Part Two of Two: Best Practices

This is the second of a two-part article discussing the use of Best Practices (BPs) in the growing drug/device (DD) combination products industry. This part details how founders/executives of three start-up DD companies use Best Practices to work effectively with the Food and Drug Administration (FDA). It lends insightful views of their interactions with the FDA, along with links to important FDA websites.

As explained in Part One of this series, a DD, combining a medical device and a drug, opens up new treatment possibilities, offering better methods of introducing medication and/or enhancing the actions of pre-existing treatments.

Part One explains that for many DD companies, the common thread is to customize BPs: to provide insight, personal responsibility, and unity of purpose to enable companies to make the best possible use of their diverse staff in order to produce the best possible products.

Following are dialogues with three executives (also from Part One): Joe Tondu, managing director, Actium Biosystems, Boulder, CO; Matthew J. Kyle, president, CEO, Circle Biologics, Minneapolis, MN (www.circlebiologics.com), and Bruce A. Hazuka, currently advisor and former chairman and CEO, Bone Biologics Inc., Thousand Oaks, CA, (www.bonebiologics.com).

Regarding the FDA
If a drug/device company wants to run a pharmacoepidemiological trial, it is required that the FDA guidelines be followed. Yet, this road can prove to be difficult; as start-up DD companies often need to hurdle numerous FDA regulations to achieve the privilege of selling their products, and in some cases, manufacturing their products. However, employing BPs in dealings with the agency often facilitates the sometimes-arduous approval process.

The bottom line is that the FDA gives their stamp of approval, in order to market and distribute the products to the medical community. The FDA further advises on how to develop the devices/products so that they conform to safety, efficiency, and to good manufacturing practices. Yet, the agency requires each company to devise its own methods of efficiency and regulatory compliance.

Applying BPs to the FDA
Joe Tondu of Actium Biosystems – a company developing thermally enhanced chemotherapy treatment via a combination of quantum particles and a chemotherapy agent – explains that no single set of BPs applies to all companies.

“Actium chooses from among the best practices of other device and pharmaceutical companies and adapts them for our own purposes. By customizing these practices, we have avoided a one size fits all view of these methods,” Tondu notes.

Tondu summarizes what his company regards as the ideal role for the FDA, stating that, “the agency should publicize the fact that their Good Manufacturing Practices (GMP), Good Clinical Practices (GCP), and Good Laboratory Practices (GLP) are indeed BPs that companies would benefit from following, rather than only offering difficult to follow regulatory processes.”

He would like the FDA regulatory relationship to be more helpful and user-friendly.

Matthew Kyle from Circle Biologics – a company focusing on using blood, bone marrow, and adipose tissue to process growth factors and stem cells – envisions a movement toward the European Union (EU) model of notified bodies, which uses a third-party entity to audit companies that report back to the EU regarding compliance with an agreed upon set of rules. He would also like to see the FDA employ a more collaborative new device application, engage in more dialogue, shorthanded processes, increased clarity in the device approval process, more proactive review teams, and better communication, instead of the current, somewhat adversarial process.

Kyle’s company also deals with the Center for Biologics Evaluation and Research Division (CBER) of the FDA: “They have been very collaborative and our experience with them has been very positive. CBER represents a progressive front for the FDA.”

Bruce A. Hazuka of Bone Biologics – a company developing a bioactive recombinant protein to promote bone growth and repairs – developed his BPs/FDA synergy through interactions with other pharmaceutical and medical device companies and with previous FDA involvement. He says that the FDA does an excellent job of following their mandate from Congress, and that it is industry’s job to manage effectively within this framework, in a proactive manner.

He adds, “When the agency tells you what they require either directly or indirectly, your response should provide them with cogent, well-documented data that address their concerns.”

Hazuka’s general philosophy is: Train all staff in BPs; create a mission statement and make products that improve patient outcomes; operate with respect to all personnel and keep your investors in mind; comply with all FDA regulations and legal requirements, while being interactive with the agency.

FDA Checklist
Best Practices LLC, Chapel Hill, NC, provides a checklist for companies using BPs in navigating the FDA approval process. These following six points, among several others, affirm the need to follow rules assiduously, take no shortcuts, and communicate regularly within your company and with the FDA.

1. Establish effective communication between your company and the FDA at each stage of this process. The company strongly stresses that though science remains the fundamental engine behind successful new drug applications, effective communication between pharmaceutical companies and the FDA at each stage of this process stands as a vital ingredient in securing approval for a new therapy.

2. Align regulatory staff structure within your company to reflect the structure of key FDA offices and divisions.

3. Keep regulatory the centralized leader in all interactions with the FDA.

4. Follow a chain of command when working with the FDA.

5. Establish a positive reputation with the FDA and in Washington.

6. When managing an NDA, avoid level-skipping to accelerate a decision. Level-skipping can cause longer-term resentment, distrust, and harm to your NDA within the FDA. A single point of contact for FDA communications during the NDA process is, by many companies, considered the most effective approach to creating and maintaining successful interactions with the agency.

From the FDA...
The companies discussed in this article deal with combination medical drug device products, which the FDA acknowledges can raise regulatory challenges, “because they involve components that were normally regulated under different types of authorities and often by different FDA Centers.” [Reference: http://1.usa.gov/VVcynV]

The FDA defines combination products as “therapeutic and diagnostic products that combine drugs, devices, and/or biological products.”

Assistance to device manufacturers is available from the FDA, with which these companies must interact to put their products on the market. Through its programs and staff assistance, the FDA offers education, advice, fellowships, and guidance at http://1.usa.gov/10itiNm.

A medical device company can request assistance via email to the FDA’s Division of Small Manufacturers, International, and Consumer Assistance (DSMICA). According to the U.S. Department of Health and Human Services, the FDA’s Center for Devices and Radiological Health (CDRH) provides information to help industry comply with FDA regulations. Information is recently available about regulatory decisions and decision rationales, and descriptions of regulatory processes. The FDA has provided data to support CDRH actions and public health activities in support of the FDA Transparency Initiative.

Three useful documents are:

1. “Guidance for Industry, Third Parties and Food and Drug Administration Staff – Medical Device ISO 13485:2003 Voluntary Audit Report Submission Pilot Program” – http://1.usa.gov/SmqkEb

2. “Investigational Device Exemption (IDE) Pivotal Study Summary Form (Updated)” – http://1.usa.gov/VmIYeu

3. “Overview of Medical Devices and Their Regulatory Pathways” – http://1.usa.gov/VVcynV

And, with medical devices, details of the FDA rules are in the Quality System Regulation (QSR) – http://1.usa.gov/10itcoU.

In addition, each DD company interacts with one or more entities: the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and Radiological Health (CDRH).