Philip K. Burns, Co-founder, CRO Consulting09.08.16
Strategic planning allows a company to prepare for its future. That includes planning within the company to improve their capability and capacity for growing current products or launching new products, or pursuing changes to meet market or financial demands. Preparation for the strategic plan includes ensuring sufficient internal staff availability, and their access to good project management tools. These tools allow pursuance of concurrent and sequential efforts.
Contract manufacturing organizations (CMOs) are a resource option to consider when planning for strategic efforts or projects. There are many CMO options available to a company, supporting research and development to commercial production of legacy products. Identifying suitable options and then selecting a CMO can be achieved in short order if there has been suitable preparation. Internal preparations for meeting the strategic plan can also prepare a company for meeting the CMO option.
Strategic planning should include specific projects to achieve any of the product strategies. Planning includes preparing a project proposal—one that captures the project information, timing, and supports. It includes:
1. Project description: A short description of the project that includes:
a. Goals—general description, followed by specific outcomes
b. Type of processes required, such as manufacturing—sterile, tablets, etc., packaging, distribution, etc.
c. Known equipment needs—models, sizes
d. Analytical processes and equipment—example: stability)
e. Specific regulatory plans—DEA registration, FDA inspection history, filing plans, etc.
2. A target completion date, with supportive timing information
3. Available internal supports and personnel, including project director or leads
4. External support needs, such as CMOs
a. Desirable CMO attributes—examples: location, size, expertise, etc.
Identifying and selecting the CMO
Use the project information to identify possible CMO candidates. Industry publications and advertisements, and the Internet, are helpful in identifying possible candidates. Perform a public level due diligence—business and financial status, FDA history, marketing information about physical plant or support capabilities—to narrow the options to a manageable number of suitable candidates.
Use the project description to prepare a non-confidential description of the project. Contact the CMO candidates that pass the first level due diligence, and initiate discussions regarding project needs and their capability and availability. Use this effort to reduce the candidate field down to a manageable effort. Once the field has been reduced—or if a single best fit is identified—the formal efforts need to begin. They include:
An audit of the CMO site for compliance and capability can be pursued as a due diligence audit of the final CMO candidates to assess their compliance or capability risk for the project. A detailed audit can be pursued at a later time if the risk appears minimal. That audit can then be specific to the product and project needs, allows for auditing of specific items vs. general systems.
Select the CMO based on fit to the project, compliance status, cost estimates, and match of capabilities. Document and communicate that selection and the reasoning. Include the audit report and any follow-up in the file. Contractual aspects of the project can be pursued post audit. Compliance issues need to be identified and addressed prior to contractual commitments. The details of the project—products, processes, quality agreements, cost structures—all contribute to the details of contracts. Development of contracts may be divided between facility and organization preparation, product trials, and ongoing commercial supports.
Project planning
In addition to the information already shared, project-planning discussions are pursued to ensure the company and the CMO can provide timely support to the project. This is influenced by the internal structure and personnel assigned to support the project. If resources are lacking from either side, the shortfall must be addressed before the project begins, as addressing later will result in delays. The internal procedure requirements—example: change control—for both parties need to be identified and supported, to minimize conflict and ensure compliance.
Develop an internal draft
Project Plan while finalizing the contracts with the CMO. This document should identify the project goals based on the proposal, personnel assigned to the project, a high level time and events schedule, and the regulatory filing requirements.
Primary Project Planning steps are:
1. Change control document preparations and approvals—both companies
2. Document transfers
a. Current or proposed master batch records
b. Specifications
c. Test methods
d. Minimum protocol requirements
3. Test method verifications or validations
4. Purchasing supplies for manufacturing/packaging/testing—pursue in advance of scheduled production, based on lead times
5. Development batch manufacturing/packaging and testing; reports
6. Application/validation batch manufacturing and packaging information
a. Protocols
b. Testing
c. Reports
d. Stability initiation and testing, reporting
7. Regulatory document preparations and filing
8. Commercialization production planning
a. Commercial volume equipment needs—pursue concurrent to project
Preparing master documents specific for the project and product will aid in the document transfer. They may reflect documents used in regulatory filings, or developed for the project. Formats can be simple outlines or detailed descriptions. Internal master documents can be used to transfer information to the CMO. The standard formatting of such documents can confuse the CMO, so it may be best to develop documents specific to the project. The CMO can then take these documents and develop the internal Masters based on their procedures. The company masters can be revised as needed as a means of communicating change or keeping a change history.
In addition to the project plan, develop a project file. Review and approve the index and contents of the file for acceptance and to ensure intellectual property is controlled, and all non-disclosures are upheld. This document is provided to the CMO so they can align their capabilities and needs to the project (see example in Table 1). Consider placement of the file in a cloud location, or some other secure point that allows for easy access, and updating, by approved personnel.
The project file includes project information to begin the project, but primarily serves as the location—physical or electronic—to hold the critical documents for the entire project as they are created. This ensures project information is available in a completed condition for the various project participants. Use the project plan and the project file for formal project discussions with the CMO. The plan structure can also be used for project communications between the joint team from both organizations, and to communicate project status to company management.
Product projects typically have technical support and production personnel available to ensure adequate technical depth for the project. The project should include similar analytical testing technical depth, even if the company intends to perform all testing internally. Internal testing can have a major impact on current testing capacity. The analytical testing demands for projects and products are multilevel and complex. The following is a summary of the types of analytical demands from a project.
Preparing for the regulatory filing is an important project effort. Since many transfers require prior approval a changes being effected 30-day notice, it is crucial that regulatory submissions be submitted as soon as possible. Most documents can be prepared concurrently to activity. This helps ensure not only that they are ready, and that the requirements are being met as the project proceeds.
The regulatory efforts should be monitored along with the project efforts. When properly planned, filing can be completed shortly after major project milestones, like an accelerated stability testing time point. The timing of the regulatory filing and subsequent approvals also figure into the scheduling for post project production. Some projects allow for implementation of commercial activity on conclusion of product projects, especially if there is a need to build inventory for post Regulatory approval distribution. Such activity should include appropriate controls to prevent distribution until the regulatory approval is received.
Proper preparation and planning is required to achieve any strategic effort, whether internal or external. External preparation includes the steps for identifying and selecting a CMO, and pursuing the plan to achieve the goals of the project. Good preparation and planning with the CMO will improve the project outcomes. CP
Phil Burns has worked in the pharma industry over 30 years, with technical and senior management roles in quality and operations. He has served as the head of quality, technical support, quality control/regulatory, and production at multiple companies. He is the co-founder of CRO-Consulting, providing compliance, regulatory and operations consulting to the pharmaceutical and medical device industry. He can be reached at phil@cro-consulting.net.
Contract manufacturing organizations (CMOs) are a resource option to consider when planning for strategic efforts or projects. There are many CMO options available to a company, supporting research and development to commercial production of legacy products. Identifying suitable options and then selecting a CMO can be achieved in short order if there has been suitable preparation. Internal preparations for meeting the strategic plan can also prepare a company for meeting the CMO option.
Strategic planning should include specific projects to achieve any of the product strategies. Planning includes preparing a project proposal—one that captures the project information, timing, and supports. It includes:
1. Project description: A short description of the project that includes:
a. Goals—general description, followed by specific outcomes
b. Type of processes required, such as manufacturing—sterile, tablets, etc., packaging, distribution, etc.
c. Known equipment needs—models, sizes
d. Analytical processes and equipment—example: stability)
e. Specific regulatory plans—DEA registration, FDA inspection history, filing plans, etc.
2. A target completion date, with supportive timing information
3. Available internal supports and personnel, including project director or leads
4. External support needs, such as CMOs
a. Desirable CMO attributes—examples: location, size, expertise, etc.
Identifying and selecting the CMO
Use the project information to identify possible CMO candidates. Industry publications and advertisements, and the Internet, are helpful in identifying possible candidates. Perform a public level due diligence—business and financial status, FDA history, marketing information about physical plant or support capabilities—to narrow the options to a manageable number of suitable candidates.
Use the project description to prepare a non-confidential description of the project. Contact the CMO candidates that pass the first level due diligence, and initiate discussions regarding project needs and their capability and availability. Use this effort to reduce the candidate field down to a manageable effort. Once the field has been reduced—or if a single best fit is identified—the formal efforts need to begin. They include:
- Non-Disclosure Agreement, or Confidentiality Agreement
- Providing the applicable sections of the project proposal file (above). This information can also be used to initiate the project financial estimates
- Project and compliance audit of the CMO site
An audit of the CMO site for compliance and capability can be pursued as a due diligence audit of the final CMO candidates to assess their compliance or capability risk for the project. A detailed audit can be pursued at a later time if the risk appears minimal. That audit can then be specific to the product and project needs, allows for auditing of specific items vs. general systems.
Select the CMO based on fit to the project, compliance status, cost estimates, and match of capabilities. Document and communicate that selection and the reasoning. Include the audit report and any follow-up in the file. Contractual aspects of the project can be pursued post audit. Compliance issues need to be identified and addressed prior to contractual commitments. The details of the project—products, processes, quality agreements, cost structures—all contribute to the details of contracts. Development of contracts may be divided between facility and organization preparation, product trials, and ongoing commercial supports.
Project planning
In addition to the information already shared, project-planning discussions are pursued to ensure the company and the CMO can provide timely support to the project. This is influenced by the internal structure and personnel assigned to support the project. If resources are lacking from either side, the shortfall must be addressed before the project begins, as addressing later will result in delays. The internal procedure requirements—example: change control—for both parties need to be identified and supported, to minimize conflict and ensure compliance.
Develop an internal draft
Project Plan while finalizing the contracts with the CMO. This document should identify the project goals based on the proposal, personnel assigned to the project, a high level time and events schedule, and the regulatory filing requirements.
Primary Project Planning steps are:
1. Change control document preparations and approvals—both companies
2. Document transfers
a. Current or proposed master batch records
b. Specifications
c. Test methods
d. Minimum protocol requirements
3. Test method verifications or validations
4. Purchasing supplies for manufacturing/packaging/testing—pursue in advance of scheduled production, based on lead times
5. Development batch manufacturing/packaging and testing; reports
6. Application/validation batch manufacturing and packaging information
a. Protocols
b. Testing
c. Reports
d. Stability initiation and testing, reporting
7. Regulatory document preparations and filing
8. Commercialization production planning
a. Commercial volume equipment needs—pursue concurrent to project
Preparing master documents specific for the project and product will aid in the document transfer. They may reflect documents used in regulatory filings, or developed for the project. Formats can be simple outlines or detailed descriptions. Internal master documents can be used to transfer information to the CMO. The standard formatting of such documents can confuse the CMO, so it may be best to develop documents specific to the project. The CMO can then take these documents and develop the internal Masters based on their procedures. The company masters can be revised as needed as a means of communicating change or keeping a change history.
In addition to the project plan, develop a project file. Review and approve the index and contents of the file for acceptance and to ensure intellectual property is controlled, and all non-disclosures are upheld. This document is provided to the CMO so they can align their capabilities and needs to the project (see example in Table 1). Consider placement of the file in a cloud location, or some other secure point that allows for easy access, and updating, by approved personnel.
The project file includes project information to begin the project, but primarily serves as the location—physical or electronic—to hold the critical documents for the entire project as they are created. This ensures project information is available in a completed condition for the various project participants. Use the project plan and the project file for formal project discussions with the CMO. The plan structure can also be used for project communications between the joint team from both organizations, and to communicate project status to company management.
Product projects typically have technical support and production personnel available to ensure adequate technical depth for the project. The project should include similar analytical testing technical depth, even if the company intends to perform all testing internally. Internal testing can have a major impact on current testing capacity. The analytical testing demands for projects and products are multilevel and complex. The following is a summary of the types of analytical demands from a project.
- General—aseptic facilities require extensive microbial testing capability for assurance of facility, process, and product sterility. The expected needs and equipment for this should be present in any aseptic CMO facility.
- Raw material—the ingredients for making products can require simple to complex testing. Most are USP/EP/JP monograph requirements, and include fairly simple wet chemistry tests. Some do require complex analysis using sophisticated equipment and methods. It is expected that any CMO should have the base equipment for testing raw materials, but may need to get specific chemicals or instruments to complete the analytical qualifications.
- Packaging components—many of these items are tested using physical measurements, and can be accomplished easily. Some are critical to drug delivery or sterility and can require complex testing.
- Finished product—like the raw materials, these tests are simple to complex, and may require specific items to complete.
- Stability—some CMOs are equipped to support the stability needs for products. This includes analytical and stability storage supports.
- Supplies and instrument consumables can run from moderate to intermediate in the cost scale, and can impact the final contract costs directly.
Preparing for the regulatory filing is an important project effort. Since many transfers require prior approval a changes being effected 30-day notice, it is crucial that regulatory submissions be submitted as soon as possible. Most documents can be prepared concurrently to activity. This helps ensure not only that they are ready, and that the requirements are being met as the project proceeds.
The regulatory efforts should be monitored along with the project efforts. When properly planned, filing can be completed shortly after major project milestones, like an accelerated stability testing time point. The timing of the regulatory filing and subsequent approvals also figure into the scheduling for post project production. Some projects allow for implementation of commercial activity on conclusion of product projects, especially if there is a need to build inventory for post Regulatory approval distribution. Such activity should include appropriate controls to prevent distribution until the regulatory approval is received.
Proper preparation and planning is required to achieve any strategic effort, whether internal or external. External preparation includes the steps for identifying and selecting a CMO, and pursuing the plan to achieve the goals of the project. Good preparation and planning with the CMO will improve the project outcomes. CP
Phil Burns has worked in the pharma industry over 30 years, with technical and senior management roles in quality and operations. He has served as the head of quality, technical support, quality control/regulatory, and production at multiple companies. He is the co-founder of CRO-Consulting, providing compliance, regulatory and operations consulting to the pharmaceutical and medical device industry. He can be reached at phil@cro-consulting.net.