REVISED_Sample_Development_Task_Order.pdf

Sample Development 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. Development of injectable dosage form‐either liquid or lyophilized. This development shall include the following:

Develop stability indicating HPLC method for the quantification of drug in the presence of excipients based on the NCI provided HPLC method.

Determine the solubility and short‐term stabilityt of clinical agent in water as a function of pH and cosolvents, if needed. Based on these studies, determine the feasibility of a liquid or a lyophilized dosage form.

Once a determination is made of a promising formulation composition, determine effect of filtration on drug concentration. Prepare about 5 ml of that solution, retain 2 ml, filter 3 ml through a 25 mm 0.2 µm PVDF filter. Assay filtered and unfiltered solution in duplicate. The difference content between solutions should be ≤ 2%. If not, evaluate filters with different composition.

Develop a freeze drying cycle for the agent in promising formulation using a 10 ml fill volume in a 20 ml 20 mm type I colorless vial. Evaluate for cake appearance, assay, impurities, and time to affect complete dissolution after addition of 10 ml 0.9% Sodium Chloride in Water and 10 ml Distilled Water. A minimum of two pilot freeze drying runs will be required.

Stability Studies: Aseptic Fill Solution vs. Freeze Dried Dosage Form. The following apply:

o The aseptic fill solution, either aqueous or cosolvent formulation should be placed on stability at two different temperaturs (for e.g., 25°C/60% relative humidity (RH) and at 40°C/75% RH) for 0, 1, 4, and 12 weeks;

evaluating appearance, assay, and impurities.

o Similar Studies are to be carried out with lyophilized dosage forms, evaluating lyophilized cake, assay, impurities, moisture, reconstitution properties (time to complete dissolution), appearance of reconstituted solution, and pH.

o Assess the stability after reconstitution of the lyophilized drug for injection vials with a) Sodium Chloride Injection USP, and b) Water for Injection USP at four time points over 3 days (e.g. 0, 6, 24, and 72 hours).

Studies to evaluate the antimicrobial properties of the drug product. The following apply:

o The Offeror is to carry out the validation test procedure (bacteriostasis/fungistasis test) for sterility by membrane method on the proposed dosage form using the current USP procedure.

o A bacterial endotoxin test, which will be part of the final product specifications. An enhancement inhibition assessment will be required on the drug product during development.

o A filter integrity test will also be required. During development, the Offeror is to determine the effect of the clinical agent solution in excipient solution on the integrity of the 0.2 micron filter using the “bubble point” method and the ability of water for the injection flushes to restore the “bubble point” to the pre‐exposure pressure.

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

Development of Dosage Form & Preparation of Master Production Records

6 months from date of award

Dosage from Development 7 months from date of and Batch Record Documentation (CTD format Preferred) 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

Development of Dosage Form & Preparation of Master Production Records

All work completed in support of formulation development will be documented in the final report.

Dosage from Development and Batch Record Documentation (CTD format Preferred)

All tasks conducted in support of this project will be documented in enough detail for the Government to have future manufacturing completed by another organization.

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 seven (7) months.

5. Anticipated Type of Task Order

This Task Order will be a Non‐severable, Cost‐Reimbursement 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.