Expert Speaks - Optimizing Stability Program during Drug Development: An interview with Charity Ogunsanya

We spoke with Charity Ogunsanya to get a scoop on Optimizing Stability Program at each phase of drug development.

Charity Ogunsanya has over 28 years of extensive experience within the Pharmaceutical, Biotechnology, Biologics, Cell-Therapy, Diagnostics, Research and Development, Radio-pharmaceutical, Contract Manufacturing Organization (CMO) and Medical Device companies.

Her technical expertise is not just limited to Stability programs but also includes interpretation, administration and set up of Quality Assurance, Quality/Compliance, Quality Engineering, Aseptic Processing, Contamination Control, Quality Control, Microbiology, Sterility Assurance, Vaccine Development, New Product Design, Product Release Testing and Medical Device Sterilization (Ethylene Oxide (EtO), Gamma, Radiation, VHP sterilization) systems and operations for compliance to various regulations.


  1. Q - How and when did you discover your passion for Quality and Compliance?
  2. A - My passion for Quality and Compliance stemmed from my initial interest in providing an effective treatment to diseases through the use of products that are safe, pure, stable, effective and manufactured under a high-quality standard. In order to achieve these key attributes a proactive and compliant process must be followed while adhering to the regulatory requirements applicable to the product type.

  3. Q - What are some common challenges your clients face with stability programs?
  4. A - Common challenges my clients and attendees of my past presentations/seminars on stability studies have been diverse. Some common challenges have been their inability to understand how to design an effective stability study program while applying the rules and regulations to their specific product type. There have been challenges associated with using data collected from these studies in an effective manner such as trending the data, applying the study results to determine their product's shelf life and how to do extrapolation and statistical analysis of the test data amongst others.

  5. Q - What challenges have you helped your clients to overcome recently?
  6. A - I have helped clients in areas of the design of an effective stability study program specific to their product requirements. I have also assisted clients with generating a Stability Testing Program Policy, Test Protocol and Report and expanded on converting their paper based system into the use of the Lab Information Management System for their data management, trending, statistical analysis and shelf life determination. I have successfully assisted clients with difficult to handle FDA's Form 483 and Warning Letter remediation work on stability testing program design/requirements and various aspects of Quality and Compliance remediation work.

  7. Q - How do you optimize stability program at each phase of drug development?
  8. A - At each phase of development are elements that can increase the probability of obtaining useful data to make critical decisions and gain FDA approval.

    At the preclinical development stage make Stability Part of a Go/No Go Development Decision, have plenty of technical data, Perform short-term, real-temperature, and accelerated stability of the active pharmaceutical ingredient (API)/drug substance (DS) and experimental drug product (DP), if available, and Assess the stability of the test article and test article in carrier during pivotal preclinical trials, as required by the regulations.

    At the early to mid-clinical development stage acquire deep stability knowledge including degradation pathways, kinetics, and products of API/DS and DP to optimize stability-indicating methods for DS and DP and get them ready to validate or re-validate. At this stage, show the stability of materials used in clinical trials, develop primary and working reference materials, fully characterize any degradants seen in real-time/temperature studies and primary accelerated, evaluate container/closure systems and develop stability specifications and finalize them before manufacture of Phase 3 material.

    To demonstrate well-constructed stability studies, moving toward full GMP compliance in preparation for pivotal efficacy trials, create protocols with the elements including manufacturer of DS, DP, and excipients, proposed retest or expiration date, type, size, and number of batches, type, size, and source of containers and closures, test parameters, validated stability-indicating test methodology for each parameter assessed, storage conditions, container orientations, sampling plan, test time points, acceptance criteria, information on how data will be reported or presented, statistical approaches and methods for evaluation of results and determining retest or expiration dates, outline of the stability commitment, how the protocol can be modified and amended.

    At the late clinical development stage which is phase 3, not only is stability performed on the API/DS, drug product intermediate (DPI) (as applicable), and DP, but also stability of diluents, reconstituted drug product, and drug product in multi-use containers (e.g., vials) must also be performed. Work performed at this stage enhances the chances of getting an approval letter (rather than a "complete response" letter). This phase requires GMP-compliant protocols, validated methods, change control, and well-documented investigations of all deviations, discrepancies, and out-of-specifications (OOSs). There is a high risk of failure at this stage. The company's commitment to quality will be evaluated here, specifically, in what you do when things go wrong (i.e., how effective you are at documenting and handling such events). Ensure success by having robust OOS, investigation, corrective and preventive actions (CAPAs), and deviation systems and rigorous training on their execution.

    It is important to include references to any deviations and/or OOS documentation. Reports should be clear and concise; include the rationale for the design, statistical handling of data, and specific conclusions to help inspectors or auditors understand the connectivity of the data to the overall development of the drug. Do your due diligence instead of waiting for the FDA to do it. Find out where the gaps are, acknowledge those gaps, and put a plan in place to mitigate them. This also is the time to prepare for an FDA inspection of your stability program. The easier you make it for an inspector to follow your drug development road map and the better you explain how stability data supports decisions made, the less likely you will have something appear in any 483s.

    At the post-approval/licensure phase, the role of stability at this phase is to demonstrate continued consistency in manufacturing. It is important to Keep stability commitments to the FDA, Make sure you have a rationale, and the data, to support everything you do, seriously consider the impact of process, formulation, and delivery method changes on existing stability data and scrutinize any protocol modifications, Investigate any trends that extrapolate to being OOS before end of shelf life and any other similar events with and determine the root cause and perform an impact assessment and execution of CAPAs, if necessary, and track the effectiveness of systemic CAPAs with all proper documentation. Submit field alert reports (FARs) and biological product deviation reports within required timelines.

  9. Q - How can a company demonstrate that their labs and quality control systems are in control
  10. A - Quality Control refers to the process of detecting analytical errors within the lab to ensure both the reliability and accuracy of test results in order to provide the best possible patient care. Unreliable performance can result in misdiagnosis, delayed treatment and increased costs due to retesting etc. it is therefore of great importance to ensure all results provided are both accurate and reliable. Lab controls involves the use of process, equipment, facility, systems and procedures to ensure compliance to the rules and regulations. A controlled Lab and Quality Control unit is one that has all applicable systems in place and their level of inadvertent errors, Invalid Assays and Deviations, Out of Specification (OOS) and failure results which are attributed to the Lab is insignificant and does not trend negatively over a period of time (during management reviews). A controlled Lab has personnel that are well trained, qualified and skilled to perform their tasks with minimal supervision.

  11. Q - What are the common pitfalls and lessons learned from warning letters received due to lack of a robust stability program?
  12. A - An FDA's Warning Letter is by itself a stain in a company's good reputation which may lead to more difficulties such as Consent Decrees, fines, injunction, prison time and a possible closure of the affected company if the compliance issues raised by the FDA are not promptly addressed. The impact of receiving a Warning Letter associated with lack of a well designed or robust Stability Program is egregious in that the data from a stability testing program is critical to the product's claim of expiry and effectiveness for the shelf life period. If a product's shelf life/expiry cannot be fully verified by an effective stability study program, then the purported claim of expiry for that product may be misleading (inaccurate). This may further create a confusing and adulterated product by the regulatory definition of adulteration of the product.

  13. Q - It's known that when a Company receives a warning letter due to lacking stability testing, the FDA precisely guides them about the next steps. What challenges do Companies face during CAPA?
  14. A - An FDA's Warning Letter should be avoided at all cost by fully complying with the rules and regulations guiding the manufacture, testing and release of products which includes having a robust and well-designed Stability Testing Program. The company has to account for their compliance deficiencies through a compliance plan and remediation work which they have to provide to the FDA during their Warning Letter response. Part of the remediation of such compliance gaps includes statements to each finding by the manufacturer of the affected product showing good faith effort to correct, prevent and show effectiveness of the corrective actions that will be applied to the deficiency. Companies sometimes face challenges in this regard in that they must expand on how they intend to correct the deficiencies that have been identified by the FDA. They also have to ensure that their CAPAs are well written to investigate and address the deficiency with detailed plan of actions and proof of all identified corrective actions. CAPA investigations are time consuming and expensive hence it is best to avoid unnecessary compliance gaps and deficiencies and ensure that all programs (including stability testing programs) are well designed, robust and compliant.

  15. Q - What did I overlook or forget to ask about Stability program?
  16. A - A critical area that is often overlooked with the Stability Testing Program is difficulties that some clients face about when and how to initiate a robust program. People sometimes get confused as to the extent and type of design of a Stability Program that they initiate for a new drug. The simple answer is that regardless of the stage of your drug development, it is best to understand your product functionality and stability from the very onset of the drug design so as to avoid costly manufacturing process by making changes to the product design at a later stage due to failed stability testing result. It is less expensive to make changes to a drug design because of an unstable excipient or buffer that when the drug is already in a defined clinical trial stage.

Summary of the Interview: GMP compliance is an intricate and important part of any drug production process. Not only do you have to execute many steps flawlessly, but you also must perform them in the correct order and per the compliance requirements. There is much to building, managing, and maintaining control of a stability program. But being in control will prepare you for any number of unforeseen developments, surprise inspections, FDA audits and avoidance of FDA's Form 483 and Warning Letter.