and its owners to every member site | No | |
| B-104-04 | Approve management plans | 5.5 | C/S: Network Quality Lead and the Network Executive (or another Network Office leader without the interest) approve; PI and person sign | S, with the Network Office consulted when a network interest is involved | No | |
| B-104-05 | Answer IRB COI questions and report changes | 5.6 | C/S: Network Regulatory Lead submits; site confirms facts | C/S: same split if the agreement includes regulatory services | No | |
| B-104-06 | Keep a person with an ownership, equity or compensation interest in a member site out of allocation decisions affecting that site, and record the interest on F-902-01 | 5.5 Network note; SOP-902 5.4.3.1 | C | C | No | |
SOP-105 Oversight of Service Providers and Vendors
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-105-01 | Categorize and risk-rank providers | 5.1, 5.2 | C | C/S: Network Office rates network-wide providers; site rates its local providers | No | |
| B-105-02 | Qualify providers and screen them for debarment and exclusion (F-105-01). The Network Office may keep a network approved provider list; a site relies on it when the PI reviews the central record and files a copy or pointer | 5.3, 5.9 | C | C/S: same split; site may rely on the Network Office record if the agreement allows | No | |
| B-105-03 | Sign provider agreements and BAAs | 5.4 | C | C/S: Network Office signs master agreements it holds; site signs where the provider serves the site entity or receives its PHI | No in N-Integrated. In N-Affiliated the entity whose PHI is shared signs the BAA (45 CFR 164.502(e)) | |
| B-105-04 | Study-level setup and PI acceptance of providers that perform investigator activities | 5.5, 5.7 | S | S | Yes: investigator keeps responsibility for delegated activities (ICH E6(R3) Annex 1, 2.3) | |
| B-105-05 | Oversee provider performance during the study | 5.6 | C/S: Network Office reviews network providers; site reports study-level problems the same day | C/S: same split | No | |
| B-105-06 | Treat the Network Office itself as a provider when it performs site activities | 5.1 to 5.6 | C: Network Quality Lead records each central service on F-105-01 as an internal service provider with an internal service description (SOP-904 5.7) | S: site records the Network Office on F-105-01 for the services the agreement lists | No | |
5. 200 series: start-up and regulatory
SOP-200 Study Feasibility and Selection
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-200-01 | Receive and log study inquiries and sign CDAs needed for feasibility. In Model N all inquiries go to central intake; a site that receives one directly forwards it and does not answer for the network | 5.1 | C | C: under SOP-902 5.1; the CDA must permit disclosure to member sites | No | |
| B-200-02 | Run patient population queries and report aggregate counts | 5.3 | C/S: Network Office may run queries across sites' EHRs where the sites are one covered entity or a designated affiliated covered entity (SOP-905 5.3); each site checks its own counts | S: each site runs its own query; only aggregate counts go to the Network Office | Yes in N-Affiliated: PHI stays with the site's covered entity (45 CFR 164.512(i)(1)(ii)) | |
| B-200-03 | Check competing studies and staff capacity at the site | 5.4 | C/S: Network Clinical Operations Lead checks across sites; Site Director confirms local capacity | S | No | |
| B-200-04 | PI review of protocol and confirmation of investigator time | 5.5 | S | S | Yes: investigator duty (21 CFR 312.53(c); ICH E6(R3) Annex 1, 2.1 and 2.2) | |
| B-200-05 | Go/no-go decision and site allocation (F-200-01, F-902-01) | 5.8 | C/S: Network Office allocates; site PI may decline | C/S: Network Office proposes; site accepts or declines | Yes for the PI's right to decline | |
| B-200-06 | Complete the sponsor feasibility questionnaire | 5.9 | C/S: Network Office compiles; each site's numbers come from its own F-200-01 | C/S: same split | No | |
SOP-201 Confidentiality Agreements, Clinical Trial Agreements and Budgets
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-201-01 | Log and track CDAs, CTAs, amendments and budgets | 5.1 | C | C/S: Network Office tracks agreements it negotiates; site tracks agreements it signs | No | |
| B-201-02 | Negotiate CDAs and CTAs, including master agreements with sponsors and CROs | 5.2, 5.3 | C | C/S: Network Office negotiates under the agreement; site approves terms that bind the site entity | No | |
| B-201-03 | PI review of investigator obligations in the CTA | 5.3.3 | S | S | Yes: the PI accepts personal obligations | |
| B-201-04 | Build the budget and approve it | 5.4 | C/S: Network Contracts and Finance Lead builds; Site Director confirms local costs and staff time | C/S: same split; site entity approves | No | |
| B-201-05 | Sign CTAs and budgets | 5.6; SOP-902 5.5.2 | C: authorized signatory of the network entity (SOP-902 5.5.2) | S or tri-party: the member entity is the contracting institution; the network entity signs alone only where the network agreement and the sponsor accept it and counsel has confirmed (SOP-902 5.5.2) | Yes in N-Affiliated: only the member entity can bind itself, except as SOP-902 5.5.2 allows | |
| B-201-06 | Invoice, collect and reconcile sponsor payments | 5.8; SOP-902 5.8 | C | C/S: the payee named in the CTA invoices (the Network Office, or the site with a copy to the Network Office, SOP-902 5.8.1); the Network Office tracks payments and reconciles by site; payments between the Network Office and the site follow the network agreement at fair market value | No | |
SOP-202 Medicare Coverage Analysis and Research Billing Compliance
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-202-01 | Decide whether the study will bill insurance | 5.1 | C/S: Network Office recommends; each member site decides for its own claims (SOP-202 Network note to 5.1) | C/S: Network Office recommends; site decides for its own claims | Yes: the decision is made for each billing member site | |
| B-202-02 | Prepare the coverage analysis (F-202-01); the billing grid is built by each billing site (B-902-08) | 5.2 to 5.7 | C | C; site keeps the approved copy | No | |
| B-202-03 | PI review of research (R) determinations for medical necessity | 5.5.3 | S | S | Yes: clinical judgment of the treating investigator | |
| B-202-04 | Flag research participants and hold, code and review claims | 5.8 | C/S: central billing office codes and reviews; site flags the participant and marks visit services | S: the billing provider is the site entity | Yes in N-Affiliated: the entity that submits the claim is responsible for it | |
| B-202-05 | Audit research claims and reconcile with sponsor payments | 5.10 | C | C/S: site audits its own claims; central audit only under a BAA and an entry on F-905-01 | No | |
SOP-203 IRB Submissions, Approval and Continuing Oversight
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-203-01 | Identify the IRB of record and sign reliance agreements | 5.1 | C | C/S: Network Regulatory Lead arranges; site entity signs reliance agreements | No in N-Integrated. In N-Affiliated the relying entity signs | |
| B-203-02 | Prepare and submit initial site submissions. The Network Regulatory Lead never uses a PI's credentials | 5.2 | C/S: Network Regulatory Lead prepares and submits; PI reviews and approves | C/S: same split if the agreement includes regulatory services | Yes for PI approval (21 CFR 312.66) | |
| B-203-03 | Check approvals and distribute approved documents to the site | 5.3, 5.4 | C/S: Network Regulatory Lead checks and sends; site Regulatory Coordinator files in the ISF and withdraws superseded copies | C/S: same split | No | |
| B-203-04 | Submit amendments, continuing review and check-ins | 5.5, 5.6 | C/S: Network Regulatory Lead tracks dates and submits; site supplies data | C/S: same split | No | |
| B-203-05 | Report to the IRB (unanticipated problems, deviations, PI changes) | 5.7 | C/S: Network Regulatory Lead may submit; PI decides and approves the report | C/S: same split | Yes: investigator reporting duty (21 CFR 312.66, 812.150(a)) | |
| B-203-06 | Keep IRB correspondence and close the study with the IRB | 5.8 to 5.10 | C/S: central eReg holds the record; site ISF holds or links to it | C/S: same split, with the site keeping a complete copy | No | |
SOP-204 Essential Documents and the Investigator Site File
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-204-01 | Choose the ISF format and eISF system | 5.1 | C | C/S: Network Office may offer a central eISF; site decides and keeps control of access | No | |
| B-204-02 | Set up the ISF and keep the index (F-204-01) | 5.2 | C/S: Network Regulatory Lead sets up; site Regulatory Coordinator maintains | S, with a network template | No | |
| B-204-03 | File site-generated records (signed consents, logs, source location map) | 5.4 | S | S | Yes: records at the site of conduct (21 CFR 312.62, 812.140) | |
| B-204-04 | Hold site-level records (SOPs, CVs, licenses, equipment files) | 5.2.3 | C, with access for each site | C/S: Network Office holds network records; site holds its own | No | |
| B-204-05 | Give monitors and inspectors access to the ISF | 5.7 | C/S: central eISF access by Network Office; site arranges on-site access | S | Yes: investigator permits inspection (21 CFR 312.68, 812.145) | |
SOP-205 Site Qualification, Initiation and Study Activation
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-205-01 | Host site qualification visit | 5.1 | S, with Network Office support | S | Yes for the PI's answers on oversight and time | |
| B-205-02 | Assemble and send the regulatory packet | 5.2 | C | C/S: Network Regulatory Lead assembles if the agreement includes it; site supplies documents | No | |
| B-205-03 | Run the site initiation visit and record training | 5.3 | S | S | Yes: investigator informs the team (ICH E6(R3) Annex 1, 2.3) | |
| B-205-04 | Complete the Study Activation Checklist (F-205-01) | 5.6 | C/S: Network Regulatory Lead maintains; PI and Site Director sign | S | Yes for PI signature | |
| B-205-05 | Approve changes after activation (new location, laboratory, Sub-I) | 5.8 | C/S: Network Regulatory Lead prepares notices; PI approves | C/S: same split | Yes for PI approval | |
6. 300 series: study conduct
SOP-300 Participant Recruitment, Pre-Screening and Advertising
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-300-01 | Write recruitment plans and network-wide campaigns | 5.1 | C/S: Network Office runs network campaigns; PI approves each site plan | C/S: same split | No | |
| B-300-02 | Submit recruitment materials to the IRB and track them (F-300-02) | 5.2 | C | C/S: Network Office submits network materials; site submits its own | No | |
| B-300-03 | Review medical records to find candidates | 5.3 | C/S: workforce of the owning covered entity (or designated affiliated covered entity) may search across sites' records under one HIPAA pathway; site PI confirms the pathway | S | Yes in N-Affiliated: PHI stays with the site's covered entity unless F-905-01 records a basis | |
| B-300-04 | Run a central research volunteer database or call center | 5.4, 5.5 | C | C/S: Network Office runs it only with each person's agreement to be contacted by the network and sites; referrals go to the site | No | |
| B-300-05 | Pre-screen candidates and keep F-300-01 | 5.5 | C/S: central call center pre-screens with the site's IRB-approved script; call center staff who pre-screen against a study's criteria are on that site's F-302-01 (a SOP-105 service log covers only tasks that are not protocol-specific); site keeps the study log | C/S: same split, with only the minimum data passed to the site | No | |
| B-300-06 | Approve staff enrollment incentives and review recruitment vendors | 5.6, 5.7 | C | C/S: each entity approves for its own staff; Network Office reviews network vendors | No | |
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-301-01 | Decide which roles may obtain consent | 5.1 | C/S: network default; PI delegates individuals | C/S: same split | Yes for delegation: PI delegates (ICH E6(R3) Annex 1, 2.3 and 2.8) | |
| B-301-02 | Control consent versions and distribute approved forms (F-301-02) | 5.2 | C/S: Network Regulatory Lead releases; site removes superseded copies | C/S: same split | No | |
| B-301-03 | Conduct the consent discussion and sign the form | 5.4 to 5.6 | S | S | Yes: investigator duty (21 CFR 50.20, 50.27, 312.60) | |
| B-301-04 | Remote consent by central staff (eConsent or video) | 5.9 | C/S: central staff may obtain consent only if on the site's delegation log and trained; site keeps the original | C/S: same, only if the agreement allows central staff to act for the site | Yes: consent is obtained under the site PI's delegation | |
| B-301-05 | Consent QC review | 5.11.3 | C/S: Network Quality Lead may supply the second reviewer; site files the result | S | No | |
SOP-302 Delegation of Authority
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-302-01 | Decide tasks and sign the delegation log (F-302-01) | 5.2, 5.4 | S | S | Yes: only the PI delegates (ICH E6(R3) Annex 1, 2.3) | |
| B-302-02 | Check training and licensure before delegation | 5.3 | C/S: Network Office supplies training and license records; site Regulatory Coordinator confirms | S | No | |
| B-302-03 | Delegate shared or central staff (SOP-904) | 5.4 | S: PI delegates each person for this site; assignment recorded on F-904-01 | S | Yes: PI delegates | |
| B-302-04 | End delegation and request access removal | 5.6 | C/S: Network Office removes central accounts; PI initials end dates | S | Yes for PI sign-off | |
| B-302-05 | PI oversight of delegated work | 5.7 | S | S | Yes: investigator duty (21 CFR 312.60) | |
SOP-303 Screening, Eligibility Verification and Enrollment
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-303-01 | Build the eligibility checklist (F-303-02) | 5.1 | C/S: Network Office builds a template per study; site checks it | S | No | |
| B-303-02 | Screening procedures and screening log (F-303-01) | 5.2 | S | S | Yes: performed at the site under the PI | |
| B-303-03 | Second-person eligibility review | 5.4.1 | C/S: may be a delegated reviewer from the Network Office or another site | S | No | |
| B-303-04 | Investigator eligibility sign-off | 5.4.2 | S | S | Yes: investigator judgment (21 CFR 312.60; ICH E6(R3) Annex 1, 2.5) | |
| B-303-05 | Check concurrent enrollment across network sites | 5.3.6 | C: network participant registry if the network has one | C/S: one-way hashed match run by the Network Office under a BAA with each participating site that expressly permits the match, where each study's consent and authorization (or IRB waiver under 45 CFR 164.512(i)) covers the check; returns only match or no match; recorded on F-905-01 (SOP-905 5.4.5) | No | |
SOP-304 Investigational Product Management
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-304-01 | Set up IP storage and list storage locations on the 1572 | 5.1 | S | S | Yes: investigator controls IP at the listed location (21 CFR 312.61, 812.110(c)) | |
| B-304-02 | Receive, store, monitor temperature and handle excursions | 5.2 to 5.5 | S, with central temperature monitoring alerts allowed | S | Yes: control of IP (21 CFR 312.61, 312.62(a)) | |
| B-304-03 | Dispense, account for and reconcile IP | 5.6 to 5.8 | S | S | Yes: investigator duty (21 CFR 312.61, 312.62(a), 812.140(a)) | |
| B-304-04 | Controlled substance registration, storage and records | 5.9 | S | S | Yes: DEA registration is by location (21 CFR 1301.12) | |
| B-304-05 | Transfer IP between network sites | 5.12 | C/S: Network Clinical Operations Lead coordinates with sponsor; both sites record the transfer | C/S: only with written sponsor authorization and an agreement between the two entities | Yes: each site records its own accountability. Controlled-substance IP moves between DEA registrations under 21 CFR 1304 and 1305 (SOP-304) | |
| B-304-06 | Central pharmacy services (preparation for several sites) | 5.6.3 | C, only where licensed and the sponsor and 1572 allow | C, only under a written agreement and the same conditions | No, but the 1572 must list the pharmacy where required | |
SOP-305 Randomization, Blinding and Emergency Unblinding
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-305-01 | Assign blinded and unblinded roles | 5.1 | S | S | Yes: PI delegates roles | |
| B-305-02 | Request IRT accounts by role | 5.1.3 | C/S: Network Regulatory Lead requests; site confirms roles | S | No | |
| B-305-03 | Randomize participants | 5.2 | S | S | Yes: after investigator eligibility sign-off (ICH E6(R3) Annex 1, 2.11) | |
| B-305-04 | Emergency unblinding | 5.4 | S | S | Yes: investigator decision (ICH E6(R3) Annex 1, 2.11) | |
| B-305-05 | Provide a shared unblinded pharmacist or IP Manager for several sites | 5.1.5 | C/S: central person delegated at each site; site keeps separated records | C/S: same, under the agreement | No | |
SOP-306 Source Documentation and Data Integrity (ALCOA+)
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-306-01 | Prepare the Source Data Location List per study | 5.2 | C/S: Network Office supplies the template and network systems; Lead CRC completes; PI signs | S | Yes for PI approval | |
| B-306-02 | Choose and run the EHR or eSource system | 5.3 | C: one network system allowed | S, or a network system under F-905-01 | No | |
| B-306-03 | Make entries, corrections and late entries | 5.1, 5.5 | S | S | Yes: case histories at the site (21 CFR 312.62(b), 812.140(a)) | |
| B-306-04 | Investigator review of results and source | 5.7 | S | S | Yes: investigator duty | |
SOP-307 Case Report Forms, EDC Entry and Query Resolution
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-307-01 | Enter data in EDC | 5.2 | C/S: central data entry staff may enter from site source if delegated on the site's F-302-01 | S | No, but the person must be delegated by the PI | |
| B-307-02 | Resolve queries | 5.4 | C/S: central staff answer non-medical queries; medical queries go to the site investigator | S | Yes for medical judgment queries | |
| B-307-03 | Investigator review and signature of CRFs | 5.5 | S | S | Yes: investigator duty (21 CFR 312.62(b)) | |
| B-307-04 | Track data entry backlog and query age | 5.8 | C | C/S: site tracks; Network Office receives metrics (SOP-903) | No | |
SOP-308 Protocol Deviations and Noncompliance
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-308-01 | Record deviations (F-308-01) | 5.3 | S | S | No | |
| B-308-02 | PI assessment of each deviation. The Network Office may comment or ask for a second look, but cannot reclassify the PI's assessment | 5.4 | S | S | Yes: investigator duty (ICH E6(R3) Annex 1, 2.5) | |
| B-308-03 | Report deviations to sponsor and IRB | 5.5 | C/S: site reports to sponsor; Network Regulatory Lead may submit IRB reports the PI approves | C/S: same split | Yes for PI approval | |
| B-308-04 | Trend deviations across studies and sites, using the PI's classification as recorded | 5.7 | C | C/S: site trends its own; Network Quality Lead trends across sites | No | |
SOP-309 Participant Retention, Withdrawal and Lost to Follow-Up
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-309-01 | Retention plan and reminders | 5.1, 5.3 | C/S: central reminder service allowed; Lead CRC approves the plan with the PI | S | No | |
| B-309-02 | Record withdrawal choices and notify the sponsor | 5.4, 5.7 | S | S | Yes: investigator discussion and records | |
| B-309-03 | Lost to follow-up attempts and PI decision | 5.8 | S | S | Yes for the PI decision | |
| B-309-04 | Transfer a participant between member sites: sponsor approval, IRB approval for the receiving site, re-consent at the receiving site, and transfer of records as certified copies with the basis recorded on F-905-01 | 5.4, 5.7; SOP-901 5.8 | C/S: Network Clinical Operations Lead coordinates; both PIs agree and the receiving PI consents the participant | C/S: same, under a written agreement between the two entities and participant authorization or another basis on F-905-01 | Yes: each PI keeps duties for the period the participant is at that PI's site | |
SOP-310 Participant Payments and Reimbursement
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-310-01 | Plan payment schedules and submit them to the IRB | 5.1 | C | C/S: Network Office proposes; site entity approves its own payments | No | |
| B-310-02 | Choose payment methods and a network payment vendor | 5.4, 5.7 | C | C/S: site uses the network vendor only under F-905-01 and a written agreement | No | |
| B-310-03 | Issue payments and keep F-310-01 | 5.5 | S, or C where a central payment program pays from the Network Office account (SOP-902 5.7.5.1); payments recorded on the site's F-310-01 | S, or C where a central payment program pays from the Network Office account (SOP-902 5.7.5.1); payments recorded on the site's F-310-01 | No | |
| B-310-04 | Collect W-9 and file Form 1099 | 5.3, 5.9 | C: the owning entity is the payer and totals across all its sites | S: each paying entity reports its own payments | Yes in N-Affiliated: the payer entity reports | |
| B-310-05 | Reconcile participant payments with sponsor payments | 5.10 | C | C/S | No | |
SOP-311 Biological Specimen Collection, Processing and Shipping
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-311-01 | Kit ordering and inventory | 5.2 | C/S: central ordering allowed; site checks expiry | S | No | |
| B-311-02 | Collect, label and process specimens | 5.3, 5.4 | S | S | Yes: performed under the PI's delegation | |
| B-311-03 | Shipper training program | 5.7 | C/S: Network Office trains; employer keeps the record | S | Yes: employer record (49 CFR 172.704(d)) | |
| B-311-04 | Track shipments and review specimen deviations | 5.10 | C/S: site tracks; Network Quality Lead trends | S | No | |
| B-311-05 | Run a central specimen processing hub for several sites, only with sponsor-approved routing in the laboratory manual or written instruction; CLIA certificate needed if the hub performs any testing | 5.4, 5.5 | C | C/S: under a written agreement; hub listed as a provider on F-105-01 | No, but collection stays at the site and the hub is overseen under SOP-105 | |
| B-311-06 | Move specimens between network sites or to the hub. Packaging, marking and shipper training rules apply even when staff carry the specimens by car | 5.6 to 5.8 | C/S: sending site packages and records on F-311-01; receiving site confirms receipt and temperature | C/S: same, with sponsor approval and F-905-01 entry where labels or requisitions carry identifiers | No | |
SOP-312 Equipment Calibration and Maintenance; Local Laboratory Requirements
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-312-01 | Keep the equipment inventory and calibration schedule (F-312-01) | 5.1, 5.2 | C/S: Network Office runs the schedule and vendor contracts; site keeps its inventory current | S, with network vendor contracts offered | No | |
| B-312-02 | Review calibration certificates | 5.3 | C | S | No | |
| B-312-03 | Assess impact of out-of-tolerance equipment | 5.5 | C/S: Network Quality Lead assesses; PI decides on participant actions | S | Yes for the PI decision | |
| B-312-04 | Hold the CLIA certificate for on-site testing | 5.7 | C/S: owning entity applies; certificate is per testing location | S | Yes: CLIA certificate is held for each testing location unless an exception applies (42 CFR 493.35(b), 493.55(b)) | |
| B-312-05 | Use a network laboratory for several sites | 5.8 | C, listed on each site's 1572 where required | C/S: under an agreement and listed on each site's 1572 where required | No | |
SOP-313 Decentralized Trial Elements (Remote Visits, Home Health, Direct-to-Participant IP)
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-313-01 | Qualify home health, telehealth and courier vendors | 5.1.4 | C | C/S | No | |
| B-313-02 | Delegate remote and home visit staff and list Sub-Is on the 1572 | 5.2 | S | S | Yes: PI delegates and signs the 1572 (21 CFR 312.53(c)) | |
| B-313-03 | Conduct telehealth visits by central staff | 5.4 | C/S: central licensed staff may conduct if delegated by the site PI and licensed in the participant's state | C/S: only if the agreement allows | Yes for PI delegation and supervision | |
| B-313-04 | Review home visit reports and assess findings | 5.5.4 | S | S | Yes: investigator assessment | |
| B-313-05 | Direct-to-participant IP shipment, from the site or from a central network pharmacy. A central pharmacy ships only with sponsor approval, is listed on the site's 1572 where required, and holds the DEA registration and state pharmacy licenses for each state shipped to (Appendix A) | 5.6 | C/S: central pharmacy ships; site PI or IP Manager approves each shipment and reconciles | S, or C/S under a written agreement with the same conditions | Yes: PI supervises supply of IP (21 CFR 312.61) | |
| B-313-06 | Track staff licensure by state for remote visits | 5.4.6 | C (F-904-01) | C/S | No | |
7. 400 series: data, privacy and systems
SOP-400 Participant Privacy and HIPAA in Research
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-400-01 | Determine HIPAA status of each entity and any affiliated covered entity or organized health care arrangement | 5.1 | C | S: each entity determines its own status; the Network Office records the result on F-905-01 | Yes in N-Affiliated: covered entity status is per legal entity (45 CFR 160.103) | |
| B-400-02 | Designate the Privacy Officer and Security Officer | 5.1 | C: one Privacy Officer for the covered entity or affiliated covered entity, with a site contact at each location | S: each covered entity designates its own (45 CFR 164.530(a), 164.308(a)(2)); the Network Office may support as a business associate | Yes in N-Affiliated | |
| B-400-03 | Approve research authorizations and waivers | 5.2, 5.3 | C/S: Network Regulatory Lead obtains IRB approval; site obtains signatures | S | Yes for obtaining the participant's signed authorization | |
| B-400-04 | Sign BAAs and DUAs and keep the business associate list | 5.1.4, 5.3.5 | C | S, with the Network Office as a party where it receives PHI | Yes in N-Affiliated: the entity disclosing PHI signs (45 CFR 164.502(e), 164.514(e)) | |
| B-400-05 | Receive privacy incident reports and assess breach | 5.10 | C | S: the covered entity assesses and notifies; the Network Office reports incidents it causes to the site as a business associate (45 CFR 164.410) | Yes in N-Affiliated | |
| B-400-06 | Privacy training | 5.11 | C | C/S: Network Office supplies the course; each entity records its workforce training (45 CFR 164.530(b)) | No | |
SOP-401 Computerized Systems and Electronic Records
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-401-01 | Keep the system inventory (F-401-01) | 5.1 | C | C/S: Network Office lists network systems; site lists its own | No | |
| B-401-02 | Assess and approve site-deployed systems for fitness for purpose | 5.2 | C | C/S: Network Office assesses network systems once for all sites; site assesses its own | No | |
| B-401-03 | Grant and remove user access; review user lists | 5.3 | C/S: System Owner in the Network Office grants; site requests and confirms delegation | C/S: same for network systems; site for its own systems | No | |
| B-401-04 | Electronic signature controls and letter of non-repudiation to FDA | 5.5 | C: one letter for the entity | S: each legal entity whose staff sign submits its own letter; one network letter cannot cover separate entities | Yes in N-Affiliated: one letter per legal entity (21 CFR 11.100(c)) | |
| B-401-05 | Security, backup and incident response | 5.7, 5.8 | C | C/S: Network Office for network systems; site for its own | No | |
| B-401-06 | Approve AI tools | 5.10 | C | C/S: Network Office approves for network systems; site approves for its own | No | |
SOP-402 Record Retention, Archiving and Destruction
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-402-01 | Set the retention period per study | 5.1 | C | C/S: Network Office records the period; site confirms | No | |
| B-402-02 | Prepare and archive records (F-402-01) | 5.2 | S | S | No | |
| B-402-03 | Run a central or off-site archive | 5.3, 5.4 | C | C/S: only under a written agreement that keeps the site's access and control | Yes: investigator retains records for the required period (21 CFR 312.62(c), 812.140(d)) | |
| B-402-04 | Retrieve records for sponsor, IRB or FDA | 5.5 | C/S | S | Yes: investigator makes records available for inspection (21 CFR 312.68) | |
| B-402-05 | Change of custody when a site leaves the network or closes | 5.6 | C | S, with the exit terms in SOP-901 | Yes: custody follows the investigator and entity unless transferred in writing | |
| B-402-06 | Approve destruction and legal holds | 5.7, 5.8 | C | S | No | |
8. 500 series: safety
SOP-500 Adverse Event Identification, Assessment and Recording
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-500-01 | Prepare study safety summary at start-up | 5.1 | C/S | S | No | |
| B-500-02 | Elicit and record AEs | 5.3 | S | S | No, but performed by site delegated staff | |
| B-500-03 | Investigator assessment of AEs (causality, severity, seriousness) | 5.5 | S | S | Yes: investigator duty (21 CFR 312.64(b); ICH E6(R3) Annex 1, 2.7) | |
| B-500-04 | Medical care and 24-hour contact | 5.8 | S, with a network after-hours line allowed | S | Yes: investigator arranges care (ICH E6(R3) Annex 1, 2.7) | |
SOP-501 Serious Adverse Event and Expedited Safety Reporting
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-501-01 | Report SAEs to the sponsor | 5.4 | S | S | Yes: investigator reports immediately (21 CFR 312.64(b)) | |
| B-501-02 | Weekend and holiday investigator coverage | 5.2.3 | C/S: Network Medical Director may run a rota of covering investigators, each delegated at the site | S | Yes: covering investigators must be delegated for the site | |
| B-501-03 | Report UADEs to sponsor and IRB | 5.9 | S | S | Yes: investigator duty (21 CFR 812.150(a)(1)) | |
| B-501-04 | Receive, log and route sponsor safety reports | 5.10 | C/S: Network Regulatory Lead logs and routes; PI reviews | C/S | Yes for PI review | |
| B-501-05 | Review SAE timeliness | 5.11 | C | C/S | No | |
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-502-01 | Keep each IRB's reportable-event policy current | 5.1 | C | C | No | |
| B-502-02 | PI determination on F-502-01 | 5.5 | S | S | Yes: investigator reports UPs to the IRB (21 CFR 312.66) | |
| B-502-03 | Prepare and submit the IRB report | 5.8 | C/S: Network Regulatory Lead prepares and submits after PI approval | C/S | Yes for PI approval | |
| B-502-04 | Share reportable information that affects other network sites | 5.4 | C | C/S: only as the agreement and F-905-01 allow | No | |
SOP-503 Pregnancy Reporting in Clinical Trials
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-503-01 | Contraception counseling and pregnancy testing | 5.2, 5.3 | S | S | No | |
| B-503-02 | Investigator decision on IP and report to sponsor | 5.4, 5.6 | S | S | Yes: investigator duty | |
| B-503-03 | Follow pregnancy to outcome | 5.7 | S | S | No | |
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-600-01 | Approve monitor accounts in site and network systems | 5.1.3 | C | C/S | No | |
| B-600-02 | Schedule and prepare for monitoring visits | 5.2, 5.3 | S | S | No | |
| B-600-03 | PI meeting with the monitor | 5.4.4 | S | S | Yes: investigator permits monitoring (ICH E6(R3) Annex 1, 2.3.5) | |
| B-600-04 | Track and escalate follow-up actions (F-600-02) | 5.6, 5.7 | C/S: site tracks; Network Quality Lead reviews across sites | S | No | |
SOP-601 Study Closeout
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-601-01 | Final data, query completion and casebook signature | 5.3 | S | S | Yes for PI signature | |
| B-601-02 | Final IP accountability and return | 5.4 | S | S | Yes: investigator returns or disposes of IP (21 CFR 312.62(a)) | |
| B-601-03 | IRB final report | 5.8 | C/S: Network Regulatory Lead submits after PI approval | C/S | Yes for PI approval | |
| B-601-04 | Financial closeout | 5.9 | C | C/S: payee entity reconciles | No | |
| B-601-05 | Archive the study records | 5.10 | C/S | S | Yes (see B-402-03) | |
SOP-700 Internal Quality Control and Quality Assurance Audits
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-700-01 | Study QC plan and sampling | 5.2 | C/S: Network Quality Lead sets the network sampling scheme; site Quality Lead applies it per study | S | No | |
| B-700-02 | Perform routine QC | 5.3, 5.4 | S, with cross-site reviewers allowed | S | No | |
| B-700-03 | Annual internal audit plan | 5.5 | C | C/S: Network Office audits as the agreement allows; site keeps its own plan | No | |
| B-700-04 | Conduct audits and issue reports | 5.6 | C: Network Quality Lead or an independent auditor | C/S | No | |
| B-700-05 | Quality metrics and trending | 5.7 | C (SOP-903) | C/S | No | |
| B-700-06 | Management review | 5.8 | C/S: network review plus a site review | S, with a network summary | No | |
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-701-01 | Receive audit notices and confirm scope | 5.2 | C/S: site forwards; Network Quality Lead coordinates | S, with notice to the Network Office as the agreement requires | No | |
| B-701-02 | Host the audit and log requests (F-702-01) | 5.4 | S | S | No | |
| B-701-03 | PI attends the closeout meeting | 5.5 | S | S | Yes | |
| B-701-04 | Write the response and CAPAs | 5.6 | C/S: Network Quality Lead drafts; PI signs | S | Yes for PI signature | |
SOP-702 FDA Inspections and Remote Regulatory Assessments
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-702-01 | Inspection readiness program and training | 5.1 | C | C/S | No | |
| B-702-02 | Receive FDA notice and notify sponsor and Network Office | 5.2 | S | S | No | |
| B-702-03 | Host the inspection; PI presents the study | 5.4, 5.5 | S, with network support in the back room | S | Yes: inspection is of the clinical investigator (21 CFR 312.68, 812.145) | |
| B-702-04 | Respond to Form FDA 483 within 15 business days | 5.7 | C/S: Network Quality Lead drafts with the PI; PI signs | S | Yes for PI signature | |
| B-702-05 | Respond to remote regulatory assessments and records requests | 5.10 | C/S: central systems provide records; the inspected PI or site entity answers | S | Yes for the inspected party | |
SOP-703 Corrective and Preventive Action (CAPA)
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-703-01 | Open and grade CAPAs | 5.1 | C/S: site opens; Network Quality Lead grades | S | No | |
| B-703-02 | Root cause analysis | 5.3 | C/S | S | No | |
| B-703-03 | Approve CAPA plans that affect study conduct | 5.4.5 | S: PI approves; Network Quality Lead approves network-wide actions | S | Yes for PI approval | |
| B-703-04 | Effectiveness checks and closure | 5.6, 5.7 | C | C/S | No | |
| B-703-05 | Trend CAPAs and open network-wide CAPAs | 5.8 | C | C/S | No | |
SOP-704 Research Misconduct and Fraud Reporting
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-704-01 | Run the reporting routes: the network integrity reporting channel (including an anonymous route) and, where a Site Director or Network Office leader is involved, escalation to [NETWORK GOVERNING BODY CONTACT] | 5.2 | C | C/S: network integrity reporting channel plus each entity's own route; concerns about the Network Office go to [NETWORK GOVERNING BODY CONTACT] | No | |
| B-704-02 | Initial assessment and evidence protection | 5.4 | C | S, with the Network Office involved when network staff or systems are concerned | No | |
| B-704-03 | Investigation | 5.5 | C: Network Quality Lead independent of the site; the Network Governing Body, through [NETWORK GOVERNING BODY CONTACT], appoints the investigator when the Network Quality Lead or Network Office leadership is implicated | S, with an independent network investigator if the agreement allows | No | |
| B-704-04 | Notify sponsor, IRB and FDA | 5.6 | C/S: PI notifies sponsor and IRB; Site Director decides on direct FDA reporting with counsel and the PI, with the Network Executive consulted (SOP-704 5.6.3), and no one is prevented from reporting to FDA | S | Yes for PI notifications | |
| B-704-05 | Debarment and exclusion screening | 5.7 | C | C/S | No | |
| B-704-06 | Personnel action | 5.5.6 | C | S: employer only | Yes in N-Affiliated: employer decision | |
SOP-705 Business Continuity and Emergency Preparedness
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-705-01 | Prepare the continuity plan (F-705-01) per location | 5.1 | C/S: Network Office template and network contacts; site completes for its location | S | No | |
| B-705-02 | Declare a continuity event and activate the contact tree | 5.2 | S, with notice to the Network Office | S | No | |
| B-705-03 | Participant safety decisions in an event | 5.2.3 | S | S | Yes: investigator duty | |
| B-705-04 | Backup storage at another network site | 5.3.3 | C | C/S: under a written agreement between the entities | No | |
| B-705-05 | Planned PI departure and study transfer | 5.8 | C/S: Network Clinical Operations Lead plans with sponsor; PI completes investigator tasks | S | Yes for investigator tasks | |
| B-705-06 | Closure, sale or exit of a site | 5.9 | C (SOP-901) | C/S (SOP-901) | No | |
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-800-01 | Approve the IIT and resources | 5.1 | C | S, with network support if the agreement allows | No | |
| B-800-02 | Prepare IND or IDE submissions and reports | 5.4, 5.7 | C/S: Network Regulatory Lead prepares; PI signs as sponsor | C/S | Yes for signature as sponsor | |
| B-800-03 | Sponsor monitoring and quality management | 5.5 | C: Network Office arranges independent monitoring | C/S | No | |
| B-800-04 | ClinicalTrials.gov registration and results | 5.8 | C/S: Network Regulatory Lead enters; responsible party approves | C/S | Yes: the responsible party is accountable (42 CFR 11.4(c)) | |
| B-800-05 | Decide who holds the IND or IDE for a study at more than one member site: the PI as sponsor-investigator, or the network entity as sponsor (then the PIs are investigators only and the network entity is the ClinicalTrials.gov responsible party) | Network note before 5.1 | C/S: PI, Site Director and Network Executive decide and record before submission | C/S: same, with written agreement of each participating entity | Yes: a sponsor-investigator must be an individual (21 CFR 312.3(b)) | |
| B-800-06 | Transfer of sponsor obligations to the Network Office (drug studies) | 5.5 | C/S: only by written transfer (21 CFR 312.52); obligations not transferred stay with the sponsor | C/S: same | Yes: the Network Office never takes the sponsor-investigator's investigator duties at the PI's own site | |
| B-800-07 | Monitoring of every participating member site, including the sponsor-investigator's own site, by someone outside that study team | 5.5.3 | C | C/S | No | |
10. 900 series: network SOPs
These rows cover the network SOPs. Where a 900-series row and a core row cover the same activity (for example CTA signature in B-201-05 and B-902-06, or invoicing in B-201-06 and B-902-09), the 900-series row governs. The paired rows are written to say the same thing.
SOP-900 Network Governance, SOP Hierarchy and Local Addenda
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-900-01 | Appoint Network Office roles and charter the Network Quality Committee; the Network Governing Body appoints the Network Executive | 5.1.1 to 5.1.3 | C | C: under the network agreement | No | |
| B-900-02 | Choose the variant, adopt Appendix B and record it on F-900-02; each member Site Director signs to accept the site's assignments | 5.2 | C, with Site Director acceptance | C/S: Network Office proposes; each member entity accepts through its Site Director, and only assignments the network agreement allows are made central | No | |
| B-900-03 | Replace network placeholders, mark network minimums and decide whether each Site decision box is resolved for the network or per site | 5.4 | C | C/S: network-level resolution only where the agreement makes it binding; the rest per site | No | |
| B-900-04 | Draft, check and approve local addenda (F-900-01) | 5.5 | C/S: Site Quality Lead drafts; Network Quality Lead checks against SOP-900 5.5.2; site approvers sign | C/S: same split | Yes for PI approval where the addendum affects investigator duties, safety, consent, IP or data integrity | |
| B-900-05 | Approve network SOPs and major revisions, circulate drafts to sites, and hold the editable master | 5.6.1, 5.6.3, 5.6.4 | C | C | No | |
| B-900-06 | Site-level adoption of each network SOP version | 5.6.2 | S | S | Yes in N-Affiliated: the member entity adopts for itself | |
| B-900-07 | Set one network effective date, assign training across sites, and confirm site training is complete before the date | 5.7 | C/S: Network Quality Lead or Network Training Lead sets dates and assigns; each Site Director confirms completion and restricts untrained staff | C/S: same split | No | |
| B-900-08 | Protect investigator duties: hear a PI's objection to a central instruction and act on reports of pressure on medical judgment | 5.8 | C/S: PI raises; Network Quality Committee decides on the network side; PI's decision on participant protection stands | C/S: same | Yes: investigator duties stay with each PI (21 CFR 312.60, 812.100) | |
| B-900-09 | Confirm the network agreement states binding SOPs, audit and data rights and the conflict clause (N-Affiliated only) | 5.9 | N/A | C, with counsel; each member entity signs | No | |
| B-900-10 | Network management review: run by the Network Quality Lead, chaired by the Network Executive, decided by the Network Quality Committee, summary to the Network Governing Body; each site still holds its own review under SOP-700 | 5.1.5, 5.10 | C, with site actions sent to each Site Director | C, with site representation | No | |
| B-900-11 | Name and publish [NETWORK GOVERNING BODY CONTACT] for integrity concerns about network leadership (not the Network Executive, the Network Quality Lead or anyone reporting to them) | 5.1.4 | C: Network Governing Body | C: joint governance board under the network agreement | No | |
| B-900-12 | Approve the network audit plan prepared by the Network Quality Lead | 5.1.5; SOP-903 5.4.1 | C: Network Quality Committee | C: Network Quality Committee, within audit rights in the agreement | No | |
| B-900-13 | Declare a network-wide continuity event (shared system or central service outage affecting more than one site); each Site Director then acts for their own site under SOP-705 | 5.1.5 | C/S: Network Executive, or Network Quality Lead when the Executive cannot be reached, declares; Site Director acts locally | C/S: same split | Yes for site-level participant safety decisions (SOP-705 5.2.3) | |
SOP-901 Member Site Onboarding, Integration and Exit
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-901-01 | Start the assessment and confirm a legal basis before receiving any PHI or confidential sponsor documents | 5.1 | C: the joining entity's Privacy Officer confirms the basis; Network Privacy Officer records it on F-905-01 | C: the joining entity's Privacy Officer confirms the basis on its side | Yes in both variants until closing: the joining entity decides on its own disclosures | |
| B-901-02 | Gap assessment of a joining site (F-901-01) and the Network Executive's decision | 5.2 | C | C | No | |
| B-901-03 | Report a critical gap in an in-flight study and decide on sponsor or IRB reports before integration | 5.2.3 | S: the joining site's PI and Site Director act under their own SOPs | S | Yes until the site is under network SOPs | |
| B-901-04 | Write and track the integration plan (F-901-02) and do the readiness check | 5.3 | C/S: Network Quality Lead and site Integration Lead | C/S | No | |
| B-901-05 | Notices to sponsors and IRBs for in-flight studies, including changed 1572s | 5.4.1, 5.4.2 | C/S: Network Regulatory Lead plans; site Regulatory Coordinator sends; PI signs any new 1572 | C/S | Yes for PI signature | |
| B-901-06 | PI-approved participant care plan for each in-flight study | 5.4.3, 5.4.4 | S | S | Yes: investigator duty (21 CFR 312.60) | |
| B-901-07 | Systems migration with data integrity checks and a recorded basis for PHI moving between entities | 5.5 | C/S: Network Office System Owner migrates; site confirms its records are complete | C/S: with an entry on F-905-01 | No | |
| B-901-08 | Change of ownership: CTA assignment or novation, DEA registration, CLIA change of ownership notice, other licenses, insurance and tail coverage, records custody | 5.6.1 | C: Network Contracts and Finance Lead with counsel | N/A: the member entity keeps its own CTAs, registrations, certificates and insurance unless the agreement says otherwise (5.7.2) | Yes: DEA registration is by registrant and location (21 CFR 1301.12, 1301.52); CLIA change of ownership notice by the laboratory within 30 days (42 CFR 493.39, 493.51) | |
| B-901-09 | Onboard employees of an acquired site, or assign network training through the member entity | 5.6.2, 5.7.3 | C | S: the member entity's employees stay its employees | Yes in N-Affiliated: employer | |
| B-901-10 | Transfer an open study to another PI or member site | 5.8 | C/S: Network Regulatory Lead prepares the transfer plan; sponsor, IRB and current PI agree; receiving PI signs a new 1572 | C/S: same, with an agreement between the entities | Yes: no gap in investigator responsibility or safety follow-up | |
| B-901-11 | Site exit: study disposition, records custody, access removal, data return, financial reconciliation, SOPs applicable from the exit date, shared staff removal, sale items (N-Integrated), removal from F-900-02 and Network Executive sign-off. Records custody: site Regulatory Coordinator records on F-402-01 and notifies sponsors; Network Regulatory Lead confirms | 5.9 | C, except records custody entries (C/S as stated) | C/S: member entity keeps its own records; network-held records returned or copied as the agreement provides | Yes for records the investigator must keep (21 CFR 312.62(c), 812.140(d)) | |
SOP-902 Network Study Feasibility, Allocation and Central Contracting
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-902-01 | Central intake of inquiries and execution of CDAs | 5.1 | C | C: the CDA must allow sharing with member sites | No | |
| B-902-02 | Allocate a study to sites (F-902-01). The Network Office recommends and records the decision; each allocated PI and Site Director accepts in writing, and the PI may decline | 5.4 | C, with written PI and Site Director acceptance | C/S: Network Office proposes; site entity accepts or declines | Yes: the PI's right to decline; the PI personally signs the investigator commitments (21 CFR 312.53(c)) | |
| B-902-03 | Site feasibility, including population data, capacity and the PI-approved estimate; PHI stays at the site | 5.2 | S | S | Yes: the PI approves the estimate; the Network Office must not raise it | |
| B-902-04 | Combine site estimates for the network response, correct for catchment overlap and check competing studies across the network | 5.3 | C | C | No | |
| B-902-05 | Negotiate MSAs, CTAs and site budget exhibits | 5.5.1, 5.5.3, 5.5.4 | C | C/S: Network Office negotiates; site confirms its budget exhibit | No | |
| B-902-06 | Sign CTAs and budgets | 5.5.2 | C: authorized signatory of the network entity (SOP-902 5.5.2) | S or tri-party: the member entity is the contracting institution; the network entity signs alone only where the network agreement and the sponsor accept it and counsel has confirmed (SOP-902 5.5.2) | Yes in N-Affiliated: only the member entity can bind itself, except as SOP-902 5.5.2 allows | |
| B-902-07 | Prepare one coverage analysis per protocol version | 5.6.1, 5.6.3 | C | C | No | |
| B-902-08 | Localize the coverage analysis and build the billing grid for each billing site | 5.6.2, 5.6.4 | S | S | Yes: the billing entity is responsible for its claims | |
| B-902-09 | Invoice, collect and reconcile sponsor payments by site | 5.8.1, 5.8.2, 5.8.5 | C | C/S: the payee named in the CTA invoices (the Network Office, or the site with a copy to the Network Office, SOP-902 5.8.1); the Network Office tracks payments and reconciles by site; payments between the Network Office and the site follow the network agreement at fair market value | No | |
| B-902-10 | Pay member entities their share at fair market value, set in advance, not tied to referrals; network fees only for documented services | 5.7, 5.8.3, 5.8.4 | N/A: internal accounting for member sites that are the same legal entity (5.7.6); a separate-entity site follows the N-Affiliated column (SOP-900 5.2.1) | C, with counsel review under 42 U.S.C. 1320a-7b(b); Site Director may review the records behind the statement | No | |
| B-902-11 | Recruitment and referral services between entities: paid only as FMV fees for services actually performed, never per referral or per enrollee, with counsel review under 42 U.S.C. 1320a-7b(b) | 5.7.2, 5.7.2.1, 5.7.3 | C: rules apply to any payment outside the network entity, including referring physicians (5.7.6) | C | No | |
| B-902-12 | Set the Network Office fee in the network agreement: listed services only, FMV basis documented, not varying with referrals, counsel review before signing and on change | 5.7.4, 5.7.5 | N/A | C, agreed by each member entity | No | |
| B-902-13 | Decide the payer entity for central participant payment programs, which holds W-9s and files Forms 1099-MISC, and record the participant data it receives on F-905-01 | 5.7.5.1; SOP-310 5.9 | C: the network entity is one payer for member sites that are the same legal entity and totals across those sites; a separate-entity site follows the N-Affiliated column (SOP-900 5.2.1) | C/S: each entity that pays from its own account reports; the Network Office reports payments it makes from its account | Yes in N-Affiliated for the paying entity | |
SOP-903 Network Oversight of Member Sites (Metrics, Central QA, Escalation)
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-903-01 | Keep the metric set; Network Quality Committee approves thresholds | 5.2.1, 5.2.4 | C | C | No | |
| B-903-02 | Submit metric data without direct identifiers. SAE timeliness is tracked centrally from dates (N-Integrated) or day counts only (N-Affiliated) | 5.2.2, 5.2.5, 5.2.6 | C/S: pulled from shared systems; site submits from its own systems | S: data cross to the Network Office only as listed on F-905-01 | No | |
| B-903-03 | Compile the scorecard (F-903-01), let the site correct data errors, and hold the review | 5.3 | C/S: Network Quality Lead compiles; Site Director corrects and attends; each PI reviews study-level metrics | C/S | Yes for PI review of the PI's own studies | |
| B-903-04 | Central QA audits of member sites | 5.4 | C | C/S: only as the agreement allows | No | |
| B-903-05 | Cross-site CAPA trending and network-wide CAPA | 5.5 | C, with site CAPAs linked | C/S: site takes part as the agreement requires | No | |
| B-903-06 | Assign escalation tiers and write the Escalation and Site Support Plan (F-903-02) | 5.6, 5.7 | C/S: Network Quality Lead and Site Director; PI of each affected study signs | C/S | Yes: pausing enrollment is a PI decision with the sponsor and IRB (5.7.4) | |
| B-903-07 | Share findings and lessons learned across sites | 5.9 | C/S: Site Director reports; Network Quality Lead writes summaries; Site Quality Lead confirms review | C/S, within CTA confidentiality | No | |
| B-903-08 | Rate member site risk, record any weights and the risk rank on F-903-01, and approve them with the audit plan | 5.4.2, 5.4.3 | C | C | No | |
SOP-904 Shared Staff, Cross-Site Coverage and Central Services
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-904-01 | Plan shared staff and check capacity before assignment | 5.2 | C | C/S | No | |
| B-904-02 | Delegate and train shared staff at each investigator site | 5.3 | S: PI signs; site Regulatory Coordinator checks F-103-02 and F-904-01 | S | Yes: only the PI delegates (ICH E6(R3) Annex 1, 2.3) | |
| B-904-03 | Check licensure in each state where the participant is located | 5.4 | C: recorded on F-904-01 | C/S | No | |
| B-904-04 | List shared Sub-Is on the 1572 or sign investigator agreements | 5.5 | C/S: Network Regulatory Lead prepares; PI and Sub-I sign | C/S | Yes: investigator signatures | |
| B-904-05 | Direct and oversee shared staff during study work; employment matters stay with the home site | 5.6 | S for study work; home site (employing unit) for employment | S for study work; home entity for employment, under a staffing agreement | Yes: PI directs trial work | |
| B-904-06 | Define, qualify and oversee central services as service providers | 5.7, 5.8 | C/S: Network Quality Lead qualifies; PI confirms which services each study uses | C/S: site lists the service on F-105-01 | Yes for PI acceptance (ICH E6(R3) Annex 1, 2.3) | |
| B-904-07 | Cross-site coverage of key roles | 5.9 | C/S: Network Clinical Operations Lead arranges; Site Director records the period on F-306-01 | C/S | Yes: covering investigator must be on the site's 1572 | |
| B-904-08 | Keep F-904-01, reconcile it quarterly and send departure notices to every site | 5.10 | C | C | No | |
| B-904-09 | Run the debarment, disqualification and exclusion screen centrally for shared staff and record date and result on F-904-01 | 5.3.3 | C | C/S: central screen allowed; the employer stays responsible (SOP-103) | No | |
| B-904-10 | Run a shared after-hours line that routes each call to an investigator listed for that participant's site and study | 5.9.4 | C | C/S: under the agreement | Yes: the answering investigator must be listed for the site and study | |
SOP-905 Network Data, Systems, Privacy and Records Across Sites
| Row ID | Activity | SOP step | N-Integrated default | N-Affiliated default | Must stay at site? | Site's choice |
|---|
| B-905-01 | Keep the network section of F-401-01 for shared systems and verify each one fit for purpose; one Part 11 letter per legal entity | 5.1 | C | C/S: Network Office verifies shared systems; each entity files its own Part 11 letter | Yes in N-Affiliated for the Part 11 letter (21 CFR 11.100(c)) | |
| B-905-02 | Configure site partitions and grant, review and remove access by site and study; Site Director approves access to the site's partition | 5.2 | C/S: System Owner grants after Site Director approval | C/S: same | No | |
| B-905-03 | Record the HIPAA status of the Network Office and each member site and the pathway for each PHI flow | 5.3 | C: Network Privacy Officer with counsel | C/S: Network Privacy Officer records; each entity's Privacy Officer confirms its own status | Yes in N-Affiliated: status is per entity (45 CFR 160.103) | |
| B-905-04 | Run network recruitment databases and registries, apply opt-outs network-wide and check duplicate or concurrent enrollment across sites | 5.4 | C | C/S: databases only with authorization naming the network or another basis on F-905-01; duplicate-enrollment check only as a one-way hashed match run by the Network Office under a BAA with each participating site that expressly permits the match, where each study's consent and authorization (or IRB waiver under 45 CFR 164.512(i)) covers the check, returning only match or no match (SOP-905 5.4.5) | No | |
| B-905-05 | Keep the Cross-Entity Data Flow Register (F-905-01) and approve each flow and its legal pathway | 5.3, 5.5 | C: Network Privacy Officer; entries for flows leaving the entity or between ACE members | C/S: Network Privacy Officer keeps; disclosing entity's Privacy Officer approves | Yes in N-Affiliated for the disclosing entity | |
| B-905-06 | Network analytics on de-identified or aggregate data with small-cell suppression | 5.6 | C | C | No | |
| B-905-07 | Record custody and access in central systems: each investigator site has its own eISF section and keeps control of its records | 5.7 | C/S | C/S: records stay under site control | Yes: investigator retains records (21 CFR 312.62(c), 812.140(d)) | |
| B-905-08 | Records and data when a member site exits. Site Regulatory Coordinator records the arrangement on F-402-01 and informs sponsors; Network Regulatory Lead confirms | 5.8 | C/S | C/S: records follow the investigator site | Yes for the investigator's records | |
| B-905-09 | Coordinate privacy incidents and breaches across entities | 5.9 | C: one assessment and one set of notices for the entity or ACE | S: each covered entity assesses and notifies for its records; Network Privacy Officer coordinates; Network Office as business associate notifies the site (45 CFR 164.410) | Yes in N-Affiliated | |
