Joe Cobb, Anshul Gupte, Metrics Contract Services 10.11.16
With 32 years of pharmaceutical industry experience between us, we have worked on hundreds of early-phase, solid-oral dosage development projects involving many different kinds of clients. The number of projects from virtual pharmaceutical companies continues to increase, however, these companies face special challenges.
Today, the typical virtual pharma company possesses one active pharmaceutical ingredient (API) it acquired from a Big Pharma company after the API failed to advance within an expected therapeutic area. Sometimes, however, that API still holds promise for another therapeutic area. With venture capital funding and a small staff, a virtual pharma company can start exploring that option.
Through collaborative partnerships with contract development and manufacturing organziations (CDMOs), virtual pharma can, ultimately, position their products for greater success in clinical studies. The following are tips for how a virtual pharma company can maximize its potential for success when partnering with a CDMO.
Conduct an internal needs assessment
Virtual pharma companies tend to have only a few people on staff, each of whom have many different responsibilities. They should conduct a frank and honest “self audit” to better understand what work they can conduct in-house, what they can’t, and what additional services or expertise they need. It’s important to understand what capabilities or limitations your company has along with which person is responsible for what critical aspects of the drug development cycle. Know exactly what your company needs and what you’re looking for in a CDMO.
Vet different CDMOs to find the best fit
CDMOs are like people—they have their individual strengths and weaknesses. And although some CDMOs claim to do it all, most have niche expertise. For example, Azopharma tried to be everything to everyone and that may be why they don’t exist anymore. Do you need speed? Do you need capacity? Are you sitting on a potential blockbuster? Do you have a capsule product? If that’s the case, don’t go to a CDMO with just one encapsulator. These are the conversations virtual pharma companies and CDMOs must have during the vetting process.
It helps when virtual pharma companies share their long-term vision with their CDMO partner. We’ve had virtual pharma companies say they just want to get into a Phase I study so they can sell the product or company, while others want to stick with their drug product all the way through to commercialization. Since we don’t know until they tell us, it’s good to know the end game. It’s important for virtual pharma companies to define their project deliverables upfront. This helps the CDMO provide a timeline and deliverables that are realistic and appropriate. And that information could help the virtual pharma company choose the right partner.
Start early—work sometimes takes longer than expected
Virtual pharma companies need to vet CDMOs well in advance of initiating a clinical study. No matter how robust you think the molecule or formulation or manufacturing process or analytical methods might be, there are often unforeseen challenges or changes that require additional time. Developing a drug is not unlike adding on to a house—no matter how well you plan ahead, things can happen outside your control and temporarily slow down the process.
Understand phase-appropriate drug development
It’s important for a virtual pharma company to ascertain whether a CDMO has enough experience with phase-appropriate development to meet what will be increasingly demanding clinical trial material needs. For example, in early Phase I studies, a simple formulation that can accommodate multiple strengths is essential. In addition, the formulation has to be developed quickly and only needs short-term stability over several months. This approach of simple formulation for early Phase I studies also ensures that the time and cost for the corresponding analytical method development and validation do not limit forward progress.
By mid-clinical, late Phase I and early Phase II studies, the formulation should have components of Quality by Design (QbD) and robustness against manufacturing variables. Also, the formulation should have reproducibility of final product quality in order to accommodate multiple manufacturing runs. With respect to analytical testing, it is typically desired to conduct a QbD study on the analytical methods at this stage as well. This ensures that the methods discriminate between various changes in formulations and processes. The methods also need to be precise, robust and reproducible and be validated for the CDMO’s Phase II method-validation requirements.
By the time the clinical program reaches late Phase II/early Phase III, the formulation needs to be commercial-ready in anticipation of efficient tech transfer to commercial production. The method must be validated for the CDMO’s Phase III method validation requirements. Similar to formulation, analytical methods must be continually challenged at this stage so that they are ready to be transferred to quality control as part of commercial production and release.
What you want to avoid are downstream issues with your drug product. For example, control-of-powder properties of a capsule’s or tablet’s final blend, such as compressibility and flow, affect product quality and manufacturing efficiency. So it’s standard practice for formulation scientists at the CDMO to investigate parameters that impact and enhance powder properties during scale up to late stage. That kind of time spent upfront can deliver major cost savings downstream.
Understand your API supply chain
Even the largest of Big Pharma companies can be hard-pressed to secure enough API for preclinical formulation. For small companies, which typically have less money and fewer industry connections, it can prove even more difficult. How much API do you have now and how much do you need in months or even years from now? If you’re working with an offshore source, these questions are even more critical, because importing an experimental drug substance complicates logistics and regulations.
Understand your molecule
Globally, the number of highly potent APIs continues to grow. The safe handling of potent API requires specialized techniques and facilities, yet virtual pharma companies sometimes don’t fully understand their API’s strength. There exist several banding systems that categorize compounds by toxicity; Safebridge is among the best known. It is recommended that virtual pharma companies conduct a safety and environmental hazard evaluation of their API before engaging a CDMO.
If the virtual pharma company can eliminate as many unknowns about their API as possible before it requests a formal proposal from the CDMO, the CDMO will respond with a more accurate project quote and timeline. Likewise, if the virtual pharma company purchased rights to the API from another company, the sale should have been accompanied by a technical package. It is also recommended that virtual company officials share the technical package with the CDMO so that everyone understands well the API involved.
Keep the lines of communication open
We both have worked with virtual pharma companies that hire subject experts as consultants to manage particular aspects of projects—and that’s fine with them. But the virtual pharma companies should remain involved.
Virtual pharma companies tend to have just a few people on staff. Those few people wear a lot of different hats, so they often outsource work to subject matter expert consultants. And truth be told, when we’re formulating their API, I’d rather speak with the formulation scientist the company hired as a consultant than the staff accountant who understands budgets but not necessarily chemistry. Having good and productive relationships with consultants are critical when it comes to the success of the project. At the same time, conversations with consultants can’t come at the expense of communication with the company.
It’s highly desirable for an in-house staff person to remain involved throughout the process, just to help ensure that there is no information gap between the consultant, the virtual pharma company, and the CDMO.
Conclusion
The virtual pharma model works. A compound Metrics Contract Services worked with since its late Phase I clinical trial recently was approved by the U.S. Food and Drug Administration. In addition to the drug’s sponsor, Metrics worked with consultants, subject matter experts, drug substance manufacturers and packaging companies on this project.
The project truly started small-scale and increasingly produced more material as the company’s clinical trials grew. It’s important to be able to keep up with changes and deliver high quality and reproducible drug product into the clinical setting.
It is also important that the sponsor considers you to be an extension of their company, and to build a relationship with the sponsor over the long drug development timeframe.
Joe Cobb As director of pharmaceutical development at Metrics Contract Services, Joe Cobb manages all aspects of projects that involve early-phase solid oral dosage development. He also oversees the company’s potent and cytotoxic drug development services, which include a dedicated and segregated potent facility. Cobb holds the highly respected ISPE Certified Pharmaceutical Industry Professional credential, the only competency-based international certification for pharmaceutical professionals. He holds a bachelor’s of science degree in chemical engineering from The Ohio State University.
Dr. Anshul Gupte manages all aspects of operations related to formulation and manufacturing of a client’s clinical trial materials. As associate director, Gupte supervises a team of formulation scientists, specialists and technicians who develop solid dose formulations for Phase I-III clinical trials—and who scale up and validate those materials as needed. He oversees clinical trial batch manufacturing and packaging under cGMP guidelines; supervises technology transfers; and documents clinical trial material batch records. Gupte earned his doctorate in pharmaceutical sciences from the University of Kentucky, and holds a master’s degree in pharmaceutical sciences from Temple University.
Today, the typical virtual pharma company possesses one active pharmaceutical ingredient (API) it acquired from a Big Pharma company after the API failed to advance within an expected therapeutic area. Sometimes, however, that API still holds promise for another therapeutic area. With venture capital funding and a small staff, a virtual pharma company can start exploring that option.
Through collaborative partnerships with contract development and manufacturing organziations (CDMOs), virtual pharma can, ultimately, position their products for greater success in clinical studies. The following are tips for how a virtual pharma company can maximize its potential for success when partnering with a CDMO.
Conduct an internal needs assessment
Virtual pharma companies tend to have only a few people on staff, each of whom have many different responsibilities. They should conduct a frank and honest “self audit” to better understand what work they can conduct in-house, what they can’t, and what additional services or expertise they need. It’s important to understand what capabilities or limitations your company has along with which person is responsible for what critical aspects of the drug development cycle. Know exactly what your company needs and what you’re looking for in a CDMO.
Vet different CDMOs to find the best fit
CDMOs are like people—they have their individual strengths and weaknesses. And although some CDMOs claim to do it all, most have niche expertise. For example, Azopharma tried to be everything to everyone and that may be why they don’t exist anymore. Do you need speed? Do you need capacity? Are you sitting on a potential blockbuster? Do you have a capsule product? If that’s the case, don’t go to a CDMO with just one encapsulator. These are the conversations virtual pharma companies and CDMOs must have during the vetting process.
It helps when virtual pharma companies share their long-term vision with their CDMO partner. We’ve had virtual pharma companies say they just want to get into a Phase I study so they can sell the product or company, while others want to stick with their drug product all the way through to commercialization. Since we don’t know until they tell us, it’s good to know the end game. It’s important for virtual pharma companies to define their project deliverables upfront. This helps the CDMO provide a timeline and deliverables that are realistic and appropriate. And that information could help the virtual pharma company choose the right partner.
Start early—work sometimes takes longer than expected
Virtual pharma companies need to vet CDMOs well in advance of initiating a clinical study. No matter how robust you think the molecule or formulation or manufacturing process or analytical methods might be, there are often unforeseen challenges or changes that require additional time. Developing a drug is not unlike adding on to a house—no matter how well you plan ahead, things can happen outside your control and temporarily slow down the process.
Understand phase-appropriate drug development
It’s important for a virtual pharma company to ascertain whether a CDMO has enough experience with phase-appropriate development to meet what will be increasingly demanding clinical trial material needs. For example, in early Phase I studies, a simple formulation that can accommodate multiple strengths is essential. In addition, the formulation has to be developed quickly and only needs short-term stability over several months. This approach of simple formulation for early Phase I studies also ensures that the time and cost for the corresponding analytical method development and validation do not limit forward progress.
By mid-clinical, late Phase I and early Phase II studies, the formulation should have components of Quality by Design (QbD) and robustness against manufacturing variables. Also, the formulation should have reproducibility of final product quality in order to accommodate multiple manufacturing runs. With respect to analytical testing, it is typically desired to conduct a QbD study on the analytical methods at this stage as well. This ensures that the methods discriminate between various changes in formulations and processes. The methods also need to be precise, robust and reproducible and be validated for the CDMO’s Phase II method-validation requirements.
By the time the clinical program reaches late Phase II/early Phase III, the formulation needs to be commercial-ready in anticipation of efficient tech transfer to commercial production. The method must be validated for the CDMO’s Phase III method validation requirements. Similar to formulation, analytical methods must be continually challenged at this stage so that they are ready to be transferred to quality control as part of commercial production and release.
What you want to avoid are downstream issues with your drug product. For example, control-of-powder properties of a capsule’s or tablet’s final blend, such as compressibility and flow, affect product quality and manufacturing efficiency. So it’s standard practice for formulation scientists at the CDMO to investigate parameters that impact and enhance powder properties during scale up to late stage. That kind of time spent upfront can deliver major cost savings downstream.
Understand your API supply chain
Even the largest of Big Pharma companies can be hard-pressed to secure enough API for preclinical formulation. For small companies, which typically have less money and fewer industry connections, it can prove even more difficult. How much API do you have now and how much do you need in months or even years from now? If you’re working with an offshore source, these questions are even more critical, because importing an experimental drug substance complicates logistics and regulations.
Understand your molecule
Globally, the number of highly potent APIs continues to grow. The safe handling of potent API requires specialized techniques and facilities, yet virtual pharma companies sometimes don’t fully understand their API’s strength. There exist several banding systems that categorize compounds by toxicity; Safebridge is among the best known. It is recommended that virtual pharma companies conduct a safety and environmental hazard evaluation of their API before engaging a CDMO.
If the virtual pharma company can eliminate as many unknowns about their API as possible before it requests a formal proposal from the CDMO, the CDMO will respond with a more accurate project quote and timeline. Likewise, if the virtual pharma company purchased rights to the API from another company, the sale should have been accompanied by a technical package. It is also recommended that virtual company officials share the technical package with the CDMO so that everyone understands well the API involved.
Keep the lines of communication open
We both have worked with virtual pharma companies that hire subject experts as consultants to manage particular aspects of projects—and that’s fine with them. But the virtual pharma companies should remain involved.
Virtual pharma companies tend to have just a few people on staff. Those few people wear a lot of different hats, so they often outsource work to subject matter expert consultants. And truth be told, when we’re formulating their API, I’d rather speak with the formulation scientist the company hired as a consultant than the staff accountant who understands budgets but not necessarily chemistry. Having good and productive relationships with consultants are critical when it comes to the success of the project. At the same time, conversations with consultants can’t come at the expense of communication with the company.
It’s highly desirable for an in-house staff person to remain involved throughout the process, just to help ensure that there is no information gap between the consultant, the virtual pharma company, and the CDMO.
Conclusion
The virtual pharma model works. A compound Metrics Contract Services worked with since its late Phase I clinical trial recently was approved by the U.S. Food and Drug Administration. In addition to the drug’s sponsor, Metrics worked with consultants, subject matter experts, drug substance manufacturers and packaging companies on this project.
The project truly started small-scale and increasingly produced more material as the company’s clinical trials grew. It’s important to be able to keep up with changes and deliver high quality and reproducible drug product into the clinical setting.
It is also important that the sponsor considers you to be an extension of their company, and to build a relationship with the sponsor over the long drug development timeframe.
Joe Cobb As director of pharmaceutical development at Metrics Contract Services, Joe Cobb manages all aspects of projects that involve early-phase solid oral dosage development. He also oversees the company’s potent and cytotoxic drug development services, which include a dedicated and segregated potent facility. Cobb holds the highly respected ISPE Certified Pharmaceutical Industry Professional credential, the only competency-based international certification for pharmaceutical professionals. He holds a bachelor’s of science degree in chemical engineering from The Ohio State University.
Dr. Anshul Gupte manages all aspects of operations related to formulation and manufacturing of a client’s clinical trial materials. As associate director, Gupte supervises a team of formulation scientists, specialists and technicians who develop solid dose formulations for Phase I-III clinical trials—and who scale up and validate those materials as needed. He oversees clinical trial batch manufacturing and packaging under cGMP guidelines; supervises technology transfers; and documents clinical trial material batch records. Gupte earned his doctorate in pharmaceutical sciences from the University of Kentucky, and holds a master’s degree in pharmaceutical sciences from Temple University.
