Draft_SOW_for_Analysis_Recompete_IDIQ_final.doc

Statement of Work (Attachment #1) SEQ CHAPTER \h \r 1Analysis of Bulk Drugs & Pharmaceutical Formulations 1.

Introduction/Background

The Pharmaceutical Resources Branch (PRB), Developmental Therapeutics Program (DTP), Division Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI) is seeking services for the analysis of bulk drug substances and formulated drug products. Reports of these analyses will be used as a basis for assessing the suitability of these materials for use in biological activity screening, pharmacological studies, toxicological studies, formulation studies and clinical trials. Data provided in these analytical reports will be supplied to the Food and Drug Administration (FDA) as part of the Investigational New Drug (IND) filings for new anti-tumor agents. Historical summaries of the data are used in preparing specifications of the various bulk drug substances. These specifications are used in procurement actions as well as for the routine quality control of these materials. Awardees selected should be experienced in the analytical assessment of bulk drug substances and clinical drug products, according to FDA regulations and guidelines, and will be expected to have operational equipment and capabilities.

Independently and not as an agent of the Government, the Awardees shall furnish services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government under terms of this contract, as needed to perform the work below.

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References

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Scope and Tasks

Contractors shall complete and deliver approximately 5-7 Task Orders (TO) each year. The actual number of Task Orders is expected to be variable, dependent upon the existing approved compounds and approval rate of new developmental compounds. These assignments will involve the following project activities:

1. Complete all work required by typical “TO-Release Analysis” on bulk drug substances.

Approximately 3-4 bulk drug lots per year are anticipated.

2. Complete all work required by typical “TO-Release Analysis” on formulated drug products.

Approximately 1-2 lots of formulated drug products per year are anticipated.

3. Develop complete physicochemical characterization and validated chromatographic methods for bulk drug substances and formulated drug products. Analytical development will be required for approximately 2-3 new drug substances per year.

4. Complete assigned work on approximately 2-3 long-term projects (6-12 months in duration) each year, usually involving stability studies on bulk drug substance, in accordance with FDA guidance.

Contractors shall perform analysis of bulk drug substances and their pharmaceutical formulations. All materials to be analyzed will be assigned and usually supplied by the NCI

Contract Officer Representative (COR). The Contract Officer Representative will transmit with each sample a Task Order. The Task Order will list the TO Number, date, NCI compound designation (NSC Number), chemical name, structure, supplier, lot number, method of preparation (where applicable), specifications (when available), and other pertinent information. Analytical tests to be performed by the Contractor will be specified by the Contract Officer Representative. The Contractor shall prepare analytical reports which detail the work performed in response to a specific Task Order. Each Task Order will address various objectives which may include the following:

a) Establish the identity of the drug substance, usually by a combination of spectroscopic and spectrometric studies.

b) Establish the purity of bulk drug substance, usually by the development of a validated chromatographic method according to FDA guidance.

c) Identify and determine the amounts of impurities present in the bulk drug substance, primarily by a combination of chromatographic and spectroscopic/spectrometric analyses and preferably by LC-MS (liquid chromatography-mass spectrometric analysis).

d) Determine physical and chemical properties of drug substances (e.g., solubility, optical rotation, thermal properties (m.p., DSC, TGA), partition coefficient and pKa’s).

e) Determine the stability of the drug substance and drug product under designated storage conditions, in accordance with FDA guidance.

f) Identify and determine the concentration of the active pharmaceutical ingredient in dosage forms.

g) Determine the content uniformity of dosage forms.

h) Develop dissolution method for solid dosage forms.

The Contractor shall consider the chemicals and drugs to be analyzed under the proposed contract as proprietary in nature. Under no circumstances are chemicals or drugs or any information associated with these chemicals or drugs to be released or divulged without prior written approval of the COR.

The Contractor shall maintain laboratory notebooks containing raw data at the contract site. All data generated under the proposed contract are property of the Government and must be supplied to the Government upon request.

The Contractor shall comply with applicable drug, health and safety regulations:

a) FDA requirements. Facilities shall meet FDA standards for Laboratory Quality Control unit, in accordance with current Good Manufacturing Practices (cGMP) regulation. If inspections by FDA during the term of the contract cite deficiencies which, in the opinion of the COR and Contracting Officer (C.O.), are judged to disqualify its function as a Laboratory Control unit, such citations could be the basis for termination of the contract unless satisfactory corrective actions are implemented.

b) Occupational Safety and Health Act (OSHA), United States Environmental Protection

Agency (EPA) and United States Department of Transportation (DOT) regulations: The

Contractor shall comply with all OSHA and DOT regulations regarding the handling of chemicals. The Contractor shall comply with all EPA regulations regarding the discharge of water and air pollutants and assure that disposal of all chemical residues meets current EPA regulations.

In order to meet the objectives listed above, the Contractor shall be expected to analyze bulk drug substance and formulated drug product. The Contractor shall also develop validated analytical methods to establish the identity and purity of the materials analyzed. The following is a list of approaches for different assignments:

1. Although each Task Order for a bulk drug substance will specify the analytical tests required, in most cases those tests will be selected from the following list:

a) Melting point or DSC (Differential Scanning Calorimetry) determination

b) Infrared spectroscopy

c) Ultraviolet spectroscopy

d) Nuclear magnetic resonance spectroscopy (proton, carbon, fluorine and phosphorus) and

2-D correlated experiments

e) Mass Spectrometry (low- and high-resolution)

f) Optical rotation

g) Thin-layer and/or paper chromatography

h) High performance liquid chromatography or gas-liquid chromatography

i) LC-MS (liquid chromatography-mass spectrometric analysis) and LC-MS/MS determinations

j) Capillary electrophoresis

k) Karl Fischer water determination

l) Trace analysis for heavy metals

Additional tests and procedures may also be required by the COR. These include solubility determinations, bulk and solution stability studies, electrochemical techniques, partition coefficient and pKa measurements, thermogravimetric analyses (TGA), AA, ICP-

MS, and other tests as needed.

2. Although each Task Order for a formulated drug will specify the analytical tests required, in most cases those tests will be selected from the following list:

a) Infrared spectroscopy

b) Ultraviolet spectroscopy

c) High performance liquid chromatography or gas-liquid chromatography

d) Any other tests (e.g., dissolution, content uniformity) appropriate to the various dosage forms (tablets, capsules, liquid fills or lyophilized products).

3. Task Orders on new drugs may require the development of validated chromatographic methods, in accordance with FDA guidance. The Contractor shall also provide data validating the assay methods developed. These data shall be submitted to the

COR in a separate Validation Report, which will include a detailed description of the assay procedure; appropriate measures of accuracy, specificity, sensitivity, precision, stability-indicating capability and other information as required.

4. It is anticipated that several (2-3) long term projects (i.e., projects of 6-12 months with approximately 200 labor hours in duration) will be assigned per year. These assignments are not intended to conflict with the more routine Task Orders. Examples of long term projects include identifying impurities and stability assessment.

It is anticipated that 3 awards of IDIQ-type contracts will be made for a period of five (5) years. Each Contractor is estimated to provide 0.5-1.0 technical staff-years per year with completion and delivery of 1 to 3 reports for approximately 1-3 Task Order assignments. A staff year is 1875 hours of direct labor per year excluding holidays and sick leaves.

It is anticipated that these contracts will commence on approximately Aug 1, 2017 and end on approximately Jul 31, 2022.

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RFP NO2-CM- 77004-16

Attachment #1