Compounders are Cost-Saving and Flexible Partners for Clinical Trials
Investigational drug trials and clinical studies are conducted to determine if a new molecule will be safe and effective in treating a disease. Clinical trial sponsors often engage contract research organizations (CROs) to plan, develop, and coordinate the protocol. Sponsors also tend to utilize contract drug manufacturing organizations (CDMOs) to manufacture an investigational new drug during the clinical trial.
Benefits of Partnering With Compounders at Phase 1
While CROs and CDMOs may be the first choice for conducting many clinical studies, some sponsors choose to partner with compounding pharmacies or outsourcing facilities to execute clinical trials. The reason for this is that pharmacy compounders can offer a streamlined approach over CDMOs for conducting phase 1 first in human clinical studies. For example, compounding pharmacies typically:
Have small batch capabilities
Require little to no chemistry manufacturing & controls (CMC) investment
Consume less active pharmaceutical ingredient (API)
Are flexible in changes to the dose or formulation design
Regulatory Considerations
Pharmacies and outsourcing facilities that would like to provide clinical trial services for first in human studies should be aware of the different regulatory requirements as compared to those compounded pursuant to a patient prescription or prescriber order. As per FDA Guidance for Industry CGMPs for Phase 1 Investigational Drugs, an investigational drug is subject to some (not all) of the current good manufacturing practices outlined in 21 CFR 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals. For example:
Personnel should be trained in quality control principles of CGMP and have experience to prepare the investigational drug
An intensive quality control program must be written and in place
The facility should provide appropriate space, lighting, ventilation, cleanliness, plumbing, etc. to prevent contamination, cross-contamination, and mix-ups of the phase 1 investigational drug
Equipment should be properly operated, maintained, calibrated, cleaned, and sanitized
The handling, review, acceptance, and control of materials should be established to identify and trace all materials used in the manufacture of a phase 1 investigational drug from receipt to use
Each step of the compounding process must be controlled, documented in detail, and available for sponsor review
Compounding records should include details of the materials, equipment, procedures used, and any problems encountered. Retain records for at least two years after a marketing application is approved for the drug.
The drug should be tested for its quality attributes including those that define the identity, strength, potency, and purity, as appropriate
A stability study should be initiated using representative samples of the drug to monitor its stability and quality
The drug should be suitably packaged to protect it from alteration, contamination, and damage during storage, handling, and shipping
Product segregation, label reconciliation, second person verification, confirmatory laboratory testing, and QC review are useful to control packaging, labeling, and distribution operations
Adherence to 21 CFR 211 increases as clinical trials progress through proof of concept studies (e.g., phases 2 and 3 clinical trials) in order to minimize batch to batch variation. This is because larger patient populations are studied and clinical conclusions are difficult to make if the compounding process is poorly reproducible or unreliable.
Which is Better Suited for Providing Clinical Trial Services - 503A or 503B?
Given the FDA requirement for 503Bs to adhere to CGMP, it makes sense that 503B outsourcing facilities may make a more strategic clinical trial partner over 503A pharmacies. This is especially true if a sponsor aims to stay with one investigational drug producer as they transition from phase 1 to phases 2 and 3 clinical studies. On the other hand, a 503A pharmacy may be a more attractive partner for phase 1 studies over a 503B since there are less testing requirements before product release. This translates into reduced laboratory testing costs and testing time. 503As are also often better equipped to communicate directly with patients over 503Bs, since pharmacies are more patient-focused and outsourcers are more product-focused. This feature may be helpful for certain study designs that require a more intensive pharmacist-patient interface. Additionally, pharmacies may be more willing to take on studies having very small batch sizes (e.g., 1 unit, less than 50 units, etc.) over 503Bs. Conversely, some outsourcers may have very flexible batch size capabilities and could be better suited for studies that start out small but grow to need hundreds or thousands of units per batch.
Necessary Qualifications and Capabilities
It is clear both 503A and 503B compounding entities have unique features that a sponsor will consider as part of the site qualification phase. Compounders that want to add clinical trial services to their offerings will win more bids if they:
Hold relevant accreditations or certifications (e.g., PCAB, NABP, URAC, ISO, etc.)
Are in good standing with pertinent state and federal regulatory agencies (e.g., Board of Pharmacy, FDA, DEA, etc.)
Integrate GMP concepts and a robust quality assurance program into their compounding operations (something 503Bs already do)
Are capable of compounding the type of formulation (e.g., lyophilized powders, sterile injectable solutions, topical creams and ointments, oral solutions and suspensions, encapsulated powders, etc.)
Provide the compounding service at a cost-effective price
Compound the preparation in the desired batch size
Maintain enough stock of the product and provide a quick turn-around time of the service
Designate space to secure the product and prevent mix-ups or unblinding
Test the product for conformance with its quality attributes
Have a deep understanding of the clinical study requirements
How to Get Started in Clinical trials
503A pharmacies and 503B outsourcing facilities interested in compounding investigational drugs for clinical studies should:
Study the unique regulatory requirements that come with preparing investigational new drugs.
Develop strong relationships with private research and development organizations, medical teaching universities, government institutions, and/or pharmaceutical companies that sponsor clinical trials.
Institute SOPs for each specific clinical trial, statistical randomization of enrolled subjects, placebo control, blinding / open labeling, a prescription template, dispensing guidelines, and a dispensing label template.
Providing clinical trial services can yield a high return on investment. Study sponsors want to partner with quality-minded compounders. To win these contracts, Restore Health Consulting can take your quality management systems beyond USP and help you get ready for a clinical trial sponsor audit.