![](media/image1.jpeg){width="2.428472222222222in"
height="0.7763888888888889in"}

One Cambridge Center

Cambridge, MA 02142

tel: 617.577.8198

fax: 617.577.7860

[www.massbio.org](http://www.massbio.org/)

July 30, 2004

VIA EMAIL: fdadockets@oc.fda.gov

Food and Drug Administration

Division of Dockets Management

5600 Fishers Lane, Room 1061 (HFA-305)

Rockville, MD 20857

Re: Docket Number \[FR Doc. 04-9147 Filed 4-21-04; 8:45 am\]

Dear Sir or Madam:

On Tuesday, July 20, 2004, a four hour focus group was held at the
Massachusetts Biotechnology Council (MBC) to aid the FDA Critical Path
effort in identifying the most pressing scientific and/or technical
hurdles causing major delays and other problems in the drug, device,
and/or biologic development process, as well as proposed approaches to
their solution.

The MBC gathered over 30 participants from local biotech companies.

The focus group identified the following hurdles and potential
solutions:

Hurdle:

Uncertainty regarding the FDA use of new cellular therapeutic knowledge
generated by genomics, proteomics and imaging technologies.

Solution:

The FDA should be aware of new technologies needed for new therapies and
should be proactive in learning about them. Further it should set
experimental and data analysis guidelines.

Hurdle:

Validation of biomarkers so the FDA accepts them as clinically sound
indicators of efficacy and toxicity.

Solution:

FDA to have an in-house mindset stressing correlation to outcome rather
than mechanism of action (MOA) understanding. The FDA should publicly
disclose the parameters/characteristics it would require for a validated
marker for a clinical endpoint, such as:

1\. Define the threshold for empirical evidence required.

2\. Create universal definitions for biomarker, surrogate, validated
surrogate.

Guidance might have to relate to both disease and therapy because a
disease could be treated with cellular therapy, gene therapy, surgery,
or a drug.

Hurdle:

Lack of accurate end point assays for many diseases makes efficacy
difficult to detect.

Solution:

The FDA could help in defining good markers, and arenas where new
markers are needed or can be improved.

Hurdle:

Long toxicology and pharmacology studies due to slow emergence of
classical end point measures.

Solution:

Shift whenever possible to molecular biomarkers.

Hurdle:

Acceptance of imaging to do pharmacokinetic studies.

Solution:

FDA to specify acceptance criteria for such data.

Hurdle:

Fear of finding sub-group toxicities through using more targeted
techniques inhibits adoption.

Solution:

Share detailed toxicology data on approved drugs to create a large
information base for future drugs, but keep it off limits for modifying
existing drugs. If not, no sponsor will share the data.

Hurdle:

Biomarkers can sub-divide diseases into non-economic units.

Solution:

FDA leadership on cooperative tasks -- encourage three or four companies
to participate cooperatively in clinical trials.

Hurdle:

Current approach makes in uneconomic to create drugs for small diseases.

Solution:

Create new low-cost regulatory processes for small diseases. Better FDA
setting of criteria could reduce trial costs. No specific criteria or
techniques suggested.

Hurdle:

Poor interaction between the FDA and NCI.

Solution:

Combine their information to move forward more quickly ad efficiently.

Hurdle:

Inability to discuss pre-clinical safety and toxicology with the FDA
unless a US clinical trial is underway -- even if foreign equivalent
trials are underway.

Solution:

Do more US clinical trials or pre-clinical meetings for a class of
compound or a target.

Create a mechanism where sponsors can have earlier dialogue when
important decisions are being made before IND or human trials anywhere
in the world.

Hurdle:

Lack of a predictive tool accessible to all companies that could help in
toxicology information and standards in animals.

Solution:

Workshop or guidance with chapters on toxicology study and what to
continue what to stop, review management, practice guideline and
toxicology support.

Hurdle:

Lack of experimental data sharing leads to duplicative testing and
associated time delays and costs.

Solution:

Create ways to share information that has been sanitized to protect
proprietary compound. Sponsors will require incentives to share
information and maintain that data. FDA will also need to set standards
for this type of data to enable comparability and technical exchange.

Hurdle:

Failures are not published -- impossible to learn from failures

Solution:

Start a journal of failed clinical studies.

Hurdle:

Killing drugs early and looking at exploratory IND.

Solution:

Ability to look at others' information to learn from successes/failures.

Hurdle:

Uncertainty regarding the differences between exploratory IND and the
traditional IND.

Solution:

A guidance will be out soon.

Hurdle:

FDA does not have all the answers

Solution:

Network with experts in academia, NIH, and industry to address
questions.

Hurdle:

Time delays with the FDA -- debilitating to sponsors.

Solution:

Sponsors must follow FDA's instructions exactly.

A transcript of the focus group session is available upon request.

Respectfully submitted,

Massachusetts Biotechnology Council

MT:lmw