Paul Skultety, PhD., Vice President, Pharmaceutical Development Services
Theodore S. Koontz, Vice President, Operations
Solid/Semi-Solid Dosage Development & Manufacturing
PharmTech: What emerging technologies or practices do drug sponsors expect your organization to provide?
Paul Skultety: Several analytical areas have been evolving over the last few years that our sponsors look for us to understand and put into practice. One area is cleaning verification and making sure we are up to date with all of the global regulatory requirements. Another area is the use of Phase specific analytical method qualification/validation and being able to do analytical work following the Quality by Design principles.
Theodore S. Koontz: In the CDMO sector, current technologies continue to hold true. Clients expect to be able to utilize the latest tools with regard to solid dosage forms, including state-of-the-art equipment. They also want flexible and creative solutions to ensure their projects are executed in a timely manner. Environmental controls (i.e. low relative humidity, cold storage, etc) are also becoming more critical.
PharmTech: What scientific or technical advances have positively or negatively impacted drug development processes in this market segment?
Paul Skultety: Sponsors would like to have one month of stability on the clinical batch to be filed in their IND and they do not want this to slow down their submission. To accomplish this, the goal is to put the CTM batch on stability as quickly as possible which in a number of projects puts analytical method qualification on the critical path. Formulators have become more proficient at developing final clinical drug product which in turn puts more pressure on analytical work. Things such as developing methods using UPLC technology will aid the analyst in getting their work completed faster and better able to meet the sponsor’s timelines.
Theodore S. Koontz: The advances in IT and communication continue to enhance our ability to improve the development process. We also see advances in manufacturing equipment that offers an increasingly wide range of capabilities. For example, many capsule-filling equipment manufacturers are able to provide many different filling techniques along with consistent filling at very low weights/volumes.
PharmTech: Are you seeing shifts in demand for particular types of services? Please describe.
Paul Skultety: Xcelience is seeing a shift in certain service areas. In particular, sponsors desire a better evaluation and understanding of their active drug substance. They want to have a full understanding of what properties of their API are critical to their drug product. This also applies to excipients that will be utilized in the drug product. The concept of Quality by Design should now be a focus of the analytical work and not just a focus of formulation development.
Theodore S. Koontz: The big shifts we are seeing involves timing, creativity and flexibility. Clients expect creative and flexible ways to achieve their needs and they expect them faster.
PharmTech: What pressing technical challenges have you seen in this market segment? What actions has your company taken to resolve the challenge? What actions does your company suggest?
Paul Skultety: A challenge is the use of mechanical calibration for dissolution apparatus. This speeds up the process and provides for fewer failures than using the traditional tablets procedure for calibration. It takes some training to get analysts used to operating this way but is well worth the effort. Labs are being pushed to get the data faster whether it is for a batch release or for stability samples. To meet the ever tighter timelines, it is necessary to evaluate all processes used in lab and become more efficient. The answer is not just hire more people.
Theodore S. Koontz: We continue to add equipment and technologies that enhance our current service offerings. Xcelience focuses on technologies and processes that can be best executed and continue to grow in these areas.
PharmTech: What advances do you see in science or technology in this market segment in the next five years?
Theodore S. Koontz: In my opinion, we will continue to see equipment designed with increased ability to consistently fill capsules at very low weights. We will also see equipment with modular capabilities that increase the overall breadth of processing options within one footprint.
PharmTech: What regulatory changes have positively or negatively impacted drug development/manufacturing processes in this market segment?
Paul Skultety: Harmonization has had a positive impact on the analytical services. This makes it easier to meet the regulations as you have one set of criteria to test against. Putting into practice Quality by Design has been both positive and negative. It will take a few years before regulatory bodies like the FDA can provide clear direction as to what this means. Right now it is up to individual companies to make their own interpretations.
Theodore S. Koontz: Phase-appropriate cGMP guidance has helped a great deal. It allows for creative solutions and flexibility to early challenges. The Lifecycle Management approach to commercial products has greatly changed the outlook for the future. In the short term it may be seen as a negative, but long-term it will serve us well.
PharmTech: What business trends have positively or negatively impacted drug development/manufacturing processes in this market segment?
Theodore S. Koontz: Overall, technology has enhanced the processes. The speed at which projects are accomplished has improved. Conversely, this can hurt by creating unrealistic expectations.
PharmTech: What changes are you observing in the organization and operations of drug sponsors in this market segment?
Paul Skultety: Sponsors are demanding more to be done with less API and it needs to be done faster. They want things as quick as possible but don not want to sacrifice quality. This is sometimes a problem as sponsors will not plan far enough ahead or leave enough time for the development work that is needed prior to manufacture of the clinical batch.
Theodore S. Koontz: We are continuing to see an increase in outsourcing across the board, as well as many new ideas and creative approaches to meet clinical needs.
PharmTech: How has quality by design influenced a drug sponsor’s expectations of suppliers?
Paul Skultety: Sponsors are looking to work with people who can put into practice Quality by Design principles in all of their development work. They expect a high level expertise not only scientifically but also in global regulations. More and more clinical studies will be done in the United States and abroad. The work has to be scientifically sound and meet all regulations.
Theodore S. Koontz: Xcelience embraced QbD as an operating principle. Most clients expect us to apply this approach to our development processes.
PharmTech: Describe the role that quality agreements play in contract services relationships. How will the FDA’s draft guidance on quality agreements affect the relationships between contract service providers and drug sponsors?
Theodore S. Koontz: Quality agreements play a large role; defining expectations and requirements at the beginning phase is crucial to the success of a project. In terms of the FDA’s draft guidance, we expect it to provide clarity and general improvement in the provider-sponsor relationship.