1.1 This Procedure Describes How Controlled Documents Are Initiated, Revised and Approved

Effective Date: Procedure ID: Rev: [Dept or Organization] DC.002 Controlled Copy #: Department(s):

Procedure Title: Document Initiation, Revision and Approval Page 1 of 8

SOP Approvals

Title Name Signature Date Technical Authority Department Head Quality Assurance

1.0 Purpose

1.1 This procedure describes how controlled documents are initiated, revised and approved for the dept.

2.0 Scope

2.1 This procedure applies to all controlled documents used within ______dept. that pertain to cellular collection, processing and therapeutic apheresis.

2.2 This procedure does not apply to documents used within the dept. that pertain to preclinical or research cellular products.

2.3 Document control personnel under the direction of the Quality Assurance (QA) Manager are responsible for the maintenance of all controlled documents.

3.0 Definitions

3.1 Archived Document: document retained by Document Control that is no longer in active use.

3.2 Controlled Document: any document required by, but not limited to, current regulations and standards to design, manufacture and control the production of cellular products. Such documents have restricted capacity for modification and controlled distribution for both hard copies and electronic versions. Controlled documents include, but are not limited to, SOPs, Batch Production Records, Policies, Plans, Protocols, Reports, Studies, Processing Worksheets, Forms and Labels.

3.3 Document Control: established processes for creating, approving and changing standardized documents.

3.4 Master Document File (MDF): contains the original document and all approved revisions and forms associated with a particular controlled document, if

CONFIDENTIAL INFORMATION Property of [Dept. or Organization Effective Date: Procedure ID: Rev: [Dept or Organization] DC.002 Controlled Copy #: Department(s):

applicable. Access to MDFs is restricted to QA and personnel with responsibilities for document control.

3.5 Superseded Document: prior version of an effective document maintained with the MDF.

4.0 Safety

4.1 Not Applicable

5.0 Materials and Equipment

5.1 Computer with secure access to the network. 5.2 Word Processing Program, Microsoft Word or equivalent

6.0 Procedure

6.1 Initiation/Revision of a Document

6.1.1 Any employee within the dept. may initiate a new document or suggest revisions of existing documents.

6.1.2 The originator of a document should discuss the need for the document or document revisions, its scope and proposed content with his/her supervisor or manager prior to initiating the draft process and obtain his/her approval signature on the Document Initiation/Revision Form. See Appendix DC.002.01.

6.1.3 Document Control personnel distribute a copy of the Document Initiation/Revision Form to the requestor, who completes Section 1 with the following information:

6.1.3.1 Originator Name 6.1.3.2 Document Type (e.g., SOP, BPR, Protocol, Report) 6.1.3.3 Document Title 6.1.3.4 Document Number (current number for an existing document, N/A for new document) 6.1.3.5 Check “New” or “Revise”, as applicable 6.1.3.6 Location of Revisions (indicate page # or step # within the document, for revisions only) 6.1.3.7 Document Changes/Justification for new or revised documents 6.1.3.8 Originator (signature/date)

6.1.4 The originator submits the Document Initiation/Revision Form to the QA Manager for review. The QA Manager completes the following information in Section 2 on the form:

6.1.4.1 Department 6.1.4.2 Quality Review

6.1.5 The QA Manager routes the form to Document Control personnel for number assignment. Only Document Control personnel can assign document numbers. Document numbers, once assigned, are not reassigned even if the document is archived.

6.1.6 Document Control personnel ensures that the originator has the appropriate electronic document(s) to begin document initiation or revision. Draft documents are maintained on a secured shared network drive for ease of review by all CCP staff. Refer to procedure, “Document Control System,” DC.003 for details on electronic document accessibility when revising documents.

6.1.7 Refer to the defined numbering system for specific document types as addressed in procedure, “Requirements of Writing Controlled Documents,” DC.001.

6.1.8 Drafts are circulated for comments and changes to appropriate personnel that will be using that document.

6.1.9 The originator informs Document Control personnel when the draft document is final and ready to assemble for the approval process. Document Control personnel edit and ensure standard formatting of the document.

6.2 SOP Qualification

6.2.1 SOP Qualification is performed on SOPs at the discretion of the Department Manager.

6.2.2 Qualification is not required for non-SOP documents.

6.2.3 The Department Manager determines the number and type of SOP qualifications to be performed for a particular procedure and communicates this information to Document Control personnel.

6.2.4 Prior to circulating an SOP for signature approval, Document Control personnel assign an SOP Qualification form as directed by the Department Manager. See Appendix DC.002.02. The person performing

the SOP qualification cannot be the same person who originated or revised the SOP.

6.2.5 Document Control personnel completes the following information on the SOP Qualification Form:

6.2.5.1 Document Title 6.2.5.2 Document Number 6.2.5.3 Revision # 6.2.5.4 Assigned to 6.2.5.5 Date Assigned 6.2.5.6 Date Due

6.2.6 Completed SOP Qualification forms are submitted back to Document Control personnel for SOP update and revision.

6.2.7 Document Control personnel or the person responsible for updating the SOP, marks “Yes” or “No” in the “Incorporated Suggestions” column, indicating whether or not they incorporated the suggestions revisions.

6.2.8 Completed SOP Qualification forms are submitted to both the Department Manager and QA Manager for review and signature approval.

6.2.9 Document Control personnel files and maintains completed and reviewed copies of the SOP Qualification form in the appropriate MDF.

6.3 Approval

6.3.1 The first signature is the person most knowledgeable about the document or the work indicated in the document. This is indicated in the approval box as the Technical Authority and may be the originator or technical lead. Technical Authority is also used for administrative or quality SOPs and other non-SOP documents and is the person with the expertise to write documents specific to those areas.

6.3.2 The second signature should be another individual knowledgeable about the work described in the document, and one who is responsible for ensuring that the work is completed as directed. This person is usually a Manager or Director. This is indicated in an approval box as Department Head.

6.3.2.1 The Department Head will approve and sign for all documents specific to his/her department, including SOPs within the sections listed below:

6.3.2.1.1 Apheresis Procedures (AP) 6.3.2.1.2 Bone Marrow Collection (BC) 6.3.2.1.3 Document Control (DC) 6.3.2.1.4 Equipment (EQ) 6.3.2.1.5 Facility (FA) 6.3.2.1.6 General/Administration (GA) 6.3.2.1.7 Inventory Control (IC) 6.3.2.1.8 Organization and Personnel (OP) 6.3.2.1.9 Process Control (PC) 6.3.2.1.10 Production (PR) 6.3.2.1.11 Quality Assurance (QA) 6.3.2.1.12 Test Methods (TM)

6.3.2.2 More than one designated Department Head signature is required for shared department documents.

6.3.3 The next signature is a person representing the QA group, usually a Manager or Director. This signature assures that the document meets all of the quality requirements for that document. This is indicated as Quality Assurance in the approval box.

6.3.3.1 The QA group will sign and approve all controlled documents.

6.3.4 The next signature is that of the Laboratory Director who will approve and sign the Laboratory Director signature box. This signature assures that the document meets all of the scientific aspects required for that document.

6.3.5 The next signature is that of the Medical Director who will approve and sign the Medical Director Signature box. The signature assures that the document meets all of the clinical aspects required for that document.

6.3.6 The QA manager consults with the Laboratory and Medical Director, to ensure that they approve and sign the appropriate non-SOP documents.

6.3.7 Document Control personnel is responsible for inserting approval titles and names within the approval box for that final draft document before the document is routed for review and signature approval. Document Control personnel will delete any unused lines in the header.

6.3.8 Document Control personnel circulate the original hard copy of the document for approval signatures.

6.3.9 The Effective Date is left blank on the original document until employees within each applicable department have read and signed the Employee

Document Review Form and appropriate training is completed. See Appendix DC.002.03.

6.4 Employee Review and Effective Date

6.4.1 Document Control personnel complete Section 1 of the Employee Document Review Form and insert the names of the employees who are required to review and sign the document. See Appendix DC.002.03.

6.4.2 Document Control personnel circulates a copy of the document along with the Employee Document Review Form for employee review. The training copy is stamped with “COPY” and circulated to the employees that will be using the document. Additional employee training may be required depending on the document. Refer to Training and Competency procedures specific to each department for training documentation requirements.

6.4.3 Employees must review and sign the Employee Document Review Form that accompanies all controlled documents.

6.4.4 Document Control personnel submits the signed Employee Document Review Form to QA for review and signature.

6.4.5 Document Control personnel files and maintains the signed Employee Document Review Form in the appropriate MDF.

6.4.6 The Effective Date of a final approved document must be a date mutually agreed upon by the QA Manager and the Department Manager(s), based upon reasonable assurance that adequate training will be completed.

6.4.7 Document Control personnel stamps the effective date on the original, final document, and ensures that all controlled copies of the document will be circulated to the appropriate areas. Refer to procedure, “Document Control System” DC.003 for details.

6.4.8 Once the document is approved, Document Control personnel maintain the original document in the associated MDF.

6.5 Annual Document Review

6.5.1 The following accreditation agencies require an annual review of all effective SOPS: Foundation for the Accreditation of Cellular Therapy (FACT) and College of American Pathologists (CAP).

6.5.2 On an annual basis, Document Control personnel submit a copy of the current effective TOC along with the associated documents to the Laboratory and Medical Director for their review.

6.5.3 The Laboratory and Medical Director sign the current effective TOC, documenting their review and approval of the SOPs, policies and plans.

6.5.4 Document Control personnel files and maintains the signed copy of the reviewed TOC.

7.0 Expected Results

7.1 All controlled documents used by the dept. will be initiated, revised and approved according to the above steps in this SOP.

8.0 References

8.1 Code of Federal Regulations (CFR) 21 CFR 211.100 and 21 CFR 1271.80.

8.2 Foundation for the Accreditation of Cellular Therapy Standards (FACT), C.5000 and D.5000, 2nd Edition, 2002.

8.3 SOP: DC.001, Requirements for Writing Controlled Documents

8.1 SOP: DC.003, Document Control System

9.0 Appendices

9.1 DC.002.01: Document Initiation/Review Form

9.2 DC.002.02: SOP Qualification Form

9.3 DC.002.03: Employee Document Review Form

CONFIDENTIAL INFORMATION Property of [Dept. or Organization Effective Date: Procedure ID: Rev: Controlled Cellular Production Controlled Copy #: Department(s): ORIGINAL

Procedure Title: Document Initiation/Revision Form Page 1 of 1

Section 1: (Completed by Originator) Originator Name: Document Title:

Document Type: New Revise Archive

Document Number (If available): Revision #: Location of Revisions Document Changes/Justifications (page #, step #)

Originator (Signature/Date): Supervisor Review (Signature/Date):

Section 2: (Completed by Quality Assurance or Document Control) New Document Number: REV#: Department(s): If Document is Archived, Record Dates Document Was In Use: Quality Review (Signature/date):

CONFIDENTIAL INFORMATION Property of [Dept. or Organization Effective Date: Procedure ID: Rev: Controlled Cellular Production Controlled Copy #: Department(s): ORIGINAL

Procedure Title: SOP Qualification Form Page 1 of 1

Document Title: Document #: REV#: Assigned To: Date Assigned: Due Date:

DC Incorporated Suggestions Y/N 1. Is the title clear and specific? Yes No Comments:

2. Are the purpose and scope clear and specific? Yes No Comments:

3. Are all of the necessary materials, equipment and forms listed in order to perform the procedure? Yes No Comments:

4. Is the test sufficiently detailed to be understood and followed by staff and does the text flow in an easy to read and comprehensive manner? Yes No Comments:

5. Are the acceptable criteria appropriate? Yes No Comments:

Qualification Results 6. Were you able to sufficiently follow and perform the procedure? Yes No Comments:

Qualification Performed by (Signature/date): Manager Review (Signature/date): Quality Review (Signature/date):

CONFIDENTIAL INFORMATION Property of [Dept. or Organization Effective Date: Procedure ID: Rev: Controlled Cellular Production 04 Controlled Copy #: Department(s): ORIGINAL

Procedure Title: Employee Document Review Form Page 1 of 1

Section 1: (Completed by Document Control) Document Title: Document Number: REV#: Department(s):

Section 2: (Completed by Document Control) Employee Name Employee Signature/Date

Quality Review (Signature/Date):

CONFIDENTIAL INFORMATION Property of [Dept. or Organization