FDA Regulatory, Policy, and Enforcement Development Key Trends in 2015 Debra S. Dunne, R.Ph., Esq. Partner | Shook, Hardy & Bacon | 2001 Market Street, Suite 3000 | Philadelphia, PA 19103

Life Sciences Growth in 2015 Aging Population Chronic Diseases Emerging Market Expansion Treatment and Technology Advances

Outlook for 2015: Era of Transformation 21st Century Cures Initiative Precision Medicine Initiative Drug Quality & Security Act Enforcement BioSimilars Personalized Medicine Telemedicine/ Digital Health Today, Think About Transformation …

2015’s Era of Transformation: Will Once Again Test Our Ability to Adapt “ It’s Not Just You: FDA Regulatory Requirements Really Are Increasing” Guidance Documents, Pre-Inspection Preparedness, Inspections, Post-Inspections Think about……. Changing Regulatory and Risk Environment Impact On Your Business…Will You Be Ready

21 st Century Cures Initiative Initiated in 2014 by House of Representatives--bipartisan examination of areas in which legislation may be needed to accelerate the development of new medicines. Legislation expected in 2015 may include: Efforts to increase efficiency and reduce burdens in clinical research Accelerate validation of biomarkers for effectiveness used in drug development Expand funding for Alzheimer’s Disease research Expand exclusivities in areas of unmet need as a way to increase development Changes to FDA’s approach to limiting the dissemination of off-label scientific information Enhancing availability of telemedicine/digital health, reducing restrictions and enhancing coverage

Obama Administration “Precision Medicine Initiative President has his own plan…what can we expect? State of the Union address, “The country that eliminated polio and mapped the human genome to lead a new era of medicine-one that delivers the right treatment at the time,” noting “launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes-and to give all of the access to the personalized information we need to keep ourselves and our families healthier.”

Relentless Pressure: Drug Manufacturing Current Good Manufacturing Practices - FFDCA § 501 Automatic adulteration if fail to comply Implementation of oversight and controls over manufacturing - Selected Regulations 21 C.F.R. § (b) (Contract manufacturers an extension of manufacturer's own facility) 21 C.F.R. § (Quality unit ultimate authority for product quality) 21 C.F.R. § (Incoming inspection and testing) 21 C.F.R. § (Component records)

Drug Quality and Security Act: Implementation Continues Some Requirements more administrative/procedural Record Keeping and information transfer Product Identifier Authorized trading partners Other requirements related to supplier quality Suspect and illegitimate product identification, investigation, quarantine, and notification Request for information Returned products

Realties of Working with a Third Party A company retains accountability for the acts or omissions of the third party. - Despite the fact that control has been surrendered to the third party - Only the third party has the direct access to thecontracted activity A company has limited monitoring and influence

Potential Regulatory Consequences Adverse Inspectional findings Warning Letters Product Recalls Cessation of Manufacturing Seizure Injunction Criminal Actions False Claims Act Actions

Cause/Effect Paradigm Shift “Our Suppliers Are Causing Problems” “We Are Causing Problems” Key Takeaway: Disciplined Process Will Focus on True Root Cause

Enforcement: Department of Justice Healthcare fraud continues to be an enforcement priority for Obama Administration Approximately $6 Billion was recovered by DOJ in fiscal year 2014 $2.3 Billion in healthcare fraud recoveries - Pharmaceutical industry accounted for substantial part of the $2.3 Billion in health care fraud recovery Whistle blowers credited with recoveries of nearly $3 Billion - $435 million paid out under qui tam provisions 1987/30 qui tam complaints vs. 2013/500 qui tam complaints 95% of the new qui tam cases coming from whistle blowers

Enforcement: FDA Warning Letters Greer Laboratories (4/21/2014) Failure to establish reliability of supplier’s certificate of testing through validation Sanquin Plasma Products (8/29/2013) Failure to perform incoming testing on supplier components Jabones Pardo S.A. (8/22/2013) Failure to perform incoming testing, failure to establish reliability of supplier’s analyses, failure to conduct identity test when relying on supplier analyses

Enforcement: New Focus on Data Integrity Trifarma S.P.A. (7/7/2014) Failure to maintain complete data Failure to prevent unauthorized access or change to data/prevent data omission Tianjin Zhongan Pharmaceutical Co, Ltd (6/10/2014) Failure to maintain appropriate documentation to record manufacturing operations performed on individual pieces of equipment

FDA Regulatory, Policy, and Enforcement Development Key Trends in 2015 Debra S. Dunne, R.Ph., Esq. Partner | Shook, Hardy & Bacon | 2001 Market Street, Suite 3000 | Philadelphia, PA 19103