SOLICITATION NOTICE
A -- Study on the Development of Quality by Design (QbD) for Lyophilized Protein Parenteral Manufacturing Processes - Deliverables Table
- Notice Date
- 9/12/2009
- Notice Type
- Combined Synopsis/Solicitation
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, Food and Drug Administration, Office of Acquisitions and Grants Services, 5630 Fishers Lane, Room 2129, Rockville, Maryland, 20857-0001
- ZIP Code
- 20857-0001
- Solicitation Number
- 1058557cc
- Archive Date
- 10/1/2009
- Point of Contact
- Christopher E. Cunningham, Phone: 301-827-7185, London L Johnson,
- E-Mail Address
-
christopher.cunningham@fda.hhs.gov, london.johnson@fda.hhs.gov
(christopher.cunningham@fda.hhs.gov, london.johnson@fda.hhs.gov)
- Small Business Set-Aside
- N/A
- Description
- QbD Deliverables Table This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in FAR 12.6, simplified acquisition procedures and the resultant purchase order will include all applicable provisions and clauses in effect through the Federal Acquisition Circular 05-30. This announcement constitutes the only solicitation and a written solicitation will not be issued. This synopsis, NAICS code 541711, is to notify contractors that the government intends to issue a Firm Fixed Price Purchase Order in accordance with FAR Part 13.106 for the following statement of work (SOW), under the simplified acquisition procedures. Any firm that believes it is capable of providing the required service as stated herein may submit a capability statement to document its ability to provide the required services. A determination to compete this procurement based on a response to this notice is solely within the discretion of the Government. The Government reserves the right to award a contract without discussions if the Contracting Officer determines that the initial offer(s) is/are providing the Best Value and discussions are not necessary. Award will be made to the offeror whose quote offers the best value to the Government, technical, price, and other factors considered. The Government may award this contract to other than the lowest price technically acceptable quote. The Government will evaluate information based on the following evaluation criteria: 1) Personnel, 2) Organizational Experience, 3) Project Management/Technical Approach. This combined synopsis/solicitation is issued as a Request for Quote (RFQ). The Food and Drug Administration (FDA) intends to award a purchase order for the Development of Quality by Design (QbD) for Lyophilized Protein Parenteral Manufacturing Processes. Background Information: This project is part of an overall effort to develop a systematic framework for the realization of Quality by Design (QbD) for drug product development and manufacture in the spirit of International Conference on Harmonization (ICH) guidances Q8, Q9, and Q10. The overarching goals of this research is to provide a scientific foundation for the development of QbD guidance elements on design space that will take into consideration the impact of product performance attributes such as stability, safety, efficacy and patient utility on the design space process. Objective: The project proposed here is designed to address the performance requirements and manufacturing constraints associated with lyophilized protein products for parenteral administration. Protein pharmaceuticals present manufacturing and product performance issues that can be unique and troublesome because of their susceptibility to physical and chemical instability, unique safety issues (e.g. immunogenicity) and efficacy based not only on chemical purity but also on higher-order structural integrity. Moreover protein pharmaceuticals are typically very surface active, highly potent and prone to molecular interactions (including self-association). Taken together, these biophysical, biochemical and pharmacological attributes present significant challenges to the design and development of protein pharmaceutical products and manufacturing processes that are much less frequently encountered with small molecular weight drugs. The goal of this project is to develop an understanding of Quality by Design (QbD) approach as applied to the protein parenteral manufacturing processes. In the current proposal, scientists from The University of Iowa, Purdue University, University of Connecticut, and Baxter Pharmaceutical Solutions will work collaboratively with the FDA to develop a case study for protein parenteral dosage forms which can form the basis for constructing some of the guidance elements on this subject. Description/Statement of Work (SOW) A typical protein API (e.g. glucagon) that is widely available and is representative of many, if not all, of the special issues associated with protein pharmaceuticals will be chosen for this study. The work will involve the following steps: 1. Define the Critical Product Attributes of the Target Product Profile. The target product profile would include: a. Potency, Physical Integrity and Chemical Purity API source and control strategy b. Maintenance of potency, purity and physical integrity upon reconstitution Ability of the protein pharmaceutical to maintain chemical purity and physical integrity during thermal and mechanical stress associated with the aqueous reconstituted solution of administration can be a significant risk for product performance. The rate of solution, propensity to aggregate or degrade, adsorption to package surfaces, interaction with packaging leachables or reconstitution solvent components can be potential problems. c. Formulation design and manufacturing issues manifested upon reconstitution In addition to the possible issues arising from reconstitution process and solvent formulation design, various potential failure modes can be manifested upon reconstitution and ascribed to manufacturing and lyophilized formulation design. For example pH control during and after lyophilization, interactions between formulation components, thermal history during freezing and the effect of collapse on reconstitution time can be relevant to product performance. d. Freedom from particulate matter In addition to contamination by extraneous particulates or incomplete solubilization, protein pharmaceuticals are susceptible to interactions between protein and packaging components and self- aggregation leading high particle counts. e. Stability Protein pharmaceuticals can be susceptible to hydrolytic and oxidative chemical instability during manufacturing, storage, shipping, and/or use. Hydrolytic instability can be influenced by moisture, temperature, pH and the presence of reactive exicipients (e.g. reducing sugars). Headspace reactive gases and trace impurities have been associated with oxidation. Moreover, proteins are susceptible to physical instability manifesting in higher order structural changes and/or aggregation. Manufacturing, shipping, and use stresses (thermal and mechanical) can conspire with environmental conditions (pH, surfaces, concentration, co-solutes, etc) to induce physical changes 2. Propose a formulation using key formulation design decisions: Pertinent formulation design decision will address both lyophilized protein formulation and reconstitution solvent compositions. Decision will be based on the likely or demonstrate susceptibility of the protein to physical and chemical instability, lyophilization behavior, biocompatibility issues and intended pharmacotherapy requirements. 3. Propose the manufacturing process: Manufacturing process unit operations will include preparation of drug solution for lyophilization, sterile filtration, freezing, primary drying, secondary drying, capping and sealing. 4. Conduct a risk analysis using cause and effect process (Ishikawa Diagram): The objective of this step is to identify the variables that are like to impact the manufacturing process. 5. Risk Evaluation: Classify the unit operations that are likely to have an impact on quality. 6. Identify the critical operating variables and material property variables: Screening studies will be used to identify variable that are like to have the maximum impact on the Critical Product Attributes. (Risk evaluation study using Risk = probability X impact and FMEA) 7. Design of Experiments: Efficient designs will be constructed to handle multivariate statistical models guided by process understanding and/or mechanistic models. 8. Conduct the experiments in laboratory/pilot plant equipment. 9. Develop Protein Formulation Design Space and Lyophilizer Design Space. 10. Propose control strategy to reduce risk. Deliverables: PLEASE SEE THE ASSOCIATED ATTACHMENT FOR THIS TABLE: Period of Performance: One (1) year Release of Information by Contractor: The contractor will not release any data generated under this project without the approval of the Project Officer. Site Visits: Site visits are not anticipated. Evaluation Factors: Personnel 30 points a) 15 points Offeror shall demonstrate that it employs the personnel requisite to perform studies in the area of freeze dried pharmaceutical products. The offeror shall describe the qualifications of the participating personnel, identify their qualifications and experience, and for each person, indicate the percentage of time that would be devoted to this contract. b) 15 points Offeror shall demonstrate that the personnel have previous interest in the topic of pharmaceutical manufacturing and the process of Lyophilization by including relevant publications or speaking engagements. Organizational Experience 30 points a) 10 points Offeror shall demonstrate its experience in conducting studies regarding active pharmaceutical ingredient (API) characterization, lyophilized powder characterization, and injectable product characterization. Provide FDA with a table containing the title of each relevant project, contracting organization, organization contact, dollar amount, and type of analysis (evaluation, cost/benefit, etc... Publications relevant to the described work should be included. b) 20 points The offeror will demonstrate national leadership in manufacturing research, engineering, and education. The offeror will demonstrate its ability to develop consensus opinion among scientists in industry, academic institutions and with the FDA. Project Management/Technical Approach/ 40 points a) 10 points The offeror shall demonstrate experience and resources to complete the deliverables, in addition to the technical capabilities. (For example, project management staff and other administrative support) b) 10 points The offeror shall provide a timetable that expands the deliverables into subordinate tasks that lead to completion of the deliverable. c) 20 points The offeror shall demonstrate an understanding of the project needs and the knowledge gaps that will be filled. In addition, the offeror shall demonstrate how it will approach the work and what equipment and software that will be used. Responses to this notice must be sent via email to Christopher.Cunningham@fda.hhs.gov; TELEPHONE CALLS WILL NOT BE ACCEPTED. QUESTIONS DEADLINE: All questions must be submitted in writing via email to Christopher.Cunningham@fda.hhs.gov no later than September 15, 2009 at 1:00 PM EST. QUOTATIONS DUE: All quotations are due, via email to: Christopher.Cunningham@fda.hhs.gov no later than 1:00 PM EST on September 16, 2009. PROVISIONS and CLAUSES: The provision at FAR 52.212-1, Instructions to Offerors Commercial Items applies to this solicitation. Offerors shall include a completed copy of the provision at FAR 52.212-3, Offeror Representations and Certifications Commercial Items. The clause at FAR 52.212-4, Contract Terms and Conditions, Commercial Items applies to this acquisition. The clause at FAR 52.212-5 Contract Terms and Conditions Required to Implement Statues or Executive Orders, Commercial Items applies to this acquisition. The following FAR clauses cited are applicable: FAR 52.217-8, FAR 52.222-26, FAR 52.222-35, FAR 52.222-36, and FAR 52.232-33. Clauses and provisions are incorporated by reference and apply to this acquisition.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/FDA/DCASC/1058557cc/listing.html)
- Place of Performance
- Address: Work shall be performed at the Contractor's facility., United States
- Record
- SN01952377-W 20090914/090912233918-836593b9d1f089468b9e6c8fb0f68a8d (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's FBO Daily Index Page |