Regulatory Update

Ellen LeinfussSVP, Life Sciences

Topics Covered Today

• US FDA Update- 6 Steps Outlined by New FDA Administrator

• European Medicines Agency (EMA) Update• Medical Device Directives Update• Trends in Warning Letters

US FDA Update

• Set Post-Inspection Deadlines- Once issue found, company to have 15 days to respond- Goal is to issue warning letters on a timely basis and facilitate

prompt corrective action

• Take Responsible Steps to Speed the Warning Letter Process

- New policy limiting the review of warning letters by the FDA’s Office of Chief Counsel to “significant” or “novel” legal issues

- Goal to streamline process

• Work More Closely with FDA’s Regulatory Partners- To develop effective risk controls and enforcement strategies

US FDA Update

• Prioritize Follow-up on Warning Letters and Other Enforcement Actions

- A Warning Letter or recall will trigger enforcement follow up - Cases will no longer be allowed to languish or remain open with uncertain

resolution. Firms will get a knock on the door and an inspection

• Be Prepared to Take Immediate Action in Response to Public Health Risks

- No multiple warning letters. The second warning letter to a firm will trigger increased scrutiny and follow up actions

• Develop and Implement a Formal Warning Letter “Close-out” Process

- For firms that have taken the necessary corrective actions

- It could play “an important motivating role” in spurring corrective actions

European Medicines Agency Update

• Changed acronym from EMEA to EMA• Priority areas for 2010

- Improve safety monitoring (pharmacovigilance)

- Focus on counterfeit medicines legislation and supply chain integrity

- Work closely with international partners and activities

- Provide more information to patients

• Incorporation of ICH Q9 and Q10- ICH Q9 (Quality Risk Management) is a systematic process for the

assessment, control and review of risk to the quality of a drug across its life cycle

- ICH Q10 (Pharmaceutical Quality System) ccis a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle.

Medical Device Directive Update

• Directive 2007/47/EC comes into effect 21 March 2010• Key impact: Device Classification

- Software now considered active medical device, whether integral to device or stand-alone product. Software validation required

- Clarification on borderline products; active implantables; products that incorporate human tissue, blood or plasma; reusable surgical instruments; combination products

• Key impact: Clinical Evaluation- Clinical investigation of devices seen as continuous process to identify,

generate, document and evaluate clinical data

- All devices, including Class I now require clinical data

- All side effects must now be reported

- Clinical investigation requirements now extend to include post-market surveillance

Medical Device Directive Update

• Key Impact: Technical Knowledge- Level of technical knowledge, experience, education or training of intended

user is now explicitly a relevant factor in the evaluation of the safety of a device

- Manufacturers must now provide a summary of characteristics for Class II and III products

- Goals are safety of device usage

• Key Impact: Increased Transparency- More information on product information and clinical data will be publicly

available

• Key Impact: European Database- Clinical data to be collected in common database and shared among

Competent Authorities

Most Frequent FDA 483 Observations

Deficiency Number of Observations

Quality Control Unit responsibilities 887Adherence to production procedures 709

Production procedures (validation) 618Laboratory controls 553Written procedures for production 518Investigations 506Testing and release 478Personnel qualification and testing 456Batch record preparation and review 449Equipment cleaning and maintenance 397

Compliance v.3.0 – Driving Behavior Change

Product Seizure

Not able to Execute Govt. Contracts

Failure to Issue Export Certifications

Refusals for Export Increased Regulatory Intervention

Legal Injunctions

Holds on Pending New Drug Applications

483 Observations Can Escalate

Most Warning Letters Issued because Company Responses Failed to Adequately Address FDA Concerns

Compliance v.3.0 – Driving Behavior ChangeSummary

The Cornerstone for the Quality Organization is the Site Compliance Program. Companies should take a risk-based approach and employ internal audits and established audit management practices to remain “inspection-ready” at all times. If issues are found, the company should respond promptly with a detail corrective action program.