Pharmaceutical Engineering EXCLUSIVE - Redefining the “C” in CGMP
Conference Highlights
ISPE and the FDA co-sponsored a very well received conference entitled: Redefining the “C” in CGMP this
past two days. More than 300 attended and heard informative points of view from FDA leaders including Janet
Woodcock, Director CDER, FD, Deb Autor, Deputy Commissioner for Global Regulatory Operations and
Policy, FDA, Ilisa Bernstein, Acting Director, Office Of Compliance, CDER, FDA, and MHRA, UK, Director of
Inspection, Enforcement and Standards; Gerald Heddell. Andy Skibo Executive Vice President, Operations
at MedImmune and Mary Oates, Vice President of Global Quality Operations at Pfizer presented from an
industry perspective. These compelling talks continued in a provocative dialogue between industry and FDA
leadership in the Meet the Press session.
Here are the highlights of that session.
Meet the Press
On 5 June, ISPE hosted an interactive “Meet the Press” session, which brought together a distinguished panel
of regulators and industry experts to engage in a thought provoking discussion about how to drive patient
safety, product quality, and compliance throughout organizations, and how the pharmaceutical industry and
regulatory agencies can work effectively in achieving these mutual goals. Expert moderators representing the
pharmaceutical industry technical press, business and public media were successful in delivering a high value,
engaging discussion. There was a clear enthusiasm and commitment from both regulators and industry to
share ideas and solve problems through this interactive dialog. The following is a recap of the discussion.
Moderators
Jeff Salkin, Host of Direct Connect, Maryland Public Television, USA
Bill Paulson, Editor-in-Chief, International Pharmaceutical Quality, USA
Judy Leon, Senior Communications Advisor, CDER, FDA, USA
Panel
Rick Friedman, Associate Director for Risk Science Intelligence and Prioritization, OMPQ, OC, CDER,
FDA
Gerald Heddell, Director of Inspection, Enforcement and Standards, MHRA, United Kingdom
Steven Lynn, Acting Director, Office of Manufacturing and Product Quality, OC, CDER, FDA
Mary Oates, Vice President of Global Quality Operations, Pfizer, USA
Andy Skibo, Executive Vice President, Operations, MedImmune, USA
Question - What are the key trends impacting the industry?
AS
Period of pressure on decreasing costs while maintaining high quality
Increasingly complex global supply chain
Emerging markets and their important role in the supply chain
Trend toward biologics becoming an ever increasing proportion of revenue and pipeline.
GH
Globalization and distribution of activities throughout the world
Two challenges:
o How to support emerging supply countries to raise standards to those acceptable to established
markets
o Collaboration between regulators. Individually they cannot cover the globe effectively. Need
information sharing and work sharing throughout the world.
MO
Limited resources
Both regulators and industry to focus even more on the patient.
If assessed and achieved, this will lead to better efficiency and less effort expended on non-important
aspects.
The supply chain is globalized, but regulators aren’t.
The rate of change is high. Change must be controlled so that manufacturing staff remain focused on
key requirements and quality and not swept away by the changes.
RF
Modernization of supplier management systems required to handle the complexities of supply
Modernization of infrastructure – leveraging the learning of other industries
IT to be better leveraged - including to identify process drift and trends
SL
Today, we are in a state of crisis and breakdown, including drug shortages so all parties must focus on
the desired state and work together (regulator-regulator and industry-industry as well as regulatorindustry).
Question - Steve mentioned crisis – do you agree? Is this caused by the convergence of all the factors
mentioned before? Are we at a breaking point?
AS
Where did we go wrong? Typically, because of “silo” thinking (e.g., finance, marketing, commercial
separately). Silo thinking and decisions may not be the best, as they are not taken at the whole
enterprise level.
Enterprise level decisions need to take into account whole-enterprise risk, and cradle-to-grave costs.
GH
Are we really in a crisis? Regulators see things going wrong, but not a crisis. Most patients are wellserved by the industry and their needs are met.
Manufacturing challenges need addressing, but not a crisis.
SL
Yes, crisis! Often acceptable results are achieved by exceptional measures and great effort rather than
being delivered by the basic processes.
Question - How can enforcement help in getting attention and driving innovation?
GH
Key aspect for enforcement is seeing to change behaviours and attitudes.
MO
Companies can and should use enforcement information to learn what regulators want and on what
they are focusing.
Question - Will things get worse as these trends continue?
RF
Complexity increases stress and risk.
Shortening and simplifying the supply chain may help.
During global expansion, not all have kept up with expected standards.
Complexity of products and processes is another secondary factor.
The QMS will need to go up a notch to meet the challenges.
Question –What is the root cause of drug shortages?
AS
Natural extension of cost pressure, product coming off-patent, business case for continued production
must be viable.
Generic production is very cost sensitive.
Innovator cannot quickly and easily bring a plant back on-stream in case of a shortage, especially in the
case of biotech.
Previously industry had more ability to carry less viable products.
MO
One solution may be for the willingness and ability of firms to supply should be more actively
considered as part of the GxP framework.
SL
This is a multi-faceted conundrum.
All parties must stop pointing fingers, roll up sleeves, work together, and find solutions.
AS
Silo effect may be a root cause. Decisions may not be taken at the enterprise level, e.g., “I can move to
a cheaper plant” or “I can outsource,” but can the alternative deliver reliably at the expected standard?
We shouldn’t automatically assume that the alternatives can achieve the same quality.
MO
Robust assessment of contractor quality commitment and culture can be challenging.
Pfizer has developed tools to help assess quality culture.
RF
That is a valuable and welcome step forward as part of the QMS – looking at attitude of management
and trying to measure.
Question - What can or should regulators and industry do better?
MO
Regulators do a good job of explaining expectations, e.g., through citations, conferences.
Focus could be improved by clarifying what is important from a patient safety perspective.
Field alerts should be focused on important aspects – don’t clutter the system, but focus on the critical.
AS
Regulations are generally transparent and open.
The global supply chain and regulatory situation is complex; however, improved harmonization on
standards and expectations would be welcome.
The challenge of dealing with licensing a product in 80 countries is significant.
Alignment and simplification would be welcome.
GH
A process of convergence rather than harmonization – may never get complete standardization.
Regulators welcome information from the industry on particular areas where improved alignment would
be most beneficial.
RF
It would be helpful for industry to speak with one voice on which areas there is most significant
difference or dissonance. Sometimes this is not always the case.
Then regulators can tackle, e.g., through PIC/S or ICH.
It would be helpful for industry to focus more on upstream controls and strong quality assurance, rather
than downstream testing and sampling.
SL
Companies should share and learn from each other, e.g., recall, warning letters.
Cooperate and learn.
Question - Have we moved from a position of revealing as little as possible and denying all risks to a
transparent discussion of risk? Is risk assessment a unifying concept?
RF
ICH Q9 is very powerful – it is a game changer.
QRM can be applied throughout the life cycle to give structured, scientific, thinking.
ICH Q9 appendix has a lot of very valuable information.
ICH Q9 can help structure thinking, simplification, and identification of root cause.
AS
Industry is fully aligned – there is so much to benefit from a transparent discussion.
Invariably leads to a better cradle-to-grave big-picture at the enterprise level.
Biotech: the increasing complexity of products and processes may lead to a simplification of the supply
chain.
Overall the lowest risk may be in-house – (“insourcing”).
Question(s) - How should the consumer feel? If the industry were new today,
how might it be differently arranged or regulated?
GH
Consumer needs to understand that all medical products involve a balance of risks and benefits.
A complete focus only on safety would mean that many benefits wouldn’t be achieved.
Entrepreneurial innovation should be encouraged.
RF
The role of entrepreneurial innovation is very important.
MO
Vast majority of those involved are ethical and concerned for the common good.
The consumer should feel confident.
SL
KISS – “Keep it simple, stupid!” Simplicity is beauty.
AS
In the absence of a regulatory structure, the industry would rightly demand it.