OCRA eNEWSLETTER October 2004

Message from the Editor

We have implemented many of the suggestions received from the members for improving the OCRA eNEWSLETTER, such as including information on other healthcare products (not just medical devices), more updates on the program calendar and others. Of course, there is always room for improvement and we will continue to entertain your suggestions and comments to improve the newsletter and increase its value to the membership. Additionally, we are always looking for individual contributions from the members, so if you are interested in contributing a valuable piece of information of significance to our profession, please forward it to my attention. All inputs need to be received by no later than the 28^th of the month in order to be considered for the next newsletter.

Thanks for your support,

Paul Kramsky

Message from the OCRA President

Hello OCRA Members,

I hope you are taking advantage of the training opportunities offered by OCRA.  We have some great seminars planned for the fall that will enhance your knowledge in the areas of regulatory and clinical requirements outside the U.S.  We are also moving forward with collaborations with local universities…stay tuned for more information and benefits for OCRA members.

The mission statement for OCRA is as follows:  To provide high quality educational programs to regulatory affairs professionals in the medical products industries, and to offer a neutral forum for the exchange of information regarding issues and activities of interest to our members. Thanks to everyone for your efforts in helping OCRA continue to achieve our common mission.

Remember to also visit the website for current information, career opportunities, or to find a consultant…

www.ocra-dg.org.

Barbara Niksch

Message from the Director FDA - Los Angeles District Office

A few weeks ago, I was installed as President of the Western Association of Food & Drug Officials [WAFDO]. The Western Association of Food and Drug Officials organized for the purpose of improving communication and cooperation with the respective local, state, and federal programs, and for promoting the development and enforcement of uniform food, drug, and consumer protection laws.

The theme of our recent conference was "Fostering Relationships". This got me thinking about other relationships whether professional or personal and the important role they play in our lives. The ability of FDA to accomplish its mission is based, on many factors but "understanding" of the requirements and "voluntary compliance" plays probably the biggest roles.

The Food and Drug Administration (FDA) recognizes that dealing with a large organization can frequently be a time consuming, frustrating experience. Although there is no acceptable panacea, FDA has instituted a number of activities aimed at easing this problem for regulated small businesses. These include the establishment of the Division of Small Manufacturers, International and Consumer Assistance (DSMICA) in the Center for Devices and Radiological Health, Small Business Assistance Programs in the five FDA regional offices, and the creation of small business assistance offices in each of the Centers. These units provide technical assistance to small companies, hold exchange meetings to hear the views and perspectives of small businesses, conduct educational workshops, develop informational materials, and provide an accessible, efficient channel through which small businesses can acquire information from the FDA. The primary purpose of these activities is to increase our communication with the small business community. This, in turn, opens the door for improved understanding and a better working relationship.

Alonza Cruse

Update on Programs

Last month’s program on Regulatory Ethics was well attended (over 40 attendees) and was also well received based on the comments received from those attending. Joyce Williams and Michael Swit did a great job presenting some very valuable information. The case-studies with subsequent discussions were real eye-openers. Would you believe the same situation may have incredibly different interpretations, conclusions, and possible solutions? Early registrations are encouraged in the future so we can better plan the sessions.

Coming on October 19 -- Latin American Regulations

What you need to know to get products approved in Mexico, Central America and South America.

- Program Managers: Kimberly Walker, Rusty Lusk

Imagine a European-style regulatory system in Latin America. What if there were a single “ethics committee” you could go to for clinical trials? Another product mark or Quality System requirement! The presenters are scheduled and planning is all but done.

Have you ever asked or been asked any of the following questions:

· How do you get a product on the market in South America, Mexico or Central America?

· What information is required in a product registration?

· Are there any import or export issues?

· What are the Post-Market requirements?

· Do any of the Latin American countries recognize product approvals in other

· countries? (e.g. If a product is CE marked, would that product be automatically

· acceptable for marketing in a Latin American country?)

· How do any of the above vary for Devices? Drugs? Biologics? Combination

· Products?

· What are the future trends in regulations for Latin America?

In this rapidly changing and demanding regulatory environment, regulatory affairs professionals need to know how to get products approved globally. One of the fastest growing and most diverse markets is Latin America. Many companies assume that there are minimal to no requirements for product approvals and clinical trials in Latin America. Please join us for presentations and group discussions on Latin American Regulations. During this program, you will learn about the various regulations governing device, pharmaceutical and biological products in Latin America from regional experts. Additionally, an update on the changing regulatory environment in South America will be discussed. Is South America the next EU?

Presenters:

Eliana Moraes, Partner, Silva de Moraes Advogados Associados, in São Paulo, Brazil

Sergio Guerrero, MD, VP/COO, Instituto Mexicano de Investigación Clínica, S.A. de C.V. in Mexico City

Register early to reserve your place; to register, go to our website at www.ocra-dg.org. We hope to see you there.

2005 Programming

We are in the early stages of planning 2005. 1^st Qtr is all but done, but there are still openings for the reminder of 2005. We welcome your ideas for monthly meeting topics. Send your suggestions to Rusty Lusk at qualitysys@sbcglobal.net.

For more information, visit our web site at www.ocra-dg.org and stay informed.

Rusty Lusk

Other Educational Opportunities

Risk Management Discussion Group

OCRA held its first Risk Management Discussion Group for pharmaceuticals on May 4 at the FDA district office in Irvine, California. During this meeting, attendees participated in discussions on the application of risk management during three key stages of drug product lifecycle: Product Development, Market Approval, and Commercial Manufacturing / Distribution. The following topics were identified for future meetings which will be held monthly:

· Glossary of Risk Management related terms

· Criteria for Risk Acceptance

· Framework for Risk Communication

· How to determine Risk Profiles

Stay alert for announcements of future meetings of the Risk Management Discussion Groups.

UC Irvine Extension’s Medical Product Development Program

UC Irvine Extension’s Medical Product Development program, which offers a comprehensive body of knowledge in medical device compliance, design and development, is offering OCRA members two discount opportunities. OCRA members qualify for a 10% discount on any continuing education courses in the Medical Product Development or Clinical Trials programs (use discount code OCRA10). In addition, OCRA members will receive a $150 discount on UCI Extension’s Combination Products course only (use discount code OCRA$150). For more information, call (949) 824-6538 or go to:

http://extension.uci.edu/courses/certificate/medical_product.asp.

FDA Center News

Applications for Combination Products May Be Subject to Two User Fees

When two separate applications are submitted for a combination product each application may be assessed a separate user fee, according to a new draft guidance from the FDA on "Application User Fees for Combination Products." To receive new drug product exclusivity, orphan status or proprietary data protection when two firms are involved, some sponsors may choose to submit two applications for a combination product when one application would suffice. In such cases, the FDA will ordinarily require two user fees because, according to the agency, the review of two applications places additional burden on its review resources.

However, sponsors who choose to submit two applications will be eligible for the corresponding exemptions, waivers and reduced fees under the Medical Device User Fee and Modernization Act of 2002 (MDUFMA) or the Prescription Drugs User Fee Act of 1992 (PDUFA). One key waiver the FDA plans to monitor closely is the "barrier to innovation" waiver under PDUFA, which allows sponsors to request a fee waiver when the fee would present a significant barrier to innovation because of a company's limited resources or other circumstances. Single applications for combination products with a device component, such as a drug-device or biologic-device product, will be subject to the fees associated with the type of application required for approval, clearance or licensure. For example, a drug-device combination product for which a premarket approval (PMA) application is required will be subject to the standard PMA user fee under MDUFMA. A biologic-device combination regulated under section 351 of the Public Health Service Act will be subject to the biologics license application fee under MDUFMA, if the biological component meets the definition of a device, while other biologic-device or biologic-drug combination products that are human drug applications will be subject to the fees under PDUFA. The draft guidance on Application User Fees for Combination Products, which will be published in the Sept. 23 Federal Register. It is available at:

http://www.fda.gov/OHRMS/DOCKETS/98fr/2004d-0410-gdl0001.pdf.

REGULATORY HIGHLIGHTS FROM CDER AND CBER

(Contributed by Dan Klassen, Principle Consultant, PAREXEL Consulting)

The following are some of the more notable recent activities within FDA’s Centers for Biologics and Drug Evaluation and Research (CBER and CDER, respectively) with the potential to affect manufacturers in the biologics, biopharmaceutics and drug industries.

New Submission Mailing Address for THERAPEUTIC Biological Products submissions – FDA/CBER/CDER (Posted: 9/27/2004)

On June 30, 2003, FDA transferred some of the therapeutic biological products that had been reviewed and regulated by the Center for Biologics Evaluation and Research (CBER) to the Center for Drug Evaluation and Research (CDER). CDER was given regulatory responsibility for these products, including premarket review and continuing oversight, over the transferred products. However, until now, materials related to these products were still sent to CBER's Document Control Center for tracking and handling.  As of October 4, 2004, all therapeutic biologic submissions (excluding CFR 600.80 postmarketing adverse experience reports; advertising and promotional labeling; and 21 CFR 600.14 biological product deviation reports) are to be sent to the CDER Therapeutic Biological Products Document Room address:

        CDER Therapeutic Biological Products Document Room
        Center for Drug Evaluation and Research
        Food and Drug Administration
 12229 Wilkins Avenue
 Rockville, MD 20852
http://www.fda.gov/cber/transfer/transfer.htm#mail

Guidance for Industry and Clinical Investigators: The Use of Clinical Holds Following Clinical Investigator Misconduct – FDA/CBER/CDER (Posted: 9/2/2004, Publish Date: 9/2/2004)

This guidance describes circumstances in which FDA may impose a clinical hold based on credible evidence that a clinical investigator conducting the study has committed serious violations of FDA regulations on clinical trials of human drugs and biologics, including 21 CFR Parts 312, 50, and 56, or has submitted false information to FDA or the sponsor in any required report. See http://www.fda.gov/cber/gdlns/clinholdinvest.pdf

Guidance for Industry: Independent Consultants for Biotechnology Clinical Trial Protocols – FDA/CBER/CDER (Posted: 8/18/2004)

As a result of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, which included the Prescription Drug User Fee Amendments of 2002 (PDUFA III), commitments were made whereby the FDA were to establish programs intended to facilitate the development and review of human drugs.

One commitment was the establishment of a program that allows a sponsors of clinical trials for certain products, to request FDA, engage an independent consultant to participate in the review of a protocol for a clinical study that is intended to serve as the primary basis of a claim of efficacy. This guidance explains when and how a company may take advantage of this program.

A product qualifies for this program if:

· It is biotechnology-derived (for example, DNA plasmid products, synthetic peptides of fewer than 40 amino acids, monoclonal antibodies for in vivo use, and recombinant DNA-derived products),

· It has the potential to represent a significant advance in the treatment, diagnosis, or prevention of a disease or condition, or to address an unmet medical need, and

· The clinical study at issue is intended to serve as the primary basis of a claim of efficacy.

See http://www.fda.gov/cber/gdlns/bioclin.pdf

Drug Substance Guidance Rewrite Sparks CMC/GMP Boundary Debate (“The Gold Sheet”, Vol.38, No.8, August 2004 )

FDA'S DRUG SUBSTANCE GUIDANCE REWRITE is sparking debate over the role of the marketing application in the agency's evolving quality regulatory paradigm. At issue is how to build more science into the filings in a way that facilitates, rather than encumbers, the review process and later manufacturing improvements. In expressing concern with the level of information requested by the new drug substance guidance draft, industry comments focus in particular on how critical process controls and starting materials are defined and how that information should be conveyed in the filing. The drug substance draft conforms to the common technical document and will aid the evolving conversion to the electronic format. FDA's effort to refine its approach to NDA/ANDA manufacturing change submissions continues with a final version of the 21 CFR 314.70 rule and a revision of the guidance.

Regulatory Tidbits

Question: How many regulatory professionals does it take to change a light bulb?

Answer: It depends on how significant the change is (not to mention the fact that the light bulb has to want to change).

With all seriousness, this isn’t about light bulbs, but a recommendation that companies should implement a standard operating procedure for determining when a change is significant or not. Not withstanding the fact that this is an expectation of regulatory agencies, such a procedure will ensure that decisions as to whether or not a change to a product, be it a drug, device, or biologic, are significant or not, are made thoughtfully, consistently, documented in accordance with the Quality management System, and can be defended. Stay tuned for more on this subject in future newsletters.