REVISED_Sample_Production_Task_Order.pdf

Sample Production Task Order

1. Statement of Work The Pharmaceutical Resources Branch (PRB) will provide the following information: 1) the active pharmaceutical ingredient (API) for formulation development studies with the certificate of analysis and a Material Safety Sheet; 2) a HPLC method; and 3) stability data on the drug substance if available.

Upon receipt of the above, the following tasks are to be performed, with the Contractor supplying consumable supplies and equipment to carry out each task:

A. Manufacture of a clinical batch based on the development task above, following cGMP’s suitable for human clinical trials. This includes the following:

Based on the dosage form development studies carried out in Part A, prepare draft manufacturing batch records for preparation of the drug product including

1) the batch formula card; 2) all the steps used to manufacture the drug product; 3) any in process testing (before and after filtration assays, appearance, pH, fill check for volume, membrane “bubble point” following filtration, etc.); 4) all steps in the freeze drying process; 5) vial stoppering, sealing, inspection, and labeling. The draft batch records are to be submitted for review and approved by the COR or designee prior to initiation of manufacture.

Batch size of 1,000 vials of injectable product either liquid or lyophilized with a freeze drying cycle of 96 hours. The offeror is required to repeat the following tests on the drug substance prior to manufacture: appearance, assay, impurities, moisture, and identity by infrared spectroscopy. Reference spectra will be provided. The offeror is to provide all consumable supplies (excipients, vials, stoppers, flip off seals, labels, etc.) except the active ingredient which will be provided by NCI.

The Offeror is to describe their approach to testing of all drug product components (API, excipients, container closure system, labels, etc.). The Offeror is responsible for all in process and final product testing, quality control testing and release of drug product as follows:

Tests Specifications

Appearance of drug product Report result

Completeness and Clarity TBD following development work of solution

Identity by HPLC Retention time agrees with reference lot

Uniformity of Dosage Units Assay

(HPLC)

Meets requirements of current USP 90.0‐110.0% of label (average of three vials)

Impurities Report % and RRT of all impurities ≥

LOQ

Particulate Matter (USP 788) Meets Requirements

Osmolality TBD following development work

Moisture (Karl Fisher) TBD following development work pH TBD following development work

Sterility (USP 71) Meets USP requirements –Membrane Method

Bacterial Endotoxins TBD depending on maximum human dose

Following release of the drug products by the Offeror, the manufacturing batch records are submitted for review and approval by the COR or designee. The Offeror is responsible for storage of the drug products at the labeled temperature until shipping instructions are provided by the COR. Use of these initial batches of drug product requires submission of an IND, receipt of a “study may proceed notice” from the US Food and Drug Administration and IRB approval. Once all approvals are obtained, the COR will provide shipping instructions to the Offeror. This process may require at least 3‐4 months.

B. Other Requirements

The above tasks are to be carried out under current Good Manufacturing Practices (cGMPs). In addition, all operations described in this SOW will be performed according to the Standard Operating Procedures of the Offeror, and any deviations will be documented.

The manufacturing facility used must be registered with the US Food and Drug Administration (FDA). Provide a list of the Inspections of the facility proposed for this work, by FDA and/or other regulatory agencies over the last 2 years.

Note if there have been any 483 observations and current status of resolution.

2. Reporting Requirements and Deliverables

A. Reporting Requirements

Bi‐weekly Team Meetings, as needed.

The Offeror shall manage either face to face or telephone meetings on a bi‐ weekly basis in order to keep the Project Team appraised of the progress, and discuss any issues or problems. Ad Hoc meetings can also be arranged by the

Offeror as needed. Meetings are expected to include: 1) securing a physical location or suitable call in number and passcode for relevant participants; 2)

Preparing an agenda for discussions; 3) Moderation of the meeting; 4)

Preparation of meeting minutes and summarization of action items resulting from meeting.

Reports and Documentation.

o Monthly Task Order Reports o Final Task Order Report

B. Deliverables

The following table contains a list of deliverables with notation of due dates. All days indentified are intended to be normal business days unless otherwise specified. The

Offeror may suggest an alternative due date for any or all deliverables in their proposal.

The final schedule will be agreed to by the COR and the Offeror and specified in the Task

Order.

Deliverable Due Date

Delivery of 1,000 vials of cGMP Drug Product

9 months from date of award

Acceptance Criteria

In addition to specific Acceptance Criteria for each Deliverable (as shown in the Table below), general quality measures as set forth below, will be applied to each deliverable received from the Offeror under this Task Order:

Accuracy: Deliverables shall be accurate in presentation, technical content, and adherence to accepted elements of style.

Clarity: Deliverables shall be clear and concise. Any/all diagrams shall be easy to understand and relevant to the supporting narrative.

Consistency to Requirements: All deliverables shall satisfy the requirements of this task order.

Timeliness: Deliverables shall be submitted on or before the due date specified in the task order, or submitted in accordance with a later schedule date determined by the Government.

Deliverable Acceptance Criteria

Delivery of 1,000 vials of cGMP Drug Product

All drug product must be manufactured and documented according to cGMP criteria, all applicable institutional standard operating procedures, and meet the specifications described in the Statement of Work and as mutually agree upon after completion of development work.

3. Proposal Due Date and Location to Deliver Proposals

The proposal shall not exceed 40 pages (excluding Appendix). The Task Order Proposal is due with the Contract Proposal, May 17, 2013 12:00 NOON Eastern Prevailing Time.

4. Period of Performance of Task Order

Project Initiation Date will commence on the date of Task Order Award. The list of deliverables includes notation of due dates based on the start date of award. The Period of Performance will be three (3) months.

5. Anticipated Type of Task Order

This Task Order will be a Non‐severable, Firm Fixed Price Task Order and follow all applicable clauses from the parent contract.

6. Technical Proposal Instructions

A. Technical Approach

i. Understanding: Provide an understanding of what needs to be done, the estimated length of time for the work to be completed, the challenges, and how the challenges will be addressed.

ii. Approach: Describe a sound technical approach to the work outlined in the

Statement of Work and critical technology challenges required for accomplishing proposed tasks. Describe any unique aspects of the approach, and why it is believed to be the most efficient and effective way of achieving project tasks.

iii. Personnel: Provide an overview of the capabilities brought by the proposed personnel, including an organizational chart illustrating the reporting relationship of the staff proposed to work on this Task Order. Provide the qualifications of any personnel proposed, as well as the number of hours being proposed. Please specify Key Personnel.

If certain tasks or tests will not be carried out in‐house, list the organizations that will carry out those functions, the basis for their selection, and audit history of those organizations.

iv. Management Approach: Provide a discussion of the following:

Controls: Describe the project management approach and what control mechanisms will be put in place to track progress and ensure project schedules will be met in according to agree‐upon schedules.

Risk Management: Describe overall risk mitigation strategy, with initial risk table. This table should include a list of project risks, an estimation of the severity (H, M, L), and a brief risk mitigation approach for that risk.

Subcontractor Management: Describe management controls to be implemented for subcontractor management if subcontractors are part of the proposed team.

Financial Tracking: Describe the mechanism you will use to control budget and cost.

v. Past Performance: Describe the teams overall experience with development, processes, and technologies similar to those described in the Statement of

Work. Provide a description of three completed projects of a similar nature that have been completed in the last 2 years. The summary should specify the personnel involved on the project, the personnel’s role, and the success criteria that were used to judge the project.

B. Project Plan and Work Breakdown Structure

Detail the methods for producing deliverables, allocation of staff, and other resources necessary to produce deliverables, and timelines. Provide a draft project plan (In MS

Project) as a separate attachment that contains tasks that demonstrate how objectives described in the Statement of Work will be accomplished. The draft project plan shall show tasks, dependences, and milestones, any milestone reviews as requested, as well as any requested Offeror‐supplied dates for deliverables.

7. Business Proposal Instructions

A. Cost Proposal

The information shall be in the format provided in the Master RFP (Attachment 12), including but not limited to labor hours and rates, travel, materials, subcontractors, and indirect costs. The Offeror shall provide substantive detail regarding the cost proposed so as to enable reviewers to objectively determine the reasonableness. Failure to provide a level of detail to facilitate this determination may result in the proposal being considered nonresponsive.

B. Cost Justification

In this section provide justifications and explanations of the proposed costs. This includes explanation of the process by which extended costs were derived and a basis for why the proposed costs should be considered reasonable. The supporting information to be provided includes, but is not limited to:

Labor Costs: Provide clear categories and description, if proposed positions have not been filled or are to be named or hired, provide description of anticipated position and estimated labor category.

Subcontractors: Cost estimates of at least three potential subcontractors

(assuming there are three capable of performing work).

8. Evaluation Factors for Awards

The Task Order proposals will be evaluated on the follow factors, in order of importance:

A. Overall Technical Feasibility

B. Total Cost

C. Projected Start Date

D. Projected Time Line

Award determination will be the best value to the Government.