The International Society of Pharmaceutical Engineering (ISPE) held their premier Global Pharmaceutical Regulatory Summit conference this past Thursday and Friday (December 5 – 6, 2019) in Bethesda, MD.  The theme of this year’s conference was “Igniting Innovation in Development & Quality During Lifecycle Management”.  The conference opened with excellent keynote presentation from Janet Woodcock (Director of FDA’s Center for Drug Evaluation and Research) and David Churchward (Deputy Unit Manager, Inspectorate Strategy and Innovation, Medicines & Healthcare products Regulatory Agency [MHRA) who provided valuable views from the FDA and the EMA, respectively, regarding how their regulatory agencies are addressing the need for innovation in the pharmaceutical sector.

Dr. Woodcock expressed her disappointment that there has not been as much innovation in the pharmaceutical sector as she had hoped for when she and her colleagues had rolled out FDA’s Quality for 21st Century Initiative seventeen years ago.  Although she acknowledged that there have been times when the FDA has erroneously impeded the implementation of innovative technologies (e.g., the use of on-line sensors in manufacturing operations), she said that CDER has taken steps to ensure that the regulatory review and inspection components are receptive to and supportive of innovation in manufacturing, including continuous manufacturing systems and novel quality assurance methods.

One change to the FDA’s policies and procedures that she referenced is the integration of the assessment and inspection components in the Office of Pharmaceutical Quality (OPQ).  Another significant step has been the establishment of the Emerging Technology Team (ETT) within the OPQ, as well.  CDER has also established the Emerging Technology Program (here) to provide companies who are developing innovative manufacturing methods to get valuable input and feedback from the members of the ETT early on in their product and process development.

Dr. Woodcock devoted a significant part of her presentation on the issue of drug shortages and mentioned that she will be testifying at the House Oversight Committee’s hearing on FDA’s foreign inspection Program (here).

She outlined three primary causes leading to drug shortages which were discussed in the Drug Shortage Report that FDA published this past October (here).  These include:

  • Lack of incentive for companies to produce low-profit drugs
  • The market doesn’t reward companies for developing mature quality management systems (QMS). No visibility to the market.
  • Logistical and regulatory challenges limit the ability of the market to recover when disruptions occur.

Other contributing factors that she mentioned are reliance on batch-wise manufacturing (as opposed to continuous manufacturing methods) and the fact that many formulation excipients are commodity products that may have inconsistent quality.

Two activities that would help to address these issues were proposed.  One is to develop a mechanism for a market-based incentive for manufacturers to have robust QMSs in place to minimize production excursions that result in lot failures or product recalls.  This was proposed by FDA in the form of Quality Metrics several years ago and is still under consideration by the Agency.  The other step that industry can take is to implement robust and effect quality risk management plans for their suppliers.

David Churchward focused his presentation on five important topic areas:

  1. Changes in the healthcare system
  2. Changes in diagnosis of specific diseases
  3. Technological advances and increased scientific understanding of diseases
  4. Development and implementation of Artificial Intelligence systems
  5. The need for regulators to establish an enabling environment that is supportive of, and conducive to, innovation.

He mentioned that, although the quality regulations were written in the 1960s, it is critical to ensure that the implementation of cGMPs in the current environment does not impede innovation that improves quality assurance.  This requires that industry and regulators have a clear understanding of the product and process factors that impact product quality and how these are controlled.

Of particular note, Dr. Churchward discussed the need to address the challenges of setting specs for patient-derived starting materials when each source results in the production of a single finished product lot.  It may be necessary to focus more on registering the process rather than the product.

Mr. Churchward also touched on an area that has yet to receive an adequate level of attention from regulators:  Artificial Intelligence and the need to ensure that the data sets used for training an AI system are appropriately representative of the real world of potential process and product variability and not biased in some manner.

Overall, the presentations from these regulatory leaders were quite encouraging in that the regulators in the U.S. and Great Britain are taking steps to support the implementation of innovative manufacturing and quality assurance methods by the pharmaceutical industry.