SOW.pdf

10/12/2017

Shelf Life Evaluation of Investigational Dosage Forms

STATEMENT OF WORK

A. Program Objectives

The Pharmaceutical Resources Branch (PRB), Developmental Therapeutics Program

(DTP), Division of Cancer Treatment, and Diagnosis (DCTD), National Cancer Institute

(NCI), is seeking a Contractor to evaluate shelf life of samples of investigational clinical drug formulations. The products may include parenteral, oral, and other types of dosage forms. The results of such testings and evaluations will be provided promptly to the PRB.

These reports will be used for:

• providing NCI and its investigators with information regarding the proper storage and handling of various drug products under investigation,

• determining appropriate expiration dates for the products, and

• to support NCI's Investigational New Drug Applications (INDs) filed with the Food and Drug Administration (FDA).

B. Background

Currently there are approximately 20 lots of NCI drug products on stability testing, including both injectable and oral products. These will require approximately 20-25 separate evaluations per year. It is anticipated that there will be 5 to 10 new clinical lots placed on shelf-life each year, some of these lots requiring analytical method qualification in addition to shelf life testing. The Contractor shall store, and properly evaluate each one of these products, insuring that no scheduled time points are missed or overlooked.

This contract is a recompetition of an existing shelf-life contract. The new Contractor shall move the existing lots in the shelf-life study and the corresponding records to the new contractor facility, if applicable, and house them accordingly for shelf-life evaluation. A complete schedule of these ongoing lots, and all of the analytical methods and protocols for these items will be available to the successful organization.

The analytical instrumentation shall include sufficient capability to perform high performance liquid chromatography, ultraviolet and infrared spectroscopy, gas liquid chromatography, moisture determinations, pH determinations, and particle size determination.

The Contractor should dedicate at least two high performance liquid chromatography

(HPLC) systems equipped with auto-samplers, variable wavelength detectors, and data acquisition system. A third HPLC should be available for use during peak periods of analysis.

The Contractor should provide other ancillary equipment needed to accomplish the work.

The Contractor shall furnish services, qualified personnel, materials, and a complete fully operational facility. The facility shall include all necessary equipment and instrumentation adequate to conduct all aspects of the shelf life evaluation of the clinical drug products. Such facility and equipment shall conform to and be maintained in accordance with current Good Manufacturing Practices (cGMPs).

The Contractor shall provide up-to-date analytical instrumentation, and pharmaceutical testing equipment to perform a thorough and complete shelf life evaluation on the clinical drug products.

C. Tasks

To guarantee continuous and proper storage conditions, the Contractor shall continuously monitor and record the condition of the storage facilities.

Laboratory notebooks with charts, records and other data be made available to the

Government upon request.

a. Adoption of the stability-indicating analytical method.

1. All shelf life evaluations will use stability-indicating analytical methods. Such methods for each drug product will be provided by

NCI. However, it is the Contractor’s responsibility to evaluate and adopt each analytical method before conducting shelf life evaluations.

NCI will provide the appropriate reference or working standards for drug substances.

2. A report of adoption performed on each analytical method, with corresponding chromatographic tracings attached, should be provided within 30 days of completion.

b. Shelf Life Evaluation

The Contracting Officer Representative (COR) will assign the protocol(s) for the shelf life evaluation(s) for each batch of the clinical drug product.

The protocol will indicate the storage condition (s) depending on the characteristics of the active ingredient in the drug product and properties of the clinical drug product.

The shelf life evaluation protocol will indicate the evaluation intervals.

The evaluation intervals, are generally, 0, 3, 6, 9, 12, 18, 24, 36, and 48 months at the labeled storage temperature. For the elevated temperature samples, the evaluation intervals will be generally 3, 6, 9, and 12 months depending on the agent and Program needs.

The Contractor shall evaluate all the samples within + 5 days of the scheduled date. The COR, in consultation with the Contractor, will supply an adequate number of samples (including a reasonable excess for repeat evaluation if needed) for storage at selected condition set forth in the protocol.

b.1. Initial Evaluation

The Contractor shall evaluate each sample at its initial time point and report the following data to the COR. Typical tests to be performed are listed below:

Injectables:

1. Assay

2. Impurities (including level of each impurity and total amounts)

3. pH determination

4. Physical observations

a) Reconstitution (If freeze dried, should observe and report the following: visual appearance prior to reconstitution, time of reconstitution, completeness of solution, color of solution)

b) Color

c) Clarity

d) Particulate matter per USP.

5. Other evaluations shall include as necessary to properly evaluate the shelf life of the clinical drug products.

Oral products:

1. Assay

2. Impurities (including level of each impurity and total amounts)

3. Dissolution

4. Physical appearance b.2. Evaluation at Testing Intervals

The evaluation will include most of the parameters as listed above

(depending on the dosage form and/or products) or as directed by the

COR.

b.3. Re-evaluation

At the discretion of the COR, the Contractor will re-evaluate the out of specification or other test results and an out of specification test investigation report submitted.

c. Other Evaluations and Requirements

The Contractor is to analyze "inert ingredients" when deemed necessary by the COR in the shelf life evaluation of the clinical drug products.

The Contractor is to design and operate an adequate data base system to keep track of and schedule at the proper intervals to evaluate the shelf life of the samples of the stored clinical drug products.

The Contractor is to maintain laboratory notebooks with charts, records and other data at the contract site and make them available to COR for review.

D. Transition to the Subsequent Contractor

a. At least twelve (12) months prior to the completion date of this contract, the

Contractor shall submit a written plan/system to the COR for the potential transfer of all compounds, arrayed sets and Government property to an offsite storage facility (potentially a successor Contractor or the NCI). A general inventory of the compounds, arrayed sets and other Government property shall be included.

b. Upon request by the COR, at least three (3) months prior to the completion of the contract, a full and complete inventory of compounds and arrayed sets in the repository and all Government-owned property including scientific equipment, software programs and databases, data files, etc., shall be provided. At this time, the Contractor shall also describe their specific plans for packaging and shipping all such compounds, arrayed sets, data and

Government property to a successor Contractor or the NCI, and a cost estimate for this transition.

c. The Contractor shall fully cooperate with any successor Contractor and the

NCI to ensure the smooth, efficient and timely transfer of all such data and

Government property, including providing access to any essential uniquely trained staff to complete the transfer of informatics and any other critical components of the operation.